Dermatologic Pharm Flashcards
4 major variables affecting cutaneous absorption
Regional — e.g., axilla more permeable than forearm
Concentration gradient — increased concentration —> drug mass/unit time
Dosing schedule — long local t1/2 of skin reservoir may permit QD dosing
Vehicles/occlusion — both can maximize drug penetration
Difference in composition of creams vs. ointments
Creams = mixture of ~half water/half oil with emulsifier (e.g., cetyl alcohol), water evaporates. Spread easily (good for large areas), are well absorbed, and wash off with water
Ointments = mixture of ~20% water in ~80% oil (oil component is made from hydrocarbons such as mineral oil or petroleum jelly). Feel greasy and are “occlusive”, meaning they stay on the surface of skin and are NOT well absorbed
Cream or ointment?: packaged in tub or tube, beter for oozing/“wet” skin conditions
Cream
Cream or ointment?: best used on dry skin since they trap moisture, provide more complete absorption of active ingredient or medication
Ointment
Cream or ointment?: Less likely to cause an allergic reaction
Ointments, because creams contain preservatives
T/F: Hands should be washed for 15-30 seconds using plain soap, although this does not reliably prevent microbial transmission
True
Alcohol-based hand disinfection is easier and faster than soap and water, and is rapidly effective against gram-positive, gram-negative, and viral pathogens. However, it is not effective against _______ so you must use soap and water to protect against transmission of that
C.difficile
Component of moisturizer that forms an oily layer on top of skin that traps water in the skin
Emollient
[common emolllients: petrolatum, lanolin, mineral oil, dimethicone]
Component of moisturizer that draws water into the outer layer of the skin
Humectants
[common humectants: glycerin, lecithin, and propylene glycol]
Component of moisturizer that loosens the bond between the top layer of cells to help dead skin cells fall off, helps the skin retain water, and gives it a smoother softer feel
Horny substance (keratin) softeners
[common agents: urea, alpha hydroxy acids (e.g., lactic, citric, glycolic), allantoin]
3 compounds found in sunscreens and their utility
p-aminobenzoic acid (PABA) and its esters — active in UVB range
Benzophenones — wider 250-360 nm range but less effective than PABA
Dibenzoylmethanes — active in UVA range, particularly useful for conditions such as drug-induced photosensitivity and cutaneous lupus erythematosus
Sunshades are opaque materials that reflect light, the classic example is _____ ______
Titanium dioxide
Broad-spectrum antimicrobial agent widely used in homes and hospitals due to general efficacy on skin (including oral mucosa) and low irritability; low concentrations affect cytoplasmic (inner) cell membrane integrity while high concentrations cause congealing of cytoplasm
Chlorhexidine
Utility of chlorhexidine against bacterial spores
Not sporicidal but prevents development of spores; inhibits spore outgrowth but not germination
Chlorhexidine action against mycobacteria
Mycobacteriostatic (mechanism unknown) but not mycobacteriocidal
Action of chlorhexidine against nonsporulating bacteria
Membrane-active agent, causing protoplast and spheroplast lysis
High concentrations cause precipitation of proteins and nucleic acids
Action of chlorhexidine against yeasts
Membrane-active agent, causing protoplast lysis and intracellular leakage, high concentrations cause intracellular coagulation
Action of chlorhexidine against viruses
Low activity against many viruses; lipid enveloped viruses more sensitive than nonenveloped; effect possibly on viral envelope (e.g., lipid moieties)
Effects of chlorhexidine on protozoa
Has activity against trophozoites, less toward cysts
Protozoan that causes diarrhea in humans, especially in HIV+ pts; oocysts are especially resistant to antiseptics and disinfectants
Coccidia (Cryptosporidium)
Organism considered to be the most resistant to antiseptic and disinfectants, after a chimp developed CJD when neurosurgical tools had been treated with 70% alcohol and formaldehyde vapor and stored for 2 years
Prions (CJD, BSE)
Organism(s) highly resistant to antiseptics and disinfectants that have increased in incidence in hospitalized pts, with CDC recommending using bleach or other EPA-approved agent with sporocidal claims
Spores (Bacillus, C.diff)
The top 3 organisms resistant to antiseptics and disinfectants are prions, coccidia, and spores. What are some others that are considered resistant?
Mycobacteria
Cysts (giardia)
Small non-enveloped viruses (polio)
Trophozoites (acanthamoeba)
Gram-negative non-sporulating bacteria (pseudomonas, providencia)
Fungi (candida, aspergillus)
Large non-enveloped viruses (enterovirus, adenovirus)
Gram positive bacteria (s.aureus, enterococcus)
Lipid enveloped viruses (HIV, HBV)
2 ways in which biofilms affect the utility of disinfectants and/or hand hygiene practices
Limited penetration of disinfectants
Antibiotic neutralization
Role of antiseptics and antibiotics in wound management
Antiseptic wash solutions such as iodine, chlorhexidine, or hydrogen peroxide are generally NOT necessary and potentially impede wound healing
Antibiotic therapy should be reserved for wounds that appear clinically infected
[exceptions: cadexomer iodine, silver]
T/F: tighter glycemic control is strongly linked to improved primary closure of surgical wounds as well as other types of wound healing
True
T/F: During wound healing it is important to ensure adequate oxygenation and nutrition
True
What type of wound debridement should be routine since it flushes bacteria and removes loose material?
Low-pressure irrigation with normal saline
What type of debridement is appropriate for removing large areas of necrotic/infected tissue?
Surgical debridement
Enzymatic debridement utilizes a variety of products with mixed results. _______ may promote endothelial cell and keratinocyte migration for angiogenesis and epithelialization
Collagenase
What is biologic debridement?
Maggot therapy — has negative perception but does result in liquefaction of necrotic tissue while leaving healthy tissue intact
Pressure ulcer healing time is not consistently reduced
Platelet derived growth factor that promotes cell proliferation and angiogenesis; only agent approved for tx of chronic diabetic foot ulcers
Becaplermin
Black box warning associated with becaplermin
Malignancy — use of >3 tubes increases risk for malignant complications x4
T/F: use of epidermal growth factor during wound healing has significant benefit in improving epithelialization
False — does NOT significantly improve epithelialization
General principles regarding wound dressings
Wounds should be kept moist, and should not be exposed to air. Occluded wounds heal 40% faster and have less scarring. Wounds are exposed to their own fluid, a mix of metalloproteases and cytokines
[consensus is to use hydrogels for debridement stage, foam and low-adherence dressings for granulation stage, and hydrocolloid + low adherence dressings for epithelialization stage]
MOA of bacitracin and clinical indications
Topical peptide antibiotic, inhibits bacterial cell wall synthesis
Active against gram-positive organisms, most anaerobic cocci, neisseriae, tetanus bacilli, diphtheria bacilli
MOA and clinical indication of neomycin
Topical aminoglycoside antibiotic, binds to 30S ribosomal subunit to inhibit protein synthesis
Active against gram-negative organisms
MOA and clinical indication for polymixin B
Topical peptide antibiotic, binds to phosphor-lipids to alter permeability and damage bacterial cytoplasmic membrane
Effective against gram-negative organisms including P.aeruginosa, E.coli, Enterobacter, and Klebsiella
MOA of topical imidazoles
Block ergosterol synthesis, have a wide range of activity against dermatophytes and yeast
[applied 1-2x/day, typically clears superficial dermatophyte infection in 2-3 wks. Local rxns may include stinging, pruritis, erythema, and local irritation]
List 4 topical imidazoles used to treat dermatophytes and yeast
Miconazole
Clotrimazole
Efinaconazole
Ketoconazole
Prescription synthetic broad-spectrum topical antimycotic agent, disrupts macromolecular synthesis; active against dermatophytes, candida, and malassezia
Ciclopirox
Allylamine, selectively inhibits squalene epoxidase, a key enzyme for the synthesis of ergosterol; highly active against dermatophytes but less active against yeasts
Terbinafine
[can cause local irritation, avoid contact with mucous membranes]
Synthetic antifungal compound, MOA uncertain but distorts hyphae/stunts mycelial growth
Effective topically against various dermatophyte and malassezia infections, but not candida
Tolnaftate
MOA of nystatin as a topical antifungal
Binds to fungal sterols, alters membrane permeability
[limited to topical tx of cutaneous and mucosal candida infections because of its narrow spectrum and negligible absorption from the GI tract following oral administration]
MOA of amphotericin B as a topical antifungal
Binds to fungal sterols, alters membrane permeability
Limited to topical tx of cutaneous candida infection
[may cause temporary yellow staining of skin]
2 oral antifungal agents used for cutaneous infections; broad spectrum and can treat tinea versicolor
Fluconazole
Itraconazole
Oral antifungal given to treat onychomycosis
Terbinafine
_______ is given orally to treat dermatophyte infections of scalp and non-hairy skin caused by epidermophyton, microsporum, and trichophyton; MOA is unclear and is ineffective against candida and malassezia
Griseofulvin
Topical antiviral agent used for tx of recurrent orolabial herpes simplex virus infection in immunocompetent adults
Acyclovir
[available as ointment, cream, and buccal tablet]
MOA of acyclovir as topical antiviral agent
Synthetic guanine analog with inhibitory activity against HSV 1 and 2
Common causes of localized pruritis
Ringworm, nail infection, seborrheic dermatitis of the scalp, head lice, grover disease (transient acantholytic dermatosis), pompholyx, hand dermatitis, vulvovaginal candida, pubic lice, lichen sclerosis, jock itch, gravitational eczema, athlete’s foot
Trigeminal trophic syndrome, brachioradial pruritis, pruritis vulvae, pruriis ani, herpes zoster during recovery phase
Systemic causes of pruritis
Chronic renal failure, cholestatic pruritis, diabetes, hyperthyroidism, hypoparathyroidism, myxedema, hypercalcemia, iron deficiency anemia, polycythemia, lymphatic leukemia, hodgkin lymphoma, generalized neuropathic pruritis, pregnancy, post-menopasual pruritis
Nonpharmacologic interventions for pruritis
Skin moisturization
Cool environment — may consider cooling lotions (calamine, those with menthol)
Avoid skin irritants
Stress reduction
Physical interventions — may consider occlusive dressings, trim fingernails, etc
Topical therapies for pruritis may include barrier repair creams, moisturizers, and emollients — and ____ pH products may be particularly useful
Low
Medication class used as topical therapy for pruritis that is not directly anti-pruritic, but may be useful in pruritis cases due to inflammatory skin dermatoses
Topical corticosteroids
Tacrolimus ointment and Pimecrolimus cream are particularly useful in anogenital pruritis, but may cause transient burning and stinging. What is the MOA of these products?
Topical calcineurin inhibitors
Possible H1 antagonist used as topical therapy for pruritis, but should be avoided in children and there is a 20-25% risk of sedation
Doxepin cream
MOA of capsaicin
Activates transient release potential vanilloid-1 (TRPV1), an ion channel in cutaneous nerve fibers
Stimulates neurons to release and eventually deplete certain neuropeptides, including substance P
Can also induce lasting desensitization of neurons to a variety of stimuli
MOA of salicylic acid as a topical therapy for pruritis
COX inhibitor and keratolytic
Keratolytic effects caused by ability to dissolve intercellular cement
[useful in lichen simplex chronicus; avoid in acute inflammatory dermatoses and children; treated areas are photosensitive]
Topical local anesthetic found in a variety of OTC remedies along with hydrocortixone; e.g., useful for pruritis on face and that associated with CKD
Pramoxine
2 Topical local anesthetics useful in neuropathic pruritis
Lidaine patch
Eutectic mixture of lidocaine and prilocaine
Guidelines for usage of topical glucocorticoids based on potency
Use low-potency (e.g., hydrocortisone, methylpredinsolone, etc.) on face, genitals, and skin folds
Elsewhere, start with high potency (e.g., budesonide, betamethasone dipropionate, etc.) to gain control and titrate downward for maintenance
Antidepressants useful in systemic tx of pruritis
NaSSA (Alpha-2 antagonist) — Mirtazapine
SSRIs — paroxetine, fluvoxamine, sertraline
u-opioid receptor antagonist useful in systemic tx of pruritis
Naltrexone
k-opioid receptor agonist/u-opioid receptor antagonist useful in systemic tx of pruritis
Butorphanol
Anticonvulsants useful in systemic tx of pruritis
Gabapentin
Pregabalin
Substance P antagonist useful in systemic tx of pruritis
Aprepitant
4 agents used to tx ectoparasitic infections
Malathion
Permethrin
Ivermectin
Lindane
Topical agent used to tx ectoparasitic infections; MOA: organophosphate cholinesterase inhibitor
Malathion
Topical agent used to tx ectoparasitic infections; MOA: binds insect Na+ channels, blocks membrane repolarization
Permethrin
Oral agent used to tx ectoparasitic infections; MOA: binds glutamate-gated Cl- channels in invertebrates, hyperpolarizes nerve and muscle cells
Ivermectin
Topical agent used to tx ectoparasitic infections; MOA: disrupts GABAergic transmission in insects; toxic and only used when other methods have failed
Lindane
Topical retinoids are often used in the tx of acne vulgaris, what is the MOA?
Metabolized to 4-oxo-RA, 4-OH-RA, 5,8-epoxy-RA
Contributes to normalization of follicular keratinization, decreased cohesiveness of keratinocytes, and reduces follicular occlusion and microcomedone formation
3 topical retinoids used in tx of acne vulgaris
Tretinoin
Adapalene
Tazarotene
AEs of tretinoin
Local irritation, dryness, flaking, sun sensitivity
Some formulations contain fish proteins, use with caution in patients with sensitivity or allergy
AEs of adapalene
Local skin irritation, dryness and flaking, sun sensitivity
Topical antimicrobials used in tx of acne vulgaris
Benzoyl peroxide (local skin irritation, may beach hair or clothing)
Clindamycin (rare risk of pseudomembranous colitis)
Erythomycin
Dapsone
Sulfacetamide
Dicarboxylic acid that kills acne bacteria and decreases production of keratin; used to treat mild to moderate acne as well as post-inflammatory hyperpigmentation; AEs include local skin irritation
Azelaic acid
Oral abx used in tx of acne vulgaris
Tetracycline Doxycycline Minocycline Erythromycin Azithromycin TMP-SMX
AEs of tetracycline and doxycyline in tx of acne vulgaris
Photosensitivity, GI distress, contraindicated in pregnancy and young children
AEs of minocycline
Dizziness
Drug-induced lupus
Skin discoloration
Contraindicated in pregnancy and young children
AEs of erythromycin and azithromycin when used in tx of acne vulgaris
GI distress
Severe AE associated with TMP-SMX used in acne vulgaris
Stevens-johnson syndrome
TEN
Hormonal agents used in tx of acne vulgaris and their AEs
Combination OCPs — cause nausea, breast tenderness, weight gain, thromboembolic events
Spironolactone — contraindicated in pregnancy; cause menstrual irregularity, breast tenderness, minor GI symptoms, orthostatic hypotension, hyperkalemia, dizziness, headaches, fatigue
AEs of oral isotretinoin used in tx of acne
Teratogenicity (absolute contraindication in pregnancy)
Mucocutaneous effects
Hypertriglyceridemia
List topical and systemic therapies used for psoriasis
Topical: emollients, corticosteroids, topical vit D analogs (calcipotriene, calcitriol), tar, tazarotene, calcineurin inhibitors, anthralin, salt water baths, UV light therapy
Systemic therapies: methotrexate, apremilast, retinoids, systemic calcineurin inhibitors, biologics
MOA of apremilast
Inhibits PDE4 —> increased cAMP levels
Decreases nitric oxide synthase, TNF-a, and IL-23
Increases IL-10
Clinical applications of apremilast include moderate to severe plaque psoriasis and active psoriatic arthritis. What are associated AEs?
Severe diarrhea, N/V, weight loss
Headache is most common CNS complaint, but depression, suicidal ideation, and mood changes have been observed
Ustekinumab is used for plaque psoriasis, psoriatic arthritis, and Crohn disease. What is the MOA?
Human monoclonal Ab — targets proinflammatory cytokines IL-12 and IL-23
Blunts IL-12/IL-23 to decrease NK cell activation, CD4 T cell differentiation/activation, and MCP-1, TNF-a, CXCL-10, IL-8 expression
AEs of ustekinumab
Generally well tolerated but increases risk for infections
May increase risk for SCC
HSR reactions
Humanized monoclonal Ab against iL-17a utilized in tx of ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis
Ixekuzumab
MOA of secukinumab (used for ankylosing spondylitis, psoriatic arthritis, psoriasis)
Human mAb
Targets proinflammatory cytokine IL-17a
AEs of secukinumab
Generally well tolerated but increases risk for infections; may cause exacerbations of IBD
HSR reactions
General Treatment options for actinic keratosis
Liquid nitrogen cryotherapy
Surgical therapy
Pharmacotherapy
Photodynamic red light therapy
Dermabrasion
Chemical peels
Topical immune response modifier that stimulates local cytokine induction; effective therapy for AK
Imiquimod
Substance derived from sap of Euphorbia peplus plant used to tx AK; works by disrupting cell PM and mitochondria leading to necrosis, then neutrophil-mediated antibody-dependent cellular cytotoxicity eliminates remaining tumor cells
Ingenol mebutate
T/F: topical diclofenac and retinoids are useful in tx of AK
True
MOA of 5-fluorourical in tx of AK
Inhibits thymidylate synthetase, a critical enzyme in synthesis of DNA
Prevents cell proliferation and leads to cell death
After 4-6 weeks, skin will have progressed from erythema through blistering, necrosis with erosion, then re-epithelialization
3 tx options for BCC or SCC
Surgical removal/ablation
Topical meds — imiquimod, 5-FU
Advanced BCC may be treated with vismodegib or sonidegib — both oral “hedgehog” inhibitors
Treatment options for melanoma
Surgical excision
Conventional chemotherapy — dacarbazine (may be combined with carmustine+tamoxifen, or cisplatin+vinblastine)
MAP kinase pathway inhibitors (if BRAF V600D mutation) — vemurafenib
List common causes of alopecia
Male pattern baldness
Female pattern hair loss (androgenic alopecia)
Alopecia areata
Treatment of male pattern baldness may involve:
________ = vasodilates d/t K+ channel opening; promotes hair growth by increasing duration of anagen phase, shortening telogen phase, and enlarging miniturized follicles
_________ = oral inhibitor of DHT production, can cause sexual dysfunction; increases hair count
Surgery = transplant of hair follicle units
Minoxidil
Finasteride
First and second line Treatment for androgenetic alopecia in women
First-line = minoxidil
Second-line = anti-androgens: spironolactone (androgen partial agonist), finasteride (blocks DHT synth), flutamide (androgen antagonist
Alopecia areata is a chronic, relapsing immune-mediated inflammatory d/o affecting hair follicles, resulting in non-scarring hair loss
What are treatment options?
Intralesional or topical corticosteroids
Topical immunotherapy — contact allergen such as diphenylcyclopropenone (DPCP) is used to cause contact dermatitis, which causes hair growth for unknown reason
