Dermatopharmacology Flashcards
MOA of Antihistamines?
H1 and H2 antihistamines are inverse agonists (downregulate constitutively activated state of receptor ) or antagonists at histamine receptors
Which Histamine receptor mediates itch in the skin?
H1
What antihistamines are safe in pregnancy? What pregnancy category?
Chlorpheniramine or Diphenhydramine have the longest safety record. Category B. Also safe in lactation.
First generation H1 antihistamine SE?
sedation and anticholinergic (dry mouth, constipation, dysuria, blurred vision)
Name 4 first generation H1 blockers.
hydroxyzine, diphenhydramine, chlorpheniramine, cyproheptadine (interferes with hypothalmic function–> increased appetitie and growth retardation in children)
Fexofenadine is an active metabolite of what drug that was withdrawn?
metabolite of terfenadine (which was withdrawn for QT elongation and torsades de pointes)
Loratadine dosage needs to be adjusted for
People with hepatic or renal impairment
Cetirizine (zyrtec) dosage needs to be adjusted for
People with hepatic or renal impairment
What is the most sedating of 2nd generation antihistamines?
Cetirizine (zyrtec). Metabolite of hydroxyzine
how are desloratadine and loratadine different?
Desloratadine is 5x more potent than loratadine
Doxepin side effects include
orthostatic hypotension, anticholinergic
Do not give doxepin to patients with
bipolar (induce manic episodes in patients with manic depressive disorder), severe heart disease (risk of heart block), severe depression (black box warning for suicides), seizure (decreases seizure threshold)
Retinoids have 3 interconvertable forms
Retinol, retinal, retinoic acid
Retinoids bind to two families of nuclear receptors
retinoic acid receptors (RAR) and retinoid X receptors (RXR). Each class has an alpha, beta and gamma
What are the most abundant retinoid receptors in skin?
RAR-gamma > RXR-alpha RARG» RXRA
What are the downstream effects of retinoids?
Inhibits AP1, NF-IL6
Inhibits TLR2
Antikeratinization (inhibits ornithine decarboxylase)
Down regulated K6, K16
Increases Th1 cytokines, Decreases TH2 cytokines
SE of systemic retinoids: mucocutaneous. name 5
cheilitis, photosensitivity, staph aureus colonization, pyogenic granuloma, sticky sensation
SE of systemic retinoids: systemic. Name one rare one.
pseudotumor cerebri, pancreatitis 2/2 hypertriglyceridemia, diffuse idiopathic skeletal hyperostosis (DISH), calcification of tendons/ligaments, premature epiphyseal closure
What triglyceride level should you discontinue isotretinoin? Highest risk retinoid?
TG> 800 because of risk of pancreatitis. Highest risk retinoid is bexarotene
What LFT value should you discontinue isotretinoin? Highest risk retinoid?
LFT> 3x ULN. Highest risk retinoid is acitretin.
What teratogenicity does isotretinoin have?
Spontaneous abortion in 20%. No defects at birth, but will have decreased mental function (30% have gross mental retardation, 60% have mild mental deficits)
What patients have the highest risk of DISH? (diffuse idiopathic skeletal hyperostosis (DISH)
People who have been on low dose isotreitnoin for many years. And people who have had multiple courses of isotretinoin.
What are specific features of retinoid embyropathy?
Craniofacial, CNS, CV, Thymic. Microtia (small ears), cleft palate, microophthalmia, hypertelorism, microcephaly, cardiac septal defects, tetralogy of Fallot, thymic aplasia
Bexarotene cannot be given with which lipid/cholesterol lowering agent?
- Gemfibrozil (inhibits CYP 3A4), causing high levels of bexarotene –> causes severe hypertriglyceridemia
- Simvastatin (CYP 3A4)
How do you treat Bexarotene induced high LDL and TG?
any statin except or simvastatin + a fenofibrate + omega 3
What can inactivate tretinoin?
UV light, benzoyl peroxide
Which retinoid can be used to treat kaposi sarcoma?
Alitretinoin, topical
Which retinoid binds both RXR and RAR?
Alitretinoin, topical
Which retinoid is light stable?
Adapalene
Which retinoid is preg category x?
Tazarotene, bexarotene, oral tretinoin (ATRA), isotretinoin, Acitretin,
Which retinoid binds to RXR?
Alitretinoin and Bexarotene
Which retinoid treats APML? Acute promyelocytic leukemia.
All-trans retinoic acid. (ATRA) 45 mg/m2/day PO in 2 divided doses
Which oral retinoid has the longest half life?
Etretinate (120 days), Acitretin (2 days)
Etretinate is 50x more lipophilic than acitretin, persists for very long
Which retinoid do you need contraception for 3 years after?
Acitretin. Concurrent alcohol use converts it to etretinate
What dosage of oral bexarotene do you use for CTCL?
75mg/day to 300 mg/day
Where in the GI tract are corticosteroids absorbed?
Upper jejunum
Name 2 short acting corticosteroids. What is their biologic half-life?
hydrocortisone and cortisone. Biologic half life is 12 hrs.
Name 4 intermediate acting corticosteroids. What is their biologic half-life?
prednisone, prednisolone, methylprednisolone and triamcinolone. Biologic half life is 24hrs.
Name 2 Long-acting corticosteroids. What is their biologic half-life in hrs.
bethamethasone, dexamethasone
Biologic half-life is 48hrs.
Describe the glucocorticoid and; mineralocorticoid correlation with short/intermediate/long acting
Short acting has highest mineralocorticoid activity, Long acting has no mineralocorticoid activity
Where does the glucocorticoid receptor bind to the CS?
Binds in the cytoplasm and translocates to the nucleus
What is the main carrier protein for steroid?
Cortisol binding globulin
What states increase cortisol binding globulin?
high estrogen, pregnancy, hyperthyroidism. Which decreases free CS
What states decrease cortisol binding globulin?
Hypothyroidism, liver disease, renal disease, and obesity
Where is steroid converted to its active form? What enzyme
Liver, 11B-hydroxysteroid dehydrogenase
For example, cortisone is converted to cortisol, prednisone is converted to prednisolone,
How do you adjust prednisone for liver disease?
Give prednisolone (active form of prednisone)
What is the MOA of corticosteroids?
Decrease NFkB, AP1, phospholipase A2, COX2,
Increase IL10, increased antiinflammatory proteins (vasocortin, lipocortin, vasoregulin)
Does steroids have more effect on cellular (T cells) or humoral immunity (B cells)?
Cellular immunity (T cells)
Describe the hormones released in the HPA axis
Hypothalamus releases CRH to the anterior pituitary, which releases ACTH to the adrenals, which secrete cortisol.
Exogenous adrenal insufficiency is typically seen in pts taking CS doses for how long?
4 weeks
What side effects of corticosteroids does QOD dosing not decrease the risk of?
Cataracts and Osteoporosis
What’s the difference between steroid withdrawal syndrome and adrenal addisonian crisis?
In addition to steroid withdrawal, an adrenal addisonian crisis will have hypotension and decreased serum cortisol.
steroid withdrawal syndrome symptoms include: arthralgias, myalgias, mood changes, headaches, fatigue and anorexia
What are the mineralocorticoid side effects of short-acting corticosteroids?
HTN, CHF, weight gain and hypokalemia
What are the lipid effects of corticosteroids?
hypertriglyceridemia (can cause acute pancreatitis), lipodystrophy (moon face, buffalo hump, central obesity)
What are the pediatric effects of corticosteroids?
growth impairment (as a result of decr in growth hormone and IGF-1 production)
What are the bone effects of corticosteroids? When does it take place? Who does it affect the most?
Greatest reduction in bone mass occurs in the first 6 months. Greatest absolute loss of bone mass occurs in young men (they have the highest baseline bone mass)
What are gastrointestinal effects of corticosteroids?
bowel perforation, peptic ulcer disease
What pregnancy category are steroids?
Preg Cat C
Do corticosteroids prevent post herpetic neuralgia in zoster?
No, but it does decrease the acute pain
What are intramuscular corticosteroid side effects?
cold abscesses, cystal deposition, menstrual irregularities, subcutaneous fat atrophy, increase RISK of HPA axis suppression because levels are constant t/o the day
What lab monitoring do you need for corticosteroids?
Fasting glucose levels, blood pressure, triglycerides, weight, height/weight for children, DEXA scan ( T score
MOA of apremilast? Dose adjusted for what patients?
PDE 4 inhibitor. Dose halved for pts with renal impairement
MOA of tofacitinib? FDA approved for?
JAK 1/3 inhibitor. FDA approved for severe RA.
SE of tofacitinib?
Increase LDL/HDL, TGs, CK and LFTs
MOA of ruxolitinib? FDA approved for?
JAK 1/2 inhibitor. FDA approved for intermediate/high-risk myelofibrosis.
MOA of azathioprine?
Azathiprine is metabolized by HGPRT to 6-mercaptopurine and then into 6-TG (thioguanine), which gets incorporated into DNA and blocks purine metabolism
What enzyme converts azathioprine to inactive metabolites?
Xanthine Oxidase and Thiopurine methyltransferase (TPMT)
What medications affect TPMT or XO?
XO is blocked by allopurinol and febuxostat
What is Azathioprine FDA approved for?
Organ transplantation. Severe RA
What are serious SE of azathioprine? Whats the most common SE?
SCC, Lymphoma, Infections (HPV, HSV, scabies)
Most common side effect; n/v and diarrhea
what SE do you see with azathioprine and TNF-alpha inhibitor?
increased risk of hepatosplenic T cell lymphoma
What is the MOA of cyclosporine?
Complexes with cyclophilin, inhibits calcineurin (an intracellular enzyme) which reduces the activity of NFAT-1–> decreasing IL2 production (decreasing numbers of CD4 and CD8 cells)
What is the max cyclosporine dose?
5mg/kg daily
For obese patients starting on cyclosporine, should you use real or ideal body weight?
Ideal body weight
FDA approval for cyclosporine?
FDA approved for psoriasis
What are the most notable SE of cyclosporine?
nephrotoxicity and hypertension (due to renal vasocontriction)
What do you give to treat HTN in cyclosporine?
CCBs (nifedipine or isradipine)
Does cyclosporine increase risk of NMSC?
yes. particularly when treated for >2 years
What are less notable SE of cyclosporine?
Hypertrichosis, gingival hyperplasia, hyperuricemia, hypomag, hyperKalemia
What do you do if creatinine bumps up in cyclosporine?
recheck cr.
- If >30% increase, decrease cyclosporine dose by 1mg/kg for 4 weeks.
- if >50% increase discontinue therapy
How does methotrexate work?
Blocks the making of a cofactor neccessary for purine synthesis. Binds dihydrofolate reductase with greater affinity than folic acid–> prevents converstion of DHF to THF
How do you bypass DHReductase in MTX?
Give leucovorin (folinic acid) or thymidine
How is folic acid different from folinic acid?
Folic acid is synthetic, folinic acid is naturally occuring version of Vit B9
What cumulative dosage of MTX to test for liver fibrosis?
4g
What lab test can you do to test of MTX liver fibrosis?
amino terminus of type 3 procollagen peptide assay
What is MTX FDA approved for?
Psoriasis and Sezary Syndrome
What are some serious SE of MTX ? Name a lung, hemotologic and cutaneous SE x2
acute pneumonitis, pancytopenia (occurs early <6 weeks), UV/radiation recall, cutaneous ulceration
What should MTX not be coadministered with? Which increase the risk of myelosuppression
dapsone, sulfonamides, trimethoprim
MOA of mycophenolate mofetil
inhibits IMPD (inosine monophosphate dehydrogenase), a key enzyme for de novo synthesis of purines
What is mycophenolate mofetil FDA approved for?
FDA approved for renal, cardiac and liver allograft rejection prevention
How should you take cellcept?
Without antacids and PPIs. It needs gastric acidity
What are some serious SE of cellcept? Not so serious SEs?
Serious ones: 1% risk of lymphoma and lymphoproliferative malignancies. Pseudo-Pelger-huet anomaly (nuclear hypolobulation with left shift which predicts the development of neutropenia)
How does hydroxyurea work?
impairs DNA synthesis through inhibition of ribonucelotide diphosphate reductase (RNDPR)
What is hydroxyurea FDA approved for (4) ?
sickle cell anemia, chronic myelogenous leukemia, SCC of head and neck, and metastatic melanoma
Most common side effect of hydroxyurea?
Megaloblastic anemia
What are some rarer SE of hydroxyurea? cutaneous x 3
DM-like eruption, leg ulcers, hyperpigmentation of nails and skin
How does cyclophosphamide work?
its an alkylating agent ( directly damaging DNA via cross-linking)
What is cyclophosphamide FDA approved for?
mycosis fungoides
What are some serious SE of cyclophosphamide? Name 3.
Hemorrhagic cystitits, (cased by acrolein), Transitional cell carcinoma of bladder, premature ovarian failure/infertility
How does chorambucil work?
Alkylating agent
What is chorambucil FDA approved for? What do we use it in derm for?
CLL
NXG, PG
What is the MOA of antimalarials?
- Inhibits UV-induced cutaneous reactions by binding to DNA and inhibiting superoxide production
- Decreases MHC expression by macrophage
What are antimalarials FDA approved for? What do we use it in derm for?
SLE, malaria, and RA
Use it in derm for anything with significant lymphocytic infiltrate
What are some mucocutaneous SE of antimalarials?
Blue-gray- black hyperpigmentation on shins
Yellow pigment of skin
Mobiliform drug eruption (dermatomyositis pts)
Nail hyperpigmentation
Which antimalarial has the most GI side effects?
chloroquine»_space; hydroxychloroquine
What can you not do while on plaquenil?
Smoke!
MOA of dapsone?
Inhibits MPO decreasing oxidative damage
How long does dapsone stay in your system?
> 30 days after a single dose. Because it undergoes significant enterohepatic recirculation.
Can you take dapsone while pregnant or nursing?
Preg class C. Hemolysis in nursing infants
What is dapsone FDA approved for?
DH and leprosy
What is the most serious idiosyncratic reaction of Dapsone?
Agranulocytosis which occurs at 8 weeks. and manifests as fever, pharyngitis and occasionally sepsis
What is the neuropathy side effect of dapson?
Distal motor (wasting of hand muscles)
What can you supplement w to decrease risk of dapsone methemoglobinemia?
Cimetidine and Vitamin E
name 3 TNF alpha inhibitors. what kinda protein is it?
etanercept (fusion) , adalimumab (fully human), infliximab (chimeric)
which TNF alpha inhibitor has the highest injection site reactions? When does it occur?
etanercept> adalimumab
Occurs during 2nd injection, b/c is a delayed type of hypersensitivity
What are some skin, neuromuscular, and malignant risks of TNF alpha inhibitors?
Psorasis, palmoplantar pustulosis, cutaneous vasculitis, demyelinating disease, lymphoma (hepatosplenic t cell lymphoma when given with azathioprine)
What do TNF alpha inhibitors do to ANAs?
High rates of ANA and anti-dsDNA
Can you use TNF alpha inhibitors in Hep B, Hep C, HIV?
Hep C and HIV okay.
Be careful in Hep B b/c of reactivation
Do TNF alpha inhibitor have anti-drug antibodies that reduce their efficacy?
Infliximab and adalimumab.
MOA of ustekinumab?
human IgG against p40subunit of IL12 and IL23. Stella bought a pack of 40 beers $12 for 2 for $23
Most common side effect of ustekinumab?
Upper respiratory infections
Most scary side effect of ustekinumab?
Reversible posterior leukoencephalopathy syndrome
-Present with confusion and memory difficulties
MOA of rituximab?
chimeric IgG against CD 20
rituximab contraindicated in people with…?
bronchospasm, hypotension, angioedema
rituximab serious SE?
progressive multifocal leukoencephalopathy, HBV reactivation, serious infection
Name 3 IL 17 inhibitors? how is their MOA different?
izekizumab, secukinumab- neutralize IL-17A
brodalumab- blocks the IL-17 receptor
Most common SE of IL17?
Nasopharyngitis, candidiasis, herpes, URI
What is omalizumab MOA? FDA indication?
anti-IgE antibody. FDA approved for allergic asthma and chronic idiopathic urticaria
How does vismodegib work?
targets SHH by inihibiting Smoothened receptor
How does vemurafenib and dabrafenib work?
BRAF inhibitor. BRAF is a serine/threonine signal transduction kinase
Which mutation does BRAF inhibitors target?
V600E mutation of BRAF where valine is replaced by glutamic acid at position 600
SE of BRAF inhibitors?
KP like eruption, SCC/keratoacanthoma, toxic erythema of chemotherapy (correlated with positive outcomes)
What is sorafenib FDA approved for ?
HCC, RCC, thyroid carcinoma (iodine resistant), AML
SE of sorafenib?
The usual BRAF + Hand Foot syndrome, and yellowing of skin
What is the dosing for vismodegib?
150mg daily. New studies show M-F and 1week on 3 weeks off dosing
How long do patients need to wait to get pregnant after taking vismodegib? sonidegib?
Women- 7 months (vismo) vs 21 months (sonidegib)
Men- 3 months (vismo) vs 9 motns (sonidegib)
MOA of trametinib?
Inhibit MEK1/2 of MAPK pathway
What is trametinib fda approved for?
late stage melanoma with V600E mutation of BRAF. Valine is replaced by E (glutamic acid) at position 600
What drug is trametinib combined with?
dabrafenib (BRAF) to reduce resistance
SE of trametinib?
MEK inhibitor. cardiomyopathy, retinal vein occlusion (like the BRAF inhibitors)
MOA of ipilimumab
Fully human antibody that binds/inhibits CTLA 4 (CD 152), which increases T cell activation against tumor cells
Most common SE of ipilimumab? Most serious SE?
common: rash, vitiligo
serious: life-threatening coliitis with bowel performation
MOA of pembrolizumab and nivolumab?
PD1 inhibitor. PD1 on T cells normally binds to PD1-L on the tumor cells and brakes on the immune system
Imatinib MOA?
Tyrosine Kinase inhibitor. It binds to the kinase domain of various tryosine kinases. LIkes Bcr-ABL, c-kit receptor (CD117), and platelet derived growth factor receptor
Imatinib is FDA approved for
DFSP, systemic mastocytosis, myeloproliferative hypereosinophilic, GIST, ALL, CML, syndrome,
Cutaneous SE of imatinib?
Most common: Superficial periorbital edema
2nd most common: rash
Other SE: hypopigmentation/depigmentation (inhibit c-kit)
MOA of sonidegib? SE of sonidegib?
Binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway.
SE: all SE of vismo + rhabdomyolysis
MOA of bacitracin
disrupts bacterial cell wall peptidoglycan synthesis
C55 prenol pyrophoshatase
MOA of polymyxin B
increase cell membrane permeability via detergent-like phospholipid interaction
MOA of neomycin
binds 30s subunit of bacterial ribosomal RNA
Which two topicals antibiotics co-react?
neomycin and bacitracin
MOA of mupirocin
Decreases RNA protein synthesis because it binds to bacterial isoleucyl tRNA synthase
What topical abx are Pregnancy category B?
Polymycin, mupirocin, silver sulfadiazene
What topical abx has activity against MRSA
Mupirocin, Retapamulin, silver sulfadiazene
MOA of retapamulin
binds to L3 protein on 50s subunit of bacterial ribosome
MOA of silver sulfadiazene
binds bacterial DNA, which decreases DNA synthesis, also disrupts cell walls and membranes
What are rare SE of silver sulfadiazene?
hemolysis in G6PD patients, methemoglobinemia, renal insufficiency, argyria, unmasking porphyria, leukopenia
Why is silver sulfadiazene not used in neonates <2 months?
neonates < 2 months. Sulfonamides may cause kernicterus in neonates.
MOA of benzoyl peroxide?
strong oxidizing properties. no bacterial resistance reported to date
MOA of metronidazole?
distrupts DNA synthesis
What is metronizdale active against?
protozoa and anaerobes. Not active against demodex, staph, strep or fungi or even p acnes
MOA of azelaic acid?
- inhibits tyrosinase
- dicarboxylic acid that disrupts mitochondrial respiration, decreasing DNA synthesis (esp in melanocytes) and ROS production by PMNs
MOA of sodium sulfacetamide?
Inhibits bacterial DHS (dihydropteroate synthetase). Prevents conversion of PABA–> folic acid.
MOA of penicillins?
The pencillin’s Beta-lactam ring binds to bacterial enzyme DD-transpeptidase, inhibiting formation of peptidoglycan cross-links in the bacterial cell wall causes cell wall breakdown
Ampicillin + what can give you a morbilliform eruption?
mononucleosis, allopurinol, lymphocytic leukemia.
You’ll see a generalized morbilliform itchy eruption 1 week after antibiotic initiation
What is the antibiotic of choice for human or animal bites? What if they’re penicillin allergic? sulfa allergic?
amoxicillin-clauvulanate (augmentin)
bactrim + clindamycin
ciprofloxacin + clindamycin
MOA of 5 fluorouracil?
binds to and inhibits thymidylate synthase (which converts deoxyuridine to thymidine)
MOA of imiquimod?
activator of Toll-like receptors 7 and 8, which activates NFkB and TNFalpha and IFNgamma
What are some SE of imiquimod?
flu -like or GI symptoms (especially if larger areas treated)
Psoriasis
MOA of diclofenac?
decreases cyclooxygenase enzymes which increases apoptosis
MOA of ingenol mebutate?
- Induces rapid cellular death (within hours) via mitochondrial swelling/plasma membrane disruption
- intense inflammatory response via protein kinase c activation
what are 4 medications used to treat AKs?
5FU, imiquimod, diclofenac, ingenol mebutate
What antibiotics do you give for diabetic foot ulcers?
Ticarcillin-clavulanate, ceftriaxone (covers Pseudomonas)
What are some side effects of ticarcillin and piperacillin?
Hypernatremia, Increased LFTs, bleeding times, hypernatremia
What are some side effects of amoxicillin?
Less GI side effects than ampicillin, but increased risk of cholestatic injury
How long do you treat b-hemolytic strep for?
10 days to prevent rheumatic fever
Abx for SSSS?
Nafcillin
Penicillin that causes onychomadesis/photo-onycolysis?
CLoxacillin
Penicillin that causes shore nails?
dicloxacillin. transverse leukonychia and onychomadesis following drug-induced erythroderma
What medication can prolong renal excretion?
Probenecid
What % of people who are cephalosporin allergic are also penicillin allergic?
2%
What % of people who are penicillin allergic are also cephalosporin allergic?
5-10%
What medication can cause a serum-sickness-like reaction
cefaclor
What medicaion causes a Jarisch-Herxheimer reaction in Lyme Disease pts?
Cefuroxime
SE of cefotetan?
disulfiram-like reaction, hemolytic anemia
What two antibiotics classes should not be given together?
Aminoglycosides and cephalosporins, because of increased risk of nephrotoxicity
MOA of vancomycin
inhibits bacterila cell wall synthesis
SE of vancomycin
LABD , Red man syndrome, nephrotoxicity
MOA of vancomycin induced Linear IgA bullous Disease?
IgA antibodies to LAD 285 and IgA/IgG to BP180
name the 3 macrolides?
erythromycin, azithromycin, clarithromycin
MOA of macrolides?
Bind the macro part of the protein aka the 50s subunit of bacterial ribosome
Macrolides are a CYP 3A4 inhibitor and must be monitored if the patient is also on what?
warfarin, statins, mexiletine, theophylline
what are the side effect so erythromycin?
GI symptoms is dose-limiting, QT prolongation, torsades de pointes
Why can’t you give erythromycin estolate in pregnancy?
it can cause hepatotoxicity (swelling of intrahepatic biliary canaliculi cause intrahepatic cholestasis) which shows as an elevated AST.
If mom exposed to erythromycin during pregnancy, what SE do you see in fetus?
Pyloric stenosis and cardiovascular malformation
What is azithromycin better than erythromycin at?
Azithromycin is better for GP coverage
MOA of fluoroquinolones ?
Inhibit bacterial topoisomerase 2 and 4
Topoisomerase 2 and 4 covers GN or GP? Which one is DNA gyrase?
Topo 2 (aka DNA gyrase) covers GN Topoisomerase 4 covers GP
First generation quinolones are what? target what?
Topo 2 (cipro, ofloxacin)
Third generation quinolones are? target what?
Topo 4 + 2 (levofloxacin, moxifloxacin)
What abx is the treatment of choice for cutaneous anthrax?
cipro
What are the most to least photosensitive quinolones? Is it UVA or UVB sensitivity?
UVA sensitivity.
lomefloxacin, enoxacin and sparfloxacin»_space; cirpofloxacin>norfloxacin>ofloxacin»levofloxacin
What can you not take concomitantly with ciprofloxacin.
Divalent cations (calcium, magnesium, aluminum, and zinc)
MOA of tetracyclines
Binds 30S subunit of bacterial ribosome
Inhibits matrix metalloproteinases
What is the abx of choice for lymphogranuloma vanereum?
doxycyline
Which tetracyclines are lipophilic?
Mino> doxy>tetracycline
What are some SE of minocycline?
vasculitis, pseudotumor cerebri, hyperpigmentation of skin/nails/teeth, serum sickness-like reaction, DRESS, lupus-like syndrome
What are minocycline induced lupus-like syndrome antibodies?
ANA +, antihistone AB-, dsDNA+
What are minocycline induced vasculitis antibodies?
pANCA+
Food decreases absorption in which tetracyline?
tetracycline more so than doxy or mino
How does rifampin work?
binds RNA polymerase, decreasing RNA protein synthesis
Rifampin will decrease efficacy of what drugs?
OCPs, warfarin, azoles, statins, cyclosporine, CCBs
CYP450 inducer
Describe rifampin-dependent antibodies
Anaphylaxis, flu-like symptoms, renal failure and hemolytic anemia
What are 2 cutaneous side effect of rifampin?
orange-red discoloration of body fluids, worsening of porphyria (induced d-ALA synthetase)
MOA of trimethoprim-sulfamethoxazole?
DHF reductase inhibitor + DHP synthetase inhibitor to decrease THF
What antibiotic is used to treat granuloma inguinale?
Bactrim
What pregnancy category is bactrim?
Cat C. Causes jaundice, hemolytic anemia and kernicterus of baby if taken in 3rd trimester
MOA of clindamycin? What is it effective against?
GP cocci and anaerobes. Not usually GNs. Binds 50S of bacterial ribosomal RNA
What is the D zone test?
To determine whether the organisms can be induced to be resistant to clindamycin who are already erythromycin-resistant
MOA of linezolid
Binds 23S portion of 50S ribosomal subunit
What are SE of linezolid?
Serotonin syndrome (if given with serotonergic drugs like SSRIs, MAOIs, and tricyclics)
How does acyclovir work? How does it get processed?
Gets phosphorylated by herpes thymidine kinase and then by human cellular GMP kinases to acyclovir triphosphate. Then it competes with doxyguanosinetriphosphate for incorporation into viral DNA
Acyclovir preg category?
Preg category B
Acyclovir has low rate of SEs except for what SE
IV infusions are rarely associated withrenal impairment (2/2 crystalline nephropathy)
What do you use if there is viral resistance to acyclovir?
use foscarnet or cidofovir
Valacyclovir has greater oral bioavailability compared to acyclovir. What rare SE can it have?
It can rarely cause TTP/HUS in HIV patients
Which antiviral is the best at decreasing VZV pain?
Famciclovir and valacyclovir
Which antiviral has the most bioavailability?
Famciclovir> valacyclovir> acyclovir
What’s penciclovir?
Topical for herpes labialis only.
MOA of cidofovir?
Like acyclovir, it’s a competitive inhibitor of viral DNA polymerase. But unlike cidofovir, it does not require viral thymidine kinase to be phosphorlyated
What is cidofovir used for?
HPV, HSV, CMV, Orf, Molluscum
MOA of foscarnet?
It binds to pyrophosphate-binding site on viral DNA polymerase
SE of bleomycin?
Injection pain, raynauds, loss of nail plate/ NAIL DYSTROPHY, flagellate hyperpigmentation
MOA of podophyllin? FDA approved for?
Antimitotic agent that binds tubulin causing cell cycle arrest in metaphase. FDA approved for genital warts.
Cantharidin is released from?
Spanish fly/Lytta vesicatoria
Which topical can cause ring wart formation?
cantharidin
MOA of azoles?
inhibit 14alpha demethylase, which catalyzes conversion from lanosterol to ergosterol
Itraconazole metabolized by which CYP?
CYP3A4
Itraconazole absorption is enhanced by what?
By an acidic environment
What is Itraconzole FDA approved for?
Blastomycosis, histopasmosis, aspergillosis refractory to Ampho B, oropharyngeal/esophageal candidiasis
Contraindications to Itraconazole?
CHF, active liver disease, other medications that are CYP34A
What is fluconazole FDA approved for? Off-label used for?
vaginal/oropharyngeal/esophageal candidiasis (like itraconazole), cryptococcal meningitis (unique). Off-label used for coccidioidal meningitis
What CYP is fluconazole metabolized by?
CYP2C9. Do not give with erythromycin
Why is ketoconzaole not used orally today? What drugs can you not administer with ketoconazole?
High rate of hepatic toxicity.
Cannot give with heart medication (cisapride, terfenadine or astemizole), which can increase QT syndrome
What is voriconazole used for?
Invasive aspergillosis, fusarium infections, candida infections. Itraconazole can also be given to aspergillosis
Unique SE of voriconazole?
Increased risk of SCC, Severe phototoxicity (pseudoporphyria and xeroderma pigmentosum-like changes)
CYP3A4 inihibitors acronym
MAGIC RACKS in GQ
Macrolide, amiodarone, grapefruit, isoniazid, cimetidine
Ritonavir, acute alcohol abuse, cipro, ketoconazole, sulfonamides
Gemfibrozil, quinidine
CYP3A4 inducers acronym
Barbie steals phen-phen, induces vomitting and refuses greasy glutonous carbs chronically
Barbituates, st. johns warts, phenytoin
Rifampin, griseo, glucocorticoids, carbamazepine, chronic alcohol abuse
MOA of terbinafine
Inhibits squalene epoxidase (which catalyzes the conversion of squalene to lanosterol)
What is terbinafine FDA approved for?
onychomycosis and tinea capitis
What is the treatment for onychomycosis?
250mg/day. 6 weeks for fingernail and 12 weeks for toenails (clinical cure is 60%)
Is Terbinafine better for endo or ectothrix?
endothrix like T tonsurans
SE of Terbinafine? Name 5
taste/smell disturbance, idiosyncratic hepatobiliary dysfunction/hepatitis/liver failure, depression, exacerbation of SLE, drug-induced SCLE
What CYP does terbinafine use? what do you not want to give with it?
CYP2D6. Don’t give with doexpin or amitriptyline.
What is griseofulvin FDA approved for?
onychomycosis and tinea corporis/cruris/pedis/capitis
Is Griseofulvin better for endo or ectothrix?
Griseo is better for ectothrix like microsporum
MOA of griseofulvin?
interferes with tubulin
MOA of nystatin?
Binds candida cell membrane sterols, increasing membrane permeability causing cell death
What are the echinocandins? MOA of echinocandins?
Echinocandins are caspofungin, micafungin, anidulafungin. They inhibit beta-1,3 D-glucan synthase
MOA of ivermectin
binds glutamate-gated chloride ion channels of parasite nerve/muscle cells causing increasing membrane permeability causing hyperpolarizaion and death
What is ivermectin FDA approved for?
onchocerciasis, intestinal strongyloidiasis
What is the mazzotti reaction? how can you treat it?
rash/systemic symptoms/ocular reactions that occurs in onchocerciasis pts. Can treat with doxycyline.
Can you be resistant to ivermectin?
Yes, resistance occurs due to SNPs of P-glycoprotein-like protein
MOA of albendazole?
stops tubulin polymerization. causing immobilization and death of parasite
What is albendazole FDA approved for?
Neurocysticercosis and hydatid disease
What are the SE of albendazole?
Bone marrow suppression(increased risk in liver disease patients)
MOA of thiobendazole?
inhibits fumarate reductase, important in anaerobic respiration
What is thiobendazole FDA approved for?
strongyloides, Cutaneous larva migrans, visceral larva migrans
What is MOA of permethrin?
Disables NA transport channels on cell membranes, causing paralysis
What permethrin cream do you use for scabies vs pediculosis capitis?
5% cream for scabies 1 week apart, 1% cream rinse for lice
MOA of malathion? What is it used for? in what age kids?
Organophosphate that inhibits acetylcholinesterase in arthropods. used for pediculosis capitis as a 0.5% lotion in children >6yo
SE of malathion?
Flammable, symptoms of organophosphate poisoning
