4/10/17 Classes of Dermatologic Medications What is that?! Common Dermatologic Conditions and ● Topical Immune Suppressants ● Immune Suppressants How to Treat Them ● Vitamin D Derivatives ● Antibiotics, Antivirals, Antiparasitic Matthew Fox, MD ● Retinoids ● Antimalarials Assistant Professor, Division of Dermatology ● Biologic Agents Dell Medical School, University of Texas at Austin Director of Dermatologic Surgery, Seton Healthcare Family ● Chemotherapeutic agents Learning Objectives Approach to Dermatologic Conditions • Know the clinical subtypes of acne *Know the mechanism and recommended dosing of topical retinoids, oral antibiotics and oral retinoids in the management of acne Acne • Understand the clinical presentation cutaneous dermatophyte infection Infectious diseases of the Skin *Know the classes and recommended dosing of antifungal treatments • Recognize the clinical manifestations of dermatitis Eczema *Know the relative potencies, side effects and indications of topical steroids Psoriasis • Describe the classic clinical findings for psoriasis *Know the mechanism of action and side effects of systemic antipsoriatic medications Sun Damage / Actinic Keratoses • Know the pertinent history and physical exam findings associated with a diagnosis of skin cancer, including the ABCDEs of melanoma Fundamentals Words to the wise… • All medications have side effects If you advise the patients of side effects ahead of time, you are informing the • Always consider drug interactions, patient. including with food and supplements If you did not tell the patient about a known • Always consider pregnancy and lactation side effect until after they experience status that side effect, it is an excuse 1 4/10/17 Reference: Approach to Dermatologic Conditions • Wolverton SE, ed. Acne Comprehensive Infectious diseases of the Skin Dermatologic Drug Eczema nd Therapy, 2 Ed. Psoriasis Elsevier, 2007. Sun Damage / Actinic Keratoses Topical Retinoids Retinoid RAR-α RAR-β RAR-γ RXR-α RXR-β RXR-γ • Small molecule hormones that activate All-trans retinol - - - - - - nuclear receptors and regulate gene All-trans retinoic acid ++ ++ ++ - - - Adapalene Weak ++ ++ - - - transcription Tazarotenic acid + +++ ++ - - - Alitretinoin +++ +++ +++ ++ ++ ++ Bexarotene - - - +++ +++ +++ Retinoids: Clinical Effects Adapalene • Affect pathways involved in: • Mild comedonal acne – Inflammation – Cellular differentiation • 0.1% gel – Apoptosis • Apply QHS – Sebaceous gland differentiation • OTC (2016) ***NORMALIZATION OF FOLLICULAR EPITHELIAL • Pregnancy: C DIFFERENTIATION AND KERATINIZATION*** 2 4/10/17 Tretinoin Tazarotene • Supplied as 0.025%, 0.05%, 0.1% cream • 0.05% and 0.1% cream and gel or as 0.01 - 0.1% gel • Apply QHS • Apply QHS • For female patients, begin during menses • May need to start with lesser frequency • Pregnancy: X • Pregnancy: C Topical Antibiotics Clindamycin Name Comments • Reversibly binds 50s subunit of ribosomal Benzoyl Beneficial effects can be neutralized with simultaneous tretinoin peroxide No association with induction of bacterial resistance RNA subunit à inhibition of protein synthesis Clindamycin Good gram + and anaerobic coverage • Broad spectrum(S. aureus, streptococci, P. Erythromycin Resistance to some P. acnes; most benefit is via anti-inflammatory effec ts acnes) Metronidazole Coverage of both aerobic and anaerobic bacteria (more for rosacea) • 1% lotion or solution, applied daily to BID Azelaic ac id Broad coverage; good for pigmentary disorders; OK during pregnancy • Pustules, inflammatory acne >> non- Sodium Broad coverage and multiple indications inflammatory lesions sulfac etamide Azelaic acid Sodium sulfacetamide • Commonly incorporated in formulation with • Activity against tyrosinase sulfur • Safe during pregnancy (B) • Inhibition pro-inflammatory enzymes • Supplied as 15% gel • Supplied as lotion for BID application 3 4/10/17 Benzoyl peroxide Combination products • Keratolytic and comedolytic properties • Improved patient adherence • Bactericidial, broad spectrum • Better results that individual agents alone • Broad range of concentrations (2.5-10%) • Many combinations: and vehicles (washes, lotion, gel, cream) – BPO/Clindamycin combinations • Little to no induction of bacterial resistance – Clindamycin/retinoid combinations • Peeling, erythema, dryness Oral antibiotics Tetracyclines • Tetracyclines • Bacteriostatic, inhibit bacterial protein synthesis • Trimethoprim/sulfonamide • Bind 30S ribosomal subunit • Clindamycin • Do not give to children < 9 – bone, teeth development • Pregnancy category D Minocycline Doxycycline • Supplied: 50, 75, 100 mg • Supplied: 20, 50, 75, 100 mg • Dosage: 50-200 mg per day (dosed daily or BID) • Dosage: 50-200 mg per day (dosed daily or BID) • Common SEs: • Common SEs: – Dizziness – GI (burning, discomfort, nausea, vomiting) – Headache (pseudotumor cerebri) • Relieved if taken with food (NON DAIRY) – GI – Photosensitivity – Photosensitivity – Headache – Pigmentation change – Pigmentary change – Hepatotoxic – Hepatotoxic • Not to be used in pregnancy, kids • Not to be used in pregnancy, kids • Not to be used with isotretinoin: increased risk of • Not to be used with isotretinoin: increased risk of pseudotumor cerebri (applies to all tetracyclines) pseudotumor cerebri (applies to all tetracyclines) 4 4/10/17 Oral retinoids - Isotretinoin Isotretinoin • Approved for severe recalcitrant nodular • Dosage: acne – Weight based dosing – Inflammatory lesions greater than 5mm in – 0.5-1 mg/kg daily, until a total cumulative dose diameter of 120-150 mg/kg is reached – Unresponsive to conventional tx (oral abx) • Rate of success approx 70% • Consider impact of disease on patient! – Relapses more likely to respond to conventional treatment ADVERSE EFFECTS Alternative acne treatment Teratogenicity Hepatic -Retinoic acid embryopathy -Elevated transaminases Ocular Other Endocrine • For ‘hormonal’ acne, may consider -Reduced night vision -Hypothyroidism -Dry eyes, infection – Spironolactone Bone Hematologic -Diffuse skeletal hyperostosis -Leukopenia • SE: Teratogenic, K+ monitoring -Premature epiphyseal closure -Agranuloc ytosis – OCPs Lipids Neuro/Psych -Elevated cholesterol, TG -Depression, pseudotumor Gastrointestinal Muscle -Inflammatory bowel disease flare -Myalgias -Pancreatitis Acne Pearls Approach to Dermatologic Conditions • For acne on the trunk, it is difficult for patients to apply lotions, gels. Use washes and oral Acne antibiotics. • For medications to work, it takes time. Advise Infectious diseases of the Skin that the earliest they will see improvement is Eczema 6-8 weeks. Psoriasis • Often need combination of products • May need oral retinoids sooner than later! Sun Damage / Actinic Keratoses 5 4/10/17 Warts Impetigo Treatment Comments Salicylic Ac id Keratolytic; consider 40% plaster under occlusion • Mupirocin Podophyllin Antimitotic agent; contraindicated in pregnanc y; applied in offic e • Staph directed antibiotic coverage Cantharidin Vesic ulating agent; applied in office – Bactrim Imiquimod Immunostimulatory (activates TLR-7); apply at bedtime three times – Clindamycin weekly on non-consecutive days (genital warts) – Doxycycline Candida Immunostimulatory, injec ted into lesion Antigen – Cephalosporins Mupirocin Acyclovir / valacyclovir • Inhibits bacterial isoleucyl-tRNA synthetase à inhibits bacterial RNA and cell wall • Guanosine analog synthesis • Requires phosphorylation by herpes • Excellent coverage against S. aureus, S. epidermidis, S.pyogenes, B-hemolytic specific thymidine kinase Streptococci • Once active, inhibits viral DNA polymerase • ? Resistance • Valacyclovir is oral prodrug • 2% ointment, to be applied BID • Exceptionally safe and well tolerated • SE: burning, itching, contact dermatitis Herpes viruses Scabies Treatments • Topical acyclovir • Permethrin: – Supplied as 5% ointment for limited disease – low efficacy – MOA: acts on arthropod cell wall by disabling sodium – applied Q3 hours, 6x/day for 7 days transport à mite paralysis • Acyclovir – Supplied as oral suspension – Applied from neck to, not just visibly affected sites – Example doses: – Two overnight applications separated by one week • Cold sore: 400 mg 5x/day for 5 days • Shingles: 800 mg 5x/day for 7-10 days – All partners and close contacts should be treated • Valacyclovir – Reasonable to wash clothes and linens concurrent – Easier dosing, possible benefit for PHN • Cold sore: 2g twice daily for one day with treatment • Shingles: 1g TID x 7 days – Pruritus may last for up to 1 month after treatment! 6 4/10/17 Scabies Treatments Azole antifungals • Sulfur: MOA: Inhibition of 14α-demethylase, leading to decreased ergosterol formation – time honored Examples include: – 6% precipitated sulfured, compounded, applied daily until improved • Ketoconazole – 2% cream, applied BID until improved • Ivermectin: – 1-2% shampoo, used in seborrheic dermatitis – MOA: blocks glutamate gated chloride ion channels à paralysis of arthropod/helminth • Econazole – 1% cream, applied BID until improved – Off label: single 100-200 μg/kg dose or two full doses separated by one week • Efinaconazole – 10% topical solution, painted topically to nails once daily for 48 weeks! Te rb i n a fi n e Oral terbinafine • Allylamine, disrupts fungal cell wall via • Severe or resistant fungal infection • 250 mg daily for: inhibition of squalene epoxidase – 2 weeks (tinea corporis) – 6 weeks (fingernails) • Highly lipophilic (high concentration in – 12 weeks (toenails) stratum corneum, hair follicles, sebum) • Common SEs: HA, GI