Derm Pharmacology 3-5 Narrated PDF

Pharmacology in Dermatology  Topical Medications =================== - Ointment: petrolatum base (i.e., Vaseline base) - Gels/solutions: have more alcohol and are oil free by design - Creams/lotions: try for non-irritating formulations are better for drier skin...

Pharmacology in Dermatology  Topical Medications =================== - Ointment: petrolatum base (i.e., Vaseline base) - Gels/solutions: have more alcohol and are oil free by design - Creams/lotions: try for non-irritating formulations are better for drier skin - Lotions/foams: will also spread on hair bearing areas - Ointment\>cream\>lotion\>gel\>solution -- order of occlusion  Topical Corticosteroids =======================  - MoA Topical Corticosteroids ======================= - Decrease cell proliferation, inhibit inflammatory mediators, cause local vasoconstriction - Dosage form depends on affected area - Areas with hair: lotions, gels, aerosols, solutions, foams - Weeping lesions: lotions, gels, creams - Dry, scaly lesions: ointments - Creams can be used in almost any area - Choice of vehicle is very important & may help minimize AE  Topical Corticosteroids ======================= - Occlusive dressings - ↑skin penetration - ↑ systemic affects - ↑secondary bacterial & fungal infections - Do NOT use with very high/ultra high potency (unless lichenified lesion) - Do NOT leave on for \> 12 hours.  Topical Corticosteroids ======================= - AEs Local - Drying/cracking of skin - Thinning of epidermis - Atrophic striae (possibly permanent) - Hypopigmentation - AEs Systemic - Usually with large areas, prolonged use, occlusive dressings - HPA suppression (esp. in pediatrics)  Topical Corticosteroids ======================= - #### Some of the same medications are classified as different potency based on - Vasoconstrictive potency ratings : I -- VII - USP potency ratings : Low, Medium, High and Very High - #### Low Potency: Face, genitals, axilla, skin folds - Medium Potency: Trunk, arms, legs - Limit weekly dose to 90-100 grams - #### Very High Potency: Palms, soles, resistant conditions - Generally treatment does not exceed 2 weeks & total 50 grams per week   Topical Corticosteroids ======================= Low Potency ----------- - Hydrocortisone, Hydrocortisone acetate - 0.25%-1% (some OTC) - 2.5% (Rx) - Desonide (DesOwen®) - Lotion, Foam Medium Potency -------------- - \*Mometasone Furoate (Elocon®) cream - Fluticasone propionate (Cutivate®) - \*Triamcinolone acetonide (Kenalog®) - Cream, ointment, lotion 0.1%  Topical Corticosteroids ======================= High Potency ------------ - \*Desoximetasone (Topicort) - Cream, Ointment 0.25%, - Gel 0.05% - \*Fluocinonide (Lidex®) - Cream, Ointment, Gel 0.05% - \*Betamethasone - Dipropionate Cream (augmented) 0.05% Very High Potency ----------------- - Clobetasol (Clobex®) - Halobetasol (Ultravate®)  Systemic Corticosteroids ======================== - Systemic Corticosteroids - Dermatologic uses: Contact dermatitis, atopic dermatitis, other - An acute exacerbation of chronic atopic dermatitis can sometimes be aborted by a short course of systemic glucocorticoids (eg, prednisone 40 to 60 mg/day for three to four days, then 20 to 30 mg/day for three to four days). - Prednisone (Deltasone) - Dexamethasone (Decadron)   - MoA - blocks inflammatory mediators by modulating T-cell function and depress cell- - Use: 2^nd^ line therapy (intermittent use) for atopic dermatitis - Off label: psoriasis; seborrheic dermatitis; rosacea; vitiligo - AE: local symptoms: temporary stinging, burning, pruritis - Box Warning: based on animal studies---skin cancer and lymphomas  Topical Calcineurin Inhibitors ============================== - Precautions: - Do Not use on pre-malignant, malignant lesions - Cutaneous bacterial/viral infections on affected area should be resolved before use - Avoid sun exposure: effects of sun exposure unknown - Avoid use with occlusive dressing: effects unknown - Pregnancy category C: unknown effects - Avoid use in immunocompromised patients  Topical Calcineurin Inhibitors ============================== - Pimecrolimus 1% (Elidel) - Cream - Adults & peds \>2 yoa - BID application - Tacrolimus 0.03%, 0.1% (Protopic) - BID application  PDE-4 Inhibitors ================  - MoA: - Results in increased intracellular cyclic adenosine monophosphate (cAMP) levels - cAMP is thought to decrease the proinflammatory response (eg, cytokine release) - AEs: - Application site pain, burning, or stinging (4%) - Crisaborole (Eucrisa) 2% ointment - Mild-to-moderate atopic dermatitis -- ages 2 years and up - Roflumilast (Zoryve) - Psoriasis (0.3%. Cream) - Seborrheic dermatitis (0.3% foam) - Atopic dermatitis (0.15% cream)  Misc. Topical Agents ====================  - Tazarotene (Tazorac®) gel 0.05 or 0.1% gel - MoA: Normalizes keratinocyte differentiation & has antiproliferative & anti-inflammatory effects (retinoid) - AEs: dryness, stinging, burning - Alternative agent for mild to mod. Psoriasis; acne - Applied Qdaily - Calcipotriene (Dovonex®), calcitriol (Vectical®) - MoA: Topical synthetic vitamin D analogues that inhibit cell proliferation - AE: erythema, dryness, stinging or burning - Tachyphylaxis does NOT occur - Can also be used as alt. agents for mild to moderate psoriasis - Applied BID for calcipotriene and QHS for calcitriol  Misc -- Topical Agents ====================== - #### Coal Tar -- used to be mainstay of treatment - MoA: Keratolytic & may have antiproliferative & anti-inflammatory effects - AE: folliculitis, stains clothing, unpleasant odor - Available in ointments, creams, shampoos & LCD - Psoraisis: Can be helpful as an adjunct to topical corticosteroids & as a photosensitizing - #### Anthralin (Zithronal-RR®), [(Psoriatec®)] - MoA: Direct antiproliferative effect - May also disrupt oxidative metabolic processes - which reduces epidermal mitosis - Used for thick plaque psoriatic areas- start with a few minutes & gradually increase application time to 2 hours  Mics -- Topical Agents ====================== - Keratolytic agents - salicylic acid in shampoos (typically 3-4% strength) can help with scalp psoriasis (as well as with dandruff) - Used to remove scale, to smooth the skin, and to treat hyperkeratosis - Apply three times per week, leave on several minutes then rinse - Help to enhance steroid penetration - Example is OTC Neutrogena product -- T/Sal shampoo® with 3% salicylic acid  JAK Inhibitor ============= - MoA: inhibit JAK - janus kinase -- group of intracellular tyrosine kinases that influence cellular processes of hematopoiesis and immune cell function including inflammation by modulating gene expression - AE: nasopharyngitis, bronchitis, increased eosinophil count, diarrhea, folliculitis, tonsillitis - Black Box Warning: serious infection, sudden cardiovascular death, malignancies, MACE (major adverse cardiovascular events), thrombosis - Indication: Atopic dermatitis - Ruxolitinib (Opzelura)  AhR Agonist =========== - MoA: - Aryl hydrocarbon receptor (AhR) agonist -- binding downregulates proinflammatory cytokines, including IL-17 - AE - Follicuitis, nasopharyngitis, contact dermatitis, headache, pruritus - Use: - Atopic dermatitis - Psoriasis - Tapinarof (Vtama) 1% cream  Systemic Agents ===============  - Acitretin (Soriatane®) - Oral retinoid- therefore not immunosuppressive - Synergistic w/phototherapy - AE: TERATOGENIC (contraindicated in women of childbearing age), hyperlipidemic & LFT changes - Avoid taking w/ethanol- causes longer elimination half-life (3yrs) - Methotrexate- PO or IM - MoA: inhibits dihydrofolic acid reductase - interferes with DNA synthesis, repair, cellular replication - AE: leukopenia, hepatotoxicity, megaloblastic anemia, pneumonitis, & pulmonary fibrosis - Low doses given weekly to prevent GI side effects - Contraindicated in pregnancy, renal impairment, hepatitis, cirrhosis, alcoholics, etc.  Systemic Agents - Psoriasis =========================== - Cyclosporine (Neoral or Sandimmune®) - MoA: suppresses T cell activation ( Calcineurin inhibitor) - Used for pts w/severe inflammatory flares of psoriasis or recalcitrant cases failing to - Contraindicated: abnormal renal fxn, uncontrolled HTN, malignancy, immunodeficiency - BP & SCr prior to start of therapy& reassessed biweekly for 1^st^ 12 wks of therapy - May ↑ risk of lymphomas & cutaneous malignancies  Systemic Agents - Psoriasis =========================== - Biologic Response Modifiers (BRM) - Some of the immunomodulatory drugs appear to be more efficacious than some older systemic therapies. - Most of these agents are expensive, as is the laboratory monitoring for side effects that may be required - None are oral -- all are injectable, used either IV, IM or SQ - Use of live or live-attenuated vaccines during therapy is generally not recommended - Generally well tolerated but carry the risk of increased susceptibility to infection - My be an increased risk of lymphoma in people who take biologics. - **MOA:** TNF α Inhibitors ================ - Inhibit TNF alpha or its receptor - ##### Adverse Effects - ↑ risk of infections (TB, Hepatitis B, and spesis) - ↑ risk of fungal opportunistic infections - ↑ risk of pancytopenia - injection site reaction, HA, ↑ resp. tract infections, GI symptoms, worsening of CHF or new onset CHF - Need to do initial PPD, Hep B & C serologies, CBC, CMP - Yearly PPD - Every 3 months CBC, CMP - Live vaccinations should not be administered while on TNF-a therapy TNF α Inhibitors ================ - Adalimumab (Humira ®) - Chimeric/human MAB - 80mg SQ 1^st^ week, then 40mg SQ following - Also indicated for RA, AS, PsA, Crohn's - Etanercept (*Enbrel®*) - Fully humanized MAB - Indicated also for RA, JRA, AS and psoriatic arthritis - 50mg SQ 2x/wk x 3 months then 50mg SQ q week - Infliximab (*Remicade®*) - Chimeric MAB - Also approved for RA, AS, Crohn's & UC - 5mg/kg IV at weeks 0, 2, 6, then every 8 weeks - AE: anaphylaxis - Very fast onset - Golimumab (Simponi®) - Given SQ monthly  IL 12/23 Inhibitor ================== - Stelara® (ustekinumab) - MoA: Targets IL-12 & IL-23 - AE: URI, nasopharyngitis, back pain, injection site erythema, - Given q 3 months - Indicated for plaque psoriasis, psoriatic arthritis, Crohn Disease, Ulcerative colitis  IL-17 Inhibitors ================ - Cosentyx ® (Secukinumab) - Inhibits IL-17A - 300mg at week 0, 1, 2, 3, 4 then once a month - Indicated for plaque psoriasis and psoriatic arthritis; ankylosing spondylitis, non-radiographic axial spondyloarthritis, hidradenitis supprativa - Taltz® (ixekizumab) - Inhibits IL-17A - SQ injection given - 160mg at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks - Indicated for plaque psoriasis and psoriatic arthritis; non-radiographic axial spondyloarthritis, ankylosing spondylitis - Bimzekizumab (Bimzelx) - Inhibits IL-17A, IL-17F - Indicated for plaque psoriasis, psoriatic arthritis, non-radiographic axial spondyloarthritis, ankylosing spondylitis, - Siliq ® (brodalumab) - Inhibits IL-17A *receptor* (inhibits binding of IL-17A, IL-17C, IL-17E, IL-17F - 210 mg SC at Weeks 0, 1, and 2, then 210 mg SC q2wk - Requires REMS monitoring  - MoA: IL-23 Inhibitors ================ - Inhibits IL-23 by selectively binding to p19 subunit of IL-23 - Decreases cytokine and chemokine release - AE: URI, headache, fatigue, injection site reaction, tinea infections - Guselkumab (Tremfya ®) - Plaque psoriasis, psoriatic arthritis - Risankizumab (Skyrizi) - Plaque psoriasis, psoriatic arthritis, Crohn disease - Tildrakizumab (Ilumya)  - MoA: PDE-4 Inhibitor =============== - Seems to inhibit cytokine & chemokine synthesis  anti-inflammatory effects - phosphodiesterase-4 inhibitor specific for cAMP - results in increased intracellular cAMP levels - may affect cytokines and chemokine synthesis leading to anti-inflammatory effects - AE: Diarrhea, nausea, URI, tension headache, vomiting, fatigue, dyspepsia, decreased appetite - Warnings: depression, weight loss, severe diarrhea/N/V - Indicated: plaque psoriasis, psoriatic arthritis, Bechet disease (oral ulcers) - Apremilast (Otezla®)  - MoA: IL 4/13 Inhibitor ================= - Monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling - inhibits IL-4 and IL-13 cytokine-induced responses, including release of proinflammatory cytokines, - AEs: - Injection site reactions (10%), Conjunctivitis (10%), Blepharitis (1-5%), Oral herpes, keratitis, dry eye - Indications: - Moderate to severe atopic dermatitis ≥ 6 months and up not controlled by topical medications - Moderate to severe asthma (ages 7 & up) - Eosinophilic Esophagitis - Dupliumab (Dupixent)  IL-13 Inhibitor =============== - MoA - Inhibits IL-13 induced proinflammatory cytokine, chemokine, IgE release - AE: URI, conjunctivitis, injection site reaction - Indication: Moderate to severe atopic dermatitis in adults not controlled on topical therapy - Tralokinumab (Adbry) ; Lebrikizumab (Ebglyss)  JAK Inhibitor ============= - MoA - JAK1 inhibitor - AE: URI, acne, herpes simplex, headache, folliculitis - Box warning: serious infection, lymphoma, thrombosis, MACE (RA pts) - Indications: Psoriatic arthritis, atopic dermatitis, RA, ulcerative colitis - Upadacitinib (Rinvoq) - Alopecia areata (Baricitinib)   TYK 2 Inhibitor =============== - #### MoA - Inhibits TYK2 -- which pairs with JAK1 to mediate multiple cytokine pathways - Also pairs with JAK2 - #### AE - Infection URI, herpes simplex, mouth ulcers, folliculitis, acne, herpes zoster, - #### Use - Plaque psoriasis - Deucravacitinib (Sotyktu)  Other Treatment Modalities ==========================  - UV radiation - may act via antiproliferative effects (slowing keratinization) and anti-inflammatory effects - Phototherapy and photochemotherapy require the supervision of a dermatologist trained in these treatment modalities - potential for UV radiation to accelerate photodamage and ↑ risk of cutaneous  Psoriasis - Phototherapy ======================== - Phototherapy refers to treatment with ultraviolet B (UVB) radiation (290 to 320 nm). - Patients receive near-erythema-inducing doses of UVB at least three times weekly until remission is achieved, then maintenance regimen is usually recommended to prolong the remission. - Photochemotherapy (PUVA) - involves treatment with either PO or bath psoralen (used as photosensitizer) followed by ultraviolet A (UVA) radiation (320 to 400 nm) - Done a few times a week until clearance of lesions  Acne/Rosacea Treatments =======================  - #### Cleanse face - No more than twice a day - Avoid abrasive scrubbing (Buf-Pufs, etc.) - #### Avoid oil containing make-up & multiple layers - Topical vehicle choice - Depends on pt skin characteristics, cosmetic elegance of product - Gels/solutions : oily skin - Creams/lotions: dry skin - #### How to apply medications (education) - Do not spot treat!! - Treat entire area - #### Psychosocial aspects  Benzoyl Peroxide ================ - MoA: antimicrobial action by releasing active oxygen (kills C. acnes) and also keratolytic and desquamative effect - Available Rx & OTC in strengths ranging from 1-10% - Various formulations: - Creams, lotions, gels, facial washes - Gels preparations tend to cause the most adverse effects - Avoid in which pt skin type/characteristic? - AE: - Dryness, irritation, erythema, stinging - Also may cause bleaching of hair/fabrics with contact - Products: Panoxyl®, Clean & Clear®, various other Rx & OTC products - Typical regimen: apply/wash affected area 1-2x daily  Topical Retinoids ================= - MoA: inhibits microcomedo formation, decreases keratinocyte cohesiveness and anti- inflammatory properties - AE - Erythema, irritation, dryness, peeling, photosensitivity - Tretinoin (Retin-A®, Renova®, Avita®), Adapalene (Differin®), Tazarotene (Tazorac®) - Come gels, creams, and solution (only tretinoin currently) - Typical Regimen - Apply QHS^\*^ - Avoid in pediatrics \< 10 yoa & pregnancy - May take 3-4 months to see effects - How would you tell patient to use this medication?  Topical Antibiotics =================== - ##### Clindamycin (Cleocin T®) - **MoA:** binds to 50S ribosomal subunit of susceptible bacteria and prevents elongation of peptide chains by suppressing protein synthesis - Rx only - Available in gel, lotion, foam and solution forms - AE: colitis (including *C. diff.*), local irritation (burning, stinging, etc.) - ##### Erythromycin - **MoA:** binds to 50S ribosomal subunit of susceptible bacteria and prevents elongation of peptide chains by suppressing protein synthesis - Rx only - Avaliable in 2% solution, gel, ointment, pledgets - AE: mild local irritation - Both have activity against *C.acnes* - Rarely are used as monotherapy due to high resistance rates Topical Antibiotics =================== - **Sodium sulfacetamide/sulfur** (various products & %) - MoA: - Sulfacetamide -- inhibits para-aminobebnzoic acid (PABA); restricts folic acid synthesis required for growth of bacteria - Sulfur -- antiseptic, antiparasictic, keratolytic actions - many products are being removed from market due to FDA mandating re-evaluation of older products that have not undergone clinical trials - Minocycline (Amzeeq, Zilxi) - AE: erythema, hyperpigmentation, dryness, itching, skin peeling - Use: acne, rosacea  Topical Acne Medications ======================== - **Combination Products** - #### Clindamycin/Benzoyl peroxide - (Benzaclin®, Acanya gel®, Duac gel®) - #### Erythromycin/Benzoyl peroxide - (Benzamycin®) - #### Clindamycin/Tretinoin - (Ziana®, Veltin®) - #### Benzoyl Peroxide/Adapalene gel - (Epiduo®)  Topical Androgen Receptor Inhibitor =================================== - #### MoA: - Competes with androgen (DHT) for binding to androgen receptor within sebaceous gland and hair follicle - #### AE: - Erythema, scaling, dryness, pruritus, edema, stinging/burning, telangiectasia - #### Use - Acne - Clascoterone (Winlevi)  - Antibiotics Systemic Acne Treatment ======================= - Used to treat moderate to severe acne - especially when topical treatments have failed - MoA: ↓ C. acnes colonization & ↓ inflammation - Improvement seen in 6-12 weeks with maximum benefit in about 6 months - Usually can d/c after 6 months when used in combination w/topical tx - 1^st^ line: doxycycline, minocycline, tetracycline - 2^nd^ line: erythromycin, clindamycin - 3rd line: SMZ/TMP, azithromycin  Systemic Acne Treatment ======================= - #### Antibiotics - MoA: - Doxycycline/Minocycline -- inhibits bacterial protein synthesis by binding to 30S and possibly 50S ribosomal subunits - Erythromycin/Clindamycin -- same as topical - AE - Doxycycline: GI upset, drug interactions, phototoxicity, pseudotumor cerebri - Minocycline: vestibular complications (HA, dizziness) & lupus like syndrome - Erythromycin: resistance, GI upset - Clindamycin: risk of pseudomembranous colitis, esp. with long-term use - Typical regimen: doxycycline 100mg PO QD or BID w/food - Prolonged administration may result in: Refractory folliculitis, Resistance - Can be mitigated by concurrent use of bpo - MoA Isotretinoin (Accutane) ======================= - Inhibits sebaceous gland function & keratinization - Stabilizes keratinization, makes the cells that are sloughed off into the sebaceous glands less adherent, inhibiting the formation of comedones. - Indication: SEVERE recalcitrant acne - BLACK BOX- pregnancy (iPledge program) - AE: - Drying & peeling of facial skin - ↑cholesterol, ↑ triglycerides (leading to pancreatitis) & ↑ hepatic enzymes - Requires monthly monitoring of LFTs, cholesterol & triglycerides - Pseudotumor cerebri, Photosensitivity, Muscle pain, Depression, mood swings, suicidal ideations, hearing impairment, IBD, ↑ BG  Oral Contraceptives =================== - Oral *Combination* Contraceptives - #### 2^nd^ line tx for moderate to severe acne in female patients - MoA: - ↓production of androgens, therefore ↓sebum production - #### AE: - nausea, weight gain, breast tenderness, ↑risk of thromboembolic events - Only 4 oral contraceptives (Ortho Tri-Cyclen®, Estrostep®, LoEstrin® and Yasmin/Yaz®) have been approved by the US Food and Drug Administration (FDA) for the treatment of acne, but all combination OCPs will help  Aldosterone Antagonist ====================== - ### Spironolactone (Aldactone®) - #### MoA: - aldosterone antagonist & androgen receptor blocker - #### Off label use- acne, hirsutisim - usually given with an oral contraceptive - Older adult women (30-40 y.o.) - #### AE: - fetal harm (ambiguous genitalia), menstrual irregularity, breast tenderness - Serum K & BP should be monitored periodically, particularly early in the course of therapy - Start low & ↑ dose as needed  Systemic Acne Agents ====================  - Metronidazole (Metrogel®) - 1% gel, 0.75% gel, cream, lotion - Unknown MoA -- antibacterial/anti-inflammatory effects - Pregnancy category B - AE: burning, stinging, erythema, etc. - Use: 1% (qday); 0.75% (BID) - Azelaic Acid (Finacea gel®) - 15% gel - Unknown MoA - Activity agains P. acnes and Staph. epidermis - Normalization of keratinization (dec. microcomedone formation) - Pregnancy category B - AE: stinging, burning, pruritis, erythema, hypopigmentation - Use: apply bid (qday also very effective)  Topical Rosacea Agents ====================== - #### Oxymetazoline (Rhofae) - MoA: Alpha-1 agonist: elicits vasoconstriction of cutaneous microvasculature - AE: application site dermatitis, pruritus, erythema, pain - Use: persistent facial erythema associated with rosacea - #### Brimonidine (Mirvaso) - MoA: alpha-2 agonist: decrease vasculature dilation - AE: Flushing, erythema, nasopharyngitis, burning, rebound erythema - Use: persistent facial erythema of rosacea  Bacterial, Viral, Parasitic Infection Treatments  - Used to treatment and prophylaxis of skin infections (Impetigo) - Mupirocin (Bactroban®, Centany®) - *Staph aureus*, beta hemolytic *strep*., *Strep spp., some gm (-)* - MoA: inhibits bacterial protein synthesis - AEs: burning, stinging, pain, erythema, contact dermatitis - Use: apply BID x 5-10days - Retapamulin (Altabax®) - Impetigo -- staph & strep spp. - MoA: inhibits bacterial protein synthesis - AEs: irritation, contact dermatitis - Use: apply BID x 5 days  Topical Antimicrobials ====================== - [Silver Sulfadiazine (Silvadene®)]---(Rx) - Used in 2^nd^ and 3^rd^ degree burns & other wounds to treat/prevent infection - Applied to affected area 1-2 x daily - Burned areas should be covered with cream at all times - AE: temporary discoloration of skin - [Bacitracin]---OTC - Good gram (+) coverage - [Bacitracin & Polymixin B (Polysporin®)] OTC - Gram (+), Pseudomonal coverage - [Triple Antibiotic Ointment (Neosporin®)] OTC - Bacitracin, Polymixin, neomycin - Neomycin: Aminoglycoside Antibiotic - may cause local skin reactions (to neomycin component) - Gram (-) coverage  Antifungals ===========  - MoA: - Accumulates in newly synthesized tissue containing keratin and causes disruption of the mitotic spindle & inhibition of fungal mitosis - AE: rash, urticaria, paresthesias of hands/feet, oral thrush, N/V/D, mental confusion - ↑ serum levels by giving w/high-fat meal - DI: OCPs, Warfarin, Barbiturates (↓ levels of those - Precautions: - possible cross-sensitivity reaction with PCN- allergic patients (derived from species of Penicillium), photosensivity, not to be used in hepatic failure - Use - Tinea infections --- NOT Tinea Versicolor - Duration depends on affected area - Capitis: 4-6 weeks - Corporis: 2-4 weeks - Pedis: 4-8 weeks - Unguium: fingernails: 4 months, toenails: 6  Fluconazole (Diflucan) ====================== - MoA: Interferes with fungal cell membrane permeability by blocking demethylation of lanosterol to - AE: Mild usually - N, headache, V, abd pain, skin rash, alopecia - DI: Most other drugs are increased when taken w/fluconazole (CYP450) - Uses: Antifungal, candidiasis infections, cryptococcal meningitis - Properties are similar for IV and PO = no dosage change when switching - Cautions: - Rare cases of hepatic toxicity- usually reversible and no obvious relationship to dose, duration, - Children may be treated successfully w/fluconazole  Antifungals =========== - Itraconazole (Sporanox®) - MoA: same as fluconazole - Precautions: not to be used in patients with ventricular dysfunction, avoid in hepatic dysfunction - DI: affects CYP450 (lots of drug interactions) - Terbinafine (Lamisil®) - MoA: inhibits squalene epoxidase (interrupts fungal cell membrane ergosterol synthesis) - SE: GI upset, liver abnormalities, rash & urticaria - Precautions: avoid in hepatic dysfunction - **Test LFTs before & periodically during treatment** - DI: affects CYP450 (lots of drug interactions) - Nail infections: 250 mg PO x 6 weeks for fingernails, 12 weeks for toenails  Topical Antifungals =================== - Azole antifungals - Clotrimazole (Lotrimin®), Miconazole (Monistat®) - Ketoconazole (Nizoral®) & Econazole (Spectazole®) - Rx only - Also tx cutaneous candida infections & tinea versicolor - Terbinafine (Lamisil®) - NOT effective against candida infections - Ciclopirox (Loprox®) - Rx only - Also tx cutaneous candida infections & tinea versicolor - In general: - Tinea cruris & corporis -- tx x 2 wks - Tinea pedis -- tx 1 month - Qday to BID  Antivirals ========== - MoA: Nucleic acid analogs - Guanosine Analogs - compete as a substrate for viral DNA polymerase & incorporation into viral DNA (causing premature chain termination) - inhibition of DNA polymerase &/or reverse transcriptase - Topical (treat HSV) - Acyclovir (Zovirax) 5% cream, ointment - Penciclovir (Denavir) 1% cream - Acyclovir/hydrocortisone (Xerese) 5%/1% cream - Oral (treat HSV and HZV) - Acyclovir - Valacyclovir - Famciclovir  Topical Antivirals ================== - Acyclovir (Zovirax®) 5% cream, ointment - Rx only - Indicated: genital & oral HSV infections - Use: q3h (6x/day) x 7 days for initial outbreak; 5x/day x 4 days for recurrent - Start at onset of symptoms - Helps mainly with associated symptoms -- does not shorten outbreak duration - May decrease viral shedding - AE: very few- burning, stinging, etc. - Penciclovir (Denavir®) 1% cream - Rx only - Indicated: recurrent herpes labialis - Use: q2h x 4 days while awake - Shown to decrease pain x 1 day compared to placebo  Parasitic Infections - Scabies ============================== - Permethrin 5% (Elimite®)- 2 month-adult - MoA: acts as a neurotoxin by depolarizing nerve cell membranes of parasites by disrupting sodium ion influx through cell membrane channels by which membrane repolarization is regulated - Delayed repolarization results in paralysis of nerves in the exoskeletal respiratory muscles of parasite leading to death - Apply from chin down & washed off after 8-14 hours & may repeat in 7 to 10 days if necessary - Ivermectin (Stromectol®): - MoA: Binds glutamate-gated Cl ion channels in invertebrate nerve and muscle cells; produces paralysis, death of parasite - 200 mcg/kg PO x 1; may repeat in 7 days - Not FDA approved  Parasitic Infections - Scabies ============================== - Crotamiton (Eurax®) - MoA: unknown - Applied from chin down for 24 hr, wash then [reapplied] x24 hrs then the skin thoroughly cleanse. May be repeated in 7 days. - Lindane (Kwell®) - MoA: cyclic chlorinated hydrocarbons like lindane presumably stimulate the nervous system, resulting in seizures & death of parasite - Rarely used due to neurological complications - Thin layer applied from chin down & washed off 8-12 hours (Only 30 g should be used,) & only 1 application required  Parasitic Infections - Lice =========================== - Permethrin 1% lotion (Nix®) - Saturate treatment area & washed off after 10 min. - may be repeated in 7 days - HIGH rates of resistance - Malathion lotion (Ovide®) - Inhibits cholinesterase - Applied to dry hair & allowed to dry naturally, wash with soap in 8-12 hours. May be repeated in 7 days (if needed) - Lindane (Kwell®)- rarely used - Head or Pubic: Shampoo or lotion applied to dry hair & washed after 4 min - Body: thin layer applied & washed off after 8-12 hours  Parasitic Infections - Lice =========================== - ### Ivermectin (Stromectol)®: - #### 200 mcg/kg PO q week x 3 doses if needed - Not FDA approved - After treatment nits should be removed by a fine tooth comb - Clothing & Bedding must be disinfected by washing & drying at high temperature  Parasitic Infections - Lice =========================== - Benzoyl alcohol 5% (Ulesfia®) lotion - Ages \> 6months - MoA: Asphyxiates lice by stunning their external breathing component - Repeat tx in 7 days - Spinosad 0.9% (Natroba®) cream rinse - Ages \> 4 years - MoA: Targets nicotinic receptors & GABA gated Cl channels - Repeat tx in 7 days if needed - Ivermectin 0.5% (Sklice®) lotion - Ages \> 6 months - MoA: Targets GABA gated Cl channels -- causes paralysis -- death - One time tx  References ========== - Clinical Resource, *Management of Head Lice. Pharmacist's Letter/Prescriber's Letter.* #### September 2018 - Clinical Resource, *Scabies FAQs. Pharmacist's Letter/Prescriber's Letter.* September #### 2019 - Clinical Resource, *Pharmacotherapy of Acne. Pharmacist's Letter/Prescriber's* - Clinical Resource, *Treatments for Rosacea. Pharmacist's Letter/Prescriber's*