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Dermatopharmacology Flashcards

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1
Q

H1 antagonists

A

1st generation: diphenhydramine, promethazine, chlorpheniramine, hydroxyzine 2nd generation: Fexofenadine, Loratidine, Cetirizine, Desloratidine

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2
Q

H2 antagonists

A

ranitidine cimetidine

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3
Q

Doxepin Side Effects Black Box Warning

A

TCA that blocks H1 and H2 Sedation, Decreased seizure threshold Not with other anti-depressants Black Box: Suicidality

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4
Q

Most abundant Retinoid receptors in skin

A

RAR-y and RXR-a

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5
Q

Medication contraindicated if history of cutaneous lymphoma

A

cyclosporine risk of progression

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6
Q

Random cyclosporine side effects

A

hypertrichosis, gingival hyperplasia, tremors, paresthesia, hyperuricemia (gout)

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7
Q

Creatinine increase on cyclosporine

A

if > 30% , decrease dose by 1 mg/kg; If > 50% then stop; can resume at a lower dose

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8
Q

Steroids with high mineralocorticoid

A

Hydrocortisone Cortisone Short-acting Less glucocorticoid effect

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9
Q

Steroid Glucocorticoid> mineralocorticoid

A

Prednisone Prednisolone Methylprednisolone Triamcinolone

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10
Q

Only glucocorticoid

A

Dexamethasone (long acting) Betamethasone Methylprednisolone (medium acting) Triamcinolone

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11
Q

11B-hydroxysteroid dehydrogenase

A

Converts steroids to active form in liver Cortisone -> cortisol Prednisone -> prednisolone

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12
Q

Every other day dosing of steroids decreases which side effects

A

Hpa axis suppression Opportunistic infections Growth suppression Does not lower risk of cataract or osteoporosis

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13
Q

Steroid pregnancy category

A

Pregnancy category C

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14
Q

Half life of isotretinoin

A

20 hours

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15
Q

Half life of etretinate

A

120 days

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16
Q

Half life of acitretin

A

2 days

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17
Q

Triglyceride level above which you should stop an oral retinoid

A

TAG> 800

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18
Q

Bexarotene should not be used with which medication? why?

A

Gemfibrozil (CYP 3A 4 inhibitor), increases levels of bexarotene

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19
Q

Tretinoin receptor

A

RAR

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20
Q

Alitretinoin receptor

A

RAR and RXR

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21
Q

Adapalene receptor

A

RAR- B/y> a

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22
Q

Tazarotene

A

RAR-By>a Pregnancy category X

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23
Q

Bexarotene

A

RXR Pregnancy category X

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24
Q

Bexarotene Side effects

A

Central hypothyroidism Neutropenia, Leukopenia

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25
Q

Isotretinoin receptor

A

None

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26
Q

Etretinate receptor

A

None

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27
Q

Acitretin receptor

A

None

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28
Q

Corticosteroids MOA

A

Decreased: NFKB, eicosanoids Increased: IL-10 (down regulates TH1, and other cell mediated immunity), increases apoptosis of eosinophils and lymphocytes

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29
Q

Risk factors for HPA axis suppression with corticosteroids

A

Divided dosing (But more effective for relief) Abrupt cessation Major Stressor

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30
Q

Types of Exogenous Adrenal Insufficiency

A

Steroid Withdrawal Syndrome (arthralgias, myalfias, anorexia; can have normal cortisol levels) Adrenal Crisis (+ Hypotension)

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31
Q

Apremilast

A

PDE Inhibitor

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32
Q

Tofacitinib

A

JAK 1, 3 inhibitor SE: URI, headaches, nausea

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33
Q

Ruxolitinib

A

JAK 1, 2 inhibitor

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34
Q

Azathioprine MOA

A

Purine analog, inhibits purine metabolism and cell division HGPRT metabolizes into active form (6=TG)? TMPT inactivates, Xanthine Oxidase Also

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35
Q

Azathioprine SE

A

SCC! GI: most common Hypersensitivity syndrome Risk of hepatosplenic T-cell lymphoma (when used with TNF-a) Pregnancy category D

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36
Q

Cyclosporine MOA

A

Binds to cyclophinin, the complex then binds to and Inhibits calcineurin. When calcineurin is inactive, NFAT does not get dephosphorylated (stays inactive), and IL-2 among other things are not transcribed

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37
Q

Cyclosporine dosing

A

2.5-5 mg/kg

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38
Q

Drug of Choice for HTN related to cyclosporine

A

CCB

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39
Q

Methotrexate MOA

A

binds dihydrofolate reductase, prevents conversion of dihydrofolate to tetrahydrofolate

(this inhibits/stops purine synthesis)

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40
Q

What does Folate help with when on MTX

A

GI adverse effects

less risk of LFT elevations (76%)

less risk of pancytopenia

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41
Q

Methotrexate and the liver

A

> 1.5-4 g may need testing

Liver biopsy is gold standard

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42
Q

Methotrexate and pregnancy

A

Category X

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43
Q

Other methotrexate side effects

A

acute pneumonitis, pulmonary fibrosis

pancytopenia (within 4-6 weeks)

phototoxicity (radiation recall)

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44
Q

Medications to avoid with methotrexate

A

trimethoprim

sulfonamides

dapsone

(tetracyclines, phenytoin, phenothiazines, sulfonamides, NSAIDs, salicylates)

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45
Q

Treatment for MTX toxicity

A

Leucovorin (folinic acid)

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46
Q

Mycophenolate Mofetil MOA

A

inhibits inosine monophosphate dehydrogenase

(inhibits de novo synthesis of purines)

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47
Q

Hydroxyurea MOA

A

inhibits ribonucelotide diphosphate reductase (impaired DNA synthesis)

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48
Q

Hydroxyurea SE

A

Megaloblastic Anemia

DM-like eruption

Leg ulcers

Hyperpigmentation of skin and nails

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49
Q

Cyclophosphamide MOA

A

alkylating agent (aka damages DNA via crosslinking)

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50
Q

Cyclophosphamide side effects

A

hemorrhagic cystitis (acrolein, metabolite)

transitional cell carcinoma of the bladder

premature ovarian failure

anagen effluvium

hyperpigmentation of hair and nails

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51
Q

Chlorambucil MOA

Side Effects

A

alkylatine agent (damaged DNA via cross linking)

Allergy to nitrogen mustard is a contraindication

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52
Q

Antimalarial MOA

A

Inhibits UV induced cutaneous reactions, suppresion of superoxide formation

decreases expression of MHC complex antigens

Reduces lysosomal size and impairs chemotaxis

Inhibits plt aggregation and adhesion

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53
Q

Chloroquine side effects

contraindications

A

psoriasis exacerbation

GI side effects

agranulocytosis

Contraindications:

myasthenia gravis

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54
Q

Ocular Side Effects

Antimalarials

A

keratopathy, retinopathy (not reversible)

Quinacrine does not have ocular toxicity

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55
Q

Skin Pigmentation

Antimalarials

A

blue/gray on shins (> 4 months therapy)

Nail hyperpigmentation

yellow pigment-> quinacrine

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56
Q

Dapsone MOA

A

inhibits myeloperoxidase

FDA approved for DH and leprosy

DH and bullous SLE respond within 24-36 hours

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57
Q

Dapsone SE

A

MOA: myeloperoxidase and inhibits bacterial synthesis of dihydrofolic acid, via competition with para-aminobenzoate for the active site of dihydropteroate synthase

hemolytic anemia

methemoglobinemia

agranulocytosis: idiosyncratic (btw 3-12 weeks)

distal motor neuropathy

Cimetidine and Vitamin E decrease risk of methemoglobinemia without decreasing efficacy

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58
Q

Etanercept

A

Fusion protein

Binds both TNF-a and TNF-B

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59
Q

Infliximab

A

Chimeric monoclonal IgG to TNF-a only

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60
Q

Adalimumab

A

Fully human monoclonal IgG TNF receptor

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61
Q

Etanercept, Infliximab, Adalimumab

Pregnancy Category

A

B

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62
Q

Infliximab associated anti-drug antibodies

A

Increase risk of infusion reactions

form before week 24

decreased efficacy of drug

MTX may help

Not seen with Etanercept!!!

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63
Q

TNF factoids and side effects

A

Injection Site Reactions Common (Etanercept> adalinumab)

CHF (Infliximab)

Demyelinating disorder (Don’t use any if FHx)

Drug induced SLE: rare, resolves after cessation

Can use in Hepatitis C infection??

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64
Q

Ustekinumab MOA

A

Fully human monoclonal IgG1

to p40 subunit (IL-12, IL-23)

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65
Q

Ustekinumab SE

A

URI

Reversible posterior leukoencephalopathy (PRES)

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66
Q

Rituximab

A

Chimeric monoclonal antibody to CD20

Depletion within 2-3 weeks, sustained for 6 months

Pregnancy Category C

Progressive Multifocal Leukoencephalopathy

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67
Q

IL-1 inhibitors

A

Canakinumab

Anakinra

Rilonacept

Gevokizumab

Monitor: Absolute neutrophil count (can decrease)

Less risk of TB reactivation

68
Q

IL-17

A

IL-17 a (Ixekizumab, secukinumab)

IL-17 R (brodalumab)

No reported risk with heart failure

No reported risk with neuromuscular disorders

SE: URI, candidiasis

69
Q

Anti-IgE

A

Omalizumab

Biggest risk of anaphylaxis

70
Q

Vismodegib MOA

A

Directly inhibits smoothened, which usually stimulates GLI1/2, and is part of the sonic the hedgehog pathway

PTCH is usually a tumor suppressor, but when mutated it does not supress smoothened, and cell proliferated

71
Q

Vizmodegib side effects

A

muscle spasms (#1)

alopecia

dysgeusia

72
Q

Vemurafenib

Dabrafenib

A

BRAF inhibitors

MAPK pathway, which regulates cell division

Exanthematous rash or papulopustular rash on face, arms, torso

Increased risk of SCC and KA

73
Q

Trametinib

A

MEK 1/2 inhibitor

Works in combo with BRAF inhibitors in melanoma

Less risk of SCC

SE: cardiomyopathy

retinal vein occlusions

74
Q

Ipilimumab MOA

A

CTLA-4 inhibitor

75
Q

Ipilimumab SE

A

Immune-related adverse events

Rash (most common)!

Colitis (most life-threatening)!!

76
Q

Pembrolizumab

Nivolimumab

A

PD-1 inhibitors

Better survival and fewer side effects than ipilimumab for advanced melanoma

77
Q

Imatinib

MOA?

Side Effects?

A

Tyrosine Kinase Inhibitor

SE:

periorbital edema

rash

hypopigmentation/depigmentation

78
Q

Mechlorethamine hydrochloride

A

nitrogen mustard alkylating agent

ACD

anaphylaxis

SCC development

Carmustine is another alkylating agent

79
Q

Bacitracin MOA

A

C55 prenol pyrophosphatase

Inhibits bacterial cell wall peptidoglycan sythesis

Activity: Neisseria and Gram positivies

SE: ACD

80
Q

Polymyxin B

MOA

Activity

SE

A

increases cell membrane permeability (detergent)

Activity: GN

Pregnancy B

81
Q

Neomycin

MOA

Activity

SE

A

30s ribosomal RNA

Activity: Gram positive and gram negative

SE: contact allergen (co-reacts) with bacitracin

Pregnancy category D

82
Q

Mupirocin

A

isoleucyl tRNA transferase

Activity against MRSA

Pregnancy category B

83
Q

Retapamulin

A

L3 protein on 50s subunit of bacterial ribosome

MRSA, Strep, anaerobes

84
Q

Gentamicin

Activity

A

30s ribosomal subunit

Activity: Gram positive and gram negative

85
Q

Silver Sulfadiazene

MOA

Activity

SE

A

bacterial DNA-> decreased DNA synthesis

Activity: Gram positive, Gram negative

Cross-react with sulfonamides

hemolysis, methemoglobinemia, argyria

unmasking porphyria?

Pregnancy category B

86
Q

Iodoquinol

A

quinolone derivative with high iodine concentration

activity: gram positive, gram negative, dermatophyte, yeast

87
Q

Benzoyl Peroxide

MOA

Activity

SE

A

strong oxidizing properties

broad spectrum

bleaching, irritant

88
Q

Metronidazole

A

disrupts DNA synthesis

protozoa, anaerobes

Pregnancy category B

89
Q

Azelaic Acid

A

disrupts mitochondrial respiration

inhibits tyrosinase (improves hyperpigmentation)

Activity: p. acnes

90
Q

Sodium sulfacetamide

A

inhibits dihydropteroate synthetase (prevents conversion of PABA to folic acid)

91
Q

% of cephalosporine allergic patients with penicillin allergy

A

2%

92
Q

What does probenicid do?

A

decreases renal excretion of penicillin and cephalosporins

93
Q

Penicillin MOA

A

B-lactam ring inhibits formation of peptidoglycan cross-links -> cell wall break down

94
Q

Serum sickness like reaction- antibiotic

A

cefaclor

95
Q

Cephalosporines

A

1st: cephalexin
2nd: cefaclor, cefuoxime, cefotetan, cefoxitin
3rd: ceftriaxone, ceftazidime, cefotaxime
4th: cefepime
5th: ceftaroline

DO NOT GIVE WITH AMINOGLYCOSIDES: nephrotoxic

96
Q

Vancomycin

A

bacterial cell wall synthesis

GP/MRSA

SE:

LABD

Red man

nephrotoxic

hearing loss

97
Q

Macrolides

MOA

Activity

SE

A

MOA: 50s inhibitor

Gram positive and negative

Erythromycin, Clarithromycin: 3A4 inhibitoris and QT prolongation

Azithromycin: some QT, very little 3A4

98
Q

DNA gyrase

A

MOA: fluoroquinolones

also topoisomerase inhibitor

cipro, ofloxacin: gram negative

levo, moxi: gram positive and gram negative

renally excreted (careful with renal failure)

photoonycholysis (lomefloxacin, enoxacin, sparfloxacin> cipro> norfloxacin> levofloxacin) UVA spectrum

CYP 1A2 inhibitors

99
Q

Tetracyclines

MOA

Activity

SE

A

30s inhibitor

also MMP inhibitors

Gram positive, gram negative

photoonycholysis (demeclocycline> doxy> tetracycline> minocycline)

All excreted renally, except doxy (GI)

serum-sickness, drug induced sweets, SLE, cutaneous PAN/vasculitis all associated with minocycline

100
Q

Minocycline pigmentation

A

I: acne scaring (iron and melanin)

II: shins (iron and melanin)

III: sun exposed areas (melanin only)

101
Q

Rifampin

A

DNA-dependent RNA polymerase

CYP inducer, decreases drug levels (OCPs, warfarin, azoles, CCB, statin, and cyclosporine)

worsening of porphyria (induces d-ALA synthetase)

102
Q

Trim-Sulfa

A

dihydrofolate reducase inhibitor (trimethroprim)

dihydropteroate synthetase inhibitor (sulfamethoxazole)

Pregnancy category C

Increases dapsone levels, increased heme tox with MTX, renal tox w/ cyclosporine, increase K with ACE/ARB

103
Q

Clindamycin

A

50S subunit

gram positive and anaerobes

Capnocytophaga

inducible resistance (erm gene, D-zone test)

104
Q

Linezolid

A

23S of the 50S

Gram positive (staph, strep)

SE: seratonin syndrome, myelosuppression

105
Q

Quinupristin/dalfopristin

A

New combo for MRSA, VRE

50s ribosomal subunit

106
Q

Daptomycin

A

depolarizes bacterial cell wall

Gram positives (MRSA, VRE)

SE: myopathy, neuropathy, eosinophilic pneumonia, nephrotoxicity

107
Q

Acyclovir MOA

A

acyclovir triphosphate (active drug) competes with deguanosine triphosphate, and chain terminates viral DNA replication

Must be converted to active form with herpes-specific thymidine kinase (valacyclovir and famciclovir are both pro-drugs, so they also must be converted)

108
Q

Valacyclovir SE

A

TTP/HUS in HIV

109
Q

Best antivirals for VZV pain

A

famciclovir and penciclovir

110
Q

Cidofovir MOA

A

nucleoside phosphate analog (inhibits viral DNA synthesis)

Does not require viral thymidine kinase

111
Q

Foscarnet

A

pyrophosphate binding site on viral DNA polymerase

TOC: acyclovir resistant HSV

SE: penile erosions

112
Q

Bleomycin

A

MOA: single strand breaks in DNA

SE: flagellate hyperpigmentation

113
Q

Podophyllin and podofilox

A

binds to tubulin-> cell cycle arrest in metaphase

DO NOT USE in PREG

114
Q

Cantharidin

A

Lyatta vesicatoria (blister beetle/spanish fly)

115
Q

Sinecatechins

A

green tea (camellia sinensis)

epigallocatechin gallate

warts

116
Q

Azoles- MOA

A

lanosterol 14a- demethylase

converts lanosterol to ergosterol

117
Q

Contraindications Itraconazole

A

CHF

Liver disease

CYP3A4 (pimozide, quinidine, cisapride, stains, midazolam, nisolidipine)

118
Q

Fluconazole Contraindications

A

CYP2C9 (do not administer with erythromycin)

Pregnancy category D

119
Q

Efinaconazole

A

topical for onychomycosis

daily for 48 weeks

120
Q

Luliconazole

A

New topical azole cream

121
Q

Terbinafine MOA

A

inhibit squalene epoxidase

122
Q

Terbinafine and Hair

A

Endothrix> Ectothrix

123
Q

Terbinafine Contraindications

A

CrCl < 50 ml/min

Liver problems

124
Q

Naftifine and Butenafine

A

Allylamines/benzylamines

Like terbinafine, but both are topical

125
Q

Griseofulvin MOA

A

interferes with tubulin

More effective for M. canis than terbinafine

126
Q

Ciclopirox

A

disrupts cell membrane transport

Better than terbinafine for candida

127
Q

Selenium Sulfide

A

CARP, Seb Derm

128
Q

Nystatin MOA

A

binds candida membrane sterols

129
Q

Echinocandin MOA

A

inhibits B (1,3)-D-glycan synthase

SE: facial swelling, hypokalemia, hematuria/proteinuria

130
Q

Ivermectin MOA

A

binds glutamate-gated chloride ion channels

hyperpolaization of nerves -> death

131
Q

Albendazole

A

stops tubulin polymerization

132
Q

Thiobendazole

A

inhibits fumarate reductase

133
Q

Permethrin

A

disables sodium transport channels

derived from Compositae (important cross reaction)

134
Q

Malathion

A

Organophosphate

inhibits acetylcholinesterase

SE:

Flammable

organophosphate poisoning (drooling, diarrhea, narrow pupils)

135
Q

Spinosad

A

instigates arthropod motor neurons

Rx: head lice

136
Q

lindane

A

organochlorine

decreases neural transmission

scabies and lice

Seizures

aplastic anemia

leukemia

137
Q

PUVA

A

8-methoxypsoralen

UVA (320-400)

psoralen intercalates into DNA

po (fasting); nausea/vomiting

phototoxic reactions

NMSC (SCC> BCC, >250 sessions)

cataracts

138
Q

UVA-1

A

340-400

SLE

Scleroderma

139
Q

UVB

A

MOA: decreases DNA synthesis

increases p53-> cell apoptosis

Decreases langerhans cells in skin

140
Q

Broad Band UVB

A

280-320

141
Q

Excimer

A

308 nm

142
Q

Extracorporeal Phototherapy

A

8-methoxypsoralen

UVA

Uses: CTCL, cGVHD

Contraindicated in severe cardiac disease

SE: nausea, photosensitivity

143
Q

Photodynamic therapy

A

MOA: neoplastic cells accumulate more porphyrins

Pregnancy category C

144
Q

Aminolevulinic acid

A

activated by blue light (410 nm)

converted to protoporphyrin IX within cells

145
Q

Methyl aminolevulinate (MAL)

A

red light (635 nm)

requires occlusion

146
Q

cause of photoallergic contact dermatitis

A

oxybenzone

147
Q

UVA Blockers

A

Oxybenzone

Avobenzone

Meradimate

Ecamsule

148
Q

UVB Blockers

A

Octinoxate

Octisalate

Octocrylene

Ensulizole

PABA

cinnamates

Pamidate O

149
Q

Eflornithine

MOA

A

ornithine decarboxylase

Rx: facial hirsutism

150
Q

Hydroquinone

A

competes with tyrosine as a substrate for tyrosinase

monobenzyl ether used for permanent depigmentation

151
Q

Bimatoprost

A

MOA: prostaglandin analog

Indication: eyelash hypotrichosis

SE:

periorbital hyperpigmentation

iris hyperpigmentation

152
Q

Pimecrolimus

Tacroliumus

MOA?

SE?

A

bind to FK506 binding protein

binds to calcineurin-> prevents dephosphorylation of NFAT-1, this preventing transcription of IL-2 and T-cell activation

Black box for malignancy

High levels of absorption in Netherton syndrome

153
Q

Amitriptyline SE

A

anticholinergic, orthostatic hypotension

154
Q

IVIG

dosing

side effects

A

3g/kg divided into 3 doses

fluid overload

aseptiv meningitis

hyperviscosity syndrome

anaphylaxis if low IgA

patients with increase RF or cryoglobulins have increase risk of renal failure

155
Q

spironolactone

A

anti-androgen (blocks androgen receptor)

SE: hyperkalemia, gynecomstia, agranulocytosis

Category X in pregnancy

156
Q

Finasteride, Dutasteride

MOA?

SE?

A

MOA: 5-a reductase inhibitor

finasteride (type II)

dutasteride (type I and II)

Use: AGA, hirsutism, HS

Increased risk of high grade prostate cancer, teratogenic

157
Q

Calcipotriene

Calcitriol

A

RXR-a binds to DNA at Vitamin D response elements

decreases keratinocyte proliferation; decreases IL-2, IFN-y

SE: hypercalcemia

158
Q

Danazol, Stanocolol

A

MOA: androgen similar to testosterone; inhibits of the first component of complement (C1 INH)

Use: hereditary angioedema

cryofibrinogenemia

lipodermatosclerosis

SE: hirsuitism, muscle problems, HTN, CHF, hyperlipidemia

159
Q

Clofazimine

A

dye, crystalizes in tissues

mycobacterial DNA leading to disruption of the cell cycle and eventually kills the bacterium

SE: orange/brown skin and body fluid (reversible)

crystal deposition in organs (spelnic infarction, eosinophilic enteritis, cardiac dysrhythmia)

160
Q

Colchicine

A

binds tubulin dimers (arrests in metaphase)

familial mediterranean fever (TOC)

SE: cramping, diarrhea; very rare BM suppression, neuropathy, myopathy

161
Q

Vitamin B3

A

Nicotinamide

MOA: inhibits PARP-1 -> decreases NFKB-> decreased function of leukocytes, lymphocytes, mast cells

USE: pellagra, NMSC chemopreventon (23% reduction)

SE: flushing, headaches

162
Q

Potassium iodide

Uses?

SE?

A

Use: sporotrichosis, erythema nodosum, erythema induratum

SE: hypothyroidism, iododerma, acne

exacerbation of DH

Preg Category D

163
Q

Thalidomide

MOA?

Use?

SE?

A

inhibits TNF-a, IFN-y, IL-12

Use: ENL, lupus, prurigo

SE: teratogenic (phocomelia)

peripheral neuropathy

venous thrombosis

sedation/drowziness (most common)

STEPS

164
Q

Pentoxifylline

A

increased erythrocyte deformability

decreased plt aggregation

Use: Raynauds, livedoid vasculopathy, NLD, venous ulcers

SE: primarily GI, dose for renal dysfunction

165
Q

Glycopyrrolate

A

Anticholinergic

SE: dry mouth, seizures, hyperthermia

Careful with: digoxin, TCA, atenolol

Other similar: Oxybutynin

166
Q

silver sulfadiazine in neonates

A

kernicterus and argyria

Dermatology Boards (7 decks)

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