Dermatology Pharmacology Flashcards
What are some topical steroids?
Clobetasol propionate, triamcinolone acetonide, hydrocortisone
Topical steroid AEs?
Chronic use AEs: skin atrophy, striae, telangiectasias, purpura, acneiform eruption
Risk of w/ high potency steroids over large BSA: Cushing’s syndrome, immunosuppression, hyperglycemia, osteoporosis, glaucoma
Masking of dermatophyte infection (can mask fungal infection) – avoid combination products
Rank the potentcy of topical steroids
Clobetasol propionate: very high potentcy
Triamcinolone acetonide: medium to high potency
Hydrocortisone: low potency
Topical steroid pearls
Ointments have better absorption than creams but poorer adherence (can alternate w/ creams for convenience)
Application post-shower/bath increases absorption
Inflammation increases absorption
Avoid fluorinated formulations on the face (can cause rosacea/perioral dermatitis)
Avoid ointments in hairy areas or intertriginous areas
Taper higher potency steroids –> can get rebound effect
General principles of topical steroid agent selection?
Super high-potency preparations: palms and soles; severe dermatoses (psoriasis, severe atopic dermatitis, severe contact dermatitis)
Medium to high-potency preparations: mild to mod nonfacial/nonintertriginous dermatoses
Low-potency preparations: eyelid and genital dermatoses for limited time periods; large body areas
Super high potency preparations are for nonfacial/nonintertriginous areas only
Topical steroid general treatment duration recommendations?
Low-to-high potency topical steroids: 3 mo of continuous use
Ultra-high potency topical steroids: 3 weeks of continuous use
Avoid in perioral dermatitis
What are some therapeutic targets for acne?
Follicular hyperproloferation and abnormal desquamation:topical retinoids, oral isotretinoin, azelaic acid, salicylic acid
Increased sebum production: oral isotretinoin, oral contraceptives, spironolactone, clascoterone
Cutibacterium acnes proliferation: benzoyl peroxide, topical and oral abx, azelaic acid
Inflammation: oral isotretinoin, oral tetracyclines, topical retinoids, azelaic acid, topical dapsone
Benzoyl Peroxide (Clearasil) indication?
Acne
Benzoyl Peroxide MOA?
Antibiotic and comedolytic
Of note: comedones are pores or hair follicles that have gotten blocked with bacteria, oil, and dead skin
Benzoyl Peroxide AEs?
Dose-dependent irritation (erythema, scaling, xerosis, or stinging, tightening, or burning sensations)
Can bleach hair/clothing
Benzoyl Peroxide effectiveness?
Visible improvement 3 weeks, max results 8-12 weeks
> 2.5% may not increase effectiveness
Higher conc. not necessarily more effective but greater AEs
Benzoyl Peroxide pearls?
Combo w/ topical abx can decrease time to effect and prevent abx resistance
Avoid applying with tretinoin
Salicylic Acid (Stridex) indication?
Acne
Salicylic Acid MOA?
desquamating agent (“exfoliating”), mild anti-inflammatory
Salicylic Acid AEs?
Dryness, peeling
Azelaic Acid Topical (Azelex, Finacea) indication?
Acne, rosaeca
Particularily useful for rosacea as it’s good at reducing redness
Azelaic Acid MOA?
Largely unknown; may be antimicrobial, comedolytic, mild antiinflammatory; reduces redness
Azelaic Acid AEs?
Burning/tingling
Clascoterone Topical (Winlevi) indication?
Acne
What is clascoterone and its MOA?
Type: androgen receptor inhibitor
MOA: reduces sebum production, inflammation
Clascoterone AEs?
Redness, dryness, itching, burning/tingling
HPA axis suppression (avoid use over large areas/occlusive dressings)
Clascoterone pearls?
M and F ≥12 yo
$$$
Minocycline Topical (Amzeeq, Zilxi) indication?
Acne and rosacea
Amzeeq indication: acne
Zilxi indication: rosacea
For mod to severe acne vulgaris (not 1st line tx)
Minocycline type and MOA?
Type: tetracycline abx
MOA: binds to bacterial 30S ribosomal subunit and interferes w/ protein synthesis
Minocycline AEs?
Generally well-tolerated
Burning, stinging, redness
Can penetrate CNS so vestibular side effects (HA, dizziness, vertigo); serum sickness reaction (typically occurs days after initiation)
Tetracycline indication?
Acne
Types of tetracyclines for acne?
Doxycycline, Minocycline, Sarecycline (Seysara)
Tetracycline type and MOA?
Type: tetracycline abx
MOA: inhibit growth of C. acnes, anti-inflammatory action
Tetracycline AEs?
Pregnant people, children < 8 yo: tooth discoloration, slowing of skeletal development
Esophagitis, photosensitivity, skin discoloration, idiopathic intracranial HTN (rare but serious AE), microbiome effects,
Minocycline: can penetrate CNS so vestibular side effects (HA, dizziness, vertigo); serum sickness reaction (typically occurs days after initiation)
Tetracycline pearls?
Sarecycline: narrower spectrum, $$$
Duration: 3-4 mo (also use topical retinoid and benzoyl peroxide – use at different times of day (retnoid usually at HS))
Avoid administration w/ antacids, calcium, iron, magnesium
Take with a full glass of water, if pill gets stuck in throat can lead to esophagitis
Dapsone Topical (Aczone) indication?
Indication: acne
Best for papulopustular acne, not first-line
Type and MOA of Dapsone topical?
Type: sulfone abx
MOA: anti-inflammatory and antimicrobial (but not confirmed for derm purposes)
Dapsone topical AEs?
Adverse effects are rare
Methemoglobinemia, hemolytic anemia in pts w/ G6PD deficiency (MC w/ systemic)
Dapsone topical pearls?
Do not combine w/ benzoyl peroxide (yellow/orange skin and hair discoloration) –> can last for days to mo
Metronidazole gel (Metrogel) indication?
Rosacea
Metrogel type and MOA?
Type: nitroimidazole antimicrobials
MOA: details unknown but overall inhibits protein synthesis by interacting with DNA; causes loss of helical DNA structure and strand breakage
Metrogel AEs?
Skin reactions (contact dermatitis), burning, dryness
Metrogel pearls?
Do not confuse w/ vaginal formulation
What can retinoids be used for?
Acne, aging
How do retinoids work?
Retinoids exhibit biological activity similar to vitamin A)
Overall MOA: if bind to retinoid receptor –> form heterodimers; if bind to DNA sequences –> activates transcription of genes
Product produces the pharmacologic effect
What are some examples of retinoids?
Adapalene, Trifarotene, Tretinoin, Tazarotene
Retinoid AEs?
Dryness, irritation, flaking (most noticeable during first mo of use)
May cause increased photosensitivity (important to wear suscreen when using retinoids)
Micronized tretinoin contains fish proteins
Retinoid pearls
Avoid Tazarotene in pregnancy
Retinoids for acne: indicated for both inflammatory and non-inflammatory acne; systemic retinoids also decrease sebum production; reduce C. acnes; has become more popular in lieu of using an antimicrobial
Retinoid administration: apply a thin layer to clean, dry skin at night (inactivated by UV light, benzoyl peroxide (adapalene, tretinoin micronized forms of tretinoin more stable)); apply to entire affected area (do not spot treat); avoid eyes
Least to most irritating: adapalene < trifarotene < tretinoin < tazarotene
What is isotretinoin?
Systemic retionoid
Isotretinoin indication?
Severe acne
Only acne medication that can permanently alter course of disorder
Isotretinoin AEs?
Mucotaneous: dose-dependent; cheilitis, dry skin and mucous membranes, epistaxis, photosensitivity, and pruritus; eye issues (dryness, irritation, conjunctivitis)
Hyperlipidemia (45% of patients see high triglycerides, 35% see high LDLs)
Psychiatric: potential depression/suicide risk
Inflammatory bowel disease (conflicting evidence)
Less frequent: acne fulminans, myalgias, hepatotoxicity, idiopathic intracranial HTN
Isotretinoin cautions/contraindications?
CI in pregnancy (causes severe, life-threatening, congenital malformations and spontaneous abortions) and soy allergy (capsules contian soy beans)
Avoid giving alongside tetracycline d/t similar AE of idiopathic intracranial HTN
Avoid blood donation as isotretinoin can linger in blood (donated blood could possibly be given to a pregnant person (which is CI))
Avoid excessive EtOH use (metabolized in liver)
Avoid vitamin A supplementation
Avoid skin procedures for 6 mo (full-face manual dermabrasion)
Avoid breastfeeding
Considerations before prescribing isotretinoin?
iPLEDGE program (provider requirements)
Initial assessment: prior contraceptive failure, assessing personal or family hx of AEs, heavy EtOH use, extreme physical activity
Isotretinoin monitoring?
Monitoring: development or worsening of AEs; vision changes and HA important to check to minitor for intracranial HTN
Baseline labs: ALT and triglyceride levels w/in 1 mo prior to the start of therapy; urine or serum pregnancy test in pts of childbearing potential (2 tests are required prior to the start of therapy for the iPLEDGE)
Isotretinoin pearls?
Sometimes in 1st month when taking systemic retinoid pts can experience a flare –> can take glucocorticoid to mitigate
What are some hormonal treatment options for acne?
OCPs, spironolactone
OCP AEs
Blood clots with taking estrogen
OCP screening before prescribing?
Smoking, HTN
OCP for acne pearls
For postmenarchal F only
Should contain estrogen and progestin (progestin only pills won’t help with acne, may make it worse)
Can take several months before seeing effects
Spironolactone type and MOA?
Type: mineralocorticoid receptor antagonist
MOA: antiandrogen (blocks receptors, inhibits production; decreases sebum production)
Spironolactone AEs?
Menstrual irregularities, breast tenderness, minor GI symptoms (anorexia, nausea, vomiting, and diarrhea), hyperkalemia, orthostatic HoTN, CNS symptoms (HA, dizziness, and fatigue)
CNS effects are not dose dependent but other AEs are
Spironolactone contraindications?
Avoid in pregnancy
Spironolactone pearls?
Start at a lower dose and titrate up to avoid HoTN
How to approach treating mild acne?
Assess for need for more aggressive tx; manage as mod-to-severe if necessary
* Comedonal lesions only: topical retinoid
* Papulopustular +/- comedonal lesions: topical retinoid + benzoyl peroxide
Assess after 3 mo – if satisfactory, continue topical retinoid maintenance
If unsatisfactory response:
* Manage as mod-to-severe (consider alt. therapies or manage as mod-to-severe)
* Add: topical clindamycin OR topical daspone
How to approach treating moderate to severe acne?
Assess for need for more aggressive tx; offer isotretinoin if appropriate
* Comedonal lesions only: topical therapy + oral contraceptive (F only) OR oral spironolactone (F only) OR oral isotretinoin
* Papulopustular +/- comedonal lesions: topical therapy + oral tetracycline OR oral contraceptive (F only) OR oral spironolactone (F only) OR oral isotretinoin
Assess after 3 mo – if satisfactory, continue OC or spironolactone + topical as maintenance; d/c antimicrobial; isotretinoin given until cumulative dose achieved
If unsatisfactory response:
* Try combo or escalate to isotretinoin
Mupirocin (Bactroban) indication?
Impetigo, MRSA dermatologic infection
Mupirocin AEs?
Resistance w/ prolonged use
Butenafine (Lotrimin) indication?
Tinea (do not use terbinafine for tinea unguium)
Butenafine AEs?
Generally well-tolerated
Itching, burning, erythema, contact dermatitis
Terbinafine (Lamisil) indication?
Tinea
Oral used to tx things like toenail fungus (toenail not a well perfused area, etc)
Terbinafine (Lamisil) AEs?
Topical:
* Generally well-tolerated
* Itching, burning, erythema, and contact dermatitis
Oral:
* Hepatotoxicity, delayed hypersensitivity reactions (TENS/SJS)
Ketoconazole (Nizoral) indication?
Tinea, seborrheic dermatitis, dandruff
Ketoconazole AEs?
Generally well-tolerated
Itching, burning, erythema, contact dermatitis, angioedema
How to approach mild to moderate psoriasis treatment?
Topicals +/- phototherapy
How to approach moderate to severe psoriasis treatment?
Topicals +/- phototherapy, biologic +/- systemic agents added
What are Tacrolimus (Protopic), Pimecrolimus (Elidel)?
Calcineurin inhibitors
Tacrolimus and Pimecrolimus indications?
Indication: atopic dermatitis
Other uses: intertriginous psoriasis, vitiligo, mucosal lichen planus, graft-versus-host disease, allergic contact dermatitis, and rosacea
MOA of calcineurin inhibitors?
Suppresses cellular immunity (inhibits T-lymphocyte activation)
AEs of calcineurin inhibitors (tacrolimus, pimecrolimus)?
Common: transient erythema, burning, and pruritus
Rare: systemic immune-related effects (tacrolimus > pimecrolimus), skin papilloma, lymphadenopathy
Do calcineurin inhibitors have a BBW?
YES: although a causal relationship has not been established, rare cases of malignancy (ie, skin cancer and lymphoma) have been reported
Avoid continuous long-term use
Limit application to areas of involvement w/ atopic dermatitis
Calcineurin inhibitor pearls
Can be used on face, intertriginous areas
Tacrolimus: more effective compare to mediumpotency steroids
Pimecrolimus: fewer AEs
Avoid in Nethertom Syndrome (rare genetic disorder, causes some skin to be thinner so these types of drugs are absorbed more systemically)
What are Calcipotriene and Calcitriol?
Vitamin D analogs
Vitamin D analog indications?
Plaque psoriasis
Vitamin D analog AEs?
Hypercalcemia and hypercalciuria may develop when the cumulative weekly dose exceeds the recommended limit
Irritation, mild photosensitivity
Vitamin D analog pearls?
Concomitant admin of topical corticosteroids will reduce irritation and provides synergistic effect
Avoid w/ vitamins/calcium supplements, occlusive dressings, sunlight/UV exposure
What is methotrexate?
Type: folate antagonist/antimetabolite
MOA: inhibits dihydrofolate reductase (targets cells during DNA synthesis, reduces hyperproliferation in psoriasis)
What is MTX indication?
Psoriasis, sarcoidosis, rheumatoid arthritis
(high-dose used in oncology)
MTX AEs?
AEs w/ low dose regimens:
Within days-weeks
* GI: nausea, stomach upset, anorexia, loose stools
* Stomatitis or soreness of the mouth
* HA, fatigue, malaise, or impaired ability to concentrate
* Macular punctate cutaneous eruption, which usually occurs on the extremities, often affecting the elbows and knees, but sparing the trunk (can cause severe SJS-like or TEN-like conditions)
* Alopecia (not dose-related)
* Fever (drug-related)
* Pancytopenia (can occur after 1 dose but up to 6 weeks later)
Weeks-months
* Abnormal liver chemistries, (typically mild elevations in hepatic transaminases)
* Hematologic abnormalities (particularly macrocytosis, in addition to infrequent but severe myelosuppression)
* Pulmonary toxicity/pneumonitis (MC in RA)
* Lymphoma
Hepatotoxicity
Does MTX have a BBW?
YES: toxicity, teratogenicity
MTX cautions/contraindications?
CI: pregnancy/breastfeeding (wait 3 mo after d/c to become pregnant); EtOH dependence, EtOH liver disease or other chronic liver disease; immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
Caution: abnormalities in renal/liver function, active infection
Dose adjust for reduced renal function
MTX drug-drug interactions?
May increase MTX concentrations (NSAIDs, sulfamethoxazole-trimethoprim, loop diuretics, thiazide diuretics, sulfonylureas, PCN, minocycline, ciprofloxacin, phenytoin, barbiturates, PPIs)
Avoid live vaccines (can increase risk of infection)
Avoid with topical immunosuppressants
Minimize alcohol intake
MTX monitoring?
Baseline/pretx: pregnancy; CBC, LFTs, serum albumin; noninvasive liver fibrosis assessment; hepatitis B and C screening; test for latent TB
Ongoing: liver/renal functioning (CBC, LFTs, serum albumin, serum creatinine, FIB-4, Fibrosure, Fibrometer, Hepascore annually)
MTX pearls?
Can be used w/ phototherapy
Supplement w/ daily folic acid to reduce adverse effects
Other medications for systemic treatment of psoriasis? What is their indication?
Acitretin, Apremilast, Cyclosporine
Moderate to severe plaque psoriasis
Acitretin pearls?
Not immunosuppressive
Place in therapy: HIV pts on antiretrovirals
What are biologics used for?
Types of classes of biologics?
TNF-⍺ inhibitors, IL-23 inhibitors. IL-17 inhibitors, IL-4 antagonists
Pretreatment screening for all biologics?
Yes: CBC w/ diff, CMP, TB test, hepatitis, HIV test, referral to ID on special case-by-case basis
What are some examples of TNF-⍺ inhibitors?
Etanercept (Enbrel), Infliximab (Remicade), Adalimumab (Humira), Certolizumab Pegol (Cimzia)
TNF-⍺ inhibitors AEs?
MS (rare); hepatotoxicity (especially w/ infliximab); drug-induced reversible lupus erythematosus w/o renal or CNS complications; exacerbation or new onset of CHF; cytopenia
Injection site reactions: mild (pruritic reaction), moderate-to-severe (macular erythema to erythematous annular plaques)
Infusion reactions w/ infliximab
TNF-⍺ inhibitors cautions/contraindications?
Untx hepatitis B infection
Hx of lymphoreticular malignancy
Active infection (including TB) or sepsis
Initiation of therapy should be done in consultation w/ an infectious disease specialist
Significant New York class III or IV CHF or pre-existing multiple sclerosis
Monitoring while taking TNF-⍺ inhibitors?
Ongoing monitoring: assessment for infections (ex: TB, histoplasmosis), esp. in those using TNF-a inhibitors + MTX; annual TB test in high-risk pts; LFTs for infliximab at 3 mo, then q 6-12 mo
Describe an acute infusion reaction with infliximab
Acute: Occur during or w/in 24 hr of infusion; mitigated and/or prevented by pretx w/ APAP and diphenhydramine
Mild and mod infusion reactions:
* Usually consist of nausea, fever, erythema, and itching
* Resolve spontaneously after reduction of the infusion rate or temporary pause of the infusion
Severe infusion reactions:
* Occur immediately after the infusion has been started
* Are characterized by hypotension, chest tightness, respiratory distress, dyspnea, bronchospasm, laryngeal edema, urticaria, or rash
* Require immediate d/c of the infusion
Describe a delayed infusion reaction with infliximab
Begin 1-14 days after infusion
Usually consist of myalgia, arthralgia, HA, fever, rash, and fatigue
Missing an infusion increases the chances of an infusion reaction
The next infusion should be done more slowly and w/ appropriate pretx (ie: w/ antihistamines)
Types of IL-23 inhibitors
Guselkumab (Tremfya), Risankizumab-Rzaa (Skyrizi), Tildrakizumab-Asmn (Ilumya), Ustekinumab (Stelara)
Types of IL-17 inhibitors
Seckinumab (Cosentyx), Ixekizumab (Taltz), Brodalumab (Siliq)
Types of IL-4 antagonists
Dupilumab (Dupixent)
Dupilumab indications/pearls?
Indications: atopic dermatitis, asthma, rhinosinusitis w/ nasal polyps
Drug interactions: can use w/ or w/out topical corticosteroids; topical calcineurin inhibitors should be reserved for problem areas only (eg, face, neck intertriginous and genital areas); may be able to reduce maintenance asthma medications; avoid live vaccines