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36 Cards in this Set
- Front
- Back
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What is the rate limiting step of topical drugs? |
partition coefficient = absorption through the stratum corneum (higher = faster absorption, better) (palm/sole thickness > body > scrotum > face) (absorption is faster w/ thinner skin, hydration, ointment, heat, & coverage) |
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What causes acne? |
1. Hyperkeratinization--> Inc loose cells, clogs follicles, caused by Incr Androgens 2. Increased Sebum production, caused by Incr Androgens--> substrate for bacteria enzymes, clogs follicles 3. Propionibacterium acnes, use lipase to form FFA (free fatty acids) from sebum 4. Inflammation, response to FFA irritation |
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Hyperkeratinization, inc sebum & P. acnes form microcomedos (acne precursor), then mechanical insult causes comedo to close & inflammation leads to........ |
inflammation causes comedo to progress to papules, pustules, nodules, cysts (acne) w/ potential to scar |
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Mild acne, localized to face is not likely to scar & should be tx w a ____________ While ___________ is preferred for severe acne on back, chest, arms, that is more likely to scar |
topical medication for mild oral medication for severe, may use topical additionally |
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_________ is used for mild acne or in combos w/ erythromycin or clindomycin for more severe acne MOA: +Keratolytic- solubilizes intracellular connections btwn keratinocytes, reducing hyperkeratinization +Comedolytic- prevents closure, reduces comedones +Bactericidal- kills P. acnes via radical formation
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Benzoyl Peroxide *lipophillic, good penetration |
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What are the SEs of Benzoyl peroxide? |
Irritation, dryness, peeling & erythema Bleaching of hair/ clothes Contact dermatitis (rare) |
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__________ is used for mild acne or psoriasis MOA: +keratolytic (solubilizes intracellular cement, reduces hyperkeratinization) What are the SE's? |
Salicylic Acid SE: salicylism (rare, life threatening) |
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________ is used for mild/ moderate acne & acne rosacea, hyperpigmentation MOA: +Keratolytic Antimicrobial- Inhibitor of thioredoxin reductase & tyrosinase, inhibits DNA synthesis Antiinflammatory- scavenger of free radicals |
Azelaic Acid (azelex) |
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What are the SEs of Azelaic Acid? |
irritation, itching hypopigmentation (tyrosinase inhibition interferes w/ melanocyte) |
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First line acne therapy- MOA? |
Retinoids (Vit A analogs) MOA: retinoic acid (RA) binds endogenous Retinoic acid (RARs) & retinoic X (RXRs) nuclear receptors--> RA-RAR complex forms transcription factor--> regulate gene transcription & translation--> altered cellular function of translated proteins--> Regulate epithelial cell proliferation (hyperkeratinization) Bone growth Immune function Reproductive function |
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1st & 2nd generation retinoids have more flexible structures, allowing them to _________ What does this cause? |
allows binding to several retinoid receptors *causes worse SE's than 3rd generation retinoids (arotinoids) |
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________, is a topical 1st gen topical retinoid, trans-retinoic acid, used for acne & as an anti-wrinkle cream MOA: (binds RAR) +Keratolysis- by incr mitosis (cell turnover)--> decr cell adhesion--> exfoliation & desquamation +Anti-comedolytic- prevents formation of new microcomedones |
Tretinoin (Retin A) |
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What are the SEs of Tretinoin? |
Irritation, erythema, peeling dryness Initial appearance of worsening acne (top layer sloughed & reveals comedones below) De-activated by UV light & Benzoyl peroxide (use at night & DONT use w/ Benzoyl peroxide) *Antiwrinkle effects (vasodilation & inc collagen) |
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_________ is a 3rd gen topical retinoid, used for acne MOA: same as Tretinon (binds RAR) +Keratolysis +Anti-comedolytic How does this drug differ from Tretinon? |
Adapalene (Differin) * NOT degraded by UV or benzoyl peroxide *similar SE's, but less severe |
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_______ is a 3rd gen topical, UV-stable retinoid, used for acne & psoriasis MOA: Pro-drug, converted to tazarotenic acid (by esterase, when rubbed on skin)--> binds RAR--> +Keratolysis- normalizes keratinocyte growth +Anti-inflammatory What are the SEs? |
Tazarotene (tazorac, avage) SE: Similar SEs to Tretinoin (use every other day to reduce skin irritation) Teratogen category X |
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_______ is a 3rd gen, ORAL, cis-retinoic acid, MOST EFFECTIVE acne tx *short term use--> permanent effects MOA: (binds RAR) +keratolysis- normalizes follicular epithelium +Decreases Sebum production +Anti-inflammatory +Bactericidal (targets all 4 causes of acne!) |
Isoretinoin (generic for accutane) |
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Despite being the most effective tx, Isoretinoin may not be used d/t neg SEs. What are they? (Accutane no longer on market d/t these) |
Dry, peeling, itchy skin Dry eyes Nosebleeds Alopecia (reversible) Inflammatory Bowel disease Joint pain Lipid profile changes Depression/ Suicidal ideations (DO NOT used in pts predisposed to depression!) Teratogen category X |
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Pts taking Isotretinoin must agree to do the following before starting; |
Use 2 forms of birth control (severe teratogenesis) Take pregnancy test Not donate blood (for at least 1 month following discontinuation) Not take Vitamin A supplements (toxicity) |
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________ is a macrolide Abx, used in BOTH Topical & Oral acne tx, alone or in combo w/ benzoyl peroxide MOA: +Bacteriostatic- binds 50s ribosomal subunit--> inhibits translocation--> inhibits translation of mRNA to protein What are the SEs? |
Erythromycin SE: (w/ oral use*) (CYT P450) Liver enzyme inhibitor--> Incr concentration of theophylline, caffeine, coumadin, digoxin, warfarin, corticosteroid (toxicity) |
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_______ abx, used in BOTH topical & oral acne tx, alone or in combo w/ Benzoyl peroxide MOA: +Bacteriostatic- binds 50s--> inhibits protein synthesis What SEs does it cause? |
Clindamycin SE: (w/ oral use) pseudomembrane Colitis |
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______ abx, used in BOTH topical & oral acne tx MOA: +Bacteriostatic- binds 30s--> inhibits translation of mRNA into protein What SEs does it cause? |
Tetracycline SE: (oral) alters normal intestinal flora Photosensitization Binds Ca2+ (tooth & bone effects)--> absorption/ efficacy is decreased w/ Antacid use-->* Avoid dairy, antacids iron** |
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_______tetracyline class abx, use in oral acne tx only MOA: +Bacteriostatic- same as tetracycline (binds 30s) How does this differ from tetracycline? |
Doxycycline Oral use only & Increased incidence of SE's |
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_____ tetracycline class Abx, use in oral acne tx only, expensive** MOA: +Bacteriostatic- same as tetracycline SE: less incidence of SEs than tetracycline Ototoxicity* (vestibular effects) |
Minocycline |
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________ is the only hormone therapy approved for acne tx in FEMALE pts MOA: Inc SHBG--> Decreased free Androgen (testosterone)--> +Keratolytic (decr hyperkeratinization) +Decreased Sebum What are the SEs? |
Ortho-Tri-Cyclen (ethinyl estradiol & noregestimate) SE: Inc risk of CVD (MI, stroke, etc) in smokers >35 Inc risk of clotting (dose related) Inc risk of breast cancer *takes a few months to see effects & acne relapse w/ discontinuation |
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What cause Plaque formation in psoriasis? |
APC presents Ag to T cell in LN--> clonal expansion--> activated TH1 cell travels to dermis--> encounters new APC--> reactivation & further clonal expansion--> cytokine release--> keratinocyte inflammatory damage--> plaque formation |
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Psoriasis is a disorder of hyperkeratinization (inc cell sloughing/turnover). Somewhat genetic, onset usually after some "trigger"--> disruption in arachidonic acid metabolism (inc rate) How does this present clinically? |
thick plaques w/ silver scale red skin (capillary dilation) inflammation (lymphocytes in dermis & neutrophils in epidermis) |
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________ & _________ target the superficial epidermis & are used topically on reduce scales |
Emolients (lotions)- minimize dryness, pruritis, soften scales & Keratolytics (Salicylic acid)- smooth skin & remove scale, decrease hyperkeratosis |
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__________ are used topically in severe psoriasis (start w/ more potent rx, followed by less potent rx) MOA: immunosuppression antimitotic effects on the epidermis--> suppress proinflammatory genes (IL-1, IL-2, IL-6)--> decrease inflammatory cell production & migration to dermis SEs? |
Corticosteroids SE: (may have systemic SE at high dose*) Steroid rosacea contact dermatitis skin atrophy bruising *NEVER use on face, only on small body areas |
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________ oral rx, used for psoriasis MOA: immunosuppression binds cyclophylin--> inhibits calcineuron--> prevents dephosphorylation of NFAT--> decr IL-2 production--> decr T cell activation What are the SEs? |
Cyclosporine (sandimmune) SE: renal dysfxn (nephrotoxicity) hirsutism HTN |
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___________ is a biologic used in the tx of moderate to severe chronic plaque psoriasis MOA: immunosuppression dimeric fusion protein binds to CD2 on T cells--> interferes w/ T cell interaction w/ APC--> reduces active T cells SE? |
Alefacept (amevive) SE: CD2 binding on T cell--> Increased CD4+ apoptosis *requires weekly CD4+ monitoring *don't use in pts w/ infections |
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_______ is a biologic used to tx psoriasis MOA: immunosuppresion humanized monoclonal anti-TNF-alpha Ab--> binds TNF-alpha--> cell-toxic effects What are the SEs? What is required before starting? |
Adalimumab (Humira) SE: allergic rxns reactivation of latent Tb* incr susceptibility to infection lupus-like syndrome Require Tb screen before starting, don't use w/ infeciton |
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___________ is a retinoid that can be used to tx moderate to severe psoriaisis (not commonly used for acne)
prodrug converted to etritinate SEs? What other retinoid can also be used to tx psoriasis? |
Acitretin (soriatane) SE: similar to isoretinoin (dry skin, dry mucous membranes, hair thinning) severe teratogenesis (worse than isoretinoin, caution in preg for 3 yr after discontinuing) wait 1 month to donate blood after stopping *Tazarotene also used to tx psoriaisis |
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________ are topicals used to tx psoriasis, dermatitis, lichen simplex chronicus (alt to corticosteroids) MOA: Keratolytic phenolic compounds--> antipruritic cytostatic epidermal thinning SE? |
Tar compounds SE: transient epidermal hyperplasia (followed by epidermal thinning) Difficult application--> staining, stinky Irritant folliculitis Phototoxicity |
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_________ topical ointment used for moderate plaque type psoriaisis MOA: Vit D3 derivative--> inhibit keratinocyte differentiation & proliferation (keratolytic)--> Decrease TH1 stimulating cytokines (IL-2) SEs? |
Calcipotriene (Dovonex) SE: Avoid mucous membrane (eyes) & open skin (prevent systemic effects) Irritation, drying, erythema |
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_______ is used in moderate to severe psoriaisis MOA: anti-inflammatory inhibits dihydrofolate reductase (DHFR)--> blocks DNA synthesis (esp of rapidly dividing cells = immune cells)--> Decrease IL-1--> death of active T cells SEs? |
Methotrexate SE: hepatic fibrosis (d/t high dose req) CI w/ sulfamethoxazole, probenecid, salicylates |
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__________ is used in combination w/ UV A light therapy (PUVA therapy) to tx psoriasis *applied prior to light exposure MOA: photoaddition to pyrimidine in DNA--> creates reactive oxygen--> anti-proliferative, immunosuppressive, & anti-inflammatory SE's? |
Methoxalen/ Psoralens SEs: Nausea, cataracts (if oral, can be used in bathwater or lotion topically) photosensitivity (UVB is more likely than UVA to cause cancer) |
