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MSK II Final > Kruse DSA: Dermatologic Pharmacology > Flashcards

Kruse DSA: Dermatologic Pharmacology Flashcards

1
Q

Which vehicles are best at stopping evaporation from the surface of the skin?

A

-pastes, creams, and ointments

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2
Q

In which area of the body is drug penetration highest?

A

-face, scalp, scrotum, in intertriginous areas, and especially in the perineum

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3
Q

why do children experience a greater systemic dose than adults?

A

-children have a greater surface area to mass ratio than adults

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4
Q

Bacitracin and gamicidin

A
  • MOA: inhibits cell wall synth (bacitracin); increases permeability of cell wall (gramcidin)
  • active against gram + organisms like strept, pneumo, and staph, and most anaerobic occi, neisseria, tetanuc bacilli, and diptheria bacilli
  • systemic toxicity limits the use of gramcidin to topical applications, usually in combo with other abx like neomycn, polymysin, bacitracin, and nystatin
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5
Q

Mupirocin (pseudomonic acid A)

A
  • MOA: inhibits ptn synth (binds to isoleucyl-tRNA synthetase)
  • effective against most gram + aerobic bacteria, including MRSA
  • effective tx for impetigo caused by S aureus and group A strep
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6
Q

Retapamulin

A
  • MOA: binds to ribosomal 50S subunit and inhibits normal bacterial ptn iosynthesis
  • effective against group A B hemolytic streptococci and S aureus including MRSA
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7
Q

Polymyxin B sulfate

A
  • MOA: increases permaility of cell wall membrane
  • effective against gram - organisms including P aeruginosa, E. coli, enterobacter, klebsiella
  • Neosporin maing ingredient
  • high levels can cause neruotoxicity and nepthrotoxicity (rare)
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8
Q

Neomycin and gentamicin

A
  • MOA: irreversibly binds 30S subunit and inhibits ptn synthesis
  • good for gram - organisms
  • excreted primarily in urine; renal failure may cause nephrotoxicity, neurotoxicity, ototoxicity if serum levels become detectable (rare)
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9
Q

Clindamycin

A
  • MOA: inhibits ptn synthesis by reversibly binding to 50S ribosomal subunit
  • approved for tx of serious infections due to S. aureus (MRSA)
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10
Q

Erythromycin

A
  • MOA: inhibits ptn synthesis by reverisbly binding to 50 S ribosomal subunit
  • complication include development of antibiotic resistance in staph; if this occurs, discontinue topic tx and begin systemic antibiotic therapy
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11
Q

Metronidazole

A
  • MOA: inhibition of nucleic acid synthesis; anti-inflammatory effects
  • effective in x of acne rosacea
  • not recommended during preggo or nursing due to carcinogenic nature
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12
Q

Sodium sufacetamide

A
  • MOA: inhibits P. acnes by competitive inhibition of p-aminobenzoic acid utilization and inhibits bacterial folic acid synthesis
  • contraindicated in pts with sensitivity to sulfonamides
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13
Q

MOA for azoles as topical antifungal preparations

A

-inhibit synth of ergosterol (an esential component of the fungal cell membrane) by inhibiting fungal cyt p 450s

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14
Q

What are Azoles used for?

A

-tinea infections

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15
Q

What are the protoypical azoled used for almost all candidiasis infections that can be treated topically?

A

-Cotimazole and miconazole

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16
Q

Ciclopirox olamine

A
  • broad spectrum antimycotic agent
  • MOA: inhibits the uptake of precursors of macromolecular synthesis
  • used to treat topical dermatomycosis, candidiasis, and tinea versicolor and mild to moderate onychomycosis of fingernails and toenails at higher topical concentrations
  • poor efficacy
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17
Q

Allylamines

A
  • Terbinafine, and naftifine
  • MOA: inhibits squalene epoxidase, a key enzyme in ergosterol biosynthesis
  • effective for topical tx of tinea corporis, tinea cruris, and tinea pedis
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18
Q

Butenafine

A

-similar to allylamines in MOA and use

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19
Q

Tolnaftate

A
  • effective in the tx of most cutaneous mycoses but is ineffective against candida
  • used for tinea pedis, cruris, and corporis
  • exact antifungal MOA unkown
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20
Q

Nystatin and amphotericin B

A

-MOA: binds to ergosterol in fungal cell membrane and alters membrane permeability, leading to the loss of potassium and other cell constituents (ineffective against dermatophytes)

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21
Q

What is nystatin used for?

A

-tx of oral candidiasis

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22
Q

What can cause yellowing of the skin if used in a cream vehicle?

A
  • Amphoterecin B
  • also causes infusion related toxicity and cumulative organ toxicity, which has given this drug the nickname “ampho-terrible”
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23
Q

Azoles as oral antifungal agents

A
  • Itraconazole and fluconazole are protoypes
  • lots of drug-drug interactions by decreasing rate of drug metabolism (statins…. rhabdomyolysis due to CYP inhibition)
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24
Q

Griseofulvin

A
  • MOA: inhibits fungal cell mitosis at metaphase and binds to human keratin, making it resistant to fungal invasion
  • treats dermatophyte infections but not candida infections
  • serious adverse effects are rare
  • induces hepatic CYPs
  • Less overall effectiveness in treating onychomycosis compared to itraconazole or terbinafine
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25
Q

Terbinafine

A
  • high first pass metabolism for oral preps; accumulates in skin, nails, and fat
  • oral preps effective for tinea corporis, capitis, and onychomycosis (better than griseofulvin)
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26
Q

What are the topical antiviral agents?

A
  • acyclovir, valacyclovir, penciclovir, famciclovir

- synthetic guanine analogs with inhibitory activity against members of the herpesvirus family

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27
Q

MOA of topical antiviral agents?

A
  • converted to pharmacologicaly active triphosphate metabolites and inhibit viral DNA synthesis and viral replication
  • oral preps available for herpes labialis
  • topical preps for recurrent orolabial HSV infaction in IC patients
  • adverse local rxns to topical preps may include pruritus and mild pain with transient stinging or burning
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28
Q

Docosanol

A
  • MOA: inhibits fusion between the plasma membrane and the HSV envelope, thereby preventing viral entry and replication
  • when applied within 12 hours of the onset of prodromal symptoms, five times daily, median healing time was shortened by 18 hours compared with placebo in recurrent orolabial herpes
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29
Q

Imiquimod

A

-tx of external genital and perianal warts in adults, actinic keratoses on the face and scalp, biopsy proven primary BCC’s on the trunk, neck, and extremities

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30
Q

MOA of Imiquimod

A

-unknown,

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31
Q

adverse effects of Imiquimod

A

-local inflammation, pruritus, erythema, superficial erosion (percutaneous absorption is minimal)

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32
Q

Tacrolimus

A
  • macrolide immunosuppressant benefical in the tx of atopic dermatitis
  • traditionally used to prevent heart, liver, and kidney allograft rejection due to potent immunosuppressive activity
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33
Q

MOA of Tacrolimus

A

-inhibit T- lymphocyte activation and prevent release of inflammatory cytokines and mediators from mast cells

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34
Q

adverse effects of tacrolimus

A

-transient erythema, burning, and pruritus

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35
Q

Pimecrolimus

A

-similar MOA and adverse effects as tacrolimus

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36
Q

Tretinoin

A

-acid form of Vit A
-unknown MOA
-metabolized by liver and excreted in bile and urine
inital therapy may aggravate acne but continual tx increases the likelihood of optimal clinical improvement

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37
Q

Common adverse effects of tretinoin

A
  • erythema, mild peeling, and dryness

- pts advised to avoid or minimize sun exposure

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38
Q

Adapalene

A
  • photochemically more stable and less irritating than tretinoin
  • used to tx mild to moderate acne vulgaris
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39
Q

Tazarotene

A

-approved for psoriasis, photoaging, acne

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40
Q

Are topical preps of retinoids good for preggo?

A
  • no

- women should receive contraceptive counseling before use because of teratogenic effects

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41
Q

The one oral drug for acne

A
  • Isotretinoin

- only for severe cystic acne

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42
Q

MOA for isotretinoin

A
  • reduces sebaceous gland size and reduces sebum production

- hepatic metabolism… highly prn bound

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43
Q

Common adverese events for isotretinoin

A
  • resemble hypervitaminosis A
  • dryness and itching of the skin and mucous membranes
  • severe side effects include headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, muscle and joint pains, suicide risk
44
Q

What must be obtained before Isotretoin tx begins?

A
  • pregnancy test 2 weeks before starting therapy

- this is a teratogen

45
Q

Benzoyl peroxide

A
  • prodrug converted to bezoic acid within the epidermis and dermis
  • MOA: releases free-radical oxygen which oxidizes bacterial ptns in the sebaceous follicles decreasing the number of anaerobic bacteria and decreasing irritating-type free fatty acids
  • antimicrobial activity against P. acnes
  • Avoid contact with eyes and mucous membranes
46
Q

Azelaic acid

A
  • MOA: antimicrobial activity against P. acnes as well as in vitro inhibitory efects on the conversion of testosterone to DHT
  • 6-8 weeks to clinical improvement
  • also used to treat hyperpigmentation
47
Q

Brimonidine

A
  • MOA: alpha-2 adrenergic agonist that when applied topically may decrease erythema through direct vasoconstriction
  • only for adults 18 years of age or older
48
Q

Acitretin

A
  • Retinoic acid derivative given orally for the tx of severe psoriasis, especialy pustular form
  • side effects: hyper vit A
49
Q

Why is alcohol bad with Acitretin?

A
  • forms etretinate, a highly teratogenic compound that may be found in plasma and sub1 fat for up to 3 years
  • this is why it is bad for preggo as well
50
Q

Tazarotene

A
  • topical retinoid prodrug used in the tx of psoriasis, acne, photoagin
  • active metabolite bind RA receptors
  • teratogenic concentrations achieved if applied to more than 20% of body surface area
  • common adverse effects: pruritus, erythema, burning/stinging, worsening of psoriasis, irritation, skin pain; avoid sun exposure
51
Q

Calcipotriene, calcitriol

A
  • synthetic vit D analog that regulates skin cell production and proliferation
  • used alone or in fixed combination with betamethasone dipropionate for the topical tx of plaque-type psoriasis
  • adverse effects include burning, itching, miild irritation, dryness, erythema
52
Q

Cyclosporine

A
  • MOA: inhibits calcineurin and thereby inhibits transcritpion of IL1 and 2 receptors; blocks T cell activation
  • side effects include significant nephrotoxicity, htn, hepatotoxicity, gingival hyperplasia, and hirsutism
53
Q

What is calcineurin?

A

-a phosphatase that enhances cytokine transcription

54
Q

Methotrexate

A
  • MOA: inhibits DHF reductase and suppresses immunocompetent cells in the skin
  • approved for tx of psoriasis, multiple cancers, RA
  • Used in combo with phototherapy or biological agents
55
Q

Alefacept

A
  • An immunosuppressive dimeric fusion ptn that consist of the extracellular CD2-binding portion of the human leukocyte function antigen 3 linked to the Fc portion of human IgG1
  • interferes with lymphocyte activation, which plays a role in the pathophysiology of psoriasis, and causes a reduction in subsets of CD2 T lymphocytes and circulating total CD3 and CD8 T- lymphocyte counts
  • discontinue if CD4 counts remain below 250
  • Do not administer to patients with a clinically significant infection or with a history of systemic malignancy
56
Q

Etanercept

A
  • dimeric fusion ptn of the EC ligand-binding portion of the human tumor necrosis factor receptor linked to the Fc portion of human IgG1
  • MOA: each molecule can bind to two molecules of TNG and prevents TNF mediated immune response
  • tx for RA, juvenile arthritis, psoriasis, and ankylosing spondylitis
57
Q

Infliximab

A
  • chimeric IgG1 monoclonal antiboyd
  • MOA: binds to soluble and transmembrane forms of TNF and inhibits TNF receptor activation
  • Tx for RA, crohn’s disease, UC, psoriasis, and AS
58
Q

Adalimumab

A
  • recombinant IgG1 monoclonal antibody
  • MOA: binds to TNF andinhibits TNF receptor activation
  • used for RA, Crohns, psoriasis, juvenile arthritis
59
Q

What adverse effect can TNF inhibitors cause?

A
  • life-threatening infections

- evaluate for TB risk factors and latnt disease prior to initaiating therapy

60
Q

Ustekinumab

A
  • human IgG1k monoclonal ab that binds with high affinity and specificity to IL12 and 23 inhibiting TH1/17 cell mediated responses
  • careful with allergies
  • infections can happen
  • do not give live vaccines will on Ustekinumab
61
Q

Where should fuorinated steroids not be used?

A

-in the face

62
Q

Adverse effects of topical corticosteroids

A
  • suppression of the pituitary-adrenal axis, Cushing’s syndrome and other systemic effects with long term use
  • atrophy, rosacea, perioral dermatitis, steroid acne, increased intraocular pressure, allergic contact dermatitis
63
Q

Tar compounds

A
  • used in the tx of psoriasis, dermatitis, lichen simplex chornicus
  • antipruritic properties
  • Avoid contact with skin if oozing or vesiculation has occurred
64
Q

common adverse effects of tar compounds

A

-folliculitis, phototoxicity, allergic contact dermatitis

65
Q

What is a keratolytic agent?

A

-a peeling agent that causes softening and dissolution or peeling of the stratum conrneum of the epidermis

66
Q

Salicylic acid

A
  • tx of acne, SD, psoriasis, hyperkeratiosis
  • can be destructive to tissues at high concentrations
  • salicylate toxicity is a thing
  • avoid concomitant use with other salicylates
  • use care in patients with diabetes orperipheral vascular disease
67
Q

Propylene glycol

A
  • vehicle for organic compunds and used in many topical preparations
  • used alone as keratolytic agent or in gel with salicylic acid
  • used as a keratolytic agent for the removal of herpkeratotic debris; also an effectiv humectant that increases the water content of the stratum corneum
68
Q

Urea

A
  • used for softening and moisturizing the stratum corneum as a compatible cream vehicle or ointment base
  • natural product of metabolism; systemic toxicities do not occur when used as a topical preparation
  • keratolytic actions due to hygroscopic characteristics
  • used for ichtyosis vulgaris, hyperkeratosis of palms and soles, xerosis
69
Q

Podophyllum resun and podofilox

A

=podophyylus is a genus of six herbaceous perennial plants native to eastern Asia and eastern north america

  • useful for the etx of condyloma acuminatum (genital warts)
  • active ingredient in podophyllum resin is podophyllotoxin
70
Q

Podofilox MOA

A

-reversibly binds tubulin and prevents microtubule formation; may interfere with keratinocytes contained in wart and local vascular structures

71
Q

Fluorouracil

A
  • fluorinated pyrimidine antimetabolite resembling uracil used in the topical tx of multiple actinic keratoses
  • MOA: inhibits thymidylate synthetase and blocks the synthesis of DNA and RNA
  • Adverse topical effects include pain, pruritus, burning, residual postinflammatory hyperpigmentation; avoid excessive exposure to sun during treatment
72
Q

NSAIDs

A
  • diclofenac shows moderat effectiveness intx of actinic keratoses
  • use with caution in pts with known aspirin hypersensitivity due to the possibility of anaphylactoid rxns
73
Q

Aminolevulinic acid (ALA)

A
  • endogenous precursor of photosensitizing porphyrin metabolites that is metabolized in the cell to protoporphyrin IX
  • approved for use on nonhyperkeratotic actinic keratoses of face or scalp
  • pts MUST avoid sun and bright indoor light exposure for at least 40 hrs after ALA application!**
74
Q

antihistamines

A
  • H1 receptor antagonists are useful in tx of pruritus

- explosive release of histmaine is typically treated with epinephrine

75
Q

first genereation H1 receptor antagonists

-

A
  • diphenhydramine and promethazine

- have some anticholinergic activity and are sedating, making them useful for the control of pruritus

76
Q

Second generation H1 receptor antagonists

A
  • lack anticholinergic side effects and are nonsedating because they do not cross the blood-brain barrier
  • cetirizine, loratidine, desloratadine, fexofenadine hydrochloride
  • metabolized by CYP3A4 and CYP2D6 and should not be coadministered with medications that inhibit these enzymes
77
Q

Tricyclic antidepressants as antipruritic agents

A
  • doxepin
  • significant drowsiness
  • contraindicated in pts with untreated narrow-angle glaucoma because of anticholinergic effects
  • urinary retention
  • allergic contact dermatitis is a common side effect
  • some TCAs have potnent H1 and H2 receptor antagonist properties
78
Q

Local anesthetics

A
  • pramoxine
  • topical anesthetic used alone or in combo with hydrocortisone acetate
  • MOA: decreases the neuronal membrane’s permeability to sodium ions by blocking voltage-gated sodium channels; both initiation and conduction of nerve impulses are blocked, thus depolarization of the neuron is inhibited
  • Avoid contact with eyes
79
Q

What is a trichogen?

A

-an agent that promotes the growth of hair

80
Q

Minoxidil (rogaine)

A
  • originally an antihypertensive
  • used for androgenic alopecial and hair transplantation, unknown MOA
  • vertex balding
  • tx must be sontinued or any drug induced hair growth will be lost
81
Q

finasteride

A
  • tx of androgenic alopecia and benign prostatic hypertrophy
  • MOA: competeitive and selective inhibitor of type 2 isoenzyme of steroid 5a-reductase: blocks the conversion of T into DHT inthe prostate gland
  • predictable adverse effects: decreased libido, ejaculation disorders, erectile dysfunction
  • tx must be continued to sustain benefit
82
Q

Bimatoprost

A
  • PG analog to tx hypothrichosis of the eyelashes

- unknown MOA

83
Q

Eflornithine

A
  • use for the reduction of unwanted facial hair
  • MOA: inhibits ornithine decarboxylase, the rate-limiting enzyme in the biosynthesis of polyamines; slows rate of hair growth
  • tx must be continued to sustain benefit
84
Q

BRAF inhibitors: vemurafenib, dabrafenib, trametinib

A

-tx of unresectable or metastatic melanoma with BRAF mutations

85
Q

Vemurafenib and dabrafenib

A
  • kinase inhibitors of BRAF V600E mutation

- Increase the risk for new primary cutaneous malignancies

86
Q

Trametinib

A
  • kinase inhibitor of BRAF V600E or V600K mutations
  • increased risk of cardiomyopathy
  • All BRAF inhibitors are associated with serious hypersensitivity rxns, including severe dermatologic rxns as well as ophthalmologic complications
87
Q

Ipilimumab

A
  • cytotoxic T lymphocyte antigen 4 (CTLA-4) blocker antibody approved for tx of unresectable or metastatic melanoma
  • may act by increasing T-cell mediated antitumor immune responses
  • can result in severe and fatal immune-mediated adverse rxns due to T cell activation and proliferation; most common adverse rxns are enterocoloitis, hepatitis, dermatitis, neuropathy, and endocrinopathy
88
Q

Pegylated interferon

A

-pegylated interferon alpha-2b is approved for adjuvant therapy of stage 3 node-positive malanoma patients

89
Q

Alitretinoin

A
  • topical formulation of 9 cis-retinoic acid approved for the tx of cutaneous lesions in pts with AIDS-related Kaposi’s sarcoma
  • localized rxns may include intense erythema, edema, and vesiculation necessitating discontinuation of therapy
  • pts who are applying alitretinoin should not concurrently use products containing deet
90
Q

Bexarotene

A
  • retinoid that selectively binds and activates retinoid X receptor subtypes
  • avaidlable both in a n oral formulation and as a topical gel for the tx of cutaneous T cell lymphoma
  • teratogenicity is a significant risk …. no women with preggo
  • may increase levels of TG’s and cholesterol; therefore, lipid levels must be monitored during tx
91
Q

Vismodegib

A
  • first hedgehog pathway inhibitor available for the oral treatment of metastatic basal cell carcinoma or locally advanced basal cell carcinoma in adults who are not candidates for surgery or radiation
  • common adverse effects include dysgeusia and ageusia, alopecia, fatigue, and muscle spasms
92
Q

Vorinostat and romidepsin

A
  • histone deacetylase inhibitor
  • approved for the tx of cutaneous T cell lymphoma in patients with progressive, persistent, or recurrent disease
  • adverse effects include pulmonary embolus, DVT, thrombocytopenia, anemia, and GI disturbances
93
Q

Antiseborrhea agents

A
  • tx for dandruff
  • betamethasone valerate
  • chloroxine
  • coal tar
  • fluocinolone
  • ketoconazole
94
Q

what is an ectoparasite?

A
  • a parasite that lives on the outside of the body of the host
  • so we have ectoparasiticides for this
95
Q

Permethrin

A
  • toxicto pediculus human, phthirus pubis, and sarcoptes scabiei
  • MOA: inhibits sodium ino flux in neurons resulting in death
  • adverse rxns include burning, stinging, pruritus
96
Q

Spinosad

A
  • approved for topical tx ofhead lice in pts 4 yrs of age and older
  • MOA: insect paralysis and death caused by CNS excitation and involuntary muscle contractions
97
Q

Ivermectin

A
  • approved for topical tx of head lice in pts 6 months of age and older
  • MOA: binds selectively and with strong affinity to glutamate-gated chloride ion channels that occur in invertebrate nerve and muscle cells; this leads to increased permeability of cell membranes to chloride ions then hyperpolarization of the nerve or muscle cell, and death of the parasite
98
Q

Lindane

A
  • causes neurotoxicity, so second line critter killer
  • MOA: induces neuronal hyperstimulation and eventual paralysis of parasites
  • concentrated in fatty tissues, including the brain; use with caution in infants, children, and pregnant women
99
Q

Crotamiton

A

-unknown MOA; scabicide with some antipruritic properties

100
Q

Malathion

A
  • organophosphate acetylcholinesterase inhibitor (hydrolyzed much faster in humans)
  • used for tx of pediculosis and scabies
101
Q

Benzyl alcohol

A
  • MOA: inhibits lice from closing their respiratory spiracles, which allows the vehicle to obstruct the spiracles and causes asphyxiation
  • may be less likely to cause resistance than traditional pesticides
102
Q

Hydroquinone, monobenzone, and mequinol

A
  • used to reduce hyperpigmentation of the skin
  • hydroquinone and mequinol result in temporary lightening; monobenzone cause irreversible depigmentation
  • MOA interference and suppression of melanin synthesis
103
Q

Trioxsalen and methoxsalen

A
  • belong to the psoralen class of agents
  • used for the repigmentation of depigmented macules of vitiligo
  • psoralens must be photoactvated by long-wavelength UV light
  • approved for tx of vitiligo, psoriasis, and cutaneous T cell Lymphoma
104
Q

MOA for trioxsalen and methoxsalen

A
  • after activation, the agent binds covalently to pyrimidine bases in DNA, inhibiting the synthesis of DNA and suppressing cell division
  • long term risks include cataracts and skin cancers
105
Q

3 classes of chemicals are most often used in sunscreens

A
  • PABA
  • Benzophenones
  • Dinzolymethanes
106
Q

What is Sun protection factor (SPF)

A
  • a measure of the ability of an intervention to prevent erythema in response to sun exposure
  • The SPF number can be multiplied by the time of exposure necessary to produce minimal erythema in an unprotected individual to obtain the expected time until minimal erythema using the SPF
107
Q

How often should you reapply sunscreen?

A

-every 2 hours

MSK II Final (13 decks)

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