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380 Cards in this Set
- Front
- Back
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What is the structure of sulfonamides?
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weakly acidic and resembles PABA
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Penetration of sulfonamides?
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good penetration into many tissues including CSF
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What is one of the most common toxicities of sulfas?
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mild hepatitis
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Are bacteriostatic or cidal drugs bad in immunocomp.?
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static
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What is the MOA for sulfas?
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bacteriostatic inhibition of folic acid synthesis via action on dihydropteroate
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What is sulfa a competitive blocker of?
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PABA
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What is the MOA for trimethoprim?
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blocks 2nd enzyme (dihydrofolate reductase) in folic acid pathway
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Which two drugs are often combined in order to block the complete folic acid pathway? What is the name of this drug?
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sulfa and trimethoprim; Cotrimoxazole
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What are the 3 MOR for sulfas?
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1)decreased intracellular accumulation of the drug
2)increased production of PABA 3)decreased sensitivity of dihydropteroate synthetase to sulfa |
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What G- organisms can be tx by sulfa?
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Neisseria meningitidis, E.coli
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What G+ organisms can be tx with sulfa?
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GABHS, Strep pneumonia, some MSSA and MRSA
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What is the DOC for chlamydia?
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sulfa
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What is the DOC for nocardia?
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sulfa
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What is the DOC for toxoplasma?
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sulfa
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What is the DOC for pneumocystis?
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sulfa
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What is the DOC for UTIs?
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sulfa, because most E.coli still sensitive to it
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What are the clinical uses for sulfas?
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uncomplicated UTIs, otitis media, topical-burn prophylaxis, ulcerative colitis, PCP prophylaxis and tx, shigella, salmonella, cholera
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Is resistance to sulfa a problem?
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yes, it can develop rapidly and is wide-spread
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What is the most problematic toxicity in pts on sulfas?
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stevens johnson syndrome
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Why are sulfas contraindicated in late pregnancy?
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can cause neonatal hyperbilirubinemia
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What are the 7 quinolones? What is the common ending?
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1)norfloxacin
2)ciprofloxacin 3)ofloxacin 4)levofloxacin 5)gatifloxacin 6)moxifloxacin 7)trovafloxacin *floxacin |
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The oral absorption of quinolones is hindered by?
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antacids
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Do quinolones penetrate well into most tissues?
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yes, including CNS, biliary tract, and prostate
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What is the MOA for quinolones?
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bacteriocidal inhibition of DNA gyrase topoisomerase II and IV
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Do quinolones exhibit post-antibiotic effect?
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yes
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What are the 3 MOR for quinolones?
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1)alteration of DNA gyrase
2)increased efflux (porins that send antibiotics out of cell) 3)alteration of bacterial permeability to the drug |
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Are quinolones useful against staph?
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no because of resistance
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Are quinolones considered broad or narrow spectrum drugs?
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broad
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What are some G- organsims that can be tx with quinolones?
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pseudomonas, H.influenza, salmonella, shigella, E.coli, and campylobactor
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What are some G+ organisms that can be tx with quinolones?
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PCN resistant strep pneumonia
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Are the quinolones good against anaerobes?
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no
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What are the clinical uses of quinolones?
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UTIs
gonorrhea enteric infections prostate infections non-staph osteomyelitis soft tissue infections resp. infections including those caused by atypical agents |
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Why are quinolones not used in pts under 18 yrs of age?
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concern of articular cartilage injury
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Can quinolones be used during pregnancy?
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no
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What is the serious toxicity of older quinolones?
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neurotoxicity --> seizures
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What drugs can cause Achilles tendon rupture in adults?
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quinolones
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What drugs can cause increased QT interval?
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quinolones
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What are some toxicities of the quinolones?
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headaches, skin rash, eosinophilia, elevated hepatic enzymes, candida overgrowth
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*What is the DOC for Listeria?
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ampicillin
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What is the drug for rheumatic fever prophylaxis?
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Benzathine-penicillin G
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Beta lactams are what type of antibiotics?
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cell wall active
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What are the 3 main organisms that cause pediatric meningitis?
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1)H.influenza
2)pneumococcus 3)meningiococcus |
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What blocks the excretion of the penicillins?
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probenecid
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Do penicillins cross well into the CNS, prostate, and eye?
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no, only minimally
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Are beta lactams bacteriostatic or cidal?
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bacteriocidal
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Cidal antibiotics work best on what type of organisms?
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actively proliferating organisms
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What is the MOA for penicillins?
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bind to specific receptors (penicillin binding proteins) located in the bacterial cytoplasmic membrane which inhibits transpeptidase enzymes that act to cross-link linear peptidoglycan chains; also have activation of autolytic enzymes that cause lesions in the bacterial cell wall
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What are the 3 MOR for penicillins?
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1)formation of beta lactamases that destry the antimicrobial agent
2)mutation of penicillin binding protein targets 3)alter porins to decrease penetrations of antimicrobial agents |
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What are the 2 narrow-spectrum penicillins?
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penicillin V and G
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What is the spectrum of activity for Penicillin V and G?
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GAS, strep pneumonia, some G+ anaerobes, treponema pallidum (syphilis)
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What are the 5 penicillinase-resistant penicillins?
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methicillin
nafcillin oxacillin cloxacillin dicloxacillin |
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What are the 2 extended-range penicillins?
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ampicillin and amoxicillin
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What is the spectrum of activity for ampicillin and amoxicillin?
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E.coli, Proteus, Salmonella, Shigella, H.influenza, H.pylori, Enterococci, Listeria, Moraxella catarrhalis (URT infections)
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What is the spectrum of activity for ticarcillin and piperacillin?
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G- microbes especially pseudomonas
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What are some clinical signs seen in pts w/ Scarlett fever?
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circumoral pallor, Pastia's lines, strawberry tongue
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What are some clincal uses for ampicillin and amoxicillin?
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otitis media, sinusitis, pneumonia, UTIs
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What are some clincal uses for piperacillin and ticarcillin?
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pseudomonas infections and mixed intra-abdominal infections
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What 2 drugs make-up augmentin?
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amoxicillin and clavulanic acid
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What is the most common toxicity seen with penicillins?
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urticaria
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What toxicities can be seen with high dose penicillin?
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seizures and personality changes
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What are the 3 first generation cephalosporins?
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cefazolin, cephalexin, cefadroxil
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What are the 6 second generation cephalosporins?
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cefuroxime
cefoxitin cefotetan cefuroxime axetil cefaclor cefprozil |
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What are the 5 third generation cephalosporins?
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cefotaxime
ceftriaxone ceftazidime cefdinir cefpodoxime |
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What is the 1 fourth generation cephalosporin?
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cefepime
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What is the most effective cephalosporin against pseudomonas?
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ceftazidime
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What 2 cephalosporins can be used for anaerobes?
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cefoxitin
cefotetan |
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What cephalosporin has recently caused increased mortality when used in hospitals?
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cefepime
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What cephalosporin is very useful for treating pediatric meningitis?
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ceftriaxone
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What three things are not sensitive to any cephalosporins?
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MRSA, Enterococcus, Listeria
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What 2 cephalosporins can be used to treat liver infections?
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cefoperazone and ceftriaxone
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What generation cephalosporins reach adequate CNS levels?
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third
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What generation cephalosporins have the best G+ coverage?
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first
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*What two cephalosporins have good anaerobe coverage?
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Cefoxitin and cefotetan
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What are the clincal uses for first generation cephalosporins?
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surgical prophylaxis and G+ soft tissue infections
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What are the clinical uses for second generation cephalosporins?
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intra-abdominal infections and gynecological infections
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What cephalosporin is good for pseudomonas tx?
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ceftazidime
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What 2 cephalosporins are good for tx serious pediatric infections especially meningitis?
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ceftriaxone and cefotaxime
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What is the main toxicity seen with cephalosporins?
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allergic/HS
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What toxicity can be seen with cefamandole or cefoperazone?
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disulfiram-like reaction - ingestion with alcohol produces headache, N/V, and abd pain
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What cephalosporin can cause biliary obstruction?
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ceftriaxone
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The combination of beta lactam antibiotics with beta lactamase inhibitors broadens the spectrum against?
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S.aureus, H.influenza, Bacteroides, Moraxella catarrhalis, G- enteric bacteria
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What are 4 other beta lactam antibiotics?
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aztreonam, imipenem, meropenem, ertapenem
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Which one of the 4 other beta lactam antibiotics has good CNS penetration?
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meropenem
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What is the spectrum for aztreonam?
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G- organisms including pseudomonas but NOT anaerobes
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What is the spectrum for carbapenems?
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very broad spectrum; often DOC for resistant organisms but NOT Listeria, MRSA, and Enterococci
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What are the toxicities seen with imipenem?
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rare neurological rxs (seizures) especially in high doses and/or renal failure
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What toxicities are seen with the 4 other beta lactams?
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GI, allergic, renal, hepatic, hematologic, drug fever, overgrowth
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What is the MOA for vancomycin?
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blocks cell wall synthesis - irreversibly inhibits biosynthesis of peptidoglycan polymers in cell wall of dividing G+ organisms
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Is vancomycin a beta lactam?
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no; it's a cell wall active antibiotic
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Will vancomycin work for Staph pneumonia?
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NO
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What is vancomycin used to tx?
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Staph aureus and Enterococci that make beta lactamases
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Where does vancomycin have inadequate penetration?
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CNS, prostate, and eye
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What is the MOR to vancomycin?
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mutation of antibiotic binding site
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What is the first DOC for C.difficile? The second?
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metranidazole; vancomycin
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What is vancomycin the DOC for?
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serious infections with resistant G+ organisms for example MRSA, PCN resistant pneumococci
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What are the 3 toxicities seen with vancomycin?
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renal, auditory (dose-related), "red-man" syndrome (not allergic rx, but due to histamine release
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Is daptomycin cidal or static?
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cidal
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What is the MOA for daptomycin?
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cell wall active - disrupts many aspects of bacterial plasma membrane fx including peptidoglycan synthesis, lipoteichoic acid synthesis, and bacterial membrane potential
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What is the MOR for daptomycin?
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none
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What is the spectrum for daptomycin?
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G+ organisms including MRSA, VRE, and those that are linazolide resistant
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What are the clincal uses for daptomycin?
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All of the following with resistant G+ infections: skin and soft tissue infections, sepsis, endocarditis
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Does daptomycin have a post-antibiotic effect?
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yes
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What is the main toxicity seen with daptomycin? How can you decrease the incidence of this toxicity?
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transient muscle weakness; once daily dosing
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What are the 9 ribosomal antibiotics?
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1)aminoglycosides
2)tetracyclines 3)tigecycline 4)chloramphenicol 5)macrolides/ketolides 6)spectinomycin 7)lincosamides 8)synercid 9)linezolid |
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Are aminoglycosides cidal or static?
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cidal
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What are some important pharmacologic aspects of aminoglycosides?
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demonstrate concentration dependent killing, demonstrate post-antibiotic effect, NOT absorbed orally, poor penetration into CNS, sputum, bile, and prostate
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Why are aminoclycosides still used?
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because of synergy and the fact that many bacteria are still sensitive to them
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What is the severe toxicity of neomycin?
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renal toxicity
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What pH causes aminoglycosides to not work well?
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acidic
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What is the MOA for aminoglycosides?
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binds to 30S subunit of bacterial ribosome preventing protein synthesis
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What are the 3 MOR for aminoglycosides?
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1)plasmid mediated formation of inactivating enzymes
2)inhibition of drug penetration into bacterial organisms 3)decreased affinity of the 30S subunit target for antimicrobial action |
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What are the 3 top causative agents for infections in neonates?
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Group B Strep, E.coli, Listeria
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Do aminogycosides have G- coverage?
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no
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The combination of what two drugs is commonly used in neonates?
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ampicillin plus an aminoglycoside
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Aminoglycosides mainly cover what organims?
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G- organisms
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What is the spectrum for aminoglycosides?
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E.coli, Proteus, Klebsiella, Enterobacter, Serratia, Pseudomonas
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Aminoglycosides are synergistic with what other drugs?
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cell wall active drugs
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What are second line drugs against mycobacterial infections?
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aminoglycosides
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Can aminoglycosides be used in pregnancy?
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NO
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*What are the 2 major toxicities seen with aminoglycosides?
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ototoxicity (dose-related) and neuromuscular blockage especially with gentamycin
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What are the 4 tetracycline drugs?
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tetracycline
oxytetracycline doxytetracycline minocycline |
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What impairs the absorption of tetracyclines?
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food
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*What is one major pharmacologic property seen with tetracyclines?
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enterohepatic cycling - maintains concentration of drug in blood and can increase risk of toxicity
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*Tetracyclines and _____ are antagonistic when used in combination.
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beta lactam antibiotics
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Are tetracyclines cidal or static?
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static
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What is the MOA of tetracyclines?
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binds reversibly to the 30S subunit of bacterial ribosome and inhibits attachment of aminoacyl-tRNA
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What are the 2 MOR against tetracyclines?
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1)plasmid mediated facilitated efflux of drug
2)decreased entry into the bacterial organism |
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What is the main spectrum for tetracyclines?
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atypical agents - Mycoplasma, Chlamydia, Chancroid, Rickettsia, Borrelia, Treponema, Entamoeba
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What is the DOC for Rocky Mtn Spotted Fever?
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tetracyclines
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What is the DOC for acne?
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tetracyclines
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What is the DOC for Lyme disease?
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tetracyclines
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Why are tetracyclines not used in children?
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due to tooth enamel dysplasia
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What drugs can cause black staining and weakness of teeth?
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tetracyclines
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What are two major toxicities seen with tetracyclines?
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GI and photosensitivity (sunburn-like rash)
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What is the mechanism of action for tigecycline?
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high affinity binding to the 30S subunit of the ribosome which blocks amino-acyl tRNA binding
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Is tigecycline static or cidal?
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static
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How is tigecycline given?
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IV
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Does tigecycline exhibit post-antibiotic effect?
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yes
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What is the spectrum for tigecycline?
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MRSA, MRSE, VRE, and other enterococci (G+ resistant organisms)
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Is tigecycline effective against pseudomonas?
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NO
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What drug is tigecycline synergistic with?
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rifampin
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What are the clincal uses for tigecycline?
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skin and skin structure infections, and intra-abdominal infections
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Can be tigecycline be used in children?
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no
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What are some toxicities seen with tigecycline?
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possible tooth discoloration, N/V, headache, transaminase elevation, cross HS with other tetracyclines
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What drug has cross HS to other tetracyclines?
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tigecycline
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What is chloramphenicol the unique antimicrobial in its class?
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bacteriostatic
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Does chloramphenicol have good oral absorption?
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excellent because it is very lipophilic
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*What hepatic metabolism does chloramphenicol undergo?
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metabolism by glucuronyltransferase
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Does chloramphenicol have enterohepatic cycling? Does it inhibit cytochrome p450?
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yes; yes
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What is the MOA for chloramphenicol?
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binds 50S subunit of bacterial ribosome inhibiting peptidyl transferase
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What are the 2 MOR for chloramphenicol?
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1)plasmid mediated production of antibiotic inactivating enzymes
2)reduced permeability of bacterial organism to drug |
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What 2 organisms can chloramphenicol not be used for?
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Staph and Pseudomonas
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What is the spectrum for chloramphenicol?
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fairly broad; H.influenza, Neisseria meningitidis, Salmonella, Anaerobes, Rickettsia
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Why is chloramphenicol not used much in the US?
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due to its toxicity
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What 4 scenarios allow the use of chloramphenicol?
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1)pts with broad-based allergy to beta lactams
2)brain abscess 3)typhoid fever 4)Rocky Mtn. Spotted Fever |
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*What are the 2 major toxicities seen with chloramphenicol?
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1)aplastic anemia
2)Gray baby syndrome - inability to conjugate drug because decreased levels of glucuronyl transferase in babies |
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What are the 3 macroglides?
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erythromycin, clarithromycin, and azithromycin
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*What are 2 important things about the pharmacology of the macroglides?
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1)concentrate in resp secretions
2)azithromycin is concentrated in phagocytic cells and other tissues |
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What is the MOA for macroglides?
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binds the 50S subunit of the bacterial ribosome and prevents ribosomal translocation down mRNA
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Are macroglides generally static or cidal?
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static
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What are the 3 MOR for macroglides?
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1)plasmid mediated alteration of receptor on ribosome
2)production of inactivating enzymes 3)decrease in the permeability of bacterial organism into the antimicrobial agent |
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*What group of organisms are good at producing inactivating enzymes against the macroglides?
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Enterobacteriacae
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What 3 things are macroglides the DOC for?
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1)Legionnaires's disease
2)Chlamydia 3)Bordetella pertussis (whooping cough) |
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All macroglides are contraindicated in pregnancy except for?
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azithromycin
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*What macroglide is used for atypical TB?
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clarithromycin
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What are the toxicities seen with macroglides?
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GI, cholestatic hepatitis, multiple drug interactions secondary to inhibition of hepatic cytochrome enzymes (not azithromycin)
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What is clindamycin?
|
a lincosaminde antibiotic, similar to macroglides
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What is the spectrum for clindamycin?
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excellent for G+ infections including Staph and invasive Strep, anaerobes
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What is clindamycin the DOC for?
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anaerobes
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What is clindamycin not good for tx?
|
G- and enterococci
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What toxicity has a higher incidence in pts on clindamycin?
|
pseudomembraneous colitis secondary to C.difficle overgrowth
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What is synercid? Cidal or static?
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streptogramin combo antibiotic; cidal
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What is the MOA for synercid?
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binds to 50S subunit on ribosome and prevents ribosome from translocating down mRNA which prevents protein synthesis at the elongation step
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What are the 3 MOR for synercid?
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1)production of inactivating enzymes
2)alteration of PBPs 3)decreased penetration |
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What is the spectrum for synercid?
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S.aureus and epidermis, and Strep pyogenes and aglacia
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Do you see toxicity with synercid?
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common; drug interactions, phlebitis, jaundice, arthralgia, and myalgia
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*What is linezolid the DOC for?
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Staph pneumonia and resistant G+ organisms (staph, strep, enterococci)
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*What is a unique pharmacologic feature of linezolid?
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oral bioavailability is 100%
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Is linezolid static or cidal?
|
generally static
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What is the MOA for linezolid?
|
binds to 50S subunit and inhibits initiation complex and translocation of tRNA
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What is the MOR to linezolid?
|
target site mutation
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What toxicities are seen with linezolid?
|
thrombocytopenia and neutropenia, weak MAO inhibitor
|
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What are some unique features of mycobacteria?
|
1)distinct cell wall composition (acid fast)
2)intracellular (live in macros which makes tx hard) 3)can develop spontaneous resistance 4)chronic nature of infection |
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Is isoniazid cidal or static?
|
cidal
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What is the MOA of isoniazid?
|
inhibits mycolic acid synthesis for mycobacterial cell wall
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What are the 2 MOR against isoniazid?
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1)deletion of bioactivation enzyme
2)target alteration |
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What is the first drug used for TB tx?
|
isoniazid (INH)
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*How is isoniazid metabolized?
|
by acylation in the liver and excreted by the kidney; acylation rate is genetically determined
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What would you tx PPD converters with for 6-9 mos?
|
isoniazid
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What are some adverse effects seen with isoniazid?
|
liver toxicity, neuropathy, hemolysis in G6PD deficient individuals, formation of ANA leading to SLE, vitamin B6 deficiency
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*What drug causes hemolysis in G6PD deficient individual?
|
isoniazid
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What are the 3 rifampins? Cidal or static?
|
rifampin, rifabutin, rifapentine; cidal
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What is the MOA for rifampin?
|
inhibits bacterial RNA pol
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What is the MOR to rifampin?
|
alteration of target - DNA dependent RNA pol
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What is the spectrum for rifampin?
|
Mycobacteria, Staph, Enterobacteraciae, and Pseudomonas
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For N. meningides and H. flu what is the DOC for prophylaxis?
|
rifampin
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Is rifampin used alone for TB?
|
no, used in combo with other drugs for active TB
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What drug causes discoloration of urine and tears?
|
rifampin
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What is the main toxicity with rifampin?
|
liver
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What are some adverse effects seen with rifampin?
|
GI, fever, skin, liver, influences metabolism of other drugs, kidney, pancytopenia
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What drug is good for chronic TB treatment?
|
pyrazinamide because it concentrates inside cells
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What is the MOA for pyrazinamide? Cidal or static?
|
converted to pyrazinoic acid by bacterial enzyme; cidal
|
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*What are the 2 problematic adverse effects of pyrazinaminde?
|
hyperuricemia and gout
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What kind of drug is streptomycin? Cidal or static?
|
aminoglycoside; cidal
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What is the MOA for streptomycin? How is it administered?
|
inhibits bacterial protein synthesis; IM injection
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Do you want to give streptomycin alone or in combo with other TB drugs?
|
in combo because it only achieves low intracellular concentrations and you want to increase the intracellular conc
|
|
|
*What are the 2 main adverse effects seen with streptomycin?
|
ototoxicity and renal toxicity
|
|
|
Can streptomycin be used for chronic tx?
|
no, because of the severe toxicities
|
|
|
What is the only first line TB drug that is static?
|
ethambutol
|
|
|
What is the MOA for ethambutol?
|
inhibits cell wall synthesis by inhibiting the formation of mycoly-arabinogalactan peptidoglycan complex via inhibiting the enzyme which causes increased permeability of the cell wall
|
|
|
*What is the main toxicity seen with ethambutol?
|
retrobulbar neuritis - can cause blindness
|
|
|
What is the MOA for para-aminosalicyclic acid? Cidal or static?
|
competes with PABA for mycobacterial dihydropteroate synthetase; static
|
|
|
Why is para-aminosalicyclic acid not a first line TB drug?
|
due to its toxicities
|
|
|
What are the 2 unique toxicities seen with para-aminosalicyclic acid?
|
goiter and hypothyroidism
|
|
|
What is the MOA for ethionamide? Cidal or static?
|
inhibits mycolic acid synthesis for mycobacterial cell wall; cidal
|
|
|
What are some adverse effects seen with ethionamide?
|
nausea, diarrhea, abd pain, hepatotoxicity, allergic rx
|
|
|
What is the MOA for clofazimine?
|
inhibits bacterial DNA synthesis
|
|
|
What are some adverse effects of clofazimine?
|
GI, discoloration of urine, feces, skin (yellow)
|
|
|
What is capreomycin? How is it administered?
|
protein synthesis inhibitor; IM injection
|
|
|
What does capreomycin have cross resistance with?
|
aminoglycosides
|
|
|
What can capreomycin be used to tx?
|
some use in mulit-drug resistant TB
|
|
|
What is the MOA for cycloserine?
|
inhibits d-alanine activity necessary for cell wall synthesis
|
|
|
What can inactivate cycloserine?
|
acid pH, so must be given with antacids
|
|
|
What toxicity deters cycloserine from being used?
|
CNS - psychotic behavior, suididal ideation, seizures
|
|
|
What is the main principal behind TB tx?
|
can develop resistance rapidly so must tx with combo antibiotics for prolonged time
|
|
|
What are the 5 first line TB drugs?
|
1)isoniazid
2)rifampin 3)pyrazinamide 4)ethambutol 5)streptomycin |
|
|
The second line TB drugs are reserved for?
|
treatment of drug resistant TB
|
|
|
What drugs are used for the initial phase of TB tx daily for 2mos in less severe cases?
|
INH, RIF, PZA
|
|
|
What drugs are used for the initial phase of TB tx daily for 2mos in more severe cases?
|
INH, RIF, PZA, SM/EMB
|
|
|
What drugs are used during the sterilizing phase of TB tx for 4mos daily or 3X/week?
|
INH, RIF
|
|
|
What 2 groups of people get monotherapy tx for TB? What drug is used for the monotherapy and how long?
|
1)person w/ + TB skin test but no evidence of organ involvement
2)contacts of infectious cases of TB INH for 6mos |
|
|
What 3 drugs are used for the tx of leprosy?
|
dapsone, rifampin, clofazimine
|
|
|
What do viruses lack?
|
cell wall and cell membranes
|
|
|
Which antivirals work by inhibiting viral DNA pol?
|
acyclovir, ganciclovir, foscarnante
|
|
|
Which antivirals work by inhibiting viral RNA pol?
|
ribavirin, foscarnate
|
|
|
Which antivirals work by inhibiting viral neuraminidase?
|
zanamivir, oseltamivir
|
|
|
Which antiviral works by blocking viral penetration or uncoating?
|
amantadine
|
|
|
Are viruses intracellular or extracellular parasites?
|
intracellular
|
|
|
*What are the 2 DOC for prophylaxis and early tx of Influenza A?
|
amantadine and rimantadine
|
|
|
*What is the MOA for amantadine and rimantadine?
|
prevents uncoating of Influenza A by binding to
M-2 protein; now virus can't infect other cells |
|
|
What is the MOA for oseltamivir and zanamivir?
|
prevents viral release from cells by selective inhibition of viral neuraminidase of Influenza A and B
|
|
|
What toxicities are seen with osteltamivir?
|
GI, CNS
|
|
|
What toxicity is seen with zanamivir? Why?
|
bronchospasm; drug given by inhalation
|
|
|
Which antiviral agent for Hep.B is approved for children over 2?
|
lamivudine
|
|
|
Which 2 antivirals are only approved for Hep.B tx in adults?
|
adefovir and entecavir
|
|
|
What is the MOA for Hep.B antivirals?
|
nucleoside analogue that disrupt Hep.B transcriptase
|
|
|
What 2 antiviral agents are used for Hep.C tx in children and adults?
|
interferon alpha and ribavirin
|
|
|
What are interferons?
|
cytokines naturally synthesized by cells with multiple antiviral actions
|
|
|
What 2 viruses are interferons effective against?
|
Hep.B and Hep.C
|
|
|
What are the 2 problematic toxicities seens with interferon tx?
|
severe, flu-like symptoms and CHF
|
|
|
What is the MOA for ribavirin?
|
guanosine analog which interferes with GTP synthesis, inhibits capping of viral mRNA, and blocks viral RNA dependent RNA pol
|
|
|
What are some toxicities of ribavirin?
|
teratogenic, mutagenic, dose-dependent hemolytic anemia, hyperbilirubinemia, CNS, GI, skin
|
|
|
What is the DOC for lassa fever and Hanta virus?
|
ribavirin
|
|
|
What 2 viruses is lamivudine effective against?
|
Hep.B and HIV
|
|
|
What is the gold standard tx for HSV?
|
acyclovir
|
|
|
What drug can attain higher serum levels than acyclovir?
|
valacyclovir
|
|
|
What must you do to the dose of acyclovir if it is used in babies?
|
double it because babies don't have T cells to fight the HSV infection
|
|
|
What can be used for varicella zoster infections?
|
acyclovir
|
|
|
Varicella zoster infections that are resistant to acyclovir can be tx with?
|
IV foscarnet
|
|
|
Antiviral agents for CMV are generally reserved for?
|
immunodeficient individuals because of drugs' toxicity
|
|
|
What is the gold standard for CMV tx?
|
ganciclovir when used IV
|
|
|
What is the oral prodrug of ganciclovir?
|
valganciclovir
|
|
|
What 2 drugs can be used against resistant CMV strains? What is the problem with these drugs?
|
foscarnet and cidofovir; more toxic
|
|
|
What cells are seen with EBV infection?
|
downey cells
|
|
|
Are there good antivirals for EBV tx?
|
no, rarely used in the normal host because there is limited proof of efficacy
|
|
|
What 2 antivirals have some efficacy against EBV?
|
acyclovir and valacyclovir
|
|
|
What is the MOA of acyclovir?
|
inhibits DNA pol (chain terminator)
|
|
|
What is the MOR against acyclovir?
|
change in viral DNA pol or TK negative viral strains (stop making thymidine kinase)
|
|
|
What 4 viruses can be tx with acyclovir?
|
HSV-1
HSV-2 HVZ EBV |
|
|
What is the MOA for valacyclovir?
|
converted to acyclovir; same mechanisms of resistance and action
|
|
|
What might valacyclovir have a benefit for?
|
post-zoster neuralgia
|
|
|
What are the adverse effects of acyclovir and valacyclovir?
|
GI, skin, headache, kidney, CNS
|
|
|
What is the MOA for cidofovir?
|
similar to acyclovir; inhibits DNA pol (chain terminator) but doesn't require TK activation because it can be activated by cellular enzymes
|
|
|
What is the spectrum for cidofovir?
|
CMV, EBV, HSV, HHV-6, Adenovirus
|
|
|
What is the MOA for ganciclovir?
|
potent inhibitor of CMV replication
|
|
|
What is the MOR against ganciclovir?
|
secondary to alterations of viral DNA pol or phosphotransferase
|
|
|
What is the main side effect seen with ganciclovir?
|
neutropenia
|
|
|
What is valgancyclovir? What can this drug be used for tx?
|
oral form of ganciclovir; CMV prophylaxis and renal transplant pts
|
|
|
What is the MOA for adefovir?
|
inhibits DNA pol and transcriptase
|
|
|
What is the spectrum for adefovir?
|
Herpes viruses, Hep.B, HIV
|
|
|
What is the MOA for foscarnet?
|
inhibits DNA pol and/or HIV reverse transcriptase
|
|
|
What can foscarnet be used for?
|
CMV, HSV, HVZ, and EBV
|
|
|
What toxicity keeps foscarnet from being used frequently?
|
renal toxicity along with hypocalcemia that can lead to cardiac and metabolic problems
|
|
|
Are any of the antivirals good for topical use?
|
no
|
|
|
Have perinatally acquired HIV infections increased or decreased?
|
decreased
|
|
|
What cells are targeted by HIV?
|
CD4 T cells
|
|
|
*What are the 4 main opportunistic infections seen in HIV pts?
|
CMV
Mucocutaneous candida Atypical Mycobacterial disease Pneumocystis corenei |
|
|
*What are the 5 goals of antiretroviral tx in HIV pts?
|
1)decrease viral load
2)decrease opportunistic infections 3)improve CD4 count 4)decrease symptoms 5)improve clinical status |
|
|
What does HAART stand for?
|
highly effective anti-retroviral tx
|
|
|
What is the mechanism of action for nucleoside reverse transcriptase inhibitors (NRTIs)?
|
phosphorylated by host cells kinases and subsequently incorporated into viral DNA by reverse transcriptase; they then terminate chain elongation once they are incorporated into the viral DNA
|
|
|
What happens in HIV pts when a NRTI is administered as a single retroviral agent?
|
HIV becomes resistant
|
|
|
What are 6 NRTIs?
|
1)zidovudine
2)abacavir 3)didanosine 4)lamivudine 5)stavudine 6)zalcitabine |
|
|
What is the MOR against zidovudine?
|
reverse transcriptase mutations
|
|
|
*What NRTI is used to prevent vertical transmission of HIV from mother to child?
|
zidovudine
|
|
|
Is toxicity to zidovudine problematic?
|
not really, most develops slowly and is manageable
|
|
|
Which NRTI can cause Stevens Johnson Syndrome?
|
abacavir
|
|
|
What is the problematic toxicity seen with zalcitabine?
|
pancreatitis
|
|
|
High grade resistance due to a single mutation in HIV can develop to what drug?
|
lamivudine
|
|
|
What drug competes with AZT for activation?
|
stavudine
|
|
|
What drug in HIV tx can cause lipid abnormalities for example a buffalo hump?
|
stavudine
|
|
|
What are the 2 major toxicities seen with didanosine?
|
pancreatitis and hyperuricemia
|
|
|
What is the MOA for NNRTIs?
|
these drugs bind to HIV's reverse transcriptase at a different site than NNRTIs and block its fx; they DON'T require phosphorylation to be active
|
|
|
What is the main toxicity associated with all NNRTIs?
|
rash
|
|
|
Do HIV pts develop resistance to NNRTIs?
|
yes, a single mutation can cause high grade resistance; resistance also occurs rapidly if any one NNRTI is used as a single agent or if a pt misses a dose (UNFORGIVING)
|
|
|
What are 4 NNRTIs?
|
1)efavirenz
2)delavirdine 3)navirapine 4)tenofovir |
|
|
What NNRTI is used to prevent vertical transmission of HIV?
|
nevirapine
|
|
|
What NNRTI is used in developing countries and not the US?
|
nevirapine
|
|
|
What 2 major toxicities are seen w/ nevirapine?
|
Stevens Johnson Syndrome and multiple drug interactions
|
|
|
What 3 toxicities are seen with delavirdine?
|
skin rashes, possibly teratogenic, multiple drug interactions
|
|
|
What is a first line NNRTI except in pregnant women and children?
|
efavirenz
|
|
|
What NNRTI is very teratogenic?
|
efavirenz
|
|
|
What is the first line/best NNRTI in adults?
|
tenofovir
|
|
|
What is the MOA of protease inhibitors?
|
inhibit HIV protease which is an enzyme needed for cleaving the viral polyprotein into essential structural and enzymatic components
|
|
|
What is MOR against protease inhibitors?
|
pol mutations (pol gene encodes viral enzyme which cleaves polyprotein into core structural protein
|
|
|
What effects do protease inhibitors have on metabolism?
|
may cause delayed and abnormal carbohydrate and lipid metabolism
|
|
|
What are the 8 protease inhibitors?
|
1)amprenavir
2)nelfinavir 3)indinavir 4)saquinavir 5)lopinavir 6)fosamprenavir 7)ritonavir 8)atazanavir |
|
|
What are some toxicities seen with indinavir?
|
nephrolithiasis and drug interactions
|
|
|
*What is an advantage to using Ritonavir in low doses?
|
in low doses in boosts serum levels and half lives of other protease inhibitors by inhibiting cytochrome p450s
|
|
|
What are some adverse effects of ritonavir?
|
GI irritation, bad taste, drug interactions due to it inhibiting cytochrome p450
|
|
|
What other protease inhibitor besides ritonavir inhibits cytochrome p450s?
|
saquinavir
|
|
|
What is the first line protease inhibitor used in HIV in pediatric pts?
|
nelfinavir
|
|
|
What is the major toxicity seen with amprenavir and fosamprenevir?
|
Stevens Johnson Syndrome
|
|
|
*Why is lopinavir co-formulated with ritonavir?
|
in order to take advantage of the cytochrome p450 inhibition by ritonavir which increases antiviral effect of lopinavir
|
|
|
What is the most potent protease inhibitor?
|
lopinavir
|
|
|
What drug is a fusion inhibitor?
|
enfuvirtide
|
|
|
What is the MOA for enfuvirtide?
|
prevents HIV from fusing to host cell membranes
|
|
|
What drug blocks gp41?
|
enfuvirtide
|
|
|
Is enfuvirtide a first line agent against HIV?
|
no, because of expense and other factors it is indicated only for pts who have failed all other antiretroviral therapies
|
|
|
What is the mode of administration for enfuvirtide? What toxicities can be seen with this drug?
|
IM injections twice daily; injection site rx and HS
|
|
|
What 3 groups of pts are at increased risk for fungal infections?
|
immunosupressed pts, pts on broad spectrum antibiotics, and pts with indwelling catheters
|
|
|
What are the 7 major fungal organisms?
|
1)Candida
2)Aspergillus 3)Blastomyces 4)Coccidiodes 5)Cryptococcus 6)Histoplasma 7)Zygomycosis (Mucor) |
|
|
*What is the DOC for non-life threatening Candida infections?
|
caspofungin
|
|
|
What are the 4 major groups of antifungal agents for systemic infections?
|
1)amphotericin B
2)flucytosine 3)azoles 4)echinocandins |
|
|
What are the 3 major antifungal agents for superficial mycoses?
|
1)griseofulvin
2)terbinafine 3)miconazole |
|
|
What is the MOA for amphotericin B? Cidal or static?
|
structurally similar to fungal cell membrane sterols for example ergosterol; disrupts fungal cell membrane permeability; cidal
|
|
|
What are some important pharmacologic properties of amphotericin B?
|
must be administered IV, widely distributed except CNS, small amount of renal excretion and is NOT dialyzable
|
|
|
What is the spectrum for amphotericin B?
|
cryptococcus
blastomyces histoplasma candida aspergillus coccidioides mucor sporothrix |
|
|
What are 3 major toxicities seen with amphotericin B?
|
infusion site thrombocytopenia, dose-related renal dysfunction, seizures
|
|
|
*What is the MOA for 5-flucytosine?
|
converted by fungal membrane enzymes into inhibitors of nucleic acid synthesis
|
|
|
Do you see resistance to 5-flucytosine?
|
yes, common and rapid
|
|
|
*5-flucytosine is synergistic with what drug? What is unique about this relationship?
|
amphotericin B; development of resistance delayed when used in this combination
|
|
|
What is the spectrum for 5-flucytosine?
|
used in combination to treat candida and cryptococcus
|
|
|
What is the problematic toxicity seen with 5-flucytosine?
|
bone marrow supression
|
|
|
What is the MOA for azoles? Cidal or static?
|
inhibits fungal cytochrome p450 mediated sterol demethylation (required normally to generate ergosterol); cidal
|
|
|
What is the MOR against azoles?
|
emerges slowly secondary to alteration of target enzymes
|
|
|
What are 4 common azoles?
|
1)ketoconazole
2)itranconazole 3)fluconazole 4)voriconazole |
|
|
*Which azole requires gastric acid for absorption?
|
ketoconazole
|
|
|
*Which azole has the best CNS penetration?
|
fluconazole
|
|
|
*Which azole has a strange endocrine toxicity?
|
ketoconazole
|
|
|
*What is the DOC for Coccioides?
|
fluconazole
|
|
|
*What is the DOC for Cryptococcus?
|
fluconazole
|
|
|
*What is the DOC for sporothrix?
|
itranconazole
|
|
|
*What is the DOC for Histoplasma?
|
itranconazole
|
|
|
*What is the DOC for Mucor?
|
posiconazole
|
|
|
*Which antifungal has a negative ionotropic effect?
|
itranconazole
|
|
|
*Which antifungal can't be used during pregnancy?
|
fluconazole
|
|
|
*Which antifungal has CNS, visual, and cardiovascular toxicity?
|
voriconazole
|
|
|
What is the MOA for caspofungin?
|
inhibits cell wall synthesis via B(1-2) glycan
|
|
|
What is the first cell wall active antifungal agent?
|
caspofungin
|
|
|
*What is the DOC for life-threatening candida infection?
|
amphotericin B
|
|
|
What is the spectrum for caspofungin?
|
Aspergillus and Candida
|
|
|
What toxicities can be seen with caspofungin?
|
infusion site irritation, histamine release, mild drug interactions
|
|
|
Which antifungal has fecal elimination?
|
anidulafungin
|
|
|
What is the spectrum for anidulafungin? What toxicity is seen with this drug?
|
Candida; histamine-mediated reactions
|
|
|
*What is the MOA for griseofulvin? What is the MOR against this drug?
|
inhibits fungal cell mitosis by affecting microtubule structure; decreased uptake of drug by fungal cells
|
|
|
*What does griseofulvin bind to?
|
human keratin cells and makes them resistant to fungal invastion
|
|
|
What is griseofulvin used for?
|
dermatophyte infection of skin, hair, and nails
|
|
|
What toxicities are seen with griseofulvin?
|
CNS, GI, liver, photosensitivity, alcohol intolerance and drug interaction, pancytopenia
|
|
|
What is the MOA for clotrimazole?
|
binds to phospholipids in cell membrane altering cell wall permeability
|
|
|
*What is the MOA for terbinafine? Cidal or static?
|
interfers with ergosterol synthesis/cell wall effects via inhibition of the fungal enzyme squalene epoxide leading to toxic accumulation of squalene; cidal
|
|
|
What type of pts can have problems with tx by antifungals?
|
diabetics
|
|
|
What toxicities are seen with terbinafine?
|
GI, rash, Stevens Johnson Syndrome, headaches, taste distubances, hepatitis, neutropenia
|
|
|
What is the MOA for nystatin? Cidal or static?
|
binds ergosterol in fungal plasma membrane changing membrane permeability; cidal
|
|
|
Is nystatin absorbed orally?
|
no, but doesn't need to be absorbed orally to treat superficial mycoses
|
|
|
What is the spectrum for nystatin?
|
Candida
|
|
|
What is the most common antifungal agent for tx of vaginal candida?
|
nystatin
|
|
|
What are the 6 antifungals used for tx of vaginal candida?
|
1)fluconazole
2)butoconazole 3)nystatin 4)clotrimazole 5)miconazole 6)gentian violet |
|
|
What antifungal for tx of vaginal candida has no resistance?
|
gentian violet
|
|
|
What 4 antibiotics exhibit post antibiotic effect?
|
1)quinolones
2)daptomycin 3)aminoglycosides 4)tigecycline |
|
|
What 6 drugs have a toxicity of Stevens Johnson syndrome?
|
1)sulfa
2)abacavir 3)nevirapine 4)amprenavir 5)fosamprenavir 6)terbinafine |
