Manual of Dermatologic Therapeutics
7th Edition
© 2007 Lippincott Williams & Wilkins
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40
Formulary
Shih-Ping Hsu
This chapter includes the topical and systemic medications most useful in treating cutaneous disease. Drugs are listed alphabetically in each instance. This chapter is not a complete listing of all the pharmaceutical preparations available for dermatologic use, and many useful products may have been omitted. For uniformity and ease of conversion, all package sizes are listed in metric terms (Table 40-1). Medications that require a prescription are noted by Rx.
Acne Preparations
I. Discussion
See Chap. 1.
II. Prescription Drugs
  • Isotretinoin (13-cis-retinoic acid, Accutane, Amnesteem)
    • Structure: cis isomer of tretinoin.
    • Use: See Chap. 1. Note: Patients allergic to parabens will also react to isotretinoin, which contains these agents as preservatives. Isotretinoin also contains glycerin and ethylenediamine tetraacetic acid (EDTA) in a soybean suspension. Isotretinoin is also useful in disorders of keratinization.
    • Adverse effects: Isotretinoin is teratogenic to humans and should not be administered to pregnant women or women contemplating pregnancy. Refer to Chap. 1 for a complete list of adverse effects. Concomitant use of isotretinoin with drugs of the tetracycline class increases the incidence of Pseudotumor cerebri. There have been recent reports of an increased risk of depression, suicide, and suicide attempts in individuals taking isotretinoin, but the causality has not been absolutely proved. The manufacturers have formulated a new informed consent to reflect these concerns. No population-based studies have documented this risk to date. The manufacturers have also initiated risk management programs to prevent adverse outcomes. The U.S. Food and Drug Administration (FDA) approved a combined program named iPledge.
    • Packaging:
      • Isotretinoin soft gelatin capsules, 10 mg, 20 mg, 30 mg, 40 mg: packs of 10.
  • Spironolactone
    • Structure: Synthetic steroid that resembles aldosterone.
      TABLE 40-1 Metric Measures with Approximate Equivalents
      Liquid measure Weight Length (exact equivalents)
      4000.0 mL = 1 gal (4 qt) 1 kg = 2.20 lb (Av.) 1 m = 39.37 in.
      30.48 cm = 1 ft.
      1000.0 mL 0.454 kg = 1 lb 2.54 cm = 1 in.
      (1 L) = 1 qt (32 oz) 454 g = 16 oz (lb Av.) 1 cm = 0.39 in.
      1 mm = 0.04 in.
      500.0 mL = 1 pt (16 oz) 30 g = 1 oz
      4 g = 60 gr (1 dr)      		  
      250.0 mL = 8 fluid oz 1 g = 15 gr
      30.0 mL = 1 fluid oz 60 mg = 1 gr
      15.0 mL = 1 tbsp  
      5.0 mL = 1 tsp
      4.0 mL = 1 dr
      0.06 mL = 1 minim, the rough equivalent of 1 drop
      Note: 1 milliliter (mL) = 1 cubic centimeter (cc): Most of these approximate dose equivalents have been approved by the U.S. Food and Drug Administration. They may be used as a convenience in prescribing, but must not be used for compounding specific pharmaceutical formulas.
      • P.274

    • Use: See Chap. 1. Also useful for other androgen-responsive disorders such as hirsutism. Poor tolerance in men owing to adverse endocrine side effects.
    • Packaging (Searle):
      • Spironolactone: 25-mg, 50-mg, 100-mg tablets
  • Tretinoin (vitamin A acid, Retin-A, Retin-A Micro, Avita, Renova)
    • Structure: trans-Retinoic acid.
    • Contains: 0.05% tretinoin (vitamin A acid) in the liquid; 0.1%, 0.05%, or 0.025% in the cream; and 0.01%, 0.025%, or 0.04% in the gel. The 0.025% cream or 0.01% gel is usually the least irritating. Tretinoin does not function as a vitamin in this therapy.
      Retin-A Micro gel 0.1% and 0.04% contain small time-released microsponges that are designed to release the drug slowly into the upper layer of skin and, therefore, to decrease irritation. Avita cream 0.025% and gel 0.025% contain a large polymer that also releases the drug slowly.
      Renova was formulated in a water-in-mineral oil emollient base for the mature complexion and for the indication of photoaging. This product could conceivably make acne worse because of the base.
      • P.275

    • Use: See Chap. 1. Tretinoin is a photosensitizing agent. Therapy need not be discontinued during times of increased ultraviolet (UV) exposure, but patients should be instructed in photoprotection. Tretinoin does not function as a vitamin in this therapy.
    • Packaging (many companies):
      • Avita, 0.025% cream, 0.025% gel: 20-g, 45-g tube
      • Renova, 0.02%, 0.05%, cream: 20-g, 40-g, 60-g tube
      • Retin-A Micro gel, 0.1%, 0.04%: 20-g, 45-g
      • Tretinoin 0.05% liquid: 28-mL bottle
      • Tretinoin 0.025%, 0.05%, 0.1% cream: 20-g, 45-g tube
      • Tretinoin 0.01%, 0.025% gel: 15-g, 45-g tube
  • Tazarotene (Tazorac)
    • Structure: Retinoid prodrug, converted to active form, the carboxylic acid of tazarotene by rapid de-esterification. This drug binds to all three retinoic acid receptors with some increased affinity for the β and γ receptors.
    • Use: See Chap. 1. Also useful in treatment of plaque psoriasis. Tazorac is a Pregnancy Category X drug; adequate birth control measures should be emphasized with women in their childbearing years.
    • Packaging:
      • Tazarotene 0.05%, 0.1% gel: 30-g, 100-g tube
      • Tazarotene 0.05%, 0.1% cream: 15-g, 30-g, 60-g tube
  • Adapalene (Differin)
    • Structure: Retinoid-like compound that binds to retinoic acid nuclear receptors, but not to cytoplasmic receptor proteins.
    • Contains: 0.1% solution in 30% alcohol.
    • Use: See Chap. 1.
    • Packaging:
      • Adapalene 0.1% solution: 30-mL bottle
      • Adapalene 0.1% cream: 45-g tube
      • Adapalene 0.1% gel: 45-g tube
      • Adapalene 0.1% pledgets: 60/box
  • Benzoyl peroxide preparations [also available over the counter (OTC)]
    • Structure: (Owing to the myriad of manufacturers and products, the following consists of only a partial list of the available preparations.)
    • Contains: 2.5%, 3%, 4%, 5%, 6%, 8%, 9%, or 10% benzoyl peroxide, oil-base lotion alcohol gel base (PanOxyl/AQ); aqueous gel base (Benzac W, Desquam-E, Desquam-X); aqueous base cleanser with EDTA (Desquam-X Wash), glycerin base cleanser (Benzac AC Wash), aqueous base cleanser with menthol, glycolic acid, lactic acid, and zinc (Triaz).
    • Use: See Chap. 1.
    • Packaging:
      • Benzagel wash, 10%: 60 g
      • Benzac 5%, 10% gel: 60 g
      • Benzac AC gel 2.5%, 5%, 10%: 60 g, 90 g
      • Benzac AC liquid wash 2.5%, 5%, 10%: 8 oz
      • Benzac W gel 2.5%, 5%, 10%: 60 g, 90 g
        • P.276

      • Benzac W liquid wash 5%, 10%: 4 oz, 8 oz
      • Brevoxyl gel 4%, 8%: 42.5 g, 90 g
      • Brevoxyl cleanser 4%, 8%: 170 g
      • Desquam-E gel 5%, 10%: 42.5 g
      • Desquam-X gel 5%, 10%: 42.5 g, 85 g
      • Desquam-X bar, 10%: 106 g
      • Pan Oxyl gel, 5%, 10%: 56.7 g, 113.4 g
      • Pan Oxyl AQ gel 2.5%, 5%, 10%: 56.7 g, 113.4 g
      • Triaz liquid 3%, 6%, 9%, 10%: 81.5 g, 170.3 g, 340.2 g
      • Triaz gel 3%, 6%, 9%, 10%: 42.5 g
      • Triaz pad 3%, 6%, 9%: 30/box
  • Topical antibiotics
    • Clindamycin phosphate (Cleocin T, Clindets, Clindagel, ClindaMax)
      • Contains: 10 mg/mL clindamycin as phosphate in 50% isopropyl alcohol and propylene glycol solution, in methylparaben as a topical gel or lotion, or in isopropyl alcohol as pledgets.
      • Structure: Semisynthetic derivative of lincomycin.
      • Use: See Chap. 1. Contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.
      • Packaging:
        • Clindamycin phosphate 1% suspension: 30 mL, 60 mL
        • Clindamycin phosphate 1% gel: 30 g, 60 g
        • Clindamycin phosphate 1% lotion: 60 mL
        • Clindamycin phosphate 1% pledgets: 60/box
    • Erythromycin base solution
      • Contains: Erythromycin base in propylene glycol and alcohol solution. The alcohol content is 92% (Erygel), 77% (EryDerm), 71% (T-stat), 66% (A/T/S), and 55% (Staticin).
      • Structure: Macrolide antibiotic derived from Streptomyces erythreus.
      • Use: See Chap. 1.
      • Packaging: The following consists of a partial list of all available preparations.
        • Akne-mycin, 2% ointment: 25 g
        • A/T/S, 2% gel: 30 g
        • A/T/S, 2% solution: 60 mL
        • Emgel, 2% gel: 27 g, 50 g
        • EryDerm, 2% solution: 60 mL
        • Erygel, 2% gel: 30 g, 60 g
        • Staticin, 1.5% solution: 60 mL
        • T-stat, 2% solution: 60 mL
        • T-stat, 2% pads: 60/box
    • Metronidazole (MetroCream, MetroGel, MetroLotion, Noritate)
      • Contains: 0.75% and 1.0% metronidazole with parabens (MetroGel), with benzyl glycol (MetroCream) or benzyl alcohol, glycerin, and mineral oil (MetroLotion); 1% metronidazole with parabens (Noritate). Patients with parabens allergies may react to formulations containing this product.
      • Use: See Chap. 28.
      • Packaging:
        • MetroCream 0.75% cream: 45 g
        • MetroGel 0.75% and 1.0% gel: 28.4 g, 45 g
        • MetroLotion 0.75% lotion: 59 mL
        • Noritate 1% cream: 30 g
    • Sodium sulfacetamide (Klaron, Novacet, Sulfacet-R, Vanocin, Plexion, and others)
      • Mechanism of action: Postulated to act as a competitive inhibitor of para-amino benzoic acid (PABA), which is essential for bacterial growth.
      • Contains: 10% sodium sulfacetamide with 5% sulfur [Novacet, Plexion, Vanocin), with parabens (Sulfacet-R)]. Patients with allergies to parabens
        P.277

        may react to Sulfacet-R. Some contain tints to camouflage the erythema associated with rosacea (Avar Green).
      • Packaging:
        • Avar cleanser 10%/5%: 226.8 g
        • Avar Gel 10%/5%: 45 g
        • Avar Green Gel 10%/5%: 45 g
        • Clenia Cream 10%/5%: 28 g
        • Clenia Foam 10%/5%: 170 mg, 340 mg
        • Klaron 10% lotion: 59 mL
        • Nicosyn Lotion 10%/5%: 45 g
        • Novacet 10% lotion/5% sulfur: 30 mL,
        • Plexion 10% cleanser/5% sulfur: 170 g, 340 g
        • Plexion SCT Cream 10%/5%: 120 g
        • Rosanil Cleanser 10%/5%: 170 g
        • Rosula Gel 10%/5%: 45 mL
        • Sulfacet-R 10% lotion/5% sulfur: 25 mL
        • Vanocin 10% lotion/5% sulfur: 30 g, 60 g
  • Oral antibiotics. Indicated for inflammatory papulopustular acne (see Chap. 1)
    • Tetracycline (Sumycin)
      • Dosage: 1 to 2 g/day divided every 6 hours. Once improvement is noted, dosage may be reduced to 125 to 500 mg/day for maintenance.
      • Adverse effects: Photosensitivity, abdominal discomfort, oral and vaginal yeast infections, onycholysis, discoloration of the nails, gram-negative folliculitis, glossitis, and cheilitis. Medication deposits in growing teeth and bones, and hence it is contraindicated during pregnancy, lactation, and childhood (<12 years of age). It may potentiate lithium and oral anticoagulants, as well as antagonize aminoglycosides and penicillins. May decrease effectiveness of oral contraceptives. Avoid administration with milk, meals, or antacids. Adjust dosage with renal impairment. P. cerebri may develop and must be managed expediently.
      • Packaging:
        • Tetracycline capsules: 250 mg, 500 mg
        • Tetracycline oral suspension, 125 mg/5 mL: 473 mL
    • Doxycycline (Vibramycin, Monodox, Doryx, Periostat, Vibra-Tabs)
      • Dosage: 50 mg b.i.d. to q.i.d.; 100 mg q.d. to b.i.d. Recent evidence suggest that sub-antimicrobial dose of 20 mg b.i.d. is also effective. No dosage adjustments needed for renal impairment.
      • Adverse effects: Same adverse effects as tetracycline. Doxycycline is the most significant photosensitizer of all the tetracyclines and its use should be avoided during increased UV exposure. May be taken with food and/or milk products.
      • Packaging:
        • Doxycycline capsules: 20 mg, 50 mg, 75 mg, 100 mg
        • Doxycycline powder for oral suspension: 25 mg/5 mL when reconstituted
        • Doxycycline syrup, 50 mg/5 mL: 473 mL
        • Doxycycline tablets: 50 mg, 75 mg, 100 mg
    • Minocycline (Minocycline HCl, Dynacin, Minocin, Vectrin)
      • Dosage: Up to 200 mg daily in divided doses.
      • Adverse effects: Vestibular reactions including headache and vertigo, abdominal discomfort, onycholysis, blue-gray pigmentation of the oral mucosa and sites of cutaneous inflammation or trauma, as well as generalized muddy brown pigmentation in sun-exposed regions. May possibly decrease effectiveness of oral contraceptives containing estrogens. Drug-induced systemic lupus erythematosus, leukemoid reaction, serum sickness–like reaction, pulmonary edema, pulmonary infiltrates with eosinophilia, and P. cerebri
        P.278

        have been described and require expedient care. Photosensitivity is less common than with other tetracyclines. May be taken with food and/or milk products.
      • Packaging:
        • Minocycline capsules: 50 mg, 75 mg, 100 mg
        • Minocycline oral suspension, 50 mg/5 mL: 60 mL
        • Minocycline pelleted capsules: 50 mg, 100 mg
    • Erythromycin (Erythromycin base, EES, Ery-tabs, PCE Dispertab, erythrocin stearate, E-mycin)
      • Dosage: 1 g/day in divided doses.
      • Adverse effects: Abdominal pain, nausea, vomiting, and diarrhea are generally dose related. Inhibits cytochrome P-450 microsomal enzyme system and thereby decreases hepatic metabolism of some drugs, including cyclosporine, theophylline, carbamazepine, lovastatin, bromocriptine, and disopyramide. Dose adjustments of these medications must be made accordingly.
      • Packaging: Available in enteric-coated or time-release forms to reduce amount of gastrointestinal irritation.
        • Erythromycin tablets: 250 mg, 333 mg, 400 mg, 500 mg
    • Trimethoprim-sulfamethoxazole [Bactrim (DS), Cotrim (DS), Septra (DS), Trimpex]
      • Contains: 80 mg trimethoprim and 400 mg sulfamethoxazole; DS contains 160 mg trimethoprim and 800 mg sulfamethoxazole. Trimethoprim is available as a single agent in a dose of 100 or 200 mg.
      • Dosage: One to two tablets a day. Trimethoprim is dosed at 200 mg/24 hours given either q.d. or b.i.d.
      • Adverse effects: Nausea, vomiting, and anorexia are generally dose related. Hypersensitivity reactions (including Stevens-Johnson syndrome and hematologic reactions) occur in <5% of patients.
      • Packaging:
        • Trimethoprim-sulfamethoxazole tablets: single or double strength (DS).
  • Other topicals
    • Benzamycin
      • Contains: 3% erythromycin and 5% benzoyl peroxide in 16% alcohol.
      • Use: Apply one to two times a day. Note: Refrigerate after mixing.
      • Packaging:
        • Benzamycin gel: 23 g, 46 g
    • Azelaic acid (Azelex, Finacea)
      • Mechanism of action: Naturally occurring dicarboxylic acid that is bacteriostatic to Propionibacterium acnes. It also decreases conversion of testosterone to 5πga-dihydrotestosterone (DHT) and alters keratinization of the microcomedone. It may also be beneficial in the treatment of melasma. The mechanism of action is not fully understood. Deoxyribonucleic acid (DNA) synthesis is reduced, and mitochondrial cellular energy products are inhibited in melanocytes.
      • Use: Apply to face b.i.d.
      • Packaging:
        • Azelaic acid cream 20%: 30 g, 50 g
        • Azelaic acid gel 15%: 30 g
    • Clindamycin/benzoyl peroxide combination (BenzaClin, Duac)
      • Contains: 1% clindamycin and 5% benzoyl peroxide in an aqueous-based gel.
      • Use: Apply one to two times a day. This topical combination is contraindicated in individuals with a known sensitivity to lincomycin or with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.
      • Packaging:
        • BenzaClin gel: 25 g
        • Duac gel: 45 g
P.279

III. OTC Drugs
  • Structure of common ingredients
  • Abrasive soaps
    • Brasivol
      • Contains: Aluminum oxide particles in a surfactant cleansing base.
      • Use: See Chap. 1.
      • Packaging:
        • Fine, medium, or rough grain
    • Pernox
      • Contains: Polyethylene granules, 2% sulfur, 1.5% to 2% salicylic acid in EDTA.
      • Use: See Chap. 1.
      • Packaging:
        • Pernox cleanser: 2 oz, 4 oz
        • Pernox lotion: 4 oz
  • Cleansers (only a few OTC products are listed in the following text)
    • Aveeno Cleansing Bar for Acne
      • Contains: 0.5% salicylic acid, 38% colloidal oatmeal, glycerin, and titanium dioxide. Soap-free.
      • Use: q.d. to b.i.d.
      • Packaging:
        • Bar: 85 g
    • Basis All Clear Bar
      • Contains: Triclosan, tea tree oil, glycerin.
      • Use: q.d. to b.i.d.
      • Packaging:
        • Bar: 113 g
    • Clearasil Antibacterial Soap
      • Contains: Triclosan
      • Use: q.d. to b.i.d.
      • Packaging:
        • Bar: 92 g
    • Clinique Antiacne Soap
      • Contains: 8% sulfur, 1% resorcinol.
      • Use: q.d. to b.i.d.
      • Packaging:
        • One bar
    • Neutrogena Medicated Cleansing Pads
      • Contains: 0.14% benzethonium chloride, witch hazel extract, octoxynol-9, methylparaben, menthol, peppermint, eucalyptus oil, rosemary oil, and camphor.
      • Use: q.d. to b.i.d.
      • Packaging:
        • Individual pads: 40/box
    • Seba-Nil Cleansing Mask
      • Contains: SC alcohol-40, castor oil, and methylparaben.
      • Use: p.r.n. for oily skin.
      • Packaging:
        • Mask: 105 g
      • P.280

    • Stri-Dex Acne Medicated Pads
      • Contains: 0.5% salicylic acid (regular strength, sensitive skin pads) and 2% salicylic acid (maximum strength, super scrub pads).
      • Use: q.d. to b.i.d.
      • Packaging:
        • Regular strength, jar: 55 pads
        • Maximum strength, jar: 32, 55, 90 pads
        • Sensitive skin pads, jar: 55, 90 pads
        • Super scrub pads, jar: 55 pads
  • Other drying and antiseptic topicals. Although benzoyl peroxide, retinoic acid preparations, and topical antibiotics are the drugs of choice, a partial list of other acne medications are listed here for comparison of ingredients.
    • Acnomel cream
      • Contains: 8% sulfur, 2% resorcinol, and 11% alcohol in tinted vehicle.
      • Use: Apply one to two times daily.
      • Packaging:
        • Bottle: 28 g
    • Clearasil Adult Care
      • Contains: 8% sulfur and 1% resorcinol.
      • Use: Apply one to two times daily.
      • Packaging:
        • Bottle: 18 g
    • Liquimat lotion
      • Contains: 4% sulfur and 22% alcohol in tinted lotion in five shades.
      • Use: Apply one to three times daily.
      • Packaging:
        • Bottle: 45 mL
Anesthetics for Topical Administration
See Antipruritic and External Analgesic Agents for more details.
I. Discussion
Before the advent of EMLA (eutectic mixture of local anesthetics) cream, topical anesthetics had limited use because the stratum corneum provided an intact barrier through which anesthetic agents could not penetrate. In addition, although benzocaine was previously considered the most effective of the topical anesthetics, it was rarely used because of its potent sensitization capacity. EMLA represents a breakthrough in transdermal delivery of anesthesia. By combining lidocaine and prilocaine, the hydrophilic and lipophilic properties of each are enhanced, thereby allowing penetration through cornified skin. Topical anesthetics provide some relief from pain in a variety of situations, including superficial surgery, split-thickness skin grafts, venipuncture, laser surgery, epilation, and debridement of infected ulcers. Other potential uses include postherpetic neuralgia and painful ulcers. Because mucosal surfaces lack a stratum corneum, the older anesthetic agents may be used in aphthous stomatitis, primary or recurrent herpes simplex infections, or painful condyloma after treatment. Additional topical anesthetics, including LMX 4% and 5%, 4% tetracaine gel, and betacaine-LA ointment, have been developed for transdermal delivery of anesthesia. Note: With topical anesthetics, esters are potential sensitizers. It is rare for amides to induce a contact dermatitis.
Amides
  • Bupivacaine
  • Carticaine
  • Dibucaine
  • Etidocaine
  • Lidocaine
  • Mepivacaine
  • Oxethazaine
    • P.281

  • Prilocaine
  • Ropivacaine
Aminobenzoate esters
  • Amylocaine
  • Benzocaine
  • Butacaine
  • Butyl aminobenzoate
  • Chloroprocaine
  • Cocaine
  • Isobucaine
  • Meprylcaine
  • Oxybuprocaine
  • Piperocaine
  • Procaine
  • Propoxycaine
  • Tetracaine hydrochloride
Nonamide, nonaminobenzoate esters
  • Benzyl alcohol
  • Cyclomethycaine sulfate
  • Diperodon
  • Dyclonine hydrochloride
  • Pramoxine hydrochloride
Local Anesthetics
Selected brand names are given, but some agents are available as generic products.
II. Prescription Drugs
  • EMLA
    • Contains: 5% eutectic mixture of 2.5% lidocaine and 2.5% prilocaine in an oil-in-water emulsion cream.
    • Use: Application of 1/2- to 1-in. thick EMLA cream to treatment site 1 to 2 hours before a procedure, under occlusion, provides safe and effective analgesia. The duration of action depends on both the amount of cream applied and the time under occlusive dressing. There are guidelines for use of EMLA in the pediatric population.
      Age and weight Maximum dose (g) Maximum area (cm2) Maximum application time (h)
      Up to 3 mo or 5 kg 1 10 1
      3–12 mo and 5–10 kg 2 20 4
      1–6 y and 10–20 kg 10 100 4
      7–12 y and <20 kg 20 200 4
    • Adverse effects: Minimal: include transient blanching or vasodilation and erythema with longer application. One case of methemoglobinemia in a child who had prolonged application of EMLA and who had also received sulfamethoxazole has been reported.
    • Structure
      • P.282

    • Packaging:
      • EMLA cream: 5-g tube with Tegaderm dressing
      • EMLA cream: 30-g tube without dressing (must supply own plastic wrap)
  • LMX
    • Contains: 4% to 5% lidocaine in a liposomal vehicle
    • Use: Apply to treatment site 15 to 45 minutes before procedure. No occlusion is required.
    • Packaging:
      • ELA-Max cream: 5-g tube box of 5, 30 g
  • Betacaine gel
    • Contains: Lidocaine 5%. Also contains an epinephrine-like vasoconstricting agent. FDA approval pending.
    • Use: Apply to treatment site 30 to 35 minutes before procedure. No occlusion required.
    • Packaging:
      • 10- and 30-g tubes, or 100-g pump bottle
  • Dyclonine HCl
    • Structure
    • Contains: Synthetic organic ketone, related in structure to antihistamine.
    • Use: Provides anesthesia of mucous membranes. Apply 5 to 10 minutes before a procedure; apply b.i.d. to t.i.d. for pain relief. Onset of action is within 2 to 10 minutes. Anesthesia lasts 30 to 60 minutes.
    • Packaging:
      • Dyclone, 0.5%, 1% solution: 1 oz
  • Dibucaine HCl is an amide-like quinoline derivative and is one of the most potent and longest acting of the commonly used local anesthetics.
    • Structure (amide-like quinoline derivative)
    • Contains: 0.5% cream in acetone, glycerin; 1% ointment in acetone, lanolin, mineral oil, and petrolatum.
    • Packaging:
      • Nupercainal 0.5% cream: 42.5 g
      • Nupercainal, 1.0% ointment: 30 g, 60 g
  • Lidocaine HCl (Lidocaine, Xylocaine, Anestacon, Dentipatch, Zilactin-L, Solarcaine, Burn-O Jel, DermaFlex, Lidoderm)
    P.283

    • Structure: Amine acyl amide anesthetic.
    • Contains: 0.5% to 5% lidocaine in cream, gel, ointment, jelly, spray, patch, or solution; dental patches.
    • Use: Apply to affected site 5 to 10 minutes before procedure. Duration of anesthesia is relatively short (<1 hour).
    • Packaging:
      • Lidocaine cream, 0.5%, 4%: 5 g, 30 g, 120 g
      • Lidocaine gel, 0.5%, 2.5%: 15 g, 85 g, 120 g, 240 g
      • Lidocaine jelly, 2%: 15 mL, 240 mL
      • Lidocaine ointment, 5%: 50 g
      • Lidocaine viscous solution, 2%, 4%: 20 mL, 50 mL, 100 mL, 450 mL
      • Lidocaine spray, 0.5%: 135 mg
      • Lidocaine liquid 2.5%: 10 mL
      • Lidocaine patch 5%: cartons of 30 patches
III. Nonprescription Drugs
  • Benzocaine
    • Structure: Ethyl aminobenzoate, a para-aminobenzoate derivative (PABA)
    • Contains: PABA-based anesthetic. Patients allergic to PABA may react to this medication and other anesthetics based on PABA (i.e., dibucaine, cocaine, procaine, monocaine, tetracaine, and propoxycaine). These patients may have a cross-sensitivity to products containing paraphenylenediamine, sulfonamides, hydrochlorothiazide, and PABA-containing sunscreens as well.
    • Use: Apply to a maximum of three to four times a day to the affected area, as directed by the physician.
    • Packaging: Numerous brands and formulations available, both OTC and by prescription. The following is an abbreviated list of these products.
      • Anbesol liquid or gel, 6.3% benzocaine with 0.5% phenol, povidone-iodine, 70% alcohol, camphor, and menthol (OTC): 9 mL, 22 mL
      • Benzodent ointment, 20% benzocaine with 0.4% eugenol and 0.1% hydroxyquinoline sulfate in a denture adhesive–like base (OTC): 7.5 g, 30 g
      • Cetacaine aerosol, gel, liquid, ointment, 14% benzocaine, 2% tetracaine HCl, 2% butamben, and 0.5% benzalkonium chloride in a water-soluble base (Rx): 30 g, 60 g, 75 mL, 150 mL
      • Dent’s Extra Strength Toothache Drops and Gum (OTC): 1 g
      • Lanacane Maximum Strength Creme, 20% benzocaine, glycerin in water-soluble base (OTC): 1 oz
      • Orajel Mouth-Aid gel, 20% benzocaine with benzalkonium chloride and 0.1% zinc chloride and saccharin (OTC): 10 g
    • P.284

  • Pramoxine HCl (Prax, PrameGel, Tronothane HCl, AmLactin AP, Itch-X, Bactine)
    • Structure: Ether-like topical anesthetic. Resembles antihistamine.
    • Contains: 1% pramoxine HCl.
    • Use: Apply to affected area t.i.d. to q.i.d., as directed by a physician. Useful for patients sensitive to ester and/or amide anesthetics. Onset of anesthesia is within minutes. Duration of anesthesia is 2 to 4 hours.
    • Packaging:
      • Pramoxine 1% cream: 28.4 g, 30 g, 113.4 g, 140 g, 1 lb
      • Pramoxine 1% lotion: 15 mL, 120 mL, 240 mL
      • PrameGel, 1% gel: 35.4 g, 118 g
      • Pramoxine 1% spray: 60 mL
      • Pramoxine 1% wipes: in 16s
Antihistamines
I. Discussion
These drugs bear a close structural resemblance to histamine and antagonize the pharmacologic actions of histamine by occupying histamine receptor sites, but only if histamine has not yet reached its target receptors (competitive inhibition). Antihistamines do not elicit any direct effect at the receptor sites, affect antibody production or antigen–antibody interactions, react chemically with histamine, or prevent histamine’s release. They may diminish capillary permeability to substances other than histamine and may also have a mild local anesthetic effect.
There are two types of histamine receptors, H1 and H2, and two corresponding groups of antihistamines. Classic antihistamines (H1 blockers) do not alter gastric acid secretion. H2 antagonists decrease gastric acid secretion and find their greatest utility in the treatment of peptic ulcer and related diseases. Cutaneous blood vessels possess both H1 and H2 receptors. If histamine is experimentally injected into the skin, combined H1 and H2 blockade reduces the histamine response better than either agent alone. The combination of H1 and H2 antihistamines is effective therapy for dermatographism, cold urticaria, and the flush associated with metastatic carcinoid.
The classic H1 antihistamines are most effective in the management of acute urticaria and seasonal rhinitis. They are also currently the drugs of choice in the therapy of chronic urticaria and other allergic cutaneous reactions, including drug reactions. They are, however, of only limited value when given systematically for the relief of nonspecific pruritus. Antihistamines have been shown to be no more effective than aspirin or a placebo for relief of non–histamine-related itching (i.e., eczematous eruptions, as opposed to urticaria), but there is an enormous placebo effect; in dealing with patients bothered by pruritus, the magnitude of this beneficial phenomenon should
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not be overlooked. The classes of antihistamines show only minor variations in their properties. However, individuals frequently react differently to each antihistamine class. One or several antihistamines of different classes may have to be used, occasionally in combination, before the best treatment effect is obtained. Many antihistamines have a sedating effect, which the patients must be made aware of, especially if they will be driving. These medications include hydroxyzine, diphenhydramine, chlorpheniramine maleate, and cyproheptadine. Hydroxyzine appears to be the most effective sedating antihistamine in suppressing histamine-induced pruritus. In one experimental system, cyproheptadine and placebo administration necessitated a 5-fold increase in the intradermal histamine dose required to produce pruritus, compared with a 10-fold increase following diphenhydramine and a 750-fold increase following hydroxyzine HCl. For general use, chlorpheniramine maleate, hydroxyzine hydrochloride, and hydroxyzine pamoate have proved consistently effective.
The development of nonsedating H1 antagonists was a significant advance in antihistamine therapy. These agents penetrate the blood–brain barrier minimally and have greater affinity for peripheral H1 receptors. Thus, compliance is often better because of fewer bothersome side effects. Examples of these medications include cetirizine, fexofenadine, and loratadine.
Antihistamines are rapidly absorbed after oral or parenteral administration. Following an oral dose, symptomatic relief is noted within 15 to 30 minutes and usually lasts 3 to 6 hours. These drugs are metabolized mainly in the liver, and excretion by the kidney is nearly complete in 24 hours. Antihistamines are also incorporated into some topical antipruritic lotions. Previous concern about antihistamine-induced contact dermatitis was based on anecdotal evidence and is unwarranted. Recent studies reveal no risk of contact hypersensitivity. The most common untoward systemic effect is sedation. Gastrointestinal side effects can also be seen. Because H1 antihistamines are structurally similar to atropine, they may all produce peripheral and central anticholinergic effects, including excitation, dry mouth, blurred vision, and urinary retention. Patients should be cautioned to avoid the use of alcoholic beverages and barbiturates during antihistamine therapy because the depressant action of these drugs is additive.
To be used most effectively, antihistamines should be increased gradually until either clinical remission occurs or side effects (most often sedation) become significant. It is unwise to start at too high a dose.
II. Specific Agents (all Rx except where noted)
  • Ethanolamine derivatives are potent antihistamines. However, there is a high incidence of sedation, and they have an additive effect with hypnotics and sedatives. Possible hypertension, tachycardia, T-wave changes, or shortened diastole may further complicate the clinical picture.
    • Diphenhydramine hydrochloride (Benadryl, Caladryl, Dermamycin, Dermarest, Sleepinal, Sominex, etc.)—OTC
      • Structure
      • Contains: 1% to 2% diphenhydramine hydrochloride as cream, gel, injection, lotion, solution, spray, capsule, and tablet.
      • Use: 25 to 50 mg PO q4h. Maximum daily dose is 300 mg in adults. The maximum oral dose for children is 150 mg/day. The topical agents are not as effective as antihistamine drugs.
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      • Packaging:
        • Diphenhydramine capsules: 25 and 50 mg
        • Diphenhydramine cream and gel, 1% to 2%: 15 g, 30 g, 180 g
        • Diphenhydramine elixir (12.5 mg/5 mL): 118 mL
        • Diphenhydramine injection (50 mg/mL): 1-mL ampules, 10-mL vials
        • Diphenhydramine liquid 12.5 mg/5 mL: 118 mL, 236 mL, 473 mL
        • Diphenhydramine oral solution: 12.5 mg/5 mL: 473 mL
        • Diphenhydramine syrup 12.5 mg/5 mL: 30 mL, 118 mL, 473 mL, 3.8 L
        • Diphenhydramine spray: 60 mL
    • Other ethanolamine antihistamines include carbinoxamine maleate (Clistin), clemastine fumarate (Tavist), and dimenhydrinate (Dramamine).
  • Ethylenediamine derivatives cause less drowsiness than ethanolamine derivatives but have more gastrointestinal side effects. These antihistamines must be avoided in individuals with contact allergy to ethylenediamine. Because of structural similarities, it would also be wise to avoid piperazine and hydroxyzine antihistamines in these patients. Ethylenediamine antihistamines include methapyrilene hydrochloride (Histadyl) and pyrilamine maleate [Triaminic (OTC)].
  • Piperazine antihistamines are sedative in nature. They include hydroxyzine hydrochloride (Atarax), hydroxyzine pamoate (Vistaril), cyclizine hydrochloride (Marezine), buclizine hydrochloride (Bucladin-S), and meclizine hydrochloride (Bonine, Antivert). They are also utilized for their antiemetic, sedative, anticholinergic, analgesic, and skeletal muscle relaxant effects.
    • Structure
    • Use: Drugs of choice for the treatment of dermatographism and cholinergic urticaria. They are also effective alone or in combination with other antihistamines in the management of acute and chronic urticaria, atopic and contact dermatoses, and histamine-induced pruritus.
    • Dosage: 25 mg, three to four times a day.
    • Packaging:
      • Hydroxyzine tablets: 10 mg, 25 mg, 50 mg, 100 mg
      • Hydroxyzine injection: 25 mg/mL, 50 mg/mL
      • Hydroxyzine syrup, 10 mg/5 mL: 118 mL, 473 mL
      • Hydroxyzine capsule: 25 mg, 50 mg, 100 mg
      • Hydroxyzine oral suspension 25 mg/5 mL: 120 mL, 473 mL
  • Alkylamine derivatives include some of the most active antihistamines effective in low dosage. There is no variation in the effectiveness of members of this antihistamine class. Emphasis should be placed on the lower cost and easy availability of these medications.
    • Brompheniramine maleate (This drug is only available in combination with other medications: Bromfed, Dimetane, Dimetapp, Drixomed, Histatab, Nasahist). The only difference between this agent and chlorpheniramine is the substitution of a bromine for a chlorine atom in brompheniramine. The side effects of this medication are similar to other classes of sedative antihistamines. Some medications include parabens. Patients sensitive to parabens may develop a sensitivity reaction.
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    • Chlorpheniramine maleate (Alka-Seltzer Plus, Allerest, Chlor-Trimeton, Comtrex, Contact, Norel Plus, Sinarest, Sinutabs, TheraFlu)
      • Structure
      • Dosage: 4 to 6 mg PO q4–6h. Maximum daily dose is 24 mg for adults and children 12 years or older. Found frequently in combination with acetaminophen and pseudoephedrine.
      • Packaging (OTC and Rx):
        • Chlorpheniramine syrup, 2 mg/5 mL: 118 mL
        • Chlorpheniramine tablets: 4 mg
        • Chlorpheniramine extended tablets: 8 mg, 12 mg, 16 mg
        • Chlorpheniramine chewable tablet: 2 mg
        • Chlorpheniramine sustained-release capsule: 8 mg, 12 mg
    • Dexchlorpheniramine maleate is the dextrorotatory isomer of chlorpheniramine.
      • Dosage: 4 or 6 mg qhs or q8–10h.
      • Packaging:
        • Dexchlorpheniramine extended-release tablets: 4 mg, 6 mg
  • Phenothiazine derivatives are used primarily as central nervous system (CNS) depressants or CNS stimulants but are also potent antihistamines. They also possess antiemetic, anticholinergic, and local anesthetic effects. They demonstrate side effects similar to those of other sedative antihistamines.
    • Promethazine hydrochloride (Phenergan)
      • Structure
      • Dosage: 12.5 mg PO q.i.d.; 25 mg PO at bedtime. May contain saccharin.
      • Packaging:
        • Promethazine injection, 25 mg/mL, 50 mg/mL: 1-mL ampules; 10-mL multidose vials
        • Promethazine suppositories: 12.5 mg, 25 mg, 50 mg
        • Promethazine syrup: 6.25 mg/5 mL, 473 mL
        • Promethazine tablets: 12.5 mg, 25 mg, 50 mg
  • Piperidine derivatives
    • Cyproheptadine hydrochloride is an antihistamine in which antiserotonin activity has been demonstrated both in vivo and in vitro. As yet, however, there is no evidence that this action contributes to clinical therapeutic effects. Anticholinergic and sedative effects are observed. Cyproheptadine
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      may be more effective than other H1 blockers in the management of cold urticaria.
      • Structure
      • Dosage: 4 mg PO t.i.d. Maximum daily dose is 0.5 mg/kg/day for adults.
      • Packaging:
        • Cyproheptadine tablets: 4 mg
        • Cyproheptadine syrup, 2 mg/5 mL: 473 mL
    • Azatadine maleate (Optimine) and phenindamine (Nolahist) are other piperidine antihistamines.
  • Nonsedating H1 antihistamines
    • Fexofenadine HCl (Allegra) is a selective, specific H1 antagonist that is structurally related to the butyrophenone tranquilizer haloperidol. It is the active carboxylic acid metabolite of terfenadine (no longer commercially available in the United States). It binds mainly to the peripheral H1 receptors, with minimal crossing of the blood–brain barrier and hence minimal sedative effects. Fexofenadine lacks the cardiotoxic effects of its parent drug, terfenadine. However, it has been associated with increased QT interval, syncope, and ventricular arrhythmia in at least one susceptible patient with preexisting cardiovascular risk. To date, no significant interactions have been demonstrated with fexofenadine when administered concomitantly with azole antifungals or macrolide antibiotics. Indicated for seasonal allergic rhinitis and chronic idiopathic urticaria.
      • Dosage: 60 mg PO b.i.d.
      • Packaging:
        • Fexofenadine capsules: 60 mg
        • Fexofenadine tablets: 30 mg, 60 mg, 180 mg
    • Loratadine (Claritin) is a long-acting, potent peripheral H1 blocker with minimal sedative effects. It does not appear to have the same adverse cardiac effects as the other nonsedating H1 antihistamines. It is indicated for allergic rhinitis and chronic urticaria.
      • Dosage: 10 mg daily. Patients with liver or renal impairment should be started on a lower dose.
      • Packaging:
        • Loratadine syrup, 1 mg/mL: 480 mL
        • Loratadine tablets: 10 mg
        • Loratadine orally disintegrating tablet: 10 mg
    • Cetirizine HCl (Zyrtec) is the carboxylic acid metabolite of hydroxyzine. It is a selective, peripheral H1 receptor antagonist. It is a long-lasting antihistamine. It does not appear to have the same adverse cardiac effects as the other nonsedating H1 antihistamines; however, additional data are required. Indicated for allergic rhinitis and chronic urticaria.
      • Dosage: 5 to 10 mg daily.
      • Packaging:
        • Cetirizine syrup, 5 mg/5 mL: 120 mL, 473 mL
        • Cetirizine tablets: 5 mg, 10 mg
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  • Thioguanidine derivatives. Block H2 histamine receptors
    • Cimetidine (Tagamet) is an H2 histamine antagonist that contains an imidazole ring and is structurally similar to histamine. It is used primarily for the treatment of peptic ulcer disease by blocking gastric parietal cell receptors and reducing gastric acid secretion. Additionally, it has an immunomodulatory effect by inhibiting suppressor T cells, apparently by competitive blockade of their H2 receptors. This effect has resulted in its use in various infections, including severe mucocutaneous candidiasis, resistant condyloma acuminata, and herpes simplex. Its antiandrogen side effects are due to its competitive inhibition of DHT at the receptor site; this side effect makes it useful in treating female androgenetic alopecia.
      • Structure
      • Dosage: 300 mg PO q.i.d. or 800 mg at bedtime.
      • Packaging:
        • Cimetidine injection, 150 mg/mL: 2-mL vials; 8-mL multidose vials
        • Cimetidine liquid, 300 mg/5 mL: 240 mL, 470 mL
        • Cimetidine tablets: 200 mg, 300 mg, 400 mg, 800 mg
    • Ranitidine (Zantac) is another H2 receptor antagonist that does not have the same antiandrogen side effects as cimetidine. Note that both cimetidine and ranitidine inhibit the cytochrome P-450 microsomal enzyme system.
      • Dosage: 150 mg b.i.d.
      • Packaging:
        • Ranitidine tablets: 75 mg, 150 mg, 300 mg
        • Ranitidine injection, 1 mg/mL, 25 mg/mL: 2-mL, 6-mL, 50-mL vials
        • Ranitidine syrup, 75 mg/5 mL: 10 mL, 480 mL
  • Doxepin (Sinequan, Zonalon) is a combined H1 and H2 receptor antagonist. It is also a tricyclic antidepressant with antianxiolytic effects. Adverse side effects include sedation and anticholinergic symptoms, in addition to tachycardia, hypotension, and prolongation of the PR and QRS intervals on electrocardiogram. A topical form of doxepin cream is available (Zonalon 5% cream) for use in patients with atopic dermatitis, lichen simplex chronicus, and other eczematous dermatoses. Side effects are usually mild and may include burning, stinging, drowsiness, and dry mouth. The incidence of side effects increases when applied to more than 10% of the body surface area or when duration of therapy exceeds 8 days. Cases of acute contact dermatitis to topical Zonalon have been reported.
    • Structure
    • Dosage: Tablets: 10 mg PO q.i.d., may increase dose as tolerated. Zonalon cream: apply to affected areas t.i.d. to q.i.d. up to 8 days.
    • Packaging:
      • Doxepin cream, 5%: 30 g
      • Doxepin capsule: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
      • Doxepin oral solution, 10 mg/mL: 120 mL
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Antiinfective Agents
I. Antibacterial and Antiseptic Agents, Topical
Antiseptic agents are applied to tissue to destroy microorganisms or inhibit their reproduction or metabolic activity. The major uses of antiseptics are as hand scrubs, cleansers, irritants, and protective dressings. Commonly used antiseptics include ethyl and isopropyl alcohols, cationic surfactants (e.g., benzalkonium), chlorhexidine, iodine compounds, and hexachlorophene. Disinfectants are used on nonliving agents to destroy microorganisms and prevent infection. Some diluted disinfectants are used as antiseptics. The most commonly used disinfectants are the aldehydes (formaldehyde and glutaraldehyde), elemental chlorine, and cresol (a phenolic compound). Topical antibiotics have long been used to prevent or treat cutaneous bacterial infection, yet it is only recently that the effectiveness of this therapy has been evaluated critically.
Numerous antibacterial agents are available for topical use. Topical erythromycin is also effective and is the drug of choice when contact irritation or allergy occurs to the poorly absorbed agents. Use of broad-spectrum germicides or topical antibiotics, singly or as mixtures, is justified for many reasons:
  • They can treat a wide range of potential pathogens in mixed infections. Frequently, more than one pathogen is present and quick identification of organisms is difficult.
  • They are used in small amounts and therefore permit use of drugs that are relatively toxic when given systemically. There is no percutaneous absorption of these antibiotics from normal, psoriatic, or eczematous skin; therefore, the possibility of producing nephrotoxicity or ototoxicity is extremely unlikely. Neomycin is a frequent cause of allergic contact dermatitis; approximately 1% of the general population is sensitized.
  • The concentration of the topical medications is high, although the total amount used is small. This represents large multiples of the minimum effective concentration for potential pathogens.
  • Topically administered drugs are in more direct contact with organisms, so that the problems of absorption, distribution, and availability to the infected site are not involved.
  • The combined effects of bactericidal agents such as bacitracin, neomycin, and polymyxin B are predominantly synergistic, thereby increasing the rate and spectrum of bactericidal action, and Staphylococcus aureus is highly susceptible to the bactericidal action of mupirocin and neomycin and bacteriostatic action of tetracyclines, whereas Streptococcus pyogenes is particularly susceptible to bacitracin and neomycin. Neomycin is approximately 50 times more active against staphylococci than bacitracin (by weight), but bacitracin is 20 times more active against streptococci. Of gram-negative invaders, all but Proteus species are sensitive to polymyxin B and all but Pseudomonas are sensitive to neomycin. Therefore, to cover this spectrum, combinations of two or three antibiotics may be necessary.
  • Another effect of combination therapy is to retard the emergence of resistant organisms, which is true particularly with use of neomycin and gentamicin. Although outbreaks of neomycin-resistant infections have been reported in closed communities, the incidence of resistance to this antibiotic has not significantly changed during the last 20 years.
Note: The risk of combination topical antibiotic use is that if a contact dermatitis/allergic reaction were to develop while on this combination therapy, it would be difficult to ascertain which antibiotic the patient is allergic to. Further testing would be required to determine the etiology.
Local treatment of secondarily infected dermatoses may not diminish the reservoir of pathogens elsewhere on the body. Systemic antibiotics may be required for full eradication of the infection. Additionally, impetigo and other bacterial pyodermas should be treated with systemic antibiotics as discussed in previous chapters.
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By reducing bacterial colony counts, topical antibiotic preparations are effective for axillary deodorization, controlling nasal carriage of staphylococci, and preventing infections in clean wounds. When used promptly, they might hasten healing and diminish the local or systemic morbidity of infected wounds. Nonetheless, some topical antibiotics and antibiotic-corticosteroid creams are classified by the FDA as lacking adequate evidence of effectiveness.
These preparations should be applied frequently (three to six times a day) after the skin is cleansed of adherent crusts and debris and should not be applied under occlusive dressings.
  • Alcohol. Both ethyl and isopropyl alcohol are used as topical antiseptics; 70% isopropyl alcohol (rubbing alcohol) is the more commonly used agent. There is a 75% reduction in surface microorganisms, specifically gram-positive bacteria, after wiping the skin with alcohol. The treated area must be allowed to dry completely for the full antiseptic effect. Spores, viruses, and fungi are resistant. Because of the short duration of action, other longer-acting antiseptics should be used for prolonged procedures. Be sure that the surface is completely dry before electrosurgery and laser surgery, for alcohol may easily be ignited.
    • Packaging:
      • Isopropyl alcohol, 70% USP: 500 mL
      • Ethyl alcohol, 60% to 70%: 500 mL
      • Alcare foam, 62%: 210, 330, 600 mL
      • Isagel gel, 60%: 120, 630, 3,840 mL
      • System TLC gel, 70%: 118 mL
      • Sebanil solution, 49%: 105, 240, 480 mL
  • Aluminum salts have strong antibacterial effects. Formulations include 1% aluminum chlorohydrate (Ostiderm), aluminum diacetate (Burow’s solution, Domeboro’s powder), and aluminum chloride hexahydrate (Drysol, Xerac AC). These compounds completely inhibit representative dermatophytes, yeasts, and gram-positive and gram-negative bacteria in vitro. In vivo, 20% aluminum chlorohydrate, 10% to 20% aluminum acetate, and 20% to 30% aluminum chloride hexahydrate have appreciable direct killing effects, with the chlorohydrate salt being most potent. The recommended use concentrations (1:20 and 1:40) of 5% aluminum diacetate exert no in vivo bacteriostatic or bactericidal effects. Aluminum chloride hexahydrate 20% to 30% solution is effective in treating symptomatic interdigital tinea pedis owing to its bactericidal effects as well as this salt’s unique astringent (drying) properties. In the management of folliculitis, notably of the buttocks, 6.25% aluminum chloride hexahydrate (Xerac AC) has been found useful. Aluminum salts are also effective as antiperspirants.
    • Packaging (OTC):
      • Aluminum chloride hexahydrate, 20% solution (Drysol): 35 mL, 60 mL
      • Aluminum chloride hexahydrate, 20% lotion (Bromil Lotion): 120 mL
      • Aluminum chloride hexahydrate, 6.25% solution (Xerac AC): 35 mL
      • Burow’s solution, tablets, and powder (Bluboro, Domeboro): 12/box, 100/box
  • Bacitracin. This polypeptide antibiotic, which is produced from Bacillus subtilis, interferes with bacterial cell wall growth and is bactericidal against many gram-positive organisms such as streptococci, staphylococci, and pneumococci but is inactive against most gram-negative organisms. All anaerobic cocci, Neisseria, and the tetanus and diphtheria bacilli are also sensitive to bacitracin. Resistance is rare, but some staphylococcal strains are inherently resistant. Hypersensitivity reactions are uncommon. Bacitracin is stable in petrolatum (but not water-miscible preparations) and is available as an ointment or as a component of antibiotic mixtures. Sensitization to bacitracin has been reported more recently, particularly in patients with leg ulcers.
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    • Structure
    • Use: Clean wound and apply one to three times a day.
    • Packaging (OTC):
      • Bacitracin ointment, 500 U/g: 1-g, 15-g, 30-g tube; 1 lb
  • Benzalkonium chloride is a quaternary ammonium detergent that treats gram-positive and gram-negative organisms. Strains of Mycobacterium tuberculosis and Pseudomonas aeruginosa are often resistant. It is not effective against spore-forming organisms. It is nonirritating to mucous membranes and may be used near the eyes. Drawbacks include lack of sustained activity and ease of contamination of this antimicrobial. It is inactivated by anionic compounds such as soap. A 0.1% solution takes 7 minutes to decrease the bacterial count by 50%. All traces of soap must be removed with 70% alcohol before use.
    • Use: Must be diluted to correct concentration before use.
      • For unbroken skin, superficial injuries: 1:750 dilution.
      • For denuded skin, deep wounds: 1:2,000 to 1:10,000 dilution
      • For mucous membranes: 1:5,000
      • For mouthwash: 1:1,000
      • For wet dressings or irrigation: 1:5,000
    • Packaging (OTC):
      • Benzalkonium chloride concentrate, 17%: 500 mL, 4,000 mL
      • Benzalkonium chloride towelettes: 24/box
      • Benzalkonium chloride solution, 1:750: 60 mL, 120 mL, 240 mL
      • Benzalkonium chloride tincture, 1:750: 1 gal
      • Benzalkonium chloride topical solution 1%: 30, mL
  • Chlorhexidine. This topical antiseptic product acts rapidly but, like hexachlorophene, persists on the skin to give a cumulative, continuing antibacterial effect. Like iodophors and alcohol, it is active against gram-positive and gram-negative bacteria, including P. aeruginosa, as well as common yeasts and fungi. It does not lose effectiveness in the presence of whole blood. Many consider it the antiseptic of choice for skin cleansing and surgical scrubs. Contact allergy is not uncommon. Chlorhexidine should not be used near the eyes or mucosal surfaces, because it may cause irritation or even anaphylaxis.
    • Structure
    • Use: Apply to treatment area and swab for >2 minutes. Repeat treatment for an additional 2 minutes.
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    • Packaging (OTC):
      • Chlorhexidine liquid, solution, 2%, 4%: 120 mL, 240 mL, 480 mL, 946 mL, 960 mL, 1 gal
      • Chlorhexidine towelettes, 0.5%: 50/box
      • Chlorhexidine 0.5% rinse: 120 mL, 240 mL,
      • Chlorhexidine 0.12% oral rinse: 480 mL
      • Chlorhexidine 4% foam: 180 mL
      • Chlorhexidine sponge/brush 4%: 22 mL
  • Gentamicin (Garamycin). This antibiotic is a combination of three related aminoglycoside agents obtained from cultures of Micromonospora purpurea and acts by interfering with the bacterial synthesis of protein. It prevents bacterial protein synthesis by irreversibly binding to 30S ribosomal subunits. Its antibiotic spectrum is similar to that of neomycin, and cross-resistance does occur. Gentamicin is active against gram-negative organisms including Escherichia coli and a high percentage of strains of Pseudomonas species and other gram-negative bacteria. Proteus organisms show a variable degree of sensitivity. Some gram-positive organisms, including S. aureus and group A β-hemolytic streptococci, are also affected. In general, higher concentrations are needed to inhibit streptococci than those needed to inhibit staphylococci and many gram-negative bacteria. It is inactive against fungi, viruses, and most anaerobic bacteria. The most important use of gentamicin is in the treatment of systemic gram-negative infections, particularly those due to Pseudomonas organisms. Widespread use is unwarranted not only because equally effective drugs are available but also because of the risk of increasing the background of gentamicin-resistant organisms. Allergic reactions to gentamicin are unusual but may occur with prolonged use. Cross-reactivity with neomycin may occur.
    • Structure
    • Use: Clean lesion and apply one to three times a day.
    • Packaging:
      • Gentamicin 0.1% cream: 15 g
      • Gentamicin 0.1% ointment: 15 g
  • Hexachlorophene is a bacteriostatic antiseptic effective against gram-positive organisms, specifically Staphylococcus. It has a cumulative and sustained effect. Although it has a slow onset of action, with repeated use a film develops on the skin that has long-acting properties. It is not effective against gram-negative organisms or yeast. It is postulated to affect bacterial electron transport and membrane function. With repeated use, it penetrates through the stratum corneum. It is often used for preoperative surgical scrubbing. One retrospective study showed that it may be teratogenic if used excessively by pregnant women, although there have been no subsequent, well-controlled studies that substantiate this. It should not be used in infants, particularly those who are premature or have dermatoses. It is toxic to tissues when applied to open wounds.
    • Use: Apply to treatment area and scrub for 3 minutes. Repeat treatment for additional 3 minutes. Not to be used on mucosal surfaces. Rinse thoroughly after use.
    • Packaging (Rx only):
      • Hexachlorophene 3% liquid: 8 mL, 150 mL, pt, gal
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  • Iodophors (Acu-Dyne, Aerodine, Betadine, Iodex, Operand, Polydine). These consist of a water-soluble organic complex of iodine with a carrier that slowly liberates iodine on contact with reducing substances in body tissues. These broad-range germicidal antiseptics are effective against bacteria, fungi, viruses, protozoa, and yeast. They are water soluble, nonirritating, and nonstinging but may lose effectiveness on contact with whole blood or serum. They are often used for preoperative skin cleansing and surgical scrubbing because their sustained action provides protection even through lengthy procedures. They are also used in treating skin infections and burns. They are available in many vehicles. The solubilizing carrier substances include polyvinyl–pyrrolidone (povidone-iodine, as in Betadine products or available as generics) and poloxamer–iodine complexes. Because iodophors may be absorbed through the skin, they should be avoided in neonates or in patients with thyroid disorders. Also, extensive use for prolonged periods should be minimized. Iodine preparations may slow wound healing on actively granulating tissue.
    • Structure
    • Use: Apply to treatment area and scrub for 2 minutes. Repeat treatment for an additional 2 minutes.
    • Packaging (OTC): Numerous products are available; the following are some examples:
      • Iodine/povidone aerosol, 5%: 909 mL
      • Iodine/povidone gel, 5%: 5 g, 151 g
      • Iodine/povidone ointment, solution, 10%: 30 g 1 lb
      • Iodine/povidone skin cleanser/surgical scrub, 7.5%: 170 g
  • Mupirocin (Bactroban, Centany) is a topical antibiotic produced by fermented Pseudomonas fluorescens. It has a narrow spectrum of activity, mostly against gram-positive aerobic bacteria (including Staphylococcus and methicillin-resistant Staphylococcus) and many strains of Streptococcus. It is also active against some gram-negative aerobic bacteria but is inactive against anaerobes, Chlamydia, and fungi. It has proved equal in efficacy in the treatment of impetigo when compared with oral erythromycin, with fewer adverse side effects.
    Mupirocin does not interfere with wound healing. It is active only on topical administration and is converted to an inert molecule on systemic administration. Prolonged use of mupirocin increases the risk of evolution of resistant organisms. The mechanism of action has not yet been fully classified, but it does differ from other available antiinfective agents, and there is little chance of cross-resistance developing. Also, unlike many other topical antibiotics, it rarely causes allergic sensitization.
    • Structure
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    • Use: Clean lesion and apply b.i.d. to t.i.d. for 10 to 14 days.
      To eradicate nasal colonization, apply b.i.d. for 14 days.
    • Packaging:
      • Bactroban cream and ointment, Centany ointment 2%: 15 g, 22 g, 30 g
      • Bactroban nasal cream, 2%: 1 g
  • Neomycin sulfate. This drug is obtained from species of the actinomycete Streptomyces and is an aminoglycoside antibiotic (as are streptomycin, gentamicin, and kanamycin) effective against most aerobic gram-negative organisms. Group A streptococci are relatively resistant. Neomycin acts to inhibit bacterial protein synthesis by irreversibly binding to the 30S subunit. It is responsible for a greater incidence of allergic contact sensitivity than any other topical antibiotic. This diagnosis often remains hidden, because morphologically the eruption is of a mild eczematous nature. Rarely, anaphylaxis may occur.
    • Structure
    • Use: Apply one to three times a day.
    • Packaging:
      • Neomycin cream, ointment, 0.5%: 15 g, 30 g
  • Polymyxin B. Polymyxin B is one of a group of cyclic polypeptides elaborated by Bacillus polymyxa. The drug is a surface-active agent. It is thought to alter the lipoprotein membrane of bacteria so that it no longer functions as an effective barrier, thereby allowing the cell contents to escape. Polymyxin B is effective against Pseudomonas, E. coli, and other gram-negative bacteria except the Proteus and Serratia species. It has little effect on gram-positive organisms.
    • Use: Apply to affected area one to three times a day.
    • Packaging (available in combination with other agents—see the following text):
  • Combination topical preparations
    • Neomycin/polymyxin B/bacitracin ointment (Neosporin)
      • Contains: 5,000 units polymyxin B sulfate, 400 U bacitracin zinc, and 3.5 mg neomycin sulfate (as base) per gram.
      • Use: Apply one to three times a day.
      • Packaging (OTC):
        • Neomycin/polymyxin B/bacitracin ointment: 0.9 g, 14 g, 15 g, 28 g, 30 g, 454 g
    • Polymyxin B/bacitracin (Polysporin) ointment
      • Contains: 10,000 U polymyxin B sulfate with 500 U zinc bacitracin per gram.
      • Packaging (OTC):
        • Polysporin ointment: 15 g, 30 g
II. Antifungal Agents
  • DISCUSSION. See Chap. 14.
  • Prescription drugs
    • Systemic therapy (Table 40-2)
      • Fluconazole is a synthetic triazole derivative that is structurally related to the imidazole antifungals. Replacement of the imidazole ring with a triazole ring increases antifungal activity and expands the antifungal spectrum. It works to inhibit fungal cytochrome P-450 14-α-demethylase, with a resultant decrease
        P.296

        P.297

        in ergosterol. Fluconazole is approved by the FDA for systemic candidiasis and is prescribed primarily in patients with oropharyngeal and esophageal candidiasis. It is also useful in cryptococcal, histoplasmosis, and Blastomycetes infections. It is ineffective against Malassezia and Scopulariopsis infections. Existing data suggest that fluconazole accumulates in the stratum corneum, where it is delivered both through sweat and direct diffusion through the dermis and epidermis. Because it concentrates in the stratum corneum and nails, it is useful for therapy of cutaneous fungal infections, although it is fungistatic. Rare side effects include hepatotoxicity, anaphylaxis, and Stevens-Johnson syndrome.
        TABLE 40-2 Comparison of Oral and Topical Antifungal Agents
        Drug Route of administration Organisms treated Mechanism Side effects
        Allylamine
        Naftifine (Naftin) Topical Dermatophytes
        1. Blocks squalene epoxidase
        2. Alters PMN chemotaxis
        		 Rarely an irritant, burning
        Terbinafine (Lamisil) Topical Dermatophytes Blocks squalene epoxidase Oral: delayed gastric emptying, hepatitis, metallic taste, and decreased white blood cells count
        Butenafine
        (Mentax) Topical Dermatophytes and yeasts Blocks squalene epoxidase  
        Azole compounds
        Clotrimazole (Lotrimin, Mycelex) Topical Dermatophytes and yeasts Inhibits ergosterol synthesis by inhibiting 14 α-demethylation of lanosterol  
        Econazole (Spectazole) Topical Dermatophytes and yeasts    
        Fluconazole (Diflucan) Oral Above plus systemic mycoses   Drug interactions
        Itraconazole (Sporonox) Oral Above plus systemic mycoses   Drug interactions, congestive heart failure, rash, hepatitis
        Ketoconazole (Nizoral) Topical/oral Dermatophytes and yeasts   Pituitary-testosterone-adrenal axis, hepatitis
        Miconazole (Micitin, Monistat) Topical Dermatophytes and yeasts    
        Oxiconazole Topical Dermatophytes and yeasts    
        Sertaconazole (Ertaczo) Topical Dermatophytes and yeasts    
        Sulconazole (Exelderm) Topical Dermatophytes and yeasts    
        Polyene antibiotics
        Fungizone Topical Yeast (Candida) Binds to cell membrane sterols (ergosterol) causing cell leakage and permeability changes Nausea, vomiting, diarrhea, with oral use
        Nystatin (Mycostatin Nilstat) Oral/topical Yeast (Candida)    
        Griseofulvin Oral Dermatophyte Inhibits synthesis of fungal cell walls Gastrointestinal side effects; headache, lupus erythematosus flares; precipitates acute intermittent porphyria; granulocytopenic
        PMN, polymorphonuclear leukocyte
        • Structure
        • Use: Coadministration with other drugs metabolized by cytochrome P-450 system may result in increased concentration of the drug. Dose adjustment may be necessary. Levels of oral contraceptives decrease when used in combination with fluconazole. Hydrochlorothiazide increases fluconazole levels.
          • Vaginal candidiasis: 150 mg PO single dose.
          • Pityrosporum infections: 200 to 400 mg PO, single dose.
          • Dermatophytosis: 150 mg/week for 4 to 6 weeks (2 additional weeks after clinical resolution of symptoms).
          • Onychomycosis: 300 mg/week for 4 months (fingernails) or 8 months (toenails).
        • Packaging:
          • Fluconazole tablets: 50 mg, 100 mg, 150 mg, 200 mg
          • Fluconazole injection, 2 mg/mL: 100 mL, 200 mL
          • Fluconazole powder for oral suspension (when reconstituted): 10 mg/mL, 40 mg/mL
        • P.298

      • Flucytosine (Ancobon) is a synthetic, fluorinated pyrimidine that is structurally related to fluorouracil (FU) and floxuridine. It can be fungistatic and fungicidal. Although it is used more frequently in the treatment of systemic infections caused by Candida and Cryptococcus, dermatologic indications may include infections due to chromomycosis, sporotrichosis, Cladosporium, and Sporothrix species. It is generally ineffective against Aspergillus species.
        • Structure
        • Use: Generally administered at 50 to 150 mg/kg daily in four divided doses.
        • Packaging:
          • Flucytosine capsule: 250 mg, 500 mg
      • Griseofulvin is an antifungal antibiotic effective against all dermatophyte fungi but not against yeast (i.e., Candida or Pityrosporum) or molds. It is derived from Penicillium species, but there is no structural homology or cross-reactivity with penicillin or the cephalosporins. Griseofulvin resembles colchicine structurally, and one of its major cellular effects is to inhibit fungal mitosis by interfering with microtubular proteins and thereby causing metaphase arrest. The rate of absorption and the total amount of drug absorbed are increased after a high-fat meal. Microsize griseofulvin is produced by a special process that fractures the particles into minute crystals of irregular shape that offer a greater surface for increased gastrointestinal absorption. Further processing to achieve ultramicrosize particles doubled the bioavailability; 125 mg was originally thought to be equivalent to 250 mg of microsize griseofulvin, but more recent data indicate that it takes 150 to 200 mg to achieve bioequivalent plasma levels.
        Griseofulvin enters the epidermis by diffusion forces from extracellular fluid (through transepidermal water loss) and from sweat and reaches higher concentrations in the horny layer than in serum. With excessive sweating in hot, humid climates, the amount of griseofulvin in skin is likely to be reduced, and more of the drug should be taken. The response to therapy depends on the rate of keratinization and the time necessary for desquamation of infected keratinized structures. Griseofulvin is deposited in newly formed nails but does not diffuse through the nail bed, which may account for the need for prolonged time of therapy for onychomycosis.
        Griseofulvin is metabolized by the liver, and its metabolites are excreted in the urine. It is highly protein bound and, therefore, may have high tissue levels. However, tissue levels decrease and fall as soon as griseofulvin is discontinued such that its presence is no longer detectable 2 to 3 days after cessation of therapy.
        Griseofulvin may cause a reversal of the hypoprothrombinemic effect of anticoagulants, necessitating an increase in the dose of anticoagulant to maintain a therapeutic range of anticoagulation. This effect occurs through increased synthesis of drug-metabolizing liver enzymes, leading to more rapid inactivation of anticoagulants. Phenobarbital has been postulated to decrease the gut absorption of griseofulvin, thereby decreasing blood levels and presumably decreasing antifungal action.
        P.299

        Griseofulvin has the following cure rates: tinea capitis, 93.1%; tinea of the glabrous skin, 64.8%; tinea of the palms and soles, 53.3%; tinea of the fingernails, 56.9%; and tinea of the toenails, 16.7%. Failure of fungal infection to respond to this therapy may occur because of inadequate dosage, poor compliance, inadequate absorption, microsomal enzyme inactivation and drug interaction, failure of griseofulvin to enter the site of infection or diminished activity within that site, or infection with an organism not sensitive to griseofulvin. The latter had long been postulated, but it has been shown that for Trichophyton rubrum infections of body, palms, and soles, a poor clinical response correlates with a diminished in vitro sensitivity to this antimycotic. Minimal inhibitory concentration determinations for griseofulvin can be used to determine the appropriateness of this therapy. Griseofulvin is contraindicated in patients with porphyria, pregnancy, and hepatocellular failure.
        • Structure
        • Dosage: See Chap. 14.
          The average treatment time for tinea capitis is 4 to 6 weeks; for tinea corporis, 2 to 4 weeks; and for tinea pedis, 4 to 8 weeks. Because of the low cure rate and length of therapy, griseofulvin is not commonly used for onychomycosis of the fingernails or toenails. Complete blood count (CBC) is monitored every 3 months during long-term therapy.
        • Packaging:
          • Griseofulvin ultramicrosize: tablets, 125 mg, 165 mg, 250 mg, 330 mg
      • Itraconazole (Sporanox) is a triazole antifungal that is related to the imidazole ketoconazole. Similar to ketoconazole, it interferes with ergosterol synthesis and cell membrane integrity. It is clinically active against dimorphic fungi, yeast, dermatophytes, Blastomycetes, histoplasmosis, sporotrichosis, and Aspergillus. It is ineffective against Scopulariopsis. Side effects are fewer compared with ketoconazole, with reportedly less hepatotoxicity. Less than 5% of patients may have asymptomatic elevations in serum transaminase. Early investigational studies showed less effect on the pituitary-testosterone-adrenal axis in patients on low doses of itraconazole. Higher doses for prolonged duration may rarely cause hypokalemia. Itraconazole is highly lipophilic, has a high affinity for keratinous tissue, and has been shown to persist in nails. One study found evidence of the drug in nail clippings 7 to 12 months after cessation of therapy, and another study showed evidence in tissue up to 6 months after treatment was discontinued. Plasma levels, in contrast, rapidly decrease after therapy is stopped.
        Itraconazole is a potent inhibitor of the cytochrome P450 3A enzyme system, which may elevate blood levels of other drugs metabolized by this system if taken concomitantly. Itraconazole levels may decrease in patients who are concurrently taking rifampin, phenobarbital, or phenytoin. Cyclosporine, felodipine, digoxin, warfarin, and oral hypoglycemic levels may increase when given in conjunction with itraconazole.
        P.300

        Itraconazole, like ketoconazole, is contraindicated in patients taking cisapride. Itraconazole may induce torsades de pointes, ventricular arrhythmias, and congestive heart failure.
        • Structure
        • Use: Monitor Liver function tests (LFTs) monthly while on medication
          • Fingernail onychomycosis: daily dosing 200 mg q.d. × 6 weeks; pulse dosing 200 mg b.i.d. × 1 week/month for 2 months
          • Toenail onychomycosis: daily dosing 200 mg q.d. × 12 weeks; pulse dosing 200 mg b.i.d. × 1 week/month for 3 to 4 months
          • Blastomycosis, histoplasmosis, aspergillosis: 200 to 400 mg q.d.
          • Candidiasis: 100 mg q.d. for 2 weeks after resolution of symptoms
        • Packaging:
          • Itraconazole capsules, 100 mg: pulsepak 28
          • Itraconazole injection, 10 mg/mL: 25-mL ampules
          • Itraconazole oral suspension, 10 mg/mL: 150 mL
      • Ketoconazole (Nizoral) is a water-soluble imidazole derivative with a wide spectrum of activity against pathogenic fungi at concentrations achievable with oral treatment. Unlike miconazole, it is well absorbed after oral administration, and unlike clotrimazole, it does not induce a liver enzyme that inactivates any absorbed drug. This drug, like other imidazoles, affects fungi by mechanisms involving increased membrane permeability, inhibition of uptake of precursors of ribonucleic acid (RNA) and DNA, and synthesis of oxidative and peroxidative enzymes. It is fungistatic. Ketoconazole’s spectrum of activity includes Candida species, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, and pathogenic dermatophytes. It is effective in chronic dermatophyte infections, including those resistant to griseofulvin. Although it is useful in treating chronic mucocutaneous candidiasis, fluconazole has been shown to be more effective against Candida albicans than ketoconazole.
        When used systemically, the most worrisome adverse reaction to ketoconazole is hepatotoxicity. Two percent to 5% of patients may experience asymptomatic elevations of hepatic enzymes. Acute hepatic injury resembling viral hepatitis is an apparently idiosyncratic reaction that occurs in approximately 1 patient in 10,000; fatalities have occurred. Appropriate liver function tests should be monitored in patients on ketoconazole, and if any evidence of hepatic injury develops, the drug should be discontinued. Hepatitis is twice as common in women than men and rarely occurs in patients on oral therapy <2 weeks.
        Nausea, gynecomastia, infertility, decreased libido, and oligospermia have also been reported, although most frequently at doses exceeding 400 mg/day. Other side effects are uncommon. Ketoconazole is best absorbed if taken on an empty stomach. Because gastric acidity facilitates absorption, concomitant use of antacids, H2 blockers, or anticholinergic agents should be avoided. Rifampin also prevents adequate therapeutic levels from
        P.301

        being achieved. Ketoconazole should not be administered in patients taking cisapride because of adverse cardiac effects, including torsades de pointes, ventricular arrhythmias, and sudden death.
        Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. This may result in increased plasma concentrations of drugs metabolized by this system if given concomitantly. Ketoconazole levels may decrease in patients who are concurrently taking rifampin, phenobarbital, or phenytoin. Cyclosporine, felodipine, digoxin, and warfarin levels may increase when given in conjunction with ketoconazole.
        Ketoconazole is extensively degraded by the liver, and very little active drug is excreted in either the urine or bile; the dose need not be modified for renal insufficiency. Adverse reactions to topical ketoconazole are very rare.
        • Structure
        • Use: See Chap. 14, Dermatophyte Infections.
        • Packaging:
          • Ketoconazole tablets: 200 mg
          • Ketoconazole cream, 2%: 15 g, 30 g, 60 g
          • Ketoconazole shampoo, 2%: 120 mL
          • Ketoconazole shampoo, 1%: 207 mL
      • Nystatin, a polyene antibiotic derived from a species of the actinomycete Streptomyces noursei, binds to sterols in fungal membranes, causing a change in the permeability of cell membranes and leakage of cell components. It is nontoxic and available for oral, vaginal, and topical administration. Nystatin is poorly absorbed from the gastrointestinal tract and will therefore rid the oral and gastrointestinal mucosa of Candida but has no effect on systemic or cutaneous lesions when given orally. Nystatin is unstable in heat, light, moisture, and air. Aqueous-alcohol suspensions are stable for 10 days under refrigeration.
        • Use: See Chap. 14, Candidiasis.
        • Packaging:
          • Nystatin cream and ointment, 100,000 U/g: 15 g, 30 g, 240 g
          • Nystatin oral suspension, 100,000 U/mL: 5 mL, 60 mL, 480 mL
          • Nystatin powder, 100,000 U/g: 15 g, 30 g
          • Nystatin oral tablets, 500,000 U: box of 100
          • Nystatin vaginal tablets, 100,000 U: 15s, 30s
        • P.302

      • Terbinafine Hydrochloride (Lamisil). A synthetic allylamine antifungal agent, structurally related to naftifine. It inhibits fungal sterol biosynthesis by inhibiting the enzyme squalene 2,3-epoxidase. The deficiency of ergosterol and concomitant accumulation of squalene within the fungal cell results in cell death. It can be fungicidal or fungistatic, depending on the concentration used, and is effective against dermatophytes, Aspergillus, blastomycosis, and histoplasmosis. It is only minimally effective against Candida.
        Adverse reactions include lens and retinal disturbances (red/green visual perception), metallic taste disturbance that may last up to 4 weeks after medication discontinuation, hepatoxicity, and pancytopenia. Five percent of patients will experience delayed gastric emptying with symptoms of nausea, fullness, and/or dyspepsia. Terbinafine does not appear to have any effect on the cytochrome P-450 systems (Check baseline CBC and LFTs; repeat if taken for >6 weeks).
        • Use:
          • Fingernail onychomycosis: 250 mg/day for 6 weeks
          • Toenail onychomycosis: 250 mg/day for 12 weeks
        • Packaging:
          • Terbinafine (Lamisil) tablets: 250 mg
    • Topical therapy (Table 40-2)
      • Amphotericin B (Fungizone) is an amphoteric polyene macrolide produced by Streptomyces nodosus. It exerts its antifungal activity principally by binding to sterols in the fungal cell membrane, resulting in loss of membrane-selective permeability, leakage, and subsequent cell death. It is used topically in the treatment of superficial C. albicans infection and is orally active against Aspergillus, Coccidioides, Cryptococcus, Exophilia, histoplasmosis, Mucor, Paracoccidioides, and Rhodotorula. It is also active against many strains of Leishmania, Naegleria, and Acanthamoeba. Fusarium, Pseudallescheria, and Scedosporium are generally resistant to amphotericin B. It is fungistatic or fungicidal, depending on the concentration used and the fungal susceptibility. It is ineffective against dermatophytes. The drug is yellow orange, odorless, and may stain skin. Adverse reactions with topical administration are limited. When administered by IV, amphotericin B may be associated with infusion reactions, nephrotoxicity, anemia, gastrointestinal distress, hepatitis, and neurologic effects.
        • Structure
          • P.303

        • Use: Oral candidiasis: use 1 mL four times a day, applying directly to tongue, then swish and swallow.
        • Packaging:
          • Fungisone oral suspension, 100 mg/mL: 24 mL
      • Butenafine (Mentax) is a synthetic benzylamine antifungal agent, related structurally and pharmacologically to terbinafine. It is thought to act by inhibiting the enzyme squalene 2,3-epoxidase, resulting in decreased ergosterol and corresponding increase in squalene, with subsequent cell membrane permeability alteration and cell death. It is active against dermatophytes, yeast, and Sporothrix.
        P.304

        • Use: Tinea corporis/cruris/pedis: apply to affected areas q.d. until fully resolved, generally 2 to 4 weeks.
        • Packaging:
          • Butenafine (Mentax) cream, 1%: 12 g, 15 g, 24 g, 30 g
      • Ciclopirox olamine (Loprox, Penlac) is a synthetic, broad-spectrum hydroxypyridone antifungal agent. It is chemically unrelated to the imidazoles or any other antifungal agent currently available in the United States. It appears to act through intracellular depletion of substrates and/or ions principally by inhibition of transmembrane transport of these substances. It is active against dermatophytes, yeast, and Pityrosporum orbiculare. It also demonstrates activity against Trichomonas vaginalis, some mycoplasma, and some gram-positive and gram-negative bacteria.
        • Structure
        • Use: Tinea corporis/cruris/pedis: apply to affected areas b.i.d. until complete resolution. Generally 2 to 4 weeks of treatment is necessary.
          Tinea versicolor: apply to affected areas b.i.d. × 2 weeks.
          Onychomycosis, mild to moderate: apply nail lacquer to nail plate (entire surface) and 5 mm surrounding skin q.d. Remove with alcohol every 7 days. No nail polish to be used when on treatment. Requires 6 to 12 months of use for effective treatment.
        • Packaging:
          • Ciclopirox (Loprox) cream or gel, 0.77%: 15 g, 45 g, 30 g, 90 g, 100 g
          • Ciclopirox (Loprox) topical suspension, 0.77%: 30 mL, 60 mL
          • Ciclopirox (Penlac) nail lacquer, 8% topical solution: 3.3 mL with applicator, 6.6 mL
          • Ciclopirox (Loprox) shampoo 1%: 120 mL
      • Econazole (Spectazole) is a synthetic imidazole. Econazole blocks C-14 demethylation of sterols, interfering with the biosynthesis of ergosterol, which results in disorganization of the fungal plasma cell membrane and increased permeability. It is active against dermatophytes, yeast, P. orbiculare, Aspergillus, Cladosporium, and Sporothrix.
        • Structure
        • Use: Cutaneous candidiasis: apply to affected areas b.i.d. until resolved, generally 2 to 4 weeks.
          Tinea corporis/cruris/pedis: apply to affected areas q.d. until resolved, generally 4 to 6 weeks.
          Tinea versicolor: apply to affected areas q.d. until resolved, generally 2 weeks.
        • Packaging:
          • Econazole (Sporonox) 1% cream: 15 g, 30 g, 85 g
      • Ketoconazole: see sec. 1.e.
      • Naftifine (Naftin) is a synthetic allylamine derivative topical antifungal agent that works by blocking squalene 2,3-epoxidase, resulting in increased cell membrane permeability and cell death. It is structurally and pharmacologically related to terbinafine. It also has some antiinflammatory properties that may be due to its ability to alter chemotaxis by polymorphonucleocytes. It is most effective against dermatophytes, moderately active against molds, and less active against yeasts, including C. albicans.
        • Structure
        • Use: Tinea corporis/cruris/pedis: apply q.d. (cream) or b.i.d. (gel) to affected areas, continuing treatment for 2 weeks after symptoms have subsided.
          • P.305

        • Packaging:
          • Naftifine (Naftin) cream, 1%: 15 g, 30 g, 60 g
          • Naftifine (Naftin) gel, 1%: 20 g, 40 g, 60 g
      • Nystatin: see sec. 1.f.
      • Oxiconazole (Oxistat) is a synthetic imidazole that works, in part, by inhibiting ergosterol 2,3-epoxidase synthesis and thereby disrupting cell membrane integrity.
        • Dosage: Apply daily to affected area, continuing treatment for 2 weeks after symptoms have subsided.
        • Packaging:
          • Oxiconazole (Oxistat) cream, 1%: 15 g, 30 g, 60 g
          • Oxiconazole (Oxistat) lotion, 1%: 30 mL
      • Sulconazole (Exelderm) is a synthetic, sulfur-substituted imidazole that is structurally related to the other imidazole antifungals (ketoconazole, econazole, and miconazole). It is postulated to inhibit 14-α-demethylase for decreased ergosterol synthesis, increased cell membrane permeability, and resultant cell death. It is active against most dermatophytes, yeast, and P. orbiculare. It also displays activity against some aerobic and anaerobic gram-positive bacteria. Sulconazole is a mild inducer of the cytochrome P-450 microsomal enzymes CYP1A1 and CYP2B1 and could theoretically induce the metabolism of other drugs.
        • Structure
        • Use: Tinea corporis/cruris/pedis: apply to affected areas b.i.d., continuing treatment for 2 weeks after symptoms have subsided.
          Tinea versicolor: apply to affected areas b.i.d. until resolved.
        • Packaging:
          • Sulconazole (Exelderm) cream 1%: 15 g, 30 g, 60 g
          • Sulconazole (Exelderm) solution 1%: 30 mL
      • Terbinafine (Lamisil) is a second-generation allylamine that is related to naftifine; however, it is 10 to 100 times more potent in vitro. It is fungicidal, whereas griseofulvin, ketoconazole, itraconazole, and other azole derivatives are all fungistatic. Because it is fungicidal, duration of therapy is shorter, and relapse rates are less than with other oral or topical therapies.
        Terbinafine acts by inhibiting squalene epoxidase and thereby decreasing synthesis of ergosterol, an essential component of fungal cell membranes. It is highly lipophilic and concentrates in the stratum corneum, sebum, and hair follicles. Slightly better cure rates are attained with b.i.d. than with daily dosing.
        • Structure
          • P.306

        • Dosing: Tinea corporis/cruris/pedis: apply to affected areas b.i.d. until clinically resolved (1 to 4 weeks). Discontinue after 4 weeks.
        • Packaging:
          • Terbinafine (Lamisil) cream, 1%: 15 g, 24 g, 30 g
          • Terbinafine (Lamisil) spray 1%: 30 mL
      • Benzoic acid and salicylic acid (Whitfield’s, Benzal HP) ointment is a potent keratolytic agent and is used in the treatment of dermatophyte infections (see also Chap. 14, Dermatophyte Infections). It has, however, a strong potential for causing irritant reactions.
        • Structure
        • Dosage: Apply to affected areas b.i.d. to t.i.d.
        • Packaging:
          • Benzoic acid 6%/salicylic acid 3%: 15 g, 30 g, 1 lb
      • Carbol-fuchsin solution (Castellani’s paint) is an aqueous alcohol-acetone solution containing phenol (4.5 g/100 mL), resorcinol (10 g/100 mL), and basic fuschin (300 mg/100 mL). The basic fuschin appears as a dark purple liquid that appears red on the skin and can stain. It has local anesthetic, bactericidal, and fungicidal properties. It has also been reported to stimulate granulation and epithelization. It is applied topically in the treatment of subacute and chronic superficial fungal infection. It is particularly effective in intertriginous areas.
        Carbol-Fuschin is poisonous when ingested and is treated in the same manner as phenol or resorcinol poisoning.
        • Structure
        • Use: Apply to affected areas one to three times a day with swab. Clean skin with soap and water before application.
        • Packaging (Pedinol):
          • Castellani’s paint, color or colorless: 30 mL, 480 mL
      • Clotrimazole (Lotrimin, Mycelex, etc.) is a synthetic imidazole agent. It acts by altering cell membrane permeability. It inhibits the growth of most dermatophyte species, yeast and Malassezia furfur.
        P.307

        • Structure
        • Use: Tinea corporis/cruris/versicolor/pedis: apply b.i.d. until eruption clears, generally 2 to 4 weeks.
        • Packaging (Rx and OTC):
          • Clotrimazole cream 1%: 12 g, 15 g, 24 g, 30 g, 45 g
          • Clotrimazole lotion 1%: 20 mL
          • Clotrimazole topical solution 1%: 10 mL, 30 mL
          • Clotrimazole vaginal cream 1%: 15 g, 30 g, 45 g
          • Clotrimazole vaginal suppositories, 100 mg, 200 mg: packs of three, packs of seven
          • Clotrimazole vaginal cream 2%: 21 g
      • Miconazole (Monistat-Derm, Micatin, etc.) is a synthetic imidazole antifungal compound that acts by altering cell membrane permeability. It is effective against most dermatophyte species, P. orbiculare, and C. albicans.
        • Structure
        • Use: Apply to affected areas b.i.d. until resolution, generally 2 to 4 weeks.
          • P.308

        • Packaging (Rx and OTC):
          • Miconazole 2% cream: 15 g, 30 g, 90 g
          • Miconazole 2% ointment: 28.4 g
          • Miconazole 2% powder: 70 g, 90 g
          • Miconazole 2% spray powder: 90 mL, 85 g, 90 g, 100 g
          • Miconazole 2% solution: 7.39 mL, 29.57 mL
          • Miconazole 2% vaginal lotion, cream: 15-g, 30-g, 35-g, 45-g tube with applicator
          • Miconazole 200 mg vaginal suppositories: pack of three
          • Miconazole 100 mg vaginal suppositories: pack of seven
          • Miconazole 1,200 mg vaginal suppositories: pack of one
          • Miconazole 2% spray liquid: 105 mL, 113 mL
      • Tolnaftate (Aftate, Tinactin, etc.) is an odorless and nonstaining synthetic antifungal agent whose exact mechanism of action is unknown. It is effective against dermatophytes and P. orbiculare and Pityrosporum ovale. It is ineffective against C. albicans and bacteria.
        • Structure
        • Dosage: Apply to affected areas b.i.d. until resolved, generally 2 to 6 weeks.
        • Packaging:
          • Tolnaftate 1% cream: 15 g, 21.3 g, 30 g
          • Tolnaftate 1% gel: 15 g
          • Tolnaftate 1% powder: 45 g, 90 g
          • Tolnaftate 1% solution: 10 mL
          • Tolnaftate 1% spray liquid: 59.2 mL, 118.3 mL, 120 mL
          • Tolnaftate 1% spray powder: 100 g, 105 g, 150 g
      • There are numerous OTC antifungal remedies that contain fatty acids and fatty acid salts (undecylenic acid CH2 = CH(CH2)8 COOH, propionic acid), organic acids and their salts (benzoic acid, salicylic acid), and miscellaneous other compounds. They are all reasonably effective (see Chap. 14, Dermatophyte Infections). Some common preparations follow.
        • Packaging:
          • Cruex cream (20% total undecylenate, as undecylenic acid and zinc undecylenate): 15 g
          • Cruex powder (10% calcium undecylenate): 45 g, 60 g, 120 g
          • Desenex powder (25% total undecylenate, as undecylenic acid and zinc undecylenate): 45 g
          • Fungoid AF solution (25% undecylenic acid): 30 mL
III. Antiviral Agents
  • Oral therapy
    • Acyclovir (Zovirax) is a synthetic purine analog derived from guanine. It exerts its effects on the herpes simplex virus (HSV) and varicella-zoster virus by interfering with DNA synthesis through phosphorylation by viral thymidine kinase and subsequent inhibition of viral DNA polymerase, thereby inhibiting viral replication. It is effective against HSV-1 and 2, varicella-zoster virus, Epstein-Barr virus, herpesvirus simiae, and cytomegalovirus. Acyclovir may be administered intravenously, orally, or topically.
      P.309

      • Structure
      • Use: See Chaps 15 and 16.
      • Packaging:
        • Acyclovir capsules: 200 mg
        • Acyclovir suspension, 200 mg/5 mL: 473 mL
        • Acyclovir tablets: 400 mg, 800 mg
    • Famciclovir (Famvir) a synthetic acyclic purine analog derived from guanine. It is the diacetyl ester (prodrug) of penciclovir, which exhibits no antiviral activity until hydrolyzed to penciclovir and its active metabolites. It is indicated for the management of acute herpes zoster infections. It has been shown to relieve acute symptoms as well as to shorten the duration of postherpetic neuralgia. It is also used for the treatment or suppression of recurrent episodes of genital herpes in immunocompetent patients and in the treatment of recurrent herpes simplex types 1 and 2 infections in patients with human immunodeficiency virus.
      • Use: See Chaps 15 and 16.
      • Packaging:
        • Famciclovir (Famvir): 125-mg, 250-mg, 500-mg tablets
    • Valacyclovir (Valtrex) is the 1-valine ester (prodrug) of acyclovir that exhibits no activity until hydrolyzed in the intestinal wall or liver to acyclovir and its active metabolite. Its modified structure allows increased intestinal absorption and concomitant higher plasma levels of acyclovir. It demonstrates activity against HSV types 1 and 2, varicella-zoster virus, and cytomegalovirus. It exerts its effects by interfering with DNA synthesis through phosphorylation by viral thymidine kinase and subsequent inhibition of viral DNA polymerase, thereby inhibiting viral replication. Valtrex is indicated for the treatment of acute herpes zoster and recurrent genital herpes in immunocompetent adults. The most common side effects are headache, nausea, and vomiting.
      • Use: See Chaps 15 and 16.
      • Packaging:
        • Valacyclovir (Valtrex): 500 mg, 1,000 mg
  • Topical therapy. Three agents (vidarabine, idoxuridine, and trifluridine) that act by interfering with viral DNA synthesis are currently approved for topical therapy of herpetic keratitis. These drugs are similarly effective in the treatment of uncomplicated dendritic keratitis, and patients allergic or resistant to one agent may be treated with another. Local allergic and irritant reactions have been observed with all three drugs. Treatment should be continued for 3 to 7 days beyond the time of apparent healing.
    A topical ointment containing 5% acyclovir in polyethylene glycol is useful in initial infections of herpes genitalis in promoting healing, relieving pain, and reducing viral shedding. It is less useful in recurrent episodes. Another indication for use is in limited mucocutaneous herpes simplex infections in immunocompromised patients. Penciclovir 1% cream (Denavir) is approved for the treatment of recurrent herpes labialis.
    P.310

    • Acyclovir (Zovirax)
      • Use: Apply 1/2-in. ointment/4 sq. in. six times a day for 7 days.
      • Packaging:
        • Acyclovir (Zovirax) 5% ointment: 3 g, 15 g
        • Acyclovir (Zovirax) 5% cream: 2 g.
    • Penciclovir (Denavir) is a topical antiviral that inhibits HSV polymerase, thereby decreasing the replication of the virus. It is indicated for oral and facial HSV caused by HSV-1 or HSV-2.
      • Use: For 4 days, apply to the affected area every 2 hours while awake.
      • Packaging:
        • Penciclovir (Denavir) 1% cream: 1.5 g
    • Vidarabine (Vira-A) is a purine nucleoside obtained from cultures of Streptomyces antibioticus. The antiviral mechanism of action has not been established, but is postulated to block viral DNA synthesis by inhibiting viral DNA polymerase.
      • Structure
      • Use: Apply 1/2-in. thick in the lower conjunctival sac(s) five times a day for 7 days.
      • Packaging:
        • Vidarabine (Vira-A) 3% ointment: 3.5 g
    • Trifluridine (Viroptic) is a pyrimidine nucleoside structurally related to idoxuridine and thymidine. Postulated to alter viral replication by incorporation into viral DNA during replication with subsequent formation of defective proteins.
      • Dosage: One drop every 2 hours while awake for maximum daily dosage of nine drops.
      • Packaging:
        • Trifluridine (Viroptic) 1% solution: 7.5 mL
IV. Scabicides and Pediculicides (For discussion, see Chap. 19)
  • Lindane (Gamma benzene hexachloride, Kwell, Thionex) is a cyclic chlorinated hydrocarbon originally developed as an agricultural insecticide. It is absorbed through the chitinous exoskeleton and stimulates the nervous system, resulting in seizures and death of the insect. It is both a pediculicide and scabicide, with a 45% to 70% ovicidal effect. Resistance has been shown to Pediculosis capitis and Sarcoptes scabiei. Lindane can be absorbed through intact skin following topical application and has the potential for CNS toxicity. It should therefore be used with great caution in infants, children <2 years of age, elderly patients, and pregnant and lactating women. It may be irritating to the eyes or mucous membranes; hence, these areas should be avoided. Irritant dermatitis may occur with use of excessive
    P.311

    amounts or over prolonged periods. Toxicity, if overused, may result in nausea, vomiting, seizures, or even bone marrow suppression.
    • Structure
    • Use: Scabies: apply lotion uniformly to all skin surfaces, including folds and creases from the neck to the toes. Rinse off in 8 to 12 hours. Head/pubic lice: with shampoo, apply to affected hairy areas and rinse off in 4 minutes. Remove all residual nits with nit comb or tweezers.
    • Packaging:
      • Lindane lotion: 30 mL, 59 mL, pharmacy-size only pint
      • Lindane shampoo: 30 mL, 59 mL, pharmacy-size only pint
  • Permethrin (Acticin, Elimite, Nix). Permethrin is a synthetic pyrethrin derivative of the flowers of the plant Chrysanthemum cinerariifolium. It has a broad spectrum of insecticidal activity. It acts to disrupt neuronal sodium channel repolarization and cause paralysis and eventual death of the insect. It is both a pediculicide and scabicide. It can cause breathing difficulty or an asthmatic episode in susceptible patients. It is generally nonirritating and offers a 90% cure rate after a single application. Although no resistance has been demonstrated in the United States to date, decreased susceptibilities have been shown, indicating the possible emergence of resistance. It is also effective against ticks, fleas, and other arthropods.
    • Structure
    • Use: Scabies: apply cream uniformly to all skin surfaces, including folds and creases from the neck to the toes. Rinse off in 8 to 14 hours. Repeat treatment is not recommended unless live organisms are detected in 1 week.
      Head/pubic lice: with lotion, apply to affected hairy areas and rinse off in 10 minutes. With cream rinse, apply to affected hairy areas and rinse off in 10 minutes. Remove all residual nits with nit comb. Repeat treatment not recommended unless live organisms are detected in 1 week.
    • Packaging:
      • Permethrin 5% cream: 60 g
      • Permethrin 1% liquid: 60 mL
      • Permethrin 1% lotion: 60 mL
  • Pyrethrin (Licide, R&C, RID, Tisit) compounds and synthetic pyrethroids are used for the treatment of pediculosis (see Chap. 19). These are currently the drugs of
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    choice in treating pediculosis. They demonstrate no scabicidal effect. Resistance has been shown to these compounds. They are absorbed through the chitinous exoskeleton and stimulate the nervous system, resulting in seizures and death of the insect.
    • Packaging:
      • Pyrethrin 0.3% gel: 30 mL
      • Pyrethrin 0.3% lotion: 59 mL, 118 mL
      • Pyrethrin 0.33% mousse: 165 mL
      • Pyrethrin 0.33% shampoo: 59 mL, 60 mL, 118 mL, 120 mL, 240 mL
  • Ivermectin (Stromectol) is a semisynthetic antihelminthic agent derived from Streptomyces avirmitilis. It acts to bind with high affinity to glutamate-gated chloride ion channels in nerve and muscle cells. Chloride ion permeability is increased, with resultant hyperpolarization, paralysis, and death of the insect. It is indicated for strongyloidiasis and onchocerciasis and for crusted scabies or scabetic infection that has failed multiple courses of topical therapies.
    • Use: 200 μg/kg as a single dose; may require to be repeated in 1 week.
    • Packaging:
      • Ivermectin (Stromectol): 3 mg, 6 mg
  • Benzyl benzoate: 20% to 25%. This agent is relatively nontoxic and is widely used in developing countries to treat scabies and pediculosis capitis and pubis. Only a veterinary preparation is available in the United States. Benzyl benzoate is synthetically derived from the esterification of benzoic acid with benzyl alcohol. Its mechanism of action is unknown. It is toxic to Sarcoptes scabei and may be toxic to Pediculosis capitis and Phthirus pubis. No resistance has been demonstrated to date.
    • Structure
    • Use: Rub into affected hairy areas, avoiding eye exposure. Rinse off in 12 to 24 hours. Repeat treatment in 1 week.
    • Packaging (prepared extemporaneously):
      • Benzyl benzoate 28% lotion: 500 mL
  • Crotamiton (N-ethyl-o-crotonotoluide, Eurax) is a synthetic chloroformate salt used for the prevention and treatment of scabies, although cure rates tend to be lower for the same number of applications compared with lindane and permethrin. It may have an antipruritic effect independent of its scabetic effect. Its mechanism of action is unknown. It is not effective as a pediculicide.
    • Structure
      • P.313

    • Use: Apply uniformly to all skin surfaces, including folds and creases from the neck to the toes. Repeat every 24 hours for 2 days. The patient should bathe 48 hours after the last application to remove the drug.
    • Packaging:
      • Eurax 10% cream: 60 g
      • Eurax 10% lotion: 60 g, 454 g
  • Malathion (Ovide) is highly effective in the prevention and treatment of pediculosis. It displays 95% ovicidal activity and has no scabicidal activity. It works through cholinesterase inhibition.
    • Structure
    • Use: Apply to affected hairy areas and rinse off in 8 to 12 hours. Remove all nits. Repeat treatment if live organisms are observed in 7 to 9 days.
    • Packaging:
      • Malathion (Ovide) 0.5% lotion: 59 mL
  • Petrolatum, physostigmine 0.025% ophthalmic ointment, and yellow oxide of mercury are useful for infestation of eyelashes with pediculosis pubis. These agents are generally thickly applied b.i.d. for 8 days with a cotton-tipped applicator.
  • Precipitated sulfur was used previously in infants and pregnant women, but with the discovery that permethrin cream 5% is equally safe, it is now prescribed less often. Although systemic effects are rare, it may stain clothing and it also has an unpleasant odor. It is applied daily for 3 days.
    • Packaging:
      • Must be compounded, generally as 6% (5% to 10%) sulfur in petrolatum or Cetaphil: 1 lb
V. Miscellaneous Agents
  • Iodochlorhydroxyquin (Clioquinol), containing 40% iodine, was originally developed as a substitute for iodoform as an antiseptic dusting powder. Although its most effective use is in the treatment of amebiasis, it also has mild antibacterial and antifungal effects and may be used alone or with steroids in the treatment of eczematous and impetiginized processes and some dermatophyte, yeast, and Trichomonas infections. However, more specific agents are available. Because of neurotoxicity, the oral form of this drug has been withdrawn in the United States. A recent study demonstrating significant percutaneous absorption when applied to intact human skin raises concern regarding its topical use as well. The medication may stain the skin, hair, and clothing yellow and may induce contact allergy.
    • Structure
      • P.314

    • Use: Apply to affected areas b.i.d.
    • Packaging:
      • Clioquinol 3% and hydrocortisone 1% (Vioform): 20 g and 50 g
  • Mafenide (Sulfamylon) is a synthetic antibacterial agent related chemically, but not pharmacologically, to the sulfonamides. The drug appears to interfere with bacterial cellular metabolism and is not antagonized by PABA, pus, or serum. It is bacteriostatic against many gram-positive and gram-negative organisms, including staphylococci, streptococci, and Pseudomonas species. Mafenide is highly soluble and diffuses easily through an eschar. After percutaneous absorption, the drug is metabolized; it acts as a weak carbonic anhydrase inhibitor and may therefore cause systemic acidosis.
    Mafenide is used primarily in the adjunctive treatment of second- and third-degree burn wounds. It may cause severe pain on application, and active allergic contact sensitivity may develop.
    • Structure
    • Use: Apply q.d. to b.i.d. with hand in a sterile glove.
    • Packaging:
      • Mafenide (Sulfamylon) cream, 85 mg/g: 37 g, 114 g, 411 g
      • Mafenide (Sulfamylon) solution, 5%: 50-g packets for reconstitution
  • Mercurial compounds have bacteriostatic effects, most likely mediated through inhibiting sulfhydryl enzymes, but fall far short of being ideal antibacterial compounds. Mercurial compounds may be absorbed and can sensitize; more effective and less hazardous antiseptic agents are available.
    • Insoluble mercury compounds are used as antibacterial and antiparasitic agents. Yellow mercury oxide ointment has been used for pediculosis involving the eyelashes; ammoniated mercury, containing 78% mercury, has been utilized in pyoderma and scaling processes.
    • The organic mercurial antiseptics are more bacteriostatic and less irritating and toxic than inorganic salts. Merbromin (Mercurochrome), containing 25% mercury, is not particularly active and suffers further from having its activity decrease in the presence of organic material. Thimerosal, containing 49% mercury, has the same drawbacks although is more effective although a significant contact sensitizer.
  • Nitrofurazone (Furacin), a synthetic nitrofuran derivative with a broad antibacterial spectrum. Although its exact mechanism of action is unknown, it is thought to inhibit bacterial enzymes involved in carbohydrate metabolism. It is not effective against fungal or viral organisms. It is used as adjunctive therapy in patients with second- and third-degree burns when bacterial resistance to other antiinfective agents is a potential problem. It is not effective in the treatment of minor burns or superficial bacterial infections involving wounds, cutaneous ulcers, or various pyodermas. It is rarely used by dermatologists as it carries a high risk of acquired contact sensitivity.
    • Structure
      • P.315

    • Use: Apply once daily.
    • Packaging:
      • Nitrofurazone 0.2% cream: 28 g
      • Nitrofurazone 0.2% ointment: 28 g, 56 g, 454 g
      • Nitrofurazone 0.2% solution: 480 mL, gal
  • Silver sulfadiazine (Silvadene, SSD) is a synthetic agent that combines the beneficial properties of silver nitrate and sulfonamides. It acts upon the cell membrane and cell wall. It is used primarily as an adjunct in the prevention and treatment of wound sepsis in patients with second- and third-degree burns and for wound care of chronic ulcers. It is bactericidal against many gram-positive and gram-negative bacteria as well as C. albicans and is reasonably effective against P. aeruginosa and S. aureus. Bacteria susceptible to sulfadiazine but resistant to silver nitrate, as well as those sensitive to silver nitrate but resistant to sulfadiazine, have shown good response to silver sulfadiazine. It does not stain, is unlikely to produce electrolyte imbalance, and does not cause systemic acidosis. Some patients note a stinging sensation on application, and because this compound can be absorbed, systemic sulfonamide reactions similar to those caused by sulfonamides may occur.
    • Structure
    • Use: Apply q.d. to b.i.d. 1/16-in. thick. Dressing not required.
    • Packaging:
      • Silver sulfadiazine cream, 10 mg/g: 20 g, 25 g, 50 g, 85 g, 400 g, 1,000 g
Antiinflammatory Agents
Topical and Intralesional Corticosteroids
  • Corticosteroids are the most potent and effective local antiinflammatory medications available and also have a striking ability to inhibit cell division. They are the therapy of choice in most inflammatory, pruritic eruptions (e.g., dermatitis) and are also effective in hyperproliferative disorders (e.g., psoriasis) and infiltrative disorders (e.g., sarcoid and granuloma annulare). Since 1952, when these preparations first became available commercially, hundreds have been marketed. Their continuous wide usage has been ensured by their numerous desirable qualities: broad applicability in treating a wide variety of common eruptions, rapidity of action in small amounts, ease of use, absence of pain or odor, relative lack of sensitization, prolonged stability, compatibility with almost all commonly used topical medications, and rarity of untoward clinical systemic effects from percutaneous absorption. The effectiveness of a topical corticosteroid is related to the potency of the drug and its percutaneous penetration. Activity of a particular preparation is dependent on binding to a cytosol glucocorticoid receptor; the order of clinical potency of different agents parallels the binding to receptor proteins. Potency is also significantly affected by the vehicle. For example, the enhanced potency of two of the strongest preparations is caused by alteration of the corticosteroid moiety in one (Temovate) and optimization of the vehicle in the other (Diprolene).
    Approximately 1% of a hydrocortisone solution will penetrate normal skin on the forearm and about twice that will penetrate through eczematous skin. There is a marked regional variation in corticosteroid penetrations; compared with the data for the forearm, hydrocortisone is absorbed 0.14 times as well through the back, 3.5 times through the scalp, 6.0 times through the forehead, 13 times through the cheeks at the jaw angle, and 42 times through scrotal skin. If the skin is completely hydrated,
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    absorption will be increased four- or fivefold. Inflamed skin, such as that found with atopic dermatitis, allows increased percutaneous penetration; with conditions such as exfoliative psoriasis, there seems to be very little barrier to absorption. Small changes in molecular structure related to enhancing the intrinsic activity of the corticosteroid moiety, increasing lipophilicity to facilitate better skin penetration, and retarding the metabolic inactivation of the molecule result in enormous alterations in clinical effectiveness. To be active, cortisone must be reduced to cortisol (hydrocortisone), just as prednisone must be converted to prednisolone before it can be utilized. Addition of halogen atoms to the steroid nucleus may dramatically increase activity. The potency of topical corticosteroids is most often assessed in vivo by their ability to produce vasoconstriction on human skin, and results of this bioassay correlate well with clinical trials. Other potency assays include suppression of experimentally induced allergic contact dermatitis (e.g., to Rhus antigen) or irritant dermatitis (produced by kerosene or croton oil) or reduction in size of histamine-induced wheals. Antimitotic activity may be assessed by in vitro fibroblast inhibition and/or in vivo epidermal mitotic assay.
    Systemic absorption of topical steroids depends on both the pharmacokinetic properties of the substance applied and the integrity of the stratum corneum. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur with medium- and high-potency agents.
    In 1960, it was discovered that placing corticosteroids on the skin under occlusion with thin, pliable plastic wraps dramatically increased their efficacy (up to 100-fold); occlusion causes hydration of the stratum corneum, increases the surface of skin almost 40%, and appears to induce a reservoir of corticosteroid in the horny layer that persists for several days after application. Percutaneous absorption of steroids under wrap, particularly through altered skin, always occurs. It should be assumed that all patients under substantial occlusive therapy have temporary suppression of the HPA axis. Adults applying a potent steroid in excess of 50 to 100 g weekly (10 to 20 g in small children) for 2 or more weeks face the possibility of having HPA axis suppression. Clobetasol has been shown to suppress the HPA axis at doses as low as 2 g/day. Occlusion and application over large areas increase the risk of suppression. Patients with liver failure or children are particularly at greater risk. Suppressed HPA axis function was noted in 5 of 13 children with atopic or seborrheic dermatitis after application of 1% hydrocortisone cream. Normal function returns within days to weeks of dressings being discontinued, depending on the duration, extent, and intensity of prior therapy. Undesirable effects from occlusive therapy include infection, miliaria, folliculitis, disagreeable odor, interference with heat exchange, and an increased tendency to sunburn, atrophy, and striae.
    Multiple potential adverse effects are associated with the use of topical corticosteroids. If used injudiciously even without occlusion, the more potent formulations may induce mild hypercortisolism, HPA axis suppression, or, rarely, Cushing’s syndrome. Burning, itching, irritation, and dryness are the most common acute problems and are usually related to the vehicle of the steroid preparation and to the pretreatment state of the skin. The prevalence of contact allergy to topical steroids is higher than initially thought; patients with stasis dermatitis and leg ulceration are at increased risk, without regard to duration of dermatitis. Ointments are better tolerated on inflamed skin than creams or gels. Miliaria, folliculitis, and maceration may occur from excessive occlusion and plastic films. Atrophy and telangiectasia are frequent findings if potent corticosteroids have been used over prolonged periods, particularly with the use of occlusive techniques. Early atrophic changes are generally limited to the epidermis, but the dermis and subcutaneous tissue may also be affected with prolonged use. The atrophy is generally due to reduction in cell size rather than in number. Minor atrophic changes as well as telangiectasia are reversible on discontinuation of the topical steroid within 6 months. Concomitant use of 12% ammonium lactate (Lac-Hydrin Lotion) reduces the amount of epidermal and dermal atrophy without influencing the bioavailability or antiinflammatory properties of the corticosteroid. Purpura may be found in atrophic areas. Thinning with or without atrophic striae can be seen within 1 month of use on more susceptible sites such as the face and intertriginous and anogenital areas. Striae are irreversible. The more potent the corticosteroid, the more rapidly and more severe the adverse effects
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    will be. Complications are related to potency but not restricted to halogenated corticosteroids. Less common side effects include perioral dermatitis or a rosacea-like dermatitis, acneiform lesions, hypertrichosis, hypopigmentation, contact dermatitis to the vehicle or to the actual corticosteroid, and ocular hypertension from application in or around the eyes. Topical steroids may also mask superficial infections or worsen fungal infections.
    Injection of small amounts of corticosteroids (betamethasone sodium phosphate and betamethasone acetate suspension, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacetonide) into cutaneous lesions has the advantage of achieving high local concentration with prolonged depot effects and no systemic side effects. Intralesional use is of particular value in the treatment of acne cysts, psoriatic plaques, circumscribed neurodermatitis, keloids, and occasionally, chronic plaques of nummular eczema, insect-bite reactions, alopecia areata, discoid lupus erythematosus, sarcoidosis, myxoid cysts, and nail disorders. Local adverse reactions include atrophy (especially when the concentration is too high or the steroid is injected too high in the dermis), hypopigmentation of deeply pigmented skin, growth of occasional tufts of hair in susceptible individuals, infection, and ulceration. Injection with a 1-mL tuberculin syringe using a 30-gauge needle is best. Air-powered guns can be used but are less precise, disrupt the dermis, and are associated with increased risk of pyogenic infection or transmission of hepatitis virus. Usually a dilution of the medication (i.e., to 2.5 mg/mL triamcinolone acetonide) will provide enough steroid to reduce inflammation while avoiding these problems. (See discussion of individual diseases for proper dilution.)
  • Dosage Considerations
    • Dose–response relationship. It is usually possible to observe a clear dose–response relationship in the use of topical corticosteroids. Compounds vary markedly in their potency and efficacy, and most products are available in standard and diluted concentrations; some may also be obtained in high-potency concentrations. Efficacy may also be altered by method of use (e.g., prior hydration, occlusion). The diluted concentration products may be equipotent to full-strength agents on vasoconstriction assays. Ointment vehicles generally give better biologic activity to the incorporated steroids than do cream or lotion vehicles.
      In most instances, initial therapy should be with one of the most potent compounds and maintenance therapy should involve a less concentrated compound such as 1% hydrocortisone. At least 33% to 50% of patients can be managed with medium- to low-strength topical corticosteroids, which should always be tried. The less potent corticosteroid formulations (e.g., 1% hydrocortisone) should be used for the scrotum, groin, axillae, eyelids, and face.
    • Frequency of application. There is a paucity of pharmacokinetic data dealing with the optimal dose–response characteristics of topical corticosteroid use. One study of 12 patients with corticosteroid-responsive dermatoses found that six treatments per day were no more effective than three applications per day. Other studies involving patients with psoriasis or atopic dermatitis have shown no advantage of application three to four times a day compared with once daily. Overnight application of corticosteroids to hydrated skin, used with or without occlusion, should be as effective and far less costly than multiple daily applications. During the day, simple lubricants can be used. If desired, topical corticosteroids may be used b.i.d. to t.i.d. but there are no data supporting the notion that more frequent use leads to better or faster resolution of hyperplastic or inflammatory processes.
    • Tachyphylaxis. Repeated application of a potent topical steroid may result in a diminished effect. Tachyphylaxis may occur within 1 week of initial use, but the ability to respond fully returns within a week of stopping drug application. It is therefore best to treat effectively for short periods of time (days to 2 weeks) followed by corticosteroid treatment–free intervals of a week or more during which time lubricants alone are applied. This regimen also avoids the possible increased percutaneous absorption of topical corticosteroids that may occur after long-term administration.
    • Relative potency. The “perfect test” to measure the relative potency of topical steroids and the bioequivalence of generic brands has yet to be established. The vasoconstrictor assay visually measures the amount of vasoconstriction produced by a glucocorticoid. The degree of pallor produced after application of a steroid
      P.318

      over a standard period of time increases with the concentration of the steroid. The assay is imprecise because of the variation between observers and other parameters within an individual study. Clinical models, such as psoriasis, have also been used to evaluate relative potency. Table 40-3 lists the relative potency of topical corticosteroids based on the summation of available information from bioassays, clinical models, and literature reviews.
    • Generics. Some discrepancy may exist in the efficacy of the trade name topical corticosteroids and the corresponding generics, with some generics demonstrating up to 50% less activity in vasoconstrictor assays. Several generics may exist for a particular trade name [i.e., Valisone (betamethasone valerate) has 28 generic forms]. The only way to ensure consistency is to prescribe brand name only, although this is often impractical with managed care pharmacy plan limitations.
    • Occlusive therapy. Some conditions such as psoriasis, lichen simplex chronicus, and hand eczema respond poorly, if at all, to creams alone. The use of occlusive (airtight) dressings will increase the efficacy of these preparations. Occlusion with class 1 agents is not recommended. Patients should be instructed to do the following:
      • Soak the area in water for up to 20 minutes.
      • Rub medication into lesions while the skin is still moist.
      • Cover the area with a plastic wrap (Saran Wrap, Handi Wrap), plastic gloves for hands, plastic bags for feet, bathing cap for scalp, and vinyl exercise suit for large areas of the legs or torso. Tubular plastic dressings are also useful.
      • Seal edges with tape or cover plastic with an ace bandage, a long stocking, panty hose, or any dressing that will ensure close adherence to skin. Blenderm tape will stick particularly well to skin. Paper tape may be less irritating.
      • Use for at least 6 hours. Overnight application is usually sufficient to induce clinical remission, but such a technique may also be used during the day. Occlusion for even a few hours may be very beneficial.
        As noted previously, significant percutaneous absorption of steroids will occur with occlusive therapy, and patients undergoing stressful procedures (i.e., operations) should be supplemented with IV corticosteroids. The most potent preparations should be used rarely, if at all, under occlusion.
  • Packaging: Because topical corticosteroids are stable preparations, buying in bulk is feasible and will frequently result in significant cost savings to the patient. Some pharmacies and institutions will buy 5-lb containers and repackage, with resultant enormous decreases in unit cost. With corticosteroids, the cost of purchasing multiple small tubes is particularly high in contrast to buying one larger size. For example, the price of four 15-g tubes of fluocinonide (Lidex) is 170% that of one 60-g tube. All topical corticosteroids are available by prescription only, with the exception of 0.5% and 1% hydrocortisone. Selected agents will be discussed in more detail in the following text.
    • Betamethasone valerate (Psorion, Beta-Val, Luxiq) is a synthetic fluorinated corticosteroid.
      • Structure
        TABLE 40-3 Topical Corticosteroid Potency
        1 (Most potent) Betamethasone dipropionate cream, ointment 0.05% (optimized vehicle) (Diprolene)
        Clobetasol propionate cream, ointment 0.05% (optimized vehicle) (Clobex, Temovate)
        Diflorasone diacetate ointment 0.05% (optimized vehicle) (Apexicon, Psorcon)
        Halobetasol propionate cream, ointment 0.05% (Ultravate)
        2 Amcinonide ointment 0.1% (Cyclocort)
        Desoximetasone cream, ointment 0.25% (Topicort)
        Desoximetasone gel 0.05% (Topicort)
        Diflorasone diacetate ointment 0.05% (Florone, Maxiflor)
        Fluocinonide cream, gel, ointment (0.05%) (Lidex)
        Halcinonide 0.1% cream (Halog)
        Mometasone furoate ointment 0.1% (Elocon)
        Triamcinolone acetonide ointment 0.5% (Kenalog)
        3 Amcinonide cream, lotion 0.1% (Cyclocort)
        Betamethasone benzoate gel 0.025% (Benisone, Uticort)
        Betamethasone valerate ointment 0.1% (Valisone)
        Diflorasone diacetate cream 0.05% (Florone, Maxiflor)
        Fluticasone propionate ointment, 0.005% (Cutivate)
        Fluocortolone cream, 0.25% (Ultralan)
        Fluocinonide cream 0.05% (Lidex E cream)
        Halcinonide ointment 0.1% (Halog)
        Triamcinolone acetonide ointment 0.1% (Aristocort A) cream 0.5% (Aristocort-HP)
        4 Betamethasone benzoate ointment 0.025% (Benisone, Uticort)
        Betamethasone valerate lotion 0.1% (Valisone)
        Desoximetasone cream 0.05% (Topicort-LP)
        Fluocinolone acetonide cream 0.2% (Synalar-HP)
        Fluocinolone acetonide ointment 0.025% (Synalar)
        Flurandrenolide ointment 0.05% (Cordran)
        Halcinonide cream 0.025% (Halog)
        Hydrocortisone valerate ointment 0.2% (Westcort)
        Mometasone furoate cream 0.1% (Elocon)
        Triamcinolone acetonide ointment 0.1% (Kenalog)
        5 Betamethasone benzoate cream 0.025% (Benisone, Uticort)
        Betamethasone dipropionate lotion 0.05% (Diprosone)
        Betamethasone valerate cream 0.1% (Betatrex, Valisone)
        Clocortolone cream 0.1% (Cloderm)
        Fluocinolone acetonide cream 0.025% (Fluonid, Synalar)
        Fluocinolone acetonide oil 0.01% (Derma-Smoothe/FS)
        Flurandrenolide cream 0.05% (Cordran)
        Fluticasone propionate cream 0.05% (Cutivate)
        Hydrocortisone butyrate cream 0.1% (Locoid)
        Hydrocortisone valerate cream 0.2% (Westcort)
        Prednicarbate 0.1% cream (Dermatop)
        Triamcinolone acetonide cream 0.1% (Kenalog)
        6 Alclometasone dipropionate cream, ointment 0.05% (Aclovate)
        Betamethasone valerate lotion 0.1% (Valisone)
        Desonide cream 0.05% (DesOwen, Tridesilon)
        Fluocinolone acetonide cream, solution 0.01% (Synalar)
        Triamcinolone acetonide cream 0.1% (Aristocort)
        7 (Least potent) Dexamethasone cream 0.1% (Decadron phosphate)
        Hydrocortisone 0.5%, 1%, 2.5% (generic, Hytone, others)
        Methylprednisolone 1% (Medrol)
        source: Modified from Cornell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol 1985;121(1):63–67.
        Stoughton RB. Are generic formulations equivalent to trade name topical glucocorticoids? Arch Dermatol 1987;123(10):1312–1314. Reproduced, with permission.
        • P.319

        P.320

      • Packaging:
        • Betamethasone valerate 0.05% cream: 15 g, 45 g
        • Betamethasone valerate 0.1% cream, ointment: 15 g, 45 g
        • Betamethasone valerate 0.1% lotion: 60 mL
        • Betamethasone valerate 1.2 mg/g foam: 100 g
    • Clobetasol propionate (Cormax, Temovate, Embeline, Olux) is one of the most potent of the currently available agents and is indicated for short-term treatment of inflammatory or hyperplastic disorders. It is a synthetic fluorinated corticosteroid. It may cause a more rapid or prolonged response than other topical corticosteroids. It is recommended that clobetasol have a maximum application of 60 g/week for no longer than 14 days without occlusion and that it should not be used in children below age 12.
      • Structure
        • P.321

      • Packaging:
        • Clobetasol propionate 0.05% cream or ointment: 15 g, 30 g, 45 g
        • Clobetasol propionate 0.05% solution: 25 mL, 50 mL
        • Clobetasol propionate 0.05% gel: 15 g, 30 g, 60 g
        • Clobetasol propionate 0.05% foam: 100 g
    • Desonide (DesOwen, Tridesilon) is a synthetic corticosteroid.
      • Structure
      • Packaging:
        • Desonide 0.05% cream, ointment: 15 g, 60 g, 90 g
        • Desonide 0.05% lotion: 60 mL, 120 mL
    • Fluocinolone acetonide (Derma-Smoothe/FS, Flurosyn, Capex, Synalar) is a synthetic fluorinated corticosteroid.
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      • Structure
      • Packaging:
        • Fluocinolone acetonide 0.01% cream: 15 g, 30 g, 42.5 g, 60 g
        • Fluocinolone acetonide 0.2% cream: 12 g
        • Fluocinolone acetonide 0.025% cream, ointment: 15 g, 30 g, 60 g, 425 g
        • Fluocinolone acetonide 0.01% shampoo: 180 mL
        • Fluocinolone acetonide 0.01% solution: 20 mL, 60 mL
        • Fluocinolone acetonide oil 0.01%: 120 mL
    • Fluocinonide (Lidex, Lidex E, Fluonex) is a synthetic fluorinated corticosteroid.
      • Structure
      • Packaging:
        • Fluocinonide 0.05% gel: 15 g, 30 g, 60 g, 120 g
        • Fluocinonide 0.05% cream, ointment: 15 g, 30 g, 60 g, 120 g
        • Fluocinonide 0.05% solution: 20 mL, 60 mL
    • Flurandrenolide (Cordran, Cordran SP) is a synthetic fluorinated corticosteroid.
      • Structure
      • Packaging:
        • Flurandrenolide 0.025% cream, ointment: 30 g, 60 g
        • Flurandrenolide 0.05% cream, ointment: 15 g, 30 g, 60 g
        • Flurandrenolide lotion 0.05%: 15 mL, 60 mL
        • Flurandrenolide tape 4 μg/sq. cm roll: 24 in. × 3 in., 80 in. × 3 in.
    • Halcinonide (Halog, Halog-E) is a synthetic fluorinated corticosteroid.
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      • Structure
      • Packaging:
        • Halog 0.025% cream: 15 g, 60 g
        • Halog 0.1% cream, ointment: 15 g, 30 g, 60 g, 240 g
        • Halog-E 0.1% cream: 15 g, 30 g, 60 g
        • Halog 0.1% solution: 20 mL, 60 mL
    • Hydrocortisone (Cortizone, Cortaid, Anusol-HC, Hytone, LactiCare-HC, Sarnol HC, Penecort, Texacort, and many other branded products) may be purchased as a generic drug.
      • Structure
      • Packaging (OTC):
        • Hydrocortisone 0.5% cream, ointment: 15 g, 30 g, 60 g, 120 g, 1 lb
        • Hydrocortisone 0.5% lotion: 30 mL, 60 mL, 120 mL
        • Hydrocortisone 1% cream, ointment: 15 g, 20 g, 28 g, 30 g, 56 g, 90 g, 120 g, 240 g, 1 lb
        • Hydrocortisone 1% gel, solution: 15 g, 30 g
        • Hydrocortisone 1% liquid, lotion: 45 mL, 60 mL, 75 mL, 118 mL, 120 mL, 600 mL
        • Hydrocortisone 1% roll-on: 14 g
        • Hydrocortisone 1% spray: 45 mL
        • Hydrocortisone 2% lotion: 30 mL
        • Hydrocortisone 2.5% cream, ointment: 15 g, 20 g, 30 g, 60 g, 120 g, 240 g, 1 lb
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    • Prednicarbate (Dermatop E) is a synthetic nonfluorinated topical corticosteroid.
      • Packaging:
        • Prednicarbate 0.1% cream, ointment: 15 g, 60 g
    • Triamcinolone acetonide (Aristocort, Kenalog) is a synthetic fluorinated corticosteroid.
      • Structure
      • Packaging:
        • Triamcinolone acetonide 0.025% cream, ointment: 15 g, 28 g, 30 g, 57 g, 60 g, 80 g, 113 g, 120 g, 240 g, 454 g, 1 lb
        • Triamcinolone acetonide 0.1% cream, ointment: 15 g, 20 g, 28 g, 30 g, 57 g, 60 g, 80 g, 90 g, 113 g, 120 g, 240 g, 454 g, 1 lb
        • Triamcinolone acetonide 0.5% cream, ointment: 15 g, 20 g, 28 g, 30 g, 57 g, 60 g, 113 g, 120 g, 240 g
        • Triamcinolone acetonide 0.1% lotion: 15 mL, 60 mL
        • Triamcinolone acetonide 0.025% lotion: 60 mL
        • Triamcinolone acetonide aerosol, 2-second spray: 23 g, 63 g
    • Steroid combinations. There are hundreds of topical corticosteroid preparations available in different vehicles and in combination with antibiotics (most frequently neomycin), other antiseptics (iodochlorhydroxyquin), and other agents (tars, keratolytic agents). Some combinations are useful, but there is more flexibility and control over therapy, often at a lower cost to the patient, if separate, identifiable agents are used.
Systemic Corticosteroids
  • Discussion. Systemic corticosteroids are used in the treatment of a number of skin diseases, ranging from pemphigus vulgaris to severe cases of allergic contact dermatitis. Because of their well-known and serious side effects, the decision to use them must be based on careful consideration of the indications, alternatives, contraindications, and risks in each clinical situation. Fortunately, many of the instances for which they are utilized in dermatology are either short-lived or rapidly responsive so that “short courses” of treatment, for which the risks are significantly diminished, may be used.
    Virtually every aspect of inflammation and immunologic reactivity is altered—usually diminished—by corticosteroids. For example, neutrophil migration and adherence to endothelium are reduced, capillary permeability and blood flow are diminished, the passage of immune complexes across basement membranes is decreased, and it is thought that lysosomal membranes are stabilized by corticosteroids, among many other effects.
    Systemic corticosteroids are either proved or generally acknowledged to be beneficial in the treatment of pemphigus vulgaris, bullous pemphigoid, id (autosensitization) reactions, severe allergic contact dermatitis (such as poison ivy), collagen-vascular diseases, pyoderma gangrenosum, and Sweet’s syndrome. Low doses at bedtime may
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    be useful in treating hormonal disorders such as hirsutism or acne. They are also often prescribed for severe erythema multiforme, severe cutaneous drug reactions, toxic epidermal necrolysis, and severe sunburn, although their efficacy in these conditions is based largely on anecdotal clinical experience and has not been demonstrated unequivocally. Experimentally, for example, prednisone was unable to alter the development or course of sunburn erythema induced artificially on small areas of the skin. On the other hand, it is probably true that patients with severe sunburn and toxic symptoms (e.g., fever and chills) may feel better when treated with systemic steroids. Corticosteroids have also been recommended for the prevention of postherpetic neuralgia, particularly when they can be given early enough in the course of herpes zoster in elderly patients.
  • General principles of corticosteroid use in cutaneous disorders
    • Assess the indications, risks, benefits, alternatives, and possible adjuvant therapies.
    • Evaluate possible contraindications and side effects, with special attention to any past history of psychiatric illness, osteoporosis, diabetes mellitus, glaucoma, hypertension, and peptic ulcer disease (Tables 40-4 and 40-5).
    • Corticosteroids are relatively contraindicated in psoriasis, in which their withdrawal may incite a generalized pustular flare, and in atopic dermatitis, in which withdrawal may be extremely difficult and may be accompanied by exacerbation.
    • Diagnose and treat any secondary infection (such as impetigo, cellulitis, or erysipelas) before starting steroids. Also, a protein-purified derivative (PPD) should be planned at the start of a long course of glucocorticoid therapy. It takes an average of 12 days for a patient to become anergic after starting glucocorticoids, so there is adequate time to discontinue steroid therapy and to start isoniazid if indicated.
    • While they are on corticosteroid treatment, patients should be monitored, at least monthly, for the presence of any adverse reactions. Development of symptoms such as polyuria, polydypsia, abdominal pain, fever, or joint pain should be assessed. Blood pressure and weight as well as fasting blood sugar, CBC, and lipid and electrolyte levels should also be followed. In addition, a stool hemoccult and eye examination should be checked biannually.
      TABLE 40-4 Contraindications to Corticosteroid Treatment
      Absolute
         Ocular herpes simplex
         Untreated tuberculosis
      Relative
         Acute or chronic infections
         Pregnancy
         Diabetes mellitus
         Hypertension
         Peptic ulcer
         Osteoporosis
         Psychotic tendencies
         Renal insufficiency
         CHF (excluding that secondary to active rheumatic carditis)
         Diverticulitis
         Recent intestinal anastomoses
      CHF, congestive heart failure.
      Modified from Storrs FJ. Use and abuse of systemic corticosteroid therapy. Man Dermatol Ther 1979;1:95.
      TABLE 40-5 Common Corticosteroid Complications
      Central nervous system
         Pseudotumor cerebri
         Psychiatric disorders
      Musculoskeletal
         Osteoporosis with spontaneous fractures
         Aseptic necrosis of bone
         Myopathy
      Ocular
         Glaucoma
         Cataracts
      Gastrointestinal
         Fatty infiltration of the liver
         Nausea, vomiting
         Intestinal perforation
         Pancreatitis
         Peptic ulceration
      Cardiovascular and fluid retention
         Hypertension
         Sodium and fluid retention
         Hypokalemic alkalosis
         Atherosclerosis
      Suppression of host defenses
         Immunosuppression, anergy
         Effects on phagocyte kinetics and function
         Increased incidence of infections
         Recurrent tuberculosis
      Endocrinologic
         Suppression of hypothalamic-pituitary-adrenal axis
         Growth failure
         Secondary amenorrhea
      Metabolic
         Hyperglycemia
         Nonketotic hyperosmolar states
         Hyperlipidemia
         Drug interactions
         Fibroblast inhibition
         Inhibition of wound healing
         Subcutaneous atrophy (striae, purpura)
      Skin
         Acne
         Alteration of fat distribution (Cushingoid appearance)
         Urticaria
         Facial erythema
         Atrophy
         Striae
         Lanugo hair
         Alopecia
      source: From Fauci AS. Glucocorticosteroid therapy. In: Wyngaarden JB, Smith LH, Bennett JK, eds. Cecil’s textbook of medicine. Philadelphia, PA: WB Saunders, 1988.
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    • If acute infection, trauma, or surgery occurs during treatment, the steroid dose must be increased appropriately. Patients exposed to acute stress are at increased risk of adrenal crisis. Symptoms of adrenal suppression include weakness, lethargy, nausea, anorexia, fever, orthostatic hypotension, hypoglycemia, and weight loss.
    • HPA axis suppression must be considered after short courses. The degree of suppression depends on the patient, dosage (including frequency and amount), duration, and route of treatment. Longer courses and divided doses increase the risk for complications. Pituitary-adrenal reserve in response to stress may be diminished for as long as 5 days after a 5-day course of 25 mg PO b.i.d. A single injection of triamcinolone acetonide may suppress adrenal responsiveness for 2 to 3 weeks or more. Patients should be informed of this potential risk.
    • In most instances, the best route of administration is oral, and the drug of choice is prednisone, which is short acting and inexpensive. To be active, prednisone must be converted to prednisolone in the liver (Table 40-6). Potency and duration of action vary among the multiple drugs available (Table 40-6).
    • Other routes of administration include intralesional, intramuscular, or intravenous. Intralesional corticosteroids allow concentrated delivery directly into the involved area with minimal risk of HPA axis suppression. Intramuscular injection is used less frequently owing to prolonged suppression of the HPA axis and inconsistent absorption. Intravenous corticosteroids may be used in stressful situations in patients already on long-term oral steroids.
    • Although prednisone is not teratogenic, there is some risk of adrenal suppression and growth suppression in infants exposed in utero or through breast-feeding.
    • To prevent glucocorticoid-induced osteoporosis, the American College of Rheumatology guidelines recommend bisphosphonate therapy for all patients beginning long-term prednisone at a dose >5 mg/day.
  • Dosage considerations in acute dermatoses. To achieve maximal therapeutic benefit, systemic corticosteroids must be given in adequate dosage for a sufficient length of time. It is also desirable to commence treatment as early as possible in the course of the illness. Alternate-day therapy starting at double the daily dose must be considered when use for >1 month is necessary. The initial dose of prednisone for an adult with conditions such as allergic contact dermatitis should be at least 60 mg daily. The course should be no <2 to 3 weeks. If the dose is too small or duration of treatment too short, a rebound phenomenon with generalized exacerbation of the rash and symptoms can occur.
    Prednisone should be given as a single daily dose (before 8:00 a.m.) to minimize suppression of the normal diurnal cortisol secretions. Occasionally, split doses are needed early on in a disease to achieve adequate therapeutic control; once achieved, conversion to an every morning or every other day schedule as soon as possible is recommended. Suggested regimens for acute dermatoses are given in the following text.
    TABLE 40-6 Relative Potencies of Some Glucocorticoids
    Drug Equivalent dose (mg)
    Cortisone 25
    Cortisol (hydrocortisone) 20
    Prednisone, prednisolone 5
    Methylprednisolone, triamcinolone 4
    Betamethasone 0.60
    Dexamethasone 0.75
    equation
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    • Preferred methods
      • Prednisone 60 mg PO each morning for 5 days, 40 mg PO each morning for 5 days, 20 mg PO each morning for 5 days, then discontinue. This is the easiest and least expensive regimen and uses 30 tablets of 20 mg over 15 days.
      • Prednisone 60 mg PO each morning for 7 days, followed by prednisone 30 mg PO each morning for 7 days, then discontinue (126 tablets of 5 mg or 63 tablets of 10 mg over 14 days).
    • Other schedules
      • Prednisone 60 mg PO each morning for 3 days, 50 mg PO each morning for 3 days, 40 mg PO each morning for 3 days, and then taper by 5 mg/day to 0 (120 tablets of 5 mg over 16 days).
      • Prednisone starting with 60 mg PO the first day and decreasing by 5 mg (i.e., 78 tablets of 5 mg over 12 days). The total amount and duration of treatment may be varied
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  • Glucocorticoid adrenocorticotropic hormone (ACTH) suppression by oral corticosteroids
    • Short acting (24 to 36 hours)
      • Cortisone
      • Cortisol (hydrocortisone)
    • Intermediate acting (48 hours)
      • Prednisone
      • Prednisolone
      • Methylprednisolone
      • Packaging:
        • Prednisone oral solution: 5 mg/5 mL: 5 mL, 500 mL
        • Prednisone oral solution: 5 mg/mL: 30 mL
        • Prednisone syrup, 5 mg/5 mL: 120 mL, 240 mL
        • Prednisone tablets: 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, 50 mg: 100 mg
          Triamcinolone
      • Packaging:
        • Triamcinolone syrup, 4 mg/5 mL: 120 mL
        • Triamcinolone tablets: 4 mg, 8 mg
    • Long acting (over 48 hours)
      • Betamethasone
      • Dexamethasone
      • Packaging:
        • Dexamethasone elixir, oral solution 0.5 mg/mL: 5 mL, 20 mL, 100 mL, 120 mL, 240 mL, 500 mL
        • Dexamethasone oral solution 0.5 mg/0.5 mL: 30 mL
        • Dexamethasone tablets, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 4 mg, 6 mg
        • Dexamethasone therapeutic pack: 6 × 1.5-mg, 8 × 0.75-mg tablets
  • Injectable glucocorticoids. Time noted is the duration of their ability to suppress inflammatory reaction (see sec. II).
    • Short acting (hours to days)
      • Dexamethasone sodium phosphate
    • Intermediate acting (1 to 2 weeks)
      • Betamethasone acetate
      • Betamethasone sodium phosphate
      • Dexamethasone acetate
      • Triamcinolone diacetate
    • Long acting (3 to 4 weeks)
      • Triamcinolone acetonide
      • Triamcinolone hexacetonide
Antiperspirants and Treatment of Hyperhidrosis
  • For hyperhidrosis of palms and soles
    • Aluminum compounds
      • For initial treatment of hyperhidrosis, apply 20% aluminum chloride hexahydrate in absolute alcohol (Drysol) to dry palm or sole at bedtime. Discomfort or irritation can be kept to a minimum by avoiding use on moist skin and by using 1% hydrocortisone cream in the morning if necessary. Sweating should decrease to less than 50% of pretreatment levels within 4 weeks. If this treatment process is unsatisfactory, use with occlusion as follows: apply 20% solution of aluminum chloride hexahydrate in 80% absolute anhydrous ethyl alcohol (Drysol; Dab-o-Matic) to affected areas at bedtime and cover with plastic wrap, socks, or gloves. Do not wash the area for close to 2 hours before applying. Wash medication off in the morning. Use for 3 to 5 consecutive nights or more the first week until the desired anhidrosis is achieved and then one to three times weekly thereafter. The number of treatments depends on the individual.
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      • The antiperspirant action of aluminum salts is unclear. Physical blockage of the sweat ducts by an aluminum-containing cast is the most widely held opinion, although the possibility that aluminum produces vacuolization and atrophy of the secretory cells has been proposed.
      • The most common adverse effects reported include stinging, burning, pruritus, and irritation. Contact dermatitis is rarely seen.
      • Another metal salt, zirconium, had been used in the past; however, aerosol zirconium–based products were banned by the FDA in 1977 owing to the development of axillary granulomas in patients who used these products. Nonaerosol formulations at concentrations <20% are still allowed.
    • Botulinum A toxin (Botox) has been utilized in the management of hyperhidrosis and is the most effective treatment available. Its mechanism of action is to block the secretion of acetylcholine, resulting in a reversible chemical denervation. Botulinum toxin is delivered to the treatment sites through a series of superficial injections spaced 1 to 2 cm apart in a checkerboard pattern. The toxin is delivered to the superficial dermis to allow for greatest effect. Treatment success depends on the concentration used, depth of injection, and skill in placement. Effects of a single injection session may last between 6 and 9 months.
    • Aldehydes. Aldehydes reduce perspiration by denaturing keratin in the superficial corneocyte, thereby blocking the sweat gland pores. Disadvantages include a short-lasting effect and an increased incidence of contact sensitization. Either formalin (5% to 10%) or nonalkalinized glutaraldehyde applied with a cotton swab is effective. Formalin is a more frequent sensitizer and hence used less often. Unbuffered generic glutaraldehyde is available as a 50% solution through drug supply houses; 2% glutaraldehyde is used most easily as a Cidex solution or Cidex Formula 7 long-life solution (obtained through hospital supply sources).
      • Glutaraldehyde solution is applied three times a week for 2 weeks and then once weekly or as needed. A 10% solution is used for the feet. It will cause a temporary brown discoloration, but this pigmentation will diminish as frequency of application decreases. A 2% solution, which will not stain, may be used on the palms; however, this concentration produces only slight diminution in sweating.
      • Methenamine mandelate is a synthetic antibacterial agent that, when applied to the skin, hydrolyzes to ammonia and formaldehyde. A 5% methenamine stick or a 10% solution is effective in mild to moderate hyperhidrosis and rarely produces allergic reactions.
        • Structure
        • Use: Apply three times a week for 2 weeks, then once weekly as needed.
        • Packaging:
          • Methenamine mandelate 10% solution
          • Methenamine mandelate 5% stick
    • Iontophoresis with tap water is a simple, safe, and economic treatment for hyperhidrosis; it involves introducing tap water through intact skin by means of an electric current. Although its mechanism of action is still unclear, it is thought to produce a physical blockage in the sweat glands at the level of the stratum corneum. Also, disruption of the electrical gradient of the sweat duct may occur; this gradient is needed for the normal flow of perspiration. Adding anticholinergic drugs such as
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      glycopyrrolate to the water may provide some extra benefit but can also lead to side effects from systemic absorption. A battery-powered iontophoresis unit (Drionic) is available for home use. One study concluded that 80% of hand sites, 33% of sole sites, and 37.5% of axillae sites responded within 14 days, and this increased to 100%, 78%, and 75%, respectively, after 20 days, although patients often report diminished effectiveness over time.
    • Systemic anticholinergic drugs are usually not tolerated in the required doses but may be tried [glycopyrrolate (Robinul) three to five times a day initially, then decreased]. Sedatives or tranquilizing drugs are sometimes helpful.
      • Structure
    • Relaxation techniques including biofeedback training may decrease excessive palmoplantar and axillary sweating and the symptoms of chronic hyperhidrosis.
    • General measures include careful hygiene of hands and feet, frequent washing with deodorant soap, changing socks daily, and wearing cotton socks and leather shoes without rubber, plastic, or wooden soles.
      • Deodorants function either by masking odor or by decreasing bacteria. Antibacterial agents in deodorants include quaternary ammonium compounds (benzethonium chloride) and cationic compounds (chlorhexidine, triclosan).
  • For Axillary Hyperhidrosis
    • Aluminum compounds. May be used as noted in the preceding text.
    • Injection of botulinum toxin A induces anhidrosis that may last 6 to 9 months.
    • Scopolamine hydrobromide 0.025% applied topically can be an effective antiperspirant. Higher concentrations produce side effects such as diplopia.
    • Systemic anticholinergic and sedative (tranquilizing) drugs, iontophoresis, and relaxation techniques may be of value.
    • Glutaraldehyde is generally not effective in the axillae.
    • Surgical management of the axillary hyperhidrosis includes excision of the sweat gland–containing axillary vault, liposuction of the axillary vault, or upper thoracic sympathectomy. Complications of the surgical approach include Horner syndrome, brachial plexus injuries, pneumothorax, compensatory hyperhidrosis in adjacent regions, and painful scars. Hyperhidrosis may recur following sympathectomy. Plantar hyperhidrosis may be relieved with lumbar sympathectomy. Permanent nonfunction of sweat glands in the palms may result in scaling and fissuring of the palms.
Antipruritic and External Analgesic Agents
I. Discussion
See Chap. 26.
  • Camphor is a ketone which, when applied in 1% to 3% concentration, has mild antipruritic effects through its anesthetic and counterirritant properties. Counterirritants are substances that, by inducing other sensations such as coolness or warmth, “crowd out” the perception of pain or itch. Camphor is used in various OTC topical analgesic products in concentrations as high as 9%.
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    • Structure
  • Menthol, a cyclic alcohol (derived from peppermint, other mint oils, or prepared synthetically), relieves itching by generating a cool sensation. It is usually used in 0.25% to 2% concentrations but is present in concentrations as high as 16% in some OTC products.
    • Structure
  • Phenol in dilute solution (0.5% to 2%) decreases itch by anesthetizing the cutaneous nerve endings. Phenol should never be used on pregnant women or infants younger than 6 months of age.
    • Structure
  • Pramoxine hydrochloride (Itch-X, PrameGel, Prax, Tronothane, AmLactin AP) is a local anesthetic that is structurally similar to dyclonine and unrelated to the ester- or amide-type compounds.
  • Chlorethane (ethyl chloride) is a highly flammable liquid that acts as a topical vapo-coolant to control pain associated with minor surgical procedures. When applied as a spray, the product produces freezing of superficial tissues to -20°C, which results in insensitivity of peripheral nerve endings and local anesthesia that is maintained up to 1 minute. Other coolant sprays can be used with the same effect.
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    • Use: Apply immediately before the procedure is initiated.
    • Packaging:
      • Ethyl chloride spray: 3.5 oz
  • Doxepin is a dibenzoxepin-derivative tricyclic compound that exhibits potent histamine H1 and H2 receptor antagonist activity. Although the sedative effect of systemically absorbed doxepin may contribute to the drug’s antipruritic activity, the antipruritic efficacy of doxepin does not depend on a sedative effect. It is used topically for the short-term (up to 8 days of therapy) relief of moderately severe pruritus associated with eczematous dermatitis, including lichen simplex chronicus. Patients must be cautioned regarding the potential sedative effects and the risk of contact dermatitis.
    • Use: Apply to affected areas t.i.d.–q.i.d. without occlusion.
    • Packaging:
      • Zonalon 5% cream: 30 g
  • Salicylic acid (1% to 2%) and tars (coal tar solution, 3% to 10%) are also occasionally useful, although their mode of action is not known.
    • Structure
  • Crotamiton (Eurax) is not only scabicidal but has also been claimed to have a direct antipruritic effect. This has never been well studied, and the evidence indicates that crotamiton is not a generally effective antipruritic.
  • Local anesthetics are often used to allay pruritus by blocking nerve impulses at sensory nerve endings (see also Anesthetics for Topical Administration).
  • Other ingredients in OTC analgesics include the following:
    • Methyl salicylate, occurring naturally as wintergreen or sweet-birch oil, which, when rubbed on the skin, produces mild irritation and is absorbed to an appreciable extent. Triethanolamine salicylate 10% acts as an analgesic without irritant properties and is readily absorbed.
    • Thymol (see Antiinfective Agents).
    • Turpentine oil is used for its “counterirritant” properties.
    • Allyl isothiocyanate, volatile oil of mustard, acts as a powerful local irritant.
    • Clove oil, which contains eugenol as its main constituent, is used in ointments and is widely used in toothache preparations.
    • Capsaicin oleoresin, an irritant, derived from the plant of Solanaceae family (cayenne pepper), produces a feeling of warmth when applied to intact skin. Capsaicin depletes and prevents reaccumulation of substance P in peripheral neurons and is useful in the treatment of postherpetic neuralgia (see Chap. 16). Substance P is felt to be the principle chemomodulator of pain impulses from the periphery to the CNS. Its use in the therapy of pruritus has not been fully evaluated.
      • Use: Apply t.i.d.–q.i.d.
      • Packaging:
        • Capsaicin cream, 0.025%, 0.075%, 0.25%: 28 g, 30 g, 45 g, 60 g, 90 g
        • Capsaicin gel, 0.025%, 0.05%: 15 g, 30 g, 42.5 g
        • Capsaicin lotion, 0.025%, 0.075%: 59 mL
        • Capsaicin roll-on, 0.075%: 60 mL
    • Methacholine chloride, histamine dihydrochloride, and methyl nicotinate are used for their local vasodilating properties.
    • Other volatile oils in OTC preparations include wormwood and eucalyptus oils.
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  • Dermatologic antipruritic formulations
    • Lotions, liniments, emulsions
      • Calamine lotion, USP (drying):
        • Calamine (zinc oxide with 0.5% ferric oxide for coloring): 8 g
        • Zinc oxide: 8 g
        • Glycerin: 2 mL
        • Bentonite magma (suspending agent): <25 mL
        • Calcium hydroxide solution, to make: 100 mL
        • Packaging:
          • Calamine lotion: 120 mL, 240 mL, 480 mL
          • Phenolated calamine, USP: 1% phenol added to calamine formulations: 120 mL, 240 mL
          • Alcoholic calamine lotion (more drying):
            • Calamine 10 g
            • Zinc oxide 10 g
            • Bentonite 2 g
            • Talc 10 g
            • Glycerin 10 g
            • Alcohol 40 mL
            • Water, to make 100 mL
          • Calamine liniment (less drying):
            • Calamine 15 g
            • Peanut oil 50 mL
            • Calcium hydroxide, to make 100 mL
          • Menthol lotion with phenol (Schamberg’s):
            • Menthol 0.5 g
            • Phenol 1 g
            • Zinc oxide 20 g
            • Calcium hydroxide solution <40 mL
            • Peanut oil, to make 100 mL
        • Packaging:
          • Schamberg’s lotion: 480 mL
    • Gels and ointments
      • Menthol 0.5%
        Pramoxine HCl 1.0%
        In gel base
        • Packaging:
          • As PrameGel: 118 g.
      • Salicylic acid 3%
        Phenol 1%
        • Packaging:
          • As Panscol 3% lotion: 120 mL
          • 3% ointment: 90 g
    • Impregnated pads
      • Glycerin 10%
        Witch hazel (gallic acid, tannin, and volatile oils) 50%
        Water 40%
        • Use: Apply p.r.n. as replacement for toilet tissue or as cleansing and antipruritic wipe in prevention and therapy of pruritus ani and other perineal pruritic processes.
        • Packaging:
          • As tucks: box of 12, box of 40, box of 100
          • Gel: 19.8 g
    • Miscellaneous antipruritic preparations (some contain potential allergic sensitizers such as benzocaine and diphenhydramine).
      • Calamatum contains benzocaine (1.05% in spray, 3% in ointment), calamine, zinc oxide, menthol (in aerosol), camphor, phenol (in ointment), isopropanol (in spray).
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        • Packaging:
          • Aerosol: 85 g
      • Caladryl contains 1% camphor, 8% calamine, 2% alcohol, 1% pramoxine HCl, cetyl alcohol, and parabens.
        • Packaging:
          • Lotion: 180 mL
      • Caladryl clear contains 1% pramoxine, 0.1% zinc acetate, 2% alcohol, camphor, diazolidinyl urea, and parabens.
        • Packaging:
          • Lotion: 180 mL
    • Miscellaneous external analgesic products. These multiingredient preparations are used by many patients for muscular aches.
      • Ben-Gay ointment contains 18.3% methyl salicylate, 16% menthol; Ultra-Strength cream contains 30% methyl salicylate, 10% menthol.
      • Mentholatum ointment contains 9% camphor, 1.35% menthol, and aromatic oils. Mentholatum Deep Heating ointment contains 12.7% methyl salicylate, 5.8% menthol, eucalyptus oil, and turpentine oil.
      • Sloan’s liniment contains 46.7% turpentine oil, 6.7% pine oil, 3.3% camphor, 2.6% methyl salicylate, 0.6% capsicum, and 40% kerosene.
Cleansing Agents
I. Discussion
Cleansers are any agents that remove sebum or foreign particles from the skin. A spectrum of cleansers exists, ranging from very drying to very moisturizing. The choice of cleanser depends largely on a particular individual’s skin type.
  • Cleaning creams and lotions are useful in patients with very dry or sensitive skin who may react adversely to common soap products. They are generally oil-based, water-based, or water-free oils, the latter being the most moisturizing. Because they may leave an oily residue, they should be avoided in acne-prone patients. Cosmetic companies market most of these products, because they are useful in removing oily cosmetics. Examples of these cleansers include Albolene liquefying cleanser, Oil of Olay daily facial cleansing lotion, Ponds cold cream deep cleanser, and Sea Breeze whipped facial cleanser.
  • Soaps. Surfactants are substances that are able to dissolve both oil and water; soaps and soap-free cleansers (SFCs) are surfactants. Soaps are sodium or potassium salts that are derived from plant and animal oils or fats, whereas SFCs are synthetically derived. The two most common soaps are sodium tallowate and sodium cocoate. Soaps are alkaline (pH 9 to 10), which may irritate intact or damaged skin. Normal skin has a slightly acidic pH of 5.6 to 5.8. Cleansers with a pH closer to normal skin may be less irritating. Modified soaps may be less irritating because they are adjusted to be slightly acidic or neutral. Badly irritated skin should not be exposed to soaps, detergents, or cleansers other than water.
    • Neutral soaps or soap-like preparations contain synthetic detergents and have a pH of 7.5 or less. Preparations include Alpha Keri, Aveeno bar, Dove, Lowila Cake, and Emulave.
    • Superfatted soaps contain increased fat or oil on the assumption that they leave a film of protective oil on the skin. Preparations include Basis, Neutrogena Dry Skin, and Oilatum Soap.
    • Antimicrobial bar soaps contain topical antiseptics such as carbanilide, triclocarban, or the substituted phenol triclosan. They have some deodorant action by inhibiting bacterial growth. Representative soaps include Clearasil Antibacterial (triclosan), Coast (tricloban), Dial (1.5% triclosan), Irish Spring (0.75% tricloban, 0.25% triclosan), Safeguard (1.5% tricloban), Zest (tricloban), Jergens clear complexion (triclocarban), Lever 2000 (triclosan), and Lifebuoy III (triclosan).
      One study comparing bar and liquid soaps found higher microbial flora in the bar form.
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  • SFCs are surfactants that are synthetically produced. They generally have a pH close to that of normal skin and, hence, are less irritating. SFCs that contain oils may be even less irritating. Examples of SFCs include Aquanil lotion, Cetaphil lotion (lipid-free), Basis facial cleanser, Oil of Olay foaming face wash; SFCs containing oils include Aveeno cleansing bar for dry skin (also for normal to oily skin). Eucerin cleansing bar, Lowila cake soap, and pHisoderm skin cleanser for oily skin, regular skin, or for babies.
  • Abrasive cleansers are advertised for acne patients to assist in exfoliating the skin, presumably to “unplug” skin pores or to remove dead sensitive skin. They may contain various amounts and kinds of particulate matter, aluminum oxide, polyethylene, or sodium tetraborate decahydrate or even ground fruit pits or nutshells. The danger of these products is that they may cause some inflammation or damage to the follicles. Preparations include Sastid scrub (20% aluminum oxide), Pernox scrub (1.5% salicylic acid, 2% sulfur, polyethylene, and docusate sodium), Brasivol (aluminum oxide with sodium lauryl sulfate, fine, medium, or rough), and Ionax (polyethylene granules with benzalkonium chloride).
  • Acne cleansers (see Acne Preparations)
  • Shampoos
    • Coal tar. Coal is a mixture of various tar acids and hydrocarbons. Coal tar is reproduced through the distillation process of coal; it is then further refined by various methods to make it aesthetically more pleasing and pharmaceutically practical.
      The exact method by which coal tars are useful in managing dandruff, seborrheic dermatitis, and psoriasis is not known. It has been suggested that coal tar removes oxygen from the skin, thereby inhibiting mitosis and decreasing the size and number of cells in the stratum germinativum and stratum corneum. It may also have a vasoconstrictive, weak antiseptic, and antipruritic effect. Coal tars have also been used in combination with other drugs (hydrocortisone, salicylic acid, and sulfur) in relieving pruritus, flaking, and irritation of the skin.
      Adverse effects include irritant dermatitis with increased concentrations; folliculitis may be seen after prolonged use. These preparations may stain blonde or gray hair.
      • Packaging:
        • Crude coal tar:
        • DHS tar gel (6.5%)
        • Doak tar shampoo (3%)
        • Zetar (1%)
        • MG217 (2%)
        • Ionil T Plus (2%)
        • Coal tar extract:
        • Neutrogena T/Gel (2%)
        • Tegrin (5%)
        • Pentrax (8.75%)
        • Coal tar solution:
        • Denorex (9%), with 1.5% menthol
        • Duplex T (15%)
        • Coal combination:
        • T/Sal (2%), with 2% salicylic acid
        • MG217 (5%), with colloidal sulfur 1.5% and salicylic acid (2%)
    • Selenium sulfide suspension (Selsun) is a mixture of selenium monosulfide and a suspension of solid selenium and amorphous sulfur. Selenium acts by inhibiting cellular proliferation, kills yeast organisms, and has high substantivity. Little or no toxicity has been observed when applied directly to normal skin or hair, but these products should not be used on inflamed or exudative skin, where absorption may be increased. They are used in the control of seborrheic dermatitis, dandruff, and tinea versicolor.
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      • Packaging:
        • Selenium sulfide 1% lotion/shampoo: 120 mL, 210 mL, 240 mL, 330 mL
        • Selenium sulfide 2.5% lotion/shampoo: 120 mL
    • Zinc pyrithione is the active ingredient in several shampoos used to control dandruff and seborrheic dermatitis and is also effective in the therapy of tinea versicolor. It remains unclear whether the beneficial effects are caused by an antiproliferative or antimicrobial effect or both. It is substantive to the hair, allowing continued therapeutic effect after washing.
      • Structure
      • Packaging:
        • Shampoos including DHS-Zinc (2%), Head & Shoulders (1%), and Zincon (1%).
    • Ketoconazole (Nizoral) shampoo. See Chap. 29.
Cosmetics and Covering Agents
I. Cosmetics
  • The FDA defines cosmetics as any agent applied to the body for purposes of “cleansing, beautifying, promoting attractiveness, or altering the appearance.” As such, the term cosmetics encompasses a broad range of consumer products. Hypoallergenic cosmetics are products intended to cause less allergic reactions, although there is no standard. Companies specifically involved in the manufacture of less allergenic compounds include Almay, Clinique, and Prescriptives.
  • A key reference for cosmetic ingredients is the Cosmetics, Toiletries, and Fragrances Association (CTFA) Cosmetic Ingredient Dictionary. This reference lists >2,500 cosmetic ingredients used to formulate cosmetic products. Also, it contains important information on suppliers of cosmetic ingredients and is recognized as the official labeling compendium by the FDA for generating cosmetic ingredient disclosures under the Fair Packaging and Labeling Act.
  • The best source for cosmetic ingredient patch test concentrations and vehicles is the manufacturer. Many companies in the cosmetic industry provide patch test samples on request. The “Industry on Call” booklet published by the American Academy of Dermatology (AAD) is useful in contacting the appropriate cosmetic company.
II. Cosmetic Camouflage
Covering agents are used by patients in a variety of skin diseases, including vitiligo, acne, nevus flammeus, tattoos, other pigmentation abnormalities, and alopecia areata. Dermablend and Covermark are perhaps the most widely used agents. They are available in various skin tones, with a high degree of opacity. They are also effective sunscreens and are waterproof. Cosmeticians can assist patients in learning proper application techniques, which often differ from those of regular cosmetics. Some of these products may require special cleansers for removal. Other brands that specialize in concealing cutaneous defects include Dermage, Chromelin, Vitadye, Recover, and Natural Cover by Linda Seidel.
Product Information
Depilatories and Removal of Excessive Hair
I. Hypertrichosis
  • Mild hypertrichosis, most often familial in nature, is a cause of cosmetic concern for many women. It is mandatory that endocrine or local factors be ruled out before dismissing excessive hair as a simple cosmetic problem.
II. Hair Removal
  • There are several ways by which the amount or appearance of excessive hair may be decreased.
    • Bleaching the hair will make it less obvious. A 6% solution of hydrogen peroxide, commonly known as 20-vol peroxide, is most often used. It may be used alone, but the addition of an alkali, usually 10 drops of ammonia per 30 mL of peroxide, immediately before use will activate the hydrogen peroxide and permit more intense bleaching.
    • Plucking hair is painful but effective. Each pluck will start another growing cycle in the hair root.
    • Wax epilation is essentially just widespread plucking. A warm wax is placed on the skin, allowed to dry, and then, as it is peeled off, the hairs are pulled out.
    • Shaving is quick and effective and does not cause the hair to regrow more rapidly or more abundantly.
    • Rubbing with a pumice stone will remove fine hair.
    • Depilatories disintegrate and destroy hair on topical application by hydrolyzing disulfide bonds. The hair is left as a gelatinous mass, which is easily wiped off the skin. The following two active ingredients are currently used:
      • Sulfides of alkali metals and alkaline earths are the most effective, but they also develop a disagreeable hydrogen sulfide odor and are more irritating than thioglycollate products. Strontium sulfide or barium sulfide is the active ingredient. Preparations available include Magic Shaving Powder and Royal Crown Shaving Powder. Both contain barium sulfide and calcium hydroxide.
      • Thioglycollate-containing agents require increased contact time but are more easily perfumed and are less irritating than other preparations. Preparations available include Nair, Neet, and Nudit.
    • Vaniqa (eflornithine hydrochloride 13.9%) cream is a unique topical cream that slows anagen hair growth by irreversibly blocking the enzyme ornithine decarboxylase. This enzyme produces polyamines in the hair matrix that are partially responsible for the growth of the anagen hair. The cream was tested only on the upper lip and chin region. The onset of action is usually within 8 weeks of starting the b.i.d. treatment, and the hair growth will return to baseline within 8 weeks of discontinuing the drug. Patients need to be reminded that this product does not remove hair but slows its growth in between whatever they use for hair removal.
      • Use: Apply a thin layer to the affected area. The most common side effects are stinging, erythema, and acneiform eruptions. It is contraindicated in inflammatory acne, pregnancy, and lactation.
      • Packaging:
        • Vaniqa cream: 30 g; 60 g (2/30 g tubes)
    • Electrolysis is a permanent method of hair removal by which the hair bulb is destroyed by a high-frequency electric current and the hair will not grow back later. A topical anesthetic cream before treatment may reduce associated discomfort. When performed by a skilled operator, this technique is useful. Pit-like perifollicular scarring and regrowth or incompletely destroyed hairs may
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      follow electrolysis or repeated plucking. Pretreatment with Retin-A cream for 2 weeks may reduce healing time.
    • Laser hair removal is a permanent form of hair removal that requires pigmented hair, with melanin as the target for hair destruction. Utilizing the principle of photothermolysis, a laser wavelength of light is selected and delivered at a specific energy to target the hair follicle, while minimizing surrounding tissue damage. Epidermal melanin decreases the efficacy of the treatment, as it may absorb a portion of the light emitter, with resultant epidermal damage. Numerous lasers and light sources are available at present. Thorough evaluation and patient selection must be performed to determine if the patient is a good candidate for this treatment. In general, patients with Fitzpatrick skin types I–III and dark hair are the best candidates. Longer wavelength lasers such as diode and 1,064 nm Nd:YAG allow for safe and efficacious treatment of patients with Fitzpatrick skin types IV–VI. Treatment should be avoided if the patient is tan. Side effects include localized edema and erythema, postinflammatory hyperpigmentation, blistering, and scarring. Approximately 10% to 20% of treated hairs are reduced with every treatment; therefore, multiple treatments are generally necessary. A topical anesthetic cream before treatment may reduce associated discomfort.
III. Stimulation of Hair Growth
  • Androgenetic alopecia. Men and women alike may be affected with androgenetic alopecia (pattern hair loss), where terminal hairs are replaced with progressively finer, smaller vellus hairs. Men are generally affected in the bitemporal and vertex regions; women often present with more diffuse alopecia, generally in a frontovertical distribution.
    • Therapy
      • Minoxidil is a piperidinopyrimadine derivative and potent vasodilator that possesses hair growth stimulant properties. Topical minoxidil solution in 10% propylene glycol has proved effective in approximately 30% of individuals in converting vellus to terminal hairs. It is most effective in younger patients with less chronic hair loss. Hair growth is more likely to be stimulated on the vertex rather than on the bitemporal areas. Its mechanism of action is unknown. Adverse reactions include local irritation and contact dermatitis. If the treatment is discontinued, clinical regression occurs within 3 months to the state of hair thinning that would have occurred had the treatment not been started. Twice-daily treatment is more efficacious than once-daily application. Women who use the 5% concentration may note the development of facial hair, which is reversible on discontinuation of the medication. The 5% concentration can be more irritating than the 2% solution: application of the 5% solution at bedtime and the 2% solution in the morning can leave the hair more manageable and the scalp less irritated. Minoxidil is also used in the treatment of alopecia areata.
        • Use: Apply to scalp b.i.d. and gently massage into scalp.
        • Packaging:
          • Minoxidil 2% solution: 60 mL with dropper
          • Minoxidil 5% solution: 60 mL with dropper
    • Finasteride (Propecia) is a synthetic 4-azasteroid compound. It acts as a specific competitive inhibitor of steroid type II 5α-reductase, an intracellular enzyme present in high concentrations in the inner root sheath of the hair follicle and prostate gland. The conversion of testosterone to the active metabolite DHT depends on the presence of this enzyme. In men with androgenetic hair loss, increased amounts of DHT and 5α-reductase lead to miniaturized hair follicles and a shortened hair growth cycle. Inhibition of type II 5α-reductase by finasteride blocks the peripheral conversion of testosterone to DHT, resulting in substantial reductions in serum and tissue DHT concentrations. Oral finasteride has been effective in promoting hair growth in men aged 18 to 41 with mild to moderate androgenetic alopecia. It is most effective for vertex and midscalp loss. Its effectiveness has not been investigated for bitemporal loss. New hair growth is generally detected 6 months after treatment initiation.
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      Cessation of the medication results in a gradual return to a pretreatment hair loss stage. It is contraindicated in pregnant women and in children, because it inhibits the conversion of testosterone to DHT, which could result in deformities in the external genitalia of a male fetus. Other side effects are rare. Less than 2% men reported sexual dysfunction, including erectile dysfunction, which was only slightly higher than the placebo group and was reversible on discontinuation of the medication. Finasteride has no effect on sperm motility/ejaculate. It slightly lowers the prostate-specific antigen (PSA); therefore, doubling the PSA value before its clinical interpretation should be considered in the evaluation of benign prostatic hypertrophy. A baseline PSA should be obtained in males over 40 or if there is a positive family history of prostate cancer.
      • Use: Take 1 mg/day
      • Packaging (Merck):
        • Propecia 1 mg tablet: pack of 30 or Pro-Pak (90-day supply)
Dermatologic Topical Preparations and Vehicles
(See also Types of Topical Medications)
Lotions, creams, ointments, and powders can be used alone or may act as vehicles for pharmacologically active substances. Ideally, they are nontoxic, stable, and do not sensitize with repeated use. It should not be assumed that “inert” vehicles or bases have no effect on the skin or epithelial metabolism.
I. Constituents of Dermatologic Products
Dermatologic vehicles are often complex substances that contain many additives. The general classes of vehicle ingredients are emulsifying agents, which are surfactants and improve stability of emulsions; stabilizers, including preservatives and antioxidants, which preserve stability of vehicles both initially and over time; solvents, which increase the solubility of the drug in the vehicle; thickening agents, used to increase viscosity or suspend ingredients in vehicles; emollients; and humectants, agents that are hygroscopic and draw moisture from the skin.
  • Emulsifying or dispersing agents provide stability and homogeneity. Glyceryl monostearate, polyethylene glycol derivatives (polyoxyl 40 stearate, polysorbate 80), and sodium lauryl sulfate are such agents used in preparations containing oily components and water. Sodium lauryl sulfate may act as an irritant.
  • The consistency and appearance of creams are improved by the addition of additives such as ethylenediamines (frequent allergic sensitizers), cetyl palmitate, and related esters.
  • Lubricants, emollients, and/or antifoaming agents include stearic acid, stearyl alcohol, isopropyl myristate, and cetyl alcohol.
  • Methylcellulose and gum tragacanth are used as suspending agents in pastes and ointments.
  • Preservatives include parabens (short alkyl esters of parahydroxybenzoic acid), benzyl alcohol, oxyquinoline sulfate, organic quaternary ammonium compounds, hexachlorophene, parachlorometaxylenol, and chlorobutanol. Methyl and propylparaben may act as allergic sensitizers.
II. Lotions, Creams, Ointments, and Powders
  • Lotions are usually liquid suspensions or dispersions intended for external application to the body. Solid-in-liquid suspensions are preparations of finely divided, undissolved drugs, or other particulate matter dispersed in liquid vehicles. These suspensions require shaking before application to ensure uniform distribution of solid in the vehicle. Liquid-in-liquid dispersions generally contain higher water content than cream emulsions and can be poured. Lotions provide a protective, drying, and cooling effect and may act as a vehicle for other agents. The addition of alcohol increases the cooling effect. If an astringent, such as aluminum, is present, it will precipitate protein and dry and seal exudating surfaces.
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    • Calamine lotion (see Antipruritic and External Analgesic Agents).
    • Alcohol, zinc oxide, and talc lotion (more drying):
      • Zinc oxide 15 g
      • Talc 15 g
      • Glycerin 10 g
      • Alcohol 30 mL
      • Water, to make 100 mL
    • Burow’s emulsion, modified (less drying):
      • Zinc oxide 10 g
      • Talc 10 g
      • Olive oil 45 mL
      • Anhydrous lanolin 10 g
      • Aluminum acetate solution 2.5 mL
      • Water, to make 100 mL
  • Oil-in-water and water-washable cream emulsions are easily washable and will take up water but are not in themselves soluble.
    • Hydrophilic ointment, USP, contains polyoxyl 40 stearate as an emulsifying and wetting agent, stearyl alcohol as a stabilizer, and parabens (parahydroxybenzoic acid) as preservatives. It is a good vehicle for water-soluble medications. If hydrophilic ointment is used under occlusion, an irritant contact dermatitis may result. Sodium lauryl sulfate is the provocative agent.
      • Contains:
        • Methylparaben 0.025 g
        • Propylparaben 0.015 g
        • Stearyl alcohol 25 g
        • White petrolatum 25 g
        • Propylene glycol 112 g
        • Sodium lauryl sulfate 5 g
        • Water, to make 100 mL
    • Glycerin is frequently found in moisturizing creams (such as Complex 15, Curel, DML Forte, Lubriderm, and Jergens). This agent has been termed a humectant, which is a substance that is purportedly absorbed into the skin to help replace missing hygroscopic substances or, if absorption does not occur, to attract water from the atmosphere and serve as a reservoir for the stratum corneum. In fact, glycerin appears to be effective in treating dry skin but its mechanism of action is not known.
    • Commercially available oil-in-water emulsion bases include Nivea cream, Purpose Dry Skin cream, and Lubriderm.
  • Ointments. These bland bases may have an antimitotic effect on stripped epidermis, perhaps related to the effects of physical occlusion. The “stickiest” preparations are the most inhibitory.
    • Water-soluble ointments [polyethylene glycols (Carbowax)] are completely water soluble and may also act as lubricants or as water-soluble bases.
    • Emulsifiable ointments
      • Water-in-oil absorbent ointments are difficult to wash off and are insoluble in water, but will take up water in significant amounts.
        • Hydrous wool fat, USP (lanolin), although insoluble in water, is capable of absorbing twice its weight in water. It is a yellow-white preparation containing 28% water and is the purified, fat-like substance from the wool of sheep
          Anhydrous lanolin, a brown-yellow absorbent ointment that contains <0.25% water, is more greasy and occlusive.
          • Packaging:
            • Anhydrous lanolin: 25 g, 500 g
        • Cold cream, USP (rose water ointment), is a pleasant-smelling, soft base used chiefly because of its cosmetic appearance and for its lubricating, emollient, and cooling effects (hence its name, cold cream). These preparations are good vehicles for the incorporation of many substances. The
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          official cold cream is a water-in-oil (W/O) emulsion, but there are many variations that approach oil-in-water (O/W) emulsions. These creams are the basis of many cosmetic products such as cleansing, night, moisturizing, and eye creams.
          • Contains:
            • Spermaceti 12.5 g
            • White wax 12.0 g
            • Mineral oil 56.0 g
            • Sodium borate 0.5 g
            • Water, to make 100 g
          • Packaging:
            • Pond’s Dry Skin Cream: 3.5 oz
      • Similar bases consisting of oils and emulsifying agents but no water are termed absorbent ointments. They are difficult to wash off and are insoluble in water, but they will soak up water to become water-in-oil emulsions.
        • Hydrophilic petrolatum, USP, is characterized by its ability to take up large amounts of water. It is less greasy than petrolatum but more greasy than hydrophilic ointment.
          • Contains:
            • Cholesterol 3 g
            • Stearyl alcohol 3 g
            • White wax 8 g
            • White petrolatum, to make 100 g
          • Packaging:
            • Hydrophilic petrolatum ointment: 1 lb
        • Commercially available hydrophilic (W/O) bases include Eucerin (which is equal parts of Aquaphor and water), Keri Cream, Nivea oil, Polysorb, and Aquaphor, the latter two when hydrated.
    • Water-repellent ointments consist of inert oils, are insoluble in water, are difficult to wash off, will not dry out, and change little with time.
      • Petrolatum, USP, is a semisolid mixture of hydrocarbons obtained from petrolatum and is the most commonly used base for ointments. White petrolatum (decolorized petrolatum) is more aesthetically appealing and is used most often.
        • Packaging:
          • Petrolatum: 454 g
      • Liquid petrolatum, USP (mineral oil, liquid paraffin), is a mixture of purified hydrocarbons obtained from petrolatum.
        • Packaging:
          • Mineral oil: 500 mL
    • Silicone (dimethicone) ointments are excellent water-protective agents because they have an extremely low surface tension and penetrate crevices in the skin to form a plastic-like barrier. Further, they are nontoxic, inert, stable, and water repellent. As such, they are useful as barrier creams in industry or wherever constant or frequent exposure to aqueous compounds is a problem. They will not, however, protect well against solvents, oils, or dusts.
      • Structure
      • Packaging:
        • Silicone 10% ointment: 30 g, 480 g
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          Because there are no all-purpose effective protective agents, it is essential to choose a particular cream for protection against a specific hazard, that is, against dusts and particular matter, aqueous compounds, or solvents.
  • Pastes are made by incorporating a fine powder into an ointment. The base is usually petrolatum, and the powders, which constitute 20% to 50% of the paste, are usually zinc oxide, talc, starch, bentonite, aluminum oxide, or titanium dioxide. Pastes are more absorptive, less greasy, and less effective vehicles than ointments and are less efficient at preventing water evaporation. However, they are excellent protective compounds and may be used in subacute and chronic dermatoses. Pastes should be applied evenly with a tongue blade or finger and may be removed most easily with a cloth soaked in mineral or vegetable oil.
    • Zinc oxide paste, USP
      • Zinc oxide 25 g
      • Starch 25 g
      • White petrolatum, to make 100 g
      • Packaging:
        • Zinc oxide paste: 28 g, 60 g, 75 g
  • Powders increase evaporation, reduce friction, and provide antipruritic and cooling sensations. Zinc oxide or stearate, magnesium stearate, talc, cornstarch, bentonite, and titanium dioxide may either be used as dusting powders or incorporated into pastes or shake lotions. Talc is the most lubricating, but it does not absorb water; starch is less lubricating and absorbs water; zinc oxide has absorptive properties intermediate between the two. Zeasorb powder, which contains 45% microporous cellulose, has a relative absorbency of water almost twice that of talc-based powders. Talc can cause a granulomatous reaction in wounds, and starch may be metabolized by organisms and cause an increase in Candida overgrowth.
    • Talc, USP (talcum), is a hydrous magnesium silicate that sometimes contains a small amount of aluminum silicate.
      • Packaging:
        • Talc: 500 g
  • Miscellaneous
    • Collodion is a mixture of pyroxylin (a nitrocellulose derivative), ether, and alcohol that forms an adherent film on the skin after drying. Flexible collodion contains collodion, camphor 0.2%, and castor oil 0.3%. It is used as a vehicle for salicylic and lactic acids in the treatment of warts, as a protective film over herpes zoster lesions, and over fissures as present in chronic hand dermatitis.
    • N6-furfuryladenine (Kinerase) is a natural plant growth factor that is purported to retard the aging process and improve fine wrinkles and dyspigmentation with continuous use, with a moisturizing effect. It is nonirritating.
      • Packaging: (ICN Pharmaceuticals):
        • Kinerase 1% cream, lotion
Insect Repellents
  • Discussion. See Chap. 5.
  • Effective insect repellents contain diethyltoluamide (DEET), ethyl hexanediol (E-H), or multiple ingredients. The mechanism of action for repellents is not clearly defined. Once applied, they are thought to evaporate a certain distance from the skin, where they are recognized by the insect, irritating their olfactory organs. Agents with faster rates of evaporation are more effective, but these products also lose their effectiveness faster. Because repellents do not kill insects, selection for resistant species does not occur. Most repellents must be reapplied after sweating or bathing.
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    • DEET is an organic liquid that is an excellent mosquito repellent; stronger preparations of DEET are also effective against stable flies, although little protection is provided against ticks. Commercial preparations are available in aerosol, cream, or lotion form and vary in concentration from 6% to 100%. Because DEET is absorbed into the bloodstream, it should be applied sparingly. Lesser concentrations of DEET should be used whenever possible, with additional applications to the skin if needed. Reports of a toxic encephalopathy and brief seizures have been documented in children after overzealous use. Less serious neurologic side effects include confusion, irritability, and insomnia. Contact dermatitis has been observed with preparations containing higher concentrations of DEET.
      Use preparations with <20% DEET in children. Avoid mucous membranes, broken skin, and hands of children, because they are often in contact with the mouth. Spray clothing instead of skin whenever possible, but avoid contact with rayon, acetate, or spandex, because these materials may be damaged by DEET.
    • Ethyl hexanediol will not irritate human skin but can cause a chemical conjunctivitis. It is a standard repellent for chiggers, mosquitoes, black flies, and other biting flies and is more useful when combined with dimethyl phthalate and indalone. The mixture of these three chemicals will repel ticks and flies when it is applied to clothing.
    • Dimethyl carbate can be applied to clothing to repel ticks.
    • Butopyronoxyl is not water soluble and can be applied to skin and clothing to repel biting stable flies, Lone Star ticks, dog and cat fleas, and chiggers.
    • Butylethylpropandiol is used together with benzyl benzoate as the U.S. Army standard for clothing impregnation to repel ticks and chiggers.
    • Benzyl benzoate can be used in a 5% emulsion to repel many arthropods and can be used as a lotion to treat sarcoptic mange and canine pediculosis.
    • Permethrin 0.5% spray kills ticks and repels mosquitoes and stable flies. It is broken down when applied to skin and, hence, should be applied to clothing, shoes, tents, and so on. Spray only enough to moisten the material. Spray on clothing at least 2 hours before wearing. One treatment should last through a few washings.
  • Systemic allergic reactions to insect stings may include urticaria, bronchospasm, laryngeal edema, hypotension, and death. Approximately 1% to 3% of adults in the United States have had systemic allergic reactions to insect stings. Fifty percent of these adults will have similar reactions if they are stung again as against <5% of such patients who are treated with immunotherapy. Preparations from venom from the honeybee, yellow jacket, yellow hornet, white-faced hornet, and Polistes wasp are available for diagnosis and immunotherapy. Fire ant whole-body extracts are also available. Risks of immunotherapy include large local reactions or systemic reactions in 5% to 15% of patients early in treatment. These reactions are less likely in the maintenance phase of therapy. Generally, venomimmunotherapy may be stopped after 5 years or sooner.
Keratolytic, Cytotoxic, and Destructive Agents
  • α-Hydroxy acids represent a group of substances derived from natural products such as fruits (citric acid), milk (lactic acid), sugar cane (glycolic acid), apples (malic acid), and wine (tartaric acid). Variations of these products are effective in treating skin problems such as xerosis, photoaging, and acne. Three prevailing theories postulate how they work, although their exact mechanism is unknown. First, dissolution of the chemical adhesion between cells within the outermost layer of the epidermis may lead to keratolysis or sloughing of excess stratum corneum. Second, alteration in the pH of the skin when the acids contact the epidermis causes irritation, with subsequent increased cell turnover rate and a renewed stratum corneum. Lastly, exposure to the acids may induce slight edema, which plumps the
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    skin, reducing fine lines and wrinkles. In acne, softening of intercellular adhesion may assist in exfoliation, with a comedolytic effect. Overall, tretinoin still seems to be more effective in comedolysis, although the combination of α-hydroxy acids and tretinoin may be synergistic. In treating xerosis, α-hydroxy acids have been shown to thicken the epidermis, as well as thin the stratum corneum. Cracks and fissures in the stratum corneum improve after treatment; histopathologically, a disorganized stratum corneum regains its well-organized, basket-weave appearance. In addition, in a double-blinded trial, Lac-Hydrin (12% ammonium lactate) was shown to increase the glycosaminoglycans in the dermis as well.
    Higher concentrations of α-hydroxy acids (30% to 70%) are available for physicians’ use in the office for light chemical peels. Rewarding results in reducing fine lines and evening skin tone may be obtained. The patient, however, will not achieve the depth of peeling with these products that can be attained with higher concentrations of trichloroacetic acid or laser resurfacing.
  • Anthralin is a synthetic derivative of a substance that was originally extracted from the araroba tree of Brazil. It is most frequently used in the treatment of psoriasis, although it may also be helpful in alopecia areata. Anthralin reduces epidermal mitotic activity, perhaps through interference with mitochondrial DNA or certain cellular enzyme systems. It may act as an irritant and will stain skin and clothing. Anthralin is most effective when incorporated into a stiff paste or ointment containing salicylic acid. However, because these preparations are messy and difficult to apply, more cosmetically acceptable anthralin creams are preferable to most patients.
    • Structure
    • Use: Apply daily as directed and rinse off. Optimal contact time will vary according to strength used and patient response. Initial contact time is between 15 and 20 minutes. Commence treatment for 1 week at the lowest strength possible and increase the strength as necessary. Continue treatment until clearance is obtained.
    • Packaging:
      • Anthralin ointments contain anthralin, petrolatum, and mineral oil (0.1%, 0.25%, 0.5%, 1%: 42.5 g).
      • Anthralin creams (Drithocreme, Micanol) contain anthralin in a vanishing cream base (0.1%, 0.25%, 0.5%, 1%: 50 g).
  • Bleomycin, a cytotoxic antineoplastic agent that inhibits DNA synthesis, is an alternative therapy for recalcitrant warts. It may be administered through a bifurcated needle intralesionally, usually reconstituted in physiologic saline or 1% lidocaine at a concentration of 0.5 to 1 U bleomycin/mL, or by injection. A maximum total dose of 2 U may be administered. The lidocaine suspension reduces the discomfort at the time of injection; however, patients may still experience pain or local tenderness at the treated site for 1 to 7 days following treatment. A hemorrhagic eschar develops that should be pared down 2 to 3 weeks after treatment. Larger warts may require a series of injections every 3 weeks. Caution should be taken when treating distal digits because Raynaud’s phenomenon and nail loss have been reported.
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    • Structure
    • Packaging:
      • Bleomycin powder: 15 U vials, 30 U vials.
  • Calcipotriene (calcipotriol) is a synthetic vitamin D3 derivative that is useful for the treatment of patients with moderate plaque psoriasis. Its effects are comparable with those of class II topical steroids, without the associated adverse effects. Its mechanism of action involves both induction of terminal differentiation of keratinocytes and inhibition of keratinocyte production. It should be applied to the face with care, as this region is more susceptible to irritation, burning, and itching, as seen in approximately 10% of patients. Other adverse effects include erythema, peeling, xerosis, dermatitis, or worsening psoriasis in 1% to 10% of patients. Fewer than 1% of patients experience hypercalcemia, atrophy, hyperpigmentation, or folliculitis. Allergic contact dermatitis to calcipotriene has been reported.
    Most patients demonstrate improvement after 2 weeks; 70% of patients improve after 8 weeks, with 10% showing complete clearing. It should be avoided in patients with documented impairment in calcium metabolism, hypercalcemia, vitamin D toxicity, or history of renal stones.
    Calcipotriene may be used as an adjuvant with psoralens plus ultraviolet A (PUVA) and ultraviolet B (UVB). Pretreatment with or subsequent addition of calcipotriol to PUVA reduces the cumulative doses of UVA needed to achieve >75% reduction in severity and distribution of psoriasis.
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    • Structure
    • Use: Calcipotriene ointment should be applied thinly to plaques twice daily, with a total dosage not >100 g/week.
    • Packaging:
      • Dovonex 0.005% cream: 30 g, 60 g, 100 g
      • Dovonex 0.005% ointment: 30 g, 60 g, 100 g
      • Dovonex 0.005% solution: 60 mL
  • Cantharidin, from the beetle Cantharis vesicatoria, causes intraepidermal vesiculation and is used in the treatment of warts and other benign cutaneous lesions. Cantharidin is extremely toxic if taken internally; it should not be prescribed for at-home use.
    • Structure
    • Packaging:
      • Cantharidin 0.7%, as Cantharone: 7.5 mL
  • Caustics are used alone in some circumstances and are often used to obtain hemostasis. They are also used in combination with electrosurgery for the superficial treatment of hyperplastic cutaneous lesions (warts, keratoses, xanthelasmas) and are also utilized in cosmetic therapy for aging, wrinkled facial skin.
    • Mono-, di-, and trichloroacetic acids [CCI3COOH (trichloroacetic acid)] are rapid and effective local cauterizing agents. They are strongly corrosive and act by precipitation and coagulation of skin proteins. The monochloroacetic derivative is more deeply destructive than the trichloroacetic preparation; 35% to 50% trichloroacetic acid is, in general, the most useful preparation.
    • Silver nitrate (AgNO3), in solid form or in solutions stronger than 5%, is used for its caustic action; 5% to 10% solutions may be applied to fissures or excessive granulation tissue. Silver nitrate sticks consist of a head of toughened silver
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      nitrate (>94.5%) prepared by fusing the silver salt with sodium chloride. They are dipped in water and applied as needed.
      • Packaging:
        • Silver nitrate 100 sticks
  • FU is a fluorinated pyrimidine antagonist that acts as an antimetabolite by interfering with DNA synthesis by inhibiting thymidylate synthetase activity. It is used topically for the treatment of multiple actinic keratoses, superficial basal cell carcinomas, and Bowen’s disease; it also has been found useful in therapy of some types of warts.
    The combination of 5-FU and topical tretinoin may be used in treating actinic keratoses resistant to 5-FU alone. Patients may be pretreated with 0.1% tretinoin cream 2 to 3 weeks before starting twice-daily applications of 5% 5-FU cream. The combination is continued until an inflammatory response to the actinic keratosis begins (approximately 2 weeks). The tretinoin is then discontinued, but the 5-FU is continued for an additional 2 to 3 weeks.
    The mechanism for the synergy is unclear but may involve enhanced penetration of the 5-FU secondary to the keratolytic effects of the tretinoin. Also, both 5-FU and tretinoin may have complementary dual effects in inhibiting cellular function and better destruction of hyperproliferative cells.
    5-FU has also been used topically in treating human papillomavirus (HPV) infections, especially flat facial warts. Erosion and ulceration are not necessary for a therapeutic response. Its use in preventing recurrent disease prophylactically has also been well recognized.
    • Structure
    • Packaging:
      • Fluorouracil 1% cream: 30 g
      • Fluorouracil 5% cream: 25 g
      • Fluorouracil 0.5% cream: 30 g
      • Fluorouracil 1% solution: 30 mL
      • Fluorouracil 2% solution: 10 mL
      • Fluorouracil 5% solution: 10 mL
  • Imiquimod (Aldara) is an imidazoquinolone amine that is an immune response modifier. Its exact mechanism is unknown in the topical treatment of HPV and molluscum contagiosum but may be related to the immunomodulating effect of the drug. It is also effective in the treatment of actinic keratoses and superficial basal cell carcinoma.
    It induces production of a variety of cytokines and can enhance cell-mediated cytolytic antiviral activity. It is a rapid and potent inducer of interferon-α, interleukin-1 α and β, interleukin 6, interleukin 8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor. Systemic absorption is minimal. It is generally well tolerated. Adverse local reactions include erythema, erosion, excoriation, flaking, and edema of the treatment sites.
    • Use: Apply to affected area three times weekly before normal sleeping hours and leave on the skin for 6 to 10 hours, then rinse off. Treatment is continued until warts have cleared, generally 8 to 12 weeks. Several protocols have been proposed for treatment of actinic keratosis, basal cell carcinomas, and squamous
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      cell carcinomas, including application every other day and application during weekdays only and breaks during weekends for 6 to 16 weeks.
    • Packaging:
      • Aldara 5% cream: 250 mg single dose packets, box of 12
  • Podophyllum resin (podophyllin) is a chemically complex extract obtained from the roots of either of the two plants: Podophyllum peltatum (American) or Podophyllum emodi (Indian) (also called Mandrake or May-apple). Podofilox is the most cytotoxic ingredient in podophyllum resin (present in concentrations of 15% to 20% in P. peltatum and 30% to 40% in P. emodi resins) and exerts its effect by binding to intracellular microtubular proteins and thereby preventing the development of the mitotic spindle. In vitro, podophyllum also inhibits RNA synthesis. Podophyllum is used in the treatment of condyloma acuminata and other warts. It can induce severe erosive changes in adjacent normal skin and may produce serious systemic effects, including peripheral neuropathy, psychotoxic confusional states, adynamic ileus, renal damage, leukopenia, and thrombocytopenia, if applied too generously, especially on mucosal surfaces. Podophyllum is applied as a 25% suspension in compound tincture of benzoin or in alcohol at weekly intervals. Its use during pregnancy is contraindicated as it is a suspected teratogen.
    Podofilox (formerly podophyllotoxin) is the active ingredient in podophyllin resin. It inhibits microtubular function by combining with free dimers of tubulin, the main structural component of microtubules. Application of 0.05 mL of podofilox 0.5% in lactate-buffered ethanol twice daily for 3 consecutive days each week appears safer than conventional podophyllin therapy, even when it is self-administered.
    • Structure
    • Use: Apply to affected areas only. Rinse off after 4 hours. Repeat treatment weekly as necessary.
    • Packaging:
      • Podofin [25% podophyllum resin (American) in compound tincture of benzoin]: 15 mL
      • Condylox (0.5% podofilox in lactate-buffered alcohol): 3.5 mL.
      • Cantharone Plus (podophyllin 5%, cantharidin 1%, salicylic acid 30% in octylphenyl polyethylene glycol 0.5%, cellosolve, ethocel, collodion, castor oil, and acetone): 7.5 mL.
  • Propylene glycol solution (40% to 60%, v/v CH2CH[OH]CH2OH, propylene glycol) applied to the skin under plastic occlusion hydrates the skin and causes desquamation of scales. Propylene glycol, isotonic in 2% concentration, is a widely used vehicle in dermatologic preparations. Hydroalcoholic gels containing propylene glycol or other substances augment the keratolytic action of salicylic acid. Keralyt gel consists of 6% salicylic acid, 19.4% alcohol, hydroxypropylcellulose, propylene glycol, and
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    water and is an extremely effective keratolytic agent. Overnight occlusion is used nightly until improvement is evident, at which time the frequency of therapy can be decreased to every third night or once weekly. This therapy is well tolerated, is usually nonirritating, and has been most successful in patients with X-linked ichthyosis vulgaris. Burning and stinging may occur when applied to damaged skin. Patients with other abnormalities of keratinization with hyperkeratosis, scaling, and dryness may also benefit.
    • Packaging:
      • Keralyt gel: 1 oz
      • Epilyt solution (40% propylene glycol): 4 oz
  • Resorcinol (resorcin), a phenol derivative, is less keratolytic than salicylic acid. This drug is an irritant and sensitizer and reported to be both bactericidal and fungicidal. Solutions containing 1% to 2% have been used in preparations for seborrhea, acne, and psoriasis.
    • Structure
  • Retinoids (for information regarding isotretinoin or tretinoin, see Chap. 1). Acitretin (Soriatane) is a synthetic derivative of vitamin A that is particularly effective in treating the pustular and erythrodermic forms of psoriasis. It is the main metabolite of etretinate; ingestion of alcohol with acitretin increases the amount of detectable etretinate. It is accumulated in fatty tissue with a prolonged elimination half-life of approximately 120 days. Most patients show improvement within 2 to 4 weeks, although some patients may need as long as 6 months of therapy before a response is noted. Other disorders of keratinization, which may respond to acitretin, include Darier’s disease, pityriasis rubra pilaris, lamellar ichthyosis, and hyperkeratotic palmaris and plantaris. Acitretin is teratogenic and is contraindicated during pregnancy. Pregnancy should be avoided for at least 1 year after discontinuation of treatment. P. cerebri, hepatotoxicity, and ocular changes may occur.
    • Structure
    • Use: Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects. Initiate treatment at 10 to 25 mg/day with food. Terminate treatment when resolution is achieved. Treat relapses as outlined for initial therapy. Baseline and treatment liver function tests, glucose, and cholesterol/triglyceride panel should be monitored throughout treatment. A baseline and monthly pregnancy test are required.
    • Packaging:
      • Soriatane capsules: 10-mg, 25-mg tablets
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  • Bexarotene (Targretin) is a member of a subclass of retinoids that selectively activate retinoid X receptors. It is used in the management of patch and plaque stages of cutaneous T-cell lymphoma (CTCL). It inhibits growth of tumor cell lines of hematopoietic and squamous cell origin. As it is a teratogen, its use is contraindicated in pregnant women.
    • Use: Apply to affected areas once every other day for the first week, then increase at weekly intervals to a final application of four times daily, depending on patient tolerance. Treatment is continued as long as benefit is appreciated.
    • Packaging:
      • Targretin 1% gel: 60 g
  • Salicylic acid is keratolytic and at concentrations between 3% and 6% causes softening of the horny layers and shedding of scales. It produces this desquamation by solubilizing the intercellular cement and enhances the shedding of corneocytes by decreasing cell-to-cell cohesion. In concentrations >6%, it can be destructive to tissue. Application of large amounts of the higher concentration of salicylic acid can also result in systemic toxicity. Salicylic acid is used in the treatment of superficial fungal infections, acne, psoriasis, seborrheic dermatitis, warts, and other scaling dermatoses. When it is combined with sulfur, some believe that a synergistic keratolytic effect is produced. Common preparations include a 3% and 6% ointment with equal concentration of sulfur; 6% propylene glycol solution (Keralyt); 5% to 20% with equal parts of lactic acid in flexible collodion for warts (Duofilm, Occlusal); in a cream base at any concentration for keratolytic effects; as a 60% ointment for plantar warts; and in a 40% plaster on velvet cloth for the treatment of calluses and warts (40% salicylic acid plaster).
    • Structure
    • Packaging:
      • Gel 17% salicylic acid: 7 g, 14 g, 14.2 g
      • Liquid 17% salicylic acid: 9 mL, 10 mL, 13.3 mL, 13.5 mL, 15 mL
      • Plasters 15%, 40%: 40% salicylic acid plasters (Dr Scholls, Mediplast)
  • SELENIUM SULFIDE (See Cleansing Agents)
  • Sulfur is incorporated into many preparations used in the treatment of acne, rosacea, ringworm, psoriasis, scabies, seborrheic dermatitis, and infestations. Sulfur inhibits the growth of microorganisms, particularly fungi and parasites. More effective keratolytic, antifungal, and antibacterial agents are available.
  • TAR COMPOUNDS. A tar is a product of destructive distillation of organic substances. Tar is obtained from various sources and, therefore, there are different types. Wood tars include oil of cade, beech, birch, and pine. They do not photosensitize but are more allergenic than coal tars. Bituminous tars include ichthyol and ammonium ichthyosulphonate, a distillation of shale deposits containing fossilized fish. Coal tars are by-products of the destructive distillation of bituminous coals and are ill-defined, aromatic, and complex substances. They contain 2% to 8% light oils (benzene, toluene, xylene), 2% to 10% middle oils (phenols, cresols, naphthaline), 8% to 10% heavy oils (naphthaline and derivatives), 16% to 20% anthracene oils, and approximately 50% pitch. Coal tars are brown black, slightly soluble in water, and partially soluble in many solvents. Only coal tar and coal tar pitch have photosensitizing properties.
    In hairless mice, coal tars have been shown to inhibit DNA synthesis. Five-percent crude coal tar ointment applied to normal human skin causes an initial
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    transient hyperplasia followed by a 20% reduction in viable epidermal thickness after 40 days’ treatment. These findings indicate that tar by itself can act as a cytostatic agent. Although coal tars are carcinogenic for the skin of experimental animals and are often used along with another oncogenic agent, ultraviolet light (UVL), the risk of developing cancer from therapeutic coal tar products remains unclear. The presence of unidentified mutagenic material(s) in the urine of patients with coal tar has been reported.
    Tars have long been found to be useful in patients with eczematous, pruritic, and hyperplastic disease. They are often used in combination with sulfur, salicylic acid, and topical steroids and are used with UVB UVL in the therapy of psoriasis (see Chap. 27).
    • Coal tar products are available OTC or may be compounded to USP, NF, or other formulas.
      • Estar gel:
        • Tar (equivalent to crude coal tar) in hydroalcoholic base 5%
      • Coal tar creams include Fototar (2%) and Tegrin (5%).
      • Tar gels include Aquatar (2.5%), Estar (5%), P&S (8%), and PsoriGel (7.5%).
      • Liquid tar preparations include MG217 lotion (5%), Oxipor (25%), and Doak Tar Distillate (40%)
      • Tar ointments include Medotar (1%), Taraphilic (1%), and MG217 (10%).
      • Bath preparations include Balnetar (2.5%), Cutar (7.5%), Polytar (25%)
      • Examples of shampoos include DHS-T, Ionil T, Pentrax, T/Gel, Tegrin, and Zetar (many other brands are available).
      • Tar soaps are Packer’s Pine Tar, Tegrin, and Polytar.
    • Coal tar solution [liquor carbonis detergens (LCD)] is prepared by extracting coal tar with alcohol and polysorbate (Tween80), an emulsifying agent. Each 100 mL of the solution represents 20 g of coal tar. When mixed with water, a fine dispersion of coal tar results. LCD may be incorporated (at 2% to 5%) in creams or ointments, in tincture of green soap for a shampoo (10%), or added (60 mL) to the bath for antipruritic and other effects.
    • Ichthammol (Ichthyol) is obtained by the destructive distillation of certain bituminous schists (shale rock). It is less irritating than coal or wood tars, is water soluble, stains linens, and is used at 2% to 5% in the treatment of some subacute and chronic dermatoses.
    • Juniper tar, USP (cade oil), is obtained by destructive distillation of the heartwood of Juniperus oxycedrus. It contains hydrocarbons, including phenolic and aromatic compounds, and is used in the management of chronic eczema and psoriasis. It is available as an ointment, shampoo, bath solution, and soap.
  • Urea-containing preparations have a softening and moisturizing effect on the stratum corneum and, at times, may provide good therapy for dry skin and the pruritus associated with it. They appear to have an antipruritic effect apart from their hydrating qualities. Urea compounds disrupt the normal hydrogen bonds of epidermal proteins; therefore, their effect in dry hyperkeratotic diseases such as ichthyosis vulgaris and psoriasis is not only to make the skin more pliable but also to help remove adherent scales. Lactic acid also has a softening and moisturizing effect on the stratum corneum.
    • Use: Apply b.i.d. to q.i.d.
    • Packaging:
      • Urea 10% cream: 75 g
      • Urea 20% cream: 75 g, 90 g, 120 g, 1 lb
      • Urea 40% cream: 18.35 g, 30 g, 85 g, 199 g
      • Urea 10% lotion: 180 mL, 240 mL
      • Urea 25% lotion: 240 mL
      • Urea 40% gel: 15 mL
  • Zinc pyrithione (see Cleaning Agents).
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Pigmenting and Depigmenting Agents, Sunscreens
I. Discussion
See Chap. 17.
II. Agents that Cause Hypopigmentation
  • Hydroquinone products act to inhibit the enzymatic oxidation of tyrosine and suppress other melanocytic metabolic processes, thereby inhibiting melanin formation. Use of daily sunscreen and sun avoidance is paramount in the prevention of pigment recurrence. Effects are seen between 2 and 6 months.
    • Structure
    • Use: Apply to hyperpigmented areas b.i.d.
    • Packaging:
      • Hydroquinone 1.5% cream: 14.2 g, 28.4 g, 85 g, 60 g, 120 g
      • Hydroquinone 2% cream: 28.4 g
      • Hydroquinone 2% gel: 14.2 g
      • Hydroquinone 3% solution: 30 mL
      • Hydroquinone 3% gel: 30 g
      • Hydroquinone 4% cream: 14.2 g, 28 g, 28.4 g, 45 g, 56.7 g
      • Hydroquinone 4% gel: 14.2 g, 28.4 g
  • Monobenzone is the monobenzyl ether of hydroquinone. It acts to increase the excretion of melanin from melanocytes and may prevent melanin production. In some patients, monobenzone causes destruction of melanocytes and permanent depigmentation. This treatment is utilized to irreversibly depigment normal skin surrounding vitiliginous lesions in patients with disseminated idiopathic vitiligo. These products should be used only when permanent depigmentation is desired, only after careful consideration by the patient and physician, and under close supervision. An irritant dermatitis may be seen with ongoing treatment.
    • Structure
    • Use: Applied to normal skin two to three times a day. Results should be obtained in 1 to 4 months. Discontinue treatment after 4 months.
    • Packaging:
      • Benoquin 20% cream: 37.4 g
III. Agents that Induce Hyperpigmentation and Repigmentation
  • Trioxsalen (Trisoralen) followed by UVA exposure is used to repigment vitiliginous areas (see Chap. 17) and in photochemotherapy (see Chaps 27 and 38).
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    • Structure
    • Packaging:
      • Trisoralen, 5-mg tablets: 28, 100, 1,000 tablet packs.
  • Methoxsalen has effects similar to those of trioxsalen. Methoxsalen is superior to trioxsalen in producing erythema and tanning and is the drug used in PUVA therapy. Methoxsalen is also available as a 1% lotion.
    • Structure
    • Packaging:
      • Oxsoralen-Ultra, 10-mg capsules: 50s
      • 8-MOP 10-mg capsules: 50s
      • Oxsoralen, 1% lotion: 1 oz
IV. Sunscreens (see Chap. 33)
  • Physical blockers reflect and scatter UV rays, infrared radiation, and visible light. Inert compounds are ground into particles and suspended in a variety of bases. Disadvantages include messiness, grittiness, and color. Recently, clothing has also been manufactured to physically block UV rays.
    • Titanium dioxide
      • Includes Neutrogena Chemical Free, Ti-Screen, Vaseline Intensive Care, Hawaiian Tropic, Durascreen, and Sundown sunblocks
    • Sun Precautions advertises tightly woven lightweight nylon garments that provide SPF 30 protection, wet or dry.
  • Chemical sunscreens absorb various wavelengths of UVL and consequently allow only a limited amount of light to enter the tissue. They can be arbitrarily classified according to their effectiveness in absorbing UVA versus UVB rays.
    • UVA sunscreens
      • Benzophenone compounds absorb UVL well from 250 to 365 nm and somewhat from 365 to 400 nm. They are less effective than PABA compounds in the UVB sunburn spectrum.
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        • Structure
        • Packaging:
          • Includes Coppertone, Hawaiian Tropic, Ti-Screen, Tropical Gold, Water Babies, Solbar, Solbar PF, Bullfrog, PreSun, PreSun Ultra, Bain de Soleil, and Shade.
      • Parsol 1789 (Arobenzone) has excellent efficacy throughout the UVA spectrum (305 to 385 nm).
        • Packaging:
          • Shade UVA guard (octyl methoxycinnamate, arobenzone, oxybenzone): 4 oz
    • UVB sunscreens
      • PABA preparations absorb UVL between 280 and 320 nm. This acid will stain white fabrics, especially cotton. The esters of PABA are slightly less effective and do not stain as much. Cross-sensitization can occur with some sunscreens. In particular, PABA and its derivatives may cross-react with sulfonamides, benzocaine, procaine, paraphenylenediamine, and azo dyes. Padimate-O, the ester form of PABA, is also used for UVB protection. See Chap. 33 for commonly used sunscreens.
        • Structure
      • Cinnamates absorb UVL from 390 to 320 nm. Salicylates absorb UVL in the 290- to 320-nm range. These sunscreen agents are often used in combination with benzophenones or PABA esters.
  • Others
    • Red veterinary petrolatum (RVP) has UVL-absorbing qualities to 340 nm and is also a water-protective agent because of its greasy base. It is available as a sunshade with zinc oxide added (RVPaque) and for lip protection with 5% PABA.
      • Packaging: and cost:
        • RVP (95% RVP): 1.25 oz
        • RV PABA lipstick (20% RVP, 5% PABA): 3.75 g
    • Sunshades physically block light, usually contain titanium dioxide or zinc oxide powders, and are opaque and usually tinted. They are not very effective unless a thick coat is applied.
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Wet Dressings, Baths, Astringents
I. Wet Dressings
  • The effects of wet dressings have been previously discussed (see Chap. 39).
    • Open wet dressings are indicated in acute inflammatory states with exudation, oozing, and crusting. They are applied as follows:
      • The patient should be in a comfortable position, usually in bed, with an impermeable material under the area to be compressed to prevent wetting the mattress.
      • The dressings, which need not be sterile, should consist of 2- to 4-in. wide Kerlix, soft gauze, or soft linen such as old sheeting or pillowcases, handkerchiefs, or shirts.
      • Moisten dressings by immersing them in the solution and then gently wringing them out. They should be sopping wet, but not dripping. Solutions should be warm or tepid. Cover with a soft towel or cloth that will allow evaporation.
      • Apply or wrap around the skin loosely. Multiple layers, at least six to eight, should be applied to prevent rapid drying and cooling.
      • Dressings should be removed, remoistened, and reapplied every 10 to 15 minutes, for between 30 minutes and 2 hours t.i.d. It is difficult to completely moisten dressings in place, and resoaking is often needed to remove accumulated and adherent exudate and crusts. If frequent changes are impracticable, an IV bottle with the wet dressing solution may be suspended over the bed and the material slowly fed into the dressing through IV tubing. Alternatively, the dressing should simply be removed every 2 to 3 hours and reapplied. It is usually difficult for patients to care for their own dressings.
      • After dressings are removed, a lotion, powder, liniment, or paste may be applied to the skin. Occlusion of exudative skin with ointments should be avoided.
      • Dressing material should be discarded daily, but some, such as Kerlix, may be laundered and reused.
      • If large areas of skin are compressed at once, chilling and hypothermia may result. In general, no more than one third of the body should be treated at any time.
    • Closed wet dressings will cause maceration and retain heat and are used in the treatment of conditions such as cellulitis and abscesses. The foregoing instructions should be followed, but warm dressings should be covered with plastic, oilcloth, or other impermeable material.
  • Solutions for wet dressings are either astringents or antiseptic agents. Astringents precipitate protein and thereby decrease oozing. The principal astringents are salts of aluminum, zinc, lead, iron, bismuth, tannins, or other polyphenolic compounds.
    • Aluminum acetate [AI(OCOCH3)3, Burow’s solution], containing approximately 5% aluminum acetate, is diluted 1:10 to 1:40 for use. Probably the most widely used astringent for wet dressings, it is easy to use, does not stain, and is drying and soothing.
      Domeboro or Bluboro powder packets or tablets quickly dissolve in water to make fresh aluminum diacetate available. One packet or tablet in 1 pt of water yields a 1:40 dilution (two packets at 1:20 dilution); 30 minutes of evaporation, however, will concentrate a 1:40 solution to 1:10, at which point the aluminum salts may become too irritating and drying.
      • Packaging:
        • Domeboro (aluminum sulfate and calcium acetate):
        • 12 packets
        • 12 tablets
        • Bluboro (aluminum sulfate, calcium acetate, FD&C blue dye):
        • 12 packets
    • Potassium permanganate (KMnO4) is an oxidizing agent that is rapidly rendered inactive in the presence of organic material. The oxidizing action of the chemical is purportedly responsible for its germicidal activity. It is also an astringent
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      and a fungicide. This preparation stains the skin and clothing, and undissolved crystals will cause a chemical burn. It is used less commonly now (primarily as an antifungal agent) and may be little better than water as a wet dressing. A 1:4,000 to 1:16,000 dilution is used on weeping or denuded surfaces (one crushed 65-mg tablet dissolved in 250 to 500 mL; one 330-mg tablet dissolved in 1,500 mL to 3,000 mL). For use as a medicated bath, 8 g (approximately 2 tsp) should be dissolved in 200 L (a full bathtub) of water to produce about a 1:25,000 dilution. Skin stains may be removed with a weak solution of oxalic acid or sodium thiosulfate.
    • Normal saline (0.9% sodium chloride) may be approximated by adding 1 level tsp of salt to 480 mL water.
    • Silver nitrate, 0.1% to 0.5%, is an excellent germicide and astringent. Its germicidal action is due to precipitation of bacterial protein by liberated silver ions. It may cause pain if applied in concentrations >0.5%. A 0.25% solution may be prepared by adding 1 tsp of the stock 50% aqueous solution to 1,000 mL of cool water. Silver nitrate stains skin dark brown after exposure to air and will stain black any metal container (including the teaspoon) and everything else that it touches.
    • Compresses with 5% acetic acid reduce the microbial count in infected wounds and are used primarily for infections involving P. aeruginosa.
II. Baths
  • Baths and soaks are useful in treating widespread eruptions. Evaporation is impeded, and, therefore, there is less drying and cooling. Nevertheless, baths and soaks may be very soothing, antipruritic, and somewhat antiinflammatory. The tub should be half full (approximately 100 L, or 25 gal, of water) and the duration of exposure limited to 30 minutes. Many of the bath oils make the tub very slippery.
    • Soothing and antipruritic colloid additives
      • Oatmeal contains 50% starch with approximately 25% protein and 9% oil. Mix one cup Aveeno oatmeal and two cups of cold tap water, shake, and pour into a tub of lukewarm water. Oilated Aveeno contains an additional 35% mineral oil and lanolin derivative for emollient action.
        • Packaging:
          • Aveeno, 30-g packets: 454 g
          • Oilated Aveeno: 240 mL
      • Starch baths are best prepared by mixing two cups of a hydrolyzed starch, such as Linit, with four cups of cold tap water to form a paste, then adding this to a tub of lukewarm water. A mixture of equal parts of sodium bicarbonate (baking soda) and starch is often used as a soothing colloidal bath powder.
    • Bath oils are added to tub water to help prevent drying of the skin. Most contain a mineral or a vegetable oil and also a surfactant. Theoretically, the patient absorbs a portion of the oil around him. There are two types of bath oils: those that are dispersed throughout the bath and those that lie on the surface of the water and coat the surface of the body as the patient leaves the tub. If nothing else, bath oils are pleasant, but patients occasionally note mild pruritus immediately after their use. The following are some pleasing preparations; some patients will prefer one to another: Alpha Keri, Aveeno, Lubriderm, Nutraderm, and RoBathol.
      • Packaging:
        • Alpha Keri oil bath: 240 mL
        • Nutraderm oil bath: 240 mL
Wound Dressings
I. Discussion
The realization that a moist wound environment facilitates healing can be dated only to the early 1950s. Several types of occlusive dressings have been developed and are currently employed in the treatment of cutaneous ulcers. Each of these dressings has certain advantages and disadvantages, which are summarized in Table 40-7.
TABLE 40-7 Summary of Selected Synthetic Dressings
Type Advantages Disadvantages Brand: packaging/ cost: s = sheet(s)
Alginates
  1. Absorbent
  2. Useful in cavities
  3. Hemostatic
  1. ± Difficult to remove
  2. ± Painful if dries
  3. ± Odor
  1. Kaltostat: 4 × 4 in. (1s)
  2. Sorbsan: 10 × 20 in. (1s)
  3. Algosteril: 3-3/4 × 3-3/4 in. (10s)
Films
  1. Adherent
  2. Transparent
  3. Bacterial barrier
  1. Nonabsorbent
  2. ± Difficult to handle
  3. May strip epithelium on removal
  1. Bioclusive: 8 × 10 in. (10s)
  2. Omniderm: 6 × 8 in. (10s)
  3. Opsite: 5 × 4 in. (1s)
  4. Tegaderm: 4 × 10 in. (1s)
Foams
  1. Absorbent
  2. Moist
  3. Conforms to contours
  1. Can adhere to wound if exudate dries
  1. Lyofoam: 11 × 9 in. (30s)
  2. Alleryn: 4 × 4 in. (1s)
Hydrocolloids
  1. Enhanced wound healing
  2. Waterproof
  3. Easy to use
  4. Adherent
  1. Unpleasant odor
  2. Yellow drainage
  3. Difficult in cavities
  4. ± Maceration of surrounding skin
  5. Opaque
  6. May stimulate excess granulation tissue
  1. Comfeel: 8 × 8 in. (5s)
  2. Duoderm: 6 × 6 in. (3s)
  3. Tegasorb: 4 × 4-3/4 in. (5s)
Hydrogels
  1. Comfortable
  2. Absorbent
  3. Semitransparent
  1. Nonadherent
  2. Maceration of skin around wound
  3. Expensive
  1. Nu-Gel: 6 × 8 in. (5s)
  2. Vigilon (nonsterile): 4 × 4 in. (10s)
  3. Vigilon (sterile): 4 × 4 in. (10s)
Laminates
  1. Absorbent
  2. Conforms to contours
  
  1. Biobrane: 10 × 10 in. (5s)
Polysaccharides
  1. Absorbent
  2. Antiseptic
  3. Desloughing
  1. Odor
  2. Difficult to handle/remove
  3. Can dry out the wound bed
  1. Debrisan: 60 g
  2. Duoderm granules: 5 g
source: Modified from Phillips TJ, Dover JS.JS. Leg ulcers. J Am Acad Dermatol 1991;25(6 Pt 1):965–987.
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Occlusive dressings alter several aspects of the wound environment that would account for their efficacy. The presence of moisture alone has been shown to enhance the rate of reepithelialization. By trapping wound fluid next to the wound surface, occlusive dressings protect the wound bed from drying and from trauma. There is a transient influx of inflammatory cells into the wound, which may not only aid in the digestion of necrotic debris but also help prevent overt bacterial infection. The wound fluid also contains a variety of growth factors that could affect epidermal migration and connective tissue formation, as well as provide an ideal environment for the survival of epidermal cells. Regardless of whether they are oxygen permeable, occlusive dressings create a low-pH, low-oxygen environment, conditions that apparently facilitate both dermal and epidermal healing. When properly applied, occlusive dressings may act as a physical barrier to outside contaminants. Furthermore, they may ameliorate pain either by a direct cooling effect or, perhaps, by interference with arachidonic acid metabolism.
Occlusive dressings are not without their drawbacks. Improper application with wrinkling and folding may allow the leakage of exudate onto surrounding normal skin with enlargement of the ulcer. A transient increase in bacterial counts is observed after the application of occlusive dressings and does not normally result in clinical signs of infection. Nonetheless, in a study of six commercially available dressings applied to wounds inoculated with bacterial pathogens (S. aureus, S. pyogenes, and P. aeruginosa), none was able to prevent clinical infection. The fact that overt infection is an uncommon complication of the use of these dressings might simply reflect clinicians’ hesitancy to use them on grossly infected wounds. Before choosing an occlusive dressing, it is critical to identify and treat any underlying causes of the wound. For instance, occlusive dressings, often used in treating distal leg ulcers, would be of little benefit in patients with untreated venous insufficiency or malignancy as the cause of the ulcer.
Specifics of the application of these dressings vary depending on the type, particularly whether it is self-adhering. Initially, the dressing should be changed once or twice a day as the amount of accumulating exudate dictates. With time, dressings may need to be changed only once a week. It cannot be overemphasized that occlusive dressings are an adjunct to wound care, and proper assessment and management of any underlying predisposing pathology are imperative.
II. Packaging (see Table 40-7)
  • 2-Octyl cyanoacrylate (Dermabond) is a fast-setting topical skin adhesive intended to close easily approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive surgery and simple, thoroughly cleansed, trauma-induced lacerations. It may be used in conjunction with, but not in place of, subcuticular sutures. It is contraindicated for use on any wounds with evidence of active infection, areas under high skin tension, mucocutaneous surfaces, or skin regularly exposed to body fluids. Patients with formaldehyde allergies may react to this topical solution.
    • Packaging (Ethicon, Inc):
      • Dermabond liquid: 0.5-mL single-use crushable glass ampules
  • Becaplermin (Regranex) is a recombinant platelet-derived growth factor that is used topically as adjunctive therapy in the treatment of lower extremity diabetic neurotropic ulcers that extend into the subcutaneous tissue or deeper.
    • Use: Apply to ulcer once daily until ulcer is healed.
    • Packaging (Ortho-McNeil):
      • Regranex 100 μg: 2-g, 7.5-g, 15-g multiuse tubes
  • Apligraf is a bioengineered human skin equivalent used in the treatment of venous ulcers. It is composed of living keratinocytes and dermal fibroblasts derived from neonatal foreskin and propagated in culture. A gel of dermal fibroblasts and type I bovine collagen is formed, allowed to contract, and overlaid with neonatal keratinocytes to form a bilayered construct. It is able to produce its own matrix proteins and growth factors. Melanocytes are absent. It has a 5-day shelf life.
    • Use: Apply to noninfected ulcer under compression dressing for 2 weeks.
    • Packaging (Organogenesis, Inc., and Novartis):
      • Apligraf: 7.5-cm diameter sheet
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