Dermatopharmacology Flashcards
1
Q
H1 antagonists
A
1st generation: diphenhydramine, promethazine, chlorpheniramine, hydroxyzine 2nd generation: Fexofenadine, Loratidine, Cetirizine, Desloratidine
2
Q
H2 antagonists
A
ranitidine cimetidine
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
4
Q
Most abundant Retinoid receptors in skin
A
RAR-y and RXR-a
5
Q
Medication contraindicated if history of cutaneous lymphoma
A
cyclosporine risk of progression
6
Q
Random cyclosporine side effects
A
hypertrichosis, gingival hyperplasia, tremors, paresthesia, hyperuricemia (gout)
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
8
Q
Steroids with high mineralocorticoid
A
Hydrocortisone Cortisone Short-acting Less glucocorticoid effect
9
Q
Steroid Glucocorticoid> mineralocorticoid
A
Prednisone Prednisolone Methylprednisolone Triamcinolone
10
Q
Only glucocorticoid
A
Dexamethasone (long acting) Betamethasone Methylprednisolone (medium acting) Triamcinolone
11
Q
11B-hydroxysteroid dehydrogenase
A
Converts steroids to active form in liver Cortisone -> cortisol Prednisone -> prednisolone
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
13
Q
Steroid pregnancy category
A
Pregnancy category C
14
Q
Half life of isotretinoin
A
20 hours
15
Q
Half life of etretinate
A
120 days
16
Q
Half life of acitretin
A
2 days
17
Q
Triglyceride level above which you should stop an oral retinoid
A
TAG> 800
18
Q
Bexarotene should not be used with which medication? why?
A
Gemfibrozil (CYP 3A 4 inhibitor), increases levels of bexarotene
19
Q
Tretinoin receptor
A
RAR
20
Q
Alitretinoin receptor
A
RAR and RXR
21
Q
Adapalene receptor
A
RAR- B/y> a
22
Q
Tazarotene
A
RAR-By>a Pregnancy category X
23
Q
Bexarotene
A
RXR Pregnancy category X
24
Q
Bexarotene Side effects
A
Central hypothyroidism Neutropenia, Leukopenia
25
Isotretinoin receptor
None
26
Etretinate receptor
None
27
Acitretin receptor
None
28
Corticosteroids MOA
Decreased: NFKB, eicosanoids Increased: IL-10 (down regulates TH1, and other cell mediated immunity), increases apoptosis of eosinophils and lymphocytes
29
Risk factors for HPA axis suppression with corticosteroids
Divided dosing (But more effective for relief) Abrupt cessation Major Stressor
30
Types of Exogenous Adrenal Insufficiency
Steroid Withdrawal Syndrome (arthralgias, myalfias, anorexia; can have normal cortisol levels) Adrenal Crisis (+ Hypotension)
31
Apremilast
PDE Inhibitor
32
Tofacitinib
JAK 1, 3 inhibitor SE: URI, headaches, nausea
33
Ruxolitinib
JAK 1, 2 inhibitor
34
Azathioprine MOA
Purine analog, inhibits purine metabolism and cell division HGPRT metabolizes into active form (6=TG)? TMPT inactivates, Xanthine Oxidase Also
35
Azathioprine SE
SCC! GI: most common Hypersensitivity syndrome Risk of hepatosplenic T-cell lymphoma (when used with TNF-a) Pregnancy category D
36
Cyclosporine MOA
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
37
Cyclosporine dosing
2.5-5 mg/kg
38
Drug of Choice for HTN related to cyclosporine
CCB
39
Methotrexate MOA
binds dihydrofolate reductase, prevents conversion of dihydrofolate to tetrahydrofolate
(this inhibits/stops purine synthesis)
40
What does Folate help with when on MTX
GI adverse effects
less risk of LFT elevations (76%)
less risk of pancytopenia
41
Methotrexate and the liver
\> 1.5-4 g may need testing
Liver biopsy is gold standard
42
Methotrexate and pregnancy
Category X
43
Other methotrexate side effects
acute pneumonitis, pulmonary fibrosis
pancytopenia (within 4-6 weeks)
phototoxicity (radiation recall)
44
Medications to avoid with methotrexate
trimethoprim
sulfonamides
dapsone
(tetracyclines, phenytoin, phenothiazines, sulfonamides, NSAIDs, salicylates)
45
Treatment for MTX toxicity
Leucovorin (folinic acid)
46
Mycophenolate Mofetil MOA
inhibits inosine monophosphate dehydrogenase
(inhibits de novo synthesis of purines)
47
Hydroxyurea MOA
inhibits ribonucelotide diphosphate reductase (impaired DNA synthesis)
48
Hydroxyurea SE
Megaloblastic Anemia
DM-like eruption
Leg ulcers
Hyperpigmentation of skin and nails
49
Cyclophosphamide MOA
alkylating agent (aka damages DNA via crosslinking)
50
Cyclophosphamide side effects
hemorrhagic cystitis (acrolein, metabolite)
transitional cell carcinoma of the bladder
premature ovarian failure
anagen effluvium
hyperpigmentation of hair and nails
51
Chlorambucil MOA
Side Effects
alkylatine agent (damaged DNA via cross linking)
Allergy to nitrogen mustard is a contraindication
52
Antimalarial MOA
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
53
Chloroquine side effects
contraindications
psoriasis exacerbation
GI side effects
agranulocytosis
Contraindications:
myasthenia gravis
54
Ocular Side Effects
Antimalarials
keratopathy, retinopathy (not reversible)
Quinacrine does not have ocular toxicity
55
Skin Pigmentation
Antimalarials
blue/gray on shins (\> 4 months therapy)
Nail hyperpigmentation
yellow pigment-\> quinacrine
56
Dapsone MOA
inhibits myeloperoxidase
FDA approved for DH and leprosy
DH and bullous SLE respond within 24-36 hours
57
Dapsone SE
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
58
Etanercept
Fusion protein
Binds both TNF-a and TNF-B
59
Infliximab
Chimeric monoclonal IgG to TNF-a only
60
Adalimumab
Fully human monoclonal IgG TNF receptor
61
Etanercept, Infliximab, Adalimumab
Pregnancy Category
B
62
Infliximab associated anti-drug antibodies
Increase risk of infusion reactions
form before week 24
decreased efficacy of drug
MTX may help
Not seen with Etanercept!!!
63
TNF factoids and side effects
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??
64
Ustekinumab MOA
Fully human monoclonal IgG1
to p40 subunit (IL-12, IL-23)
65
Ustekinumab SE
URI
Reversible posterior leukoencephalopathy (PRES)
66
Rituximab
Chimeric monoclonal antibody to CD20
Depletion within 2-3 weeks, sustained for 6 months
Pregnancy Category C
Progressive Multifocal Leukoencephalopathy
67
IL-1 inhibitors
Canakinumab
Anakinra
Rilonacept
Gevokizumab
Monitor: Absolute neutrophil count (can decrease)
Less risk of TB reactivation
68
IL-17
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
Anti-IgE
Omalizumab
Biggest risk of anaphylaxis
70
Vismodegib MOA
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
Vizmodegib side effects
muscle spasms (#1)
alopecia
dysgeusia
72
Vemurafenib
Dabrafenib
BRAF inhibitors
MAPK pathway, which regulates cell division
Exanthematous rash or papulopustular rash on face, arms, torso
Increased risk of SCC and KA
73
Trametinib
MEK 1/2 inhibitor
Works in combo with BRAF inhibitors in melanoma
Less risk of SCC
SE: cardiomyopathy
retinal vein occlusions
74
Ipilimumab MOA
CTLA-4 inhibitor
75
Ipilimumab SE
Immune-related adverse events
Rash (most common)!
Colitis (most life-threatening)!!
76
Pembrolizumab
Nivolimumab
PD-1 inhibitors
Better survival and fewer side effects than ipilimumab for advanced melanoma
77
Imatinib
MOA?
Side Effects?
Tyrosine Kinase Inhibitor
SE:
periorbital edema
rash
**hypopigmentation/depigmentation**
78
Mechlorethamine hydrochloride
nitrogen mustard alkylating agent
ACD
anaphylaxis
SCC development
**Carmustine** is another alkylating agent
79
Bacitracin MOA
C55 prenol pyrophosphatase
Inhibits bacterial cell wall peptidoglycan sythesis
Activity: Neisseria and Gram positivies
SE: ACD
80
Polymyxin B
MOA
Activity
SE
increases cell membrane permeability (detergent)
Activity: GN
**Pregnancy B**
81
Neomycin
MOA
Activity
SE
30s ribosomal RNA
Activity: Gram positive and gram negative
SE: contact allergen (**co-reacts)** with bacitracin
Pregnancy category D
82
Mupirocin
isoleucyl tRNA transferase
Activity against MRSA
**Pregnancy category B**
83
Retapamulin
L3 protein on 50s subunit of bacterial ribosome
MRSA, Strep, anaerobes
84
Gentamicin
Activity
30s ribosomal subunit
Activity: Gram positive and gram negative
85
Silver Sulfadiazene
MOA
Activity
SE
bacterial DNA-\> decreased DNA synthesis
Activity: Gram positive, Gram negative
Cross-react with sulfonamides
hemolysis, methemoglobinemia, argyria
unmasking porphyria?
**Pregnancy category B**
86
Iodoquinol
quinolone derivative with high iodine concentration
activity: gram positive, gram negative, dermatophyte, yeast
87
Benzoyl Peroxide
MOA
Activity
SE
strong oxidizing properties
broad spectrum
bleaching, irritant
88
Metronidazole
disrupts DNA synthesis
protozoa, anaerobes
Pregnancy category B
89
Azelaic Acid
disrupts mitochondrial respiration
inhibits tyrosinase (improves hyperpigmentation)
Activity: p. acnes
90
Sodium sulfacetamide
inhibits dihydropteroate synthetase (prevents conversion of PABA to folic acid)
91
% of cephalosporine allergic patients with penicillin allergy
2%
92
What does probenicid do?
decreases renal excretion of penicillin and cephalosporins
93
Penicillin MOA
B-lactam ring inhibits formation of peptidoglycan cross-links -\> cell wall break down
94
Serum sickness like reaction- antibiotic
cefaclor
95
Cephalosporines
1st: cephalexin
2nd: cefaclor, cefuoxime, cefotetan, cefoxitin
3rd: ceftriaxone, ceftazidime, cefotaxime
4th: cefepime
5th: ceftaroline
DO NOT GIVE WITH AMINOGLYCOSIDES: nephrotoxic
96
Vancomycin
bacterial cell wall synthesis
GP/MRSA
SE:
LABD
Red man
nephrotoxic
hearing loss
97
Macrolides
MOA
Activity
SE
MOA: 50s inhibitor
Gram positive and negative
Erythromycin, Clarithromycin: 3A4 inhibitoris and QT prolongation
Azithromycin: some QT, very little 3A4
98
DNA gyrase
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
Tetracyclines
MOA
Activity
SE
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
Minocycline pigmentation
I: acne scaring (iron and melanin)
II: shins (iron and melanin)
III: sun exposed areas (melanin only)
101
Rifampin
DNA-dependent RNA polymerase
CYP inducer, decreases drug levels (OCPs, warfarin, azoles, CCB, statin, and cyclosporine)
worsening of porphyria (induces d-ALA synthetase)
102
Trim-Sulfa
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
Clindamycin
50S subunit
gram positive and anaerobes
Capnocytophaga
inducible resistance (erm gene, D-zone test)
104
Linezolid
23S of the 50S
Gram positive (staph, strep)
SE: seratonin syndrome, myelosuppression
105
Quinupristin/dalfopristin
New combo for MRSA, VRE
50s ribosomal subunit
106
Daptomycin
depolarizes bacterial cell wall
Gram positives (MRSA, VRE)
SE: myopathy, neuropathy, eosinophilic pneumonia, nephrotoxicity
107
Acyclovir MOA
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
Valacyclovir SE
TTP/HUS in HIV
109
Best antivirals for VZV pain
famciclovir and penciclovir
110
Cidofovir MOA
nucleoside phosphate analog (inhibits viral DNA synthesis)
Does not require viral thymidine kinase
111
Foscarnet
pyrophosphate binding site on viral DNA polymerase
TOC: acyclovir resistant HSV
SE: penile erosions
112
Bleomycin
MOA: single strand breaks in DNA
SE: flagellate hyperpigmentation
113
Podophyllin and podofilox
binds to tubulin-\> cell cycle arrest in metaphase
DO NOT USE in PREG
114
Cantharidin
Lyatta vesicatoria (blister beetle/spanish fly)
115
Sinecatechins
green tea (camellia sinensis)
epigallocatechin gallate
warts
116
Azoles- MOA
lanosterol 14a- demethylase
converts lanosterol to ergosterol
117
Contraindications Itraconazole
CHF
Liver disease
CYP3A4 (pimozide, quinidine, cisapride, stains, midazolam, nisolidipine)
118
Fluconazole Contraindications
CYP2C9 (do not administer with erythromycin)
Pregnancy category D
119
Efinaconazole
topical for onychomycosis
daily for 48 weeks
120
Luliconazole
New topical azole cream
121
Terbinafine MOA
inhibit squalene epoxidase
122
Terbinafine and Hair
Endothrix\> Ectothrix
123
Terbinafine Contraindications
CrCl \< 50 ml/min
Liver problems
124
Naftifine and Butenafine
Allylamines/benzylamines
Like terbinafine, but both are topical
125
Griseofulvin MOA
interferes with tubulin
More effective for M. canis than terbinafine
126
Ciclopirox
disrupts cell membrane transport
Better than terbinafine for candida
127
Selenium Sulfide
CARP, Seb Derm
128
Nystatin MOA
binds candida membrane sterols
129
Echinocandin MOA
inhibits B (1,3)-D-glycan synthase
SE: facial swelling, hypokalemia, hematuria/proteinuria
130
Ivermectin MOA
binds glutamate-gated chloride ion channels
hyperpolaization of nerves -\> death
131
Albendazole
stops tubulin polymerization
132
Thiobendazole
inhibits fumarate reductase
133
Permethrin
disables sodium transport channels
derived from Compositae (important cross reaction)
134
Malathion
Organophosphate
inhibits acetylcholinesterase
SE:
Flammable
organophosphate poisoning (drooling, diarrhea, narrow pupils)
135
Spinosad
instigates arthropod motor neurons
Rx: head lice
136
lindane
organochlorine
decreases neural transmission
scabies and lice
Seizures
aplastic anemia
leukemia
137
PUVA
8-methoxypsoralen
UVA (320-400)
psoralen intercalates into DNA
po (fasting); nausea/vomiting
phototoxic reactions
NMSC (SCC\> BCC, \>250 sessions)
cataracts
138
UVA-1
340-400
SLE
Scleroderma
139
UVB
MOA: decreases DNA synthesis
increases p53-\> cell apoptosis
Decreases langerhans cells in skin
140
Broad Band UVB
280-320
141
Excimer
308 nm
142
Extracorporeal Phototherapy
8-methoxypsoralen
UVA
Uses: CTCL, cGVHD
Contraindicated in severe cardiac disease
SE: nausea, photosensitivity
143
Photodynamic therapy
MOA: neoplastic cells accumulate more porphyrins
Pregnancy category C
144
Aminolevulinic acid
activated by blue light (410 nm)
converted to protoporphyrin IX within cells
145
Methyl aminolevulinate (MAL)
red light (635 nm)
requires occlusion
146
cause of photoallergic contact dermatitis
oxybenzone
147
UVA Blockers
Oxybenzone
Avobenzone
Meradimate
Ecamsule
148
UVB Blockers
Octinoxate
Octisalate
Octocrylene
Ensulizole
PABA
cinnamates
Pamidate O
149
Eflornithine
MOA
ornithine decarboxylase
Rx: facial hirsutism
150
Hydroquinone
competes with tyrosine as a substrate for tyrosinase
**monobenzyl ether** used for permanent depigmentation
151
Bimatoprost
MOA: prostaglandin analog
Indication: eyelash hypotrichosis
SE:
periorbital hyperpigmentation
iris hyperpigmentation
152
Pimecrolimus
Tacroliumus
MOA?
SE?
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
Amitriptyline SE
anticholinergic, orthostatic hypotension
154
IVIG
dosing
side effects
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
spironolactone
anti-androgen (blocks androgen receptor)
SE: hyperkalemia, gynecomstia, agranulocytosis
Category X in pregnancy
156
Finasteride, Dutasteride
MOA?
SE?
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
Calcipotriene
Calcitriol
RXR-a binds to DNA at Vitamin D response elements
decreases keratinocyte proliferation; decreases IL-2, IFN-y
SE: hypercalcemia
158
Danazol, Stanocolol
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
Clofazimine
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
Colchicine
binds tubulin dimers (arrests in **metaphase**)
familial mediterranean fever (TOC)
SE: cramping, diarrhea; very rare BM suppression, neuropathy, myopathy
161
Vitamin B3
Nicotinamide
MOA: inhibits PARP-1 -\> decreases NFKB-\> decreased function of leukocytes, lymphocytes, mast cells
USE: pellagra, NMSC chemopreventon (23% reduction)
SE: flushing, headaches
162
Potassium iodide
Uses?
SE?
Use: sporotrichosis, erythema nodosum, erythema induratum
SE: hypothyroidism, iododerma, acne
**exacerbation of DH**
Preg Category D
163
Thalidomide
MOA?
Use?
SE?
inhibits TNF-a, IFN-y, IL-12
Use: ENL, lupus, prurigo
SE: teratogenic (phocomelia)
peripheral neuropathy
venous thrombosis
sedation/drowziness (most common)
STEPS
164
Pentoxifylline
increased erythrocyte deformability
decreased plt aggregation
Use: Raynauds, livedoid vasculopathy, NLD, venous ulcers
SE: primarily GI, dose for renal dysfunction
165
Glycopyrrolate
Anticholinergic
SE: dry mouth, seizures, hyperthermia
Careful with: digoxin, TCA, atenolol
Other similar: Oxybutynin
166
silver sulfadiazine in neonates
kernicterus and argyria
