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381 Cards in this Set
- Front
- Back
- 3rd side (hint)
Which classes of antibiotic are bactericidal?
|
bacitracin
beta-lactams isoniazid metronidazole polymyxins pyrazinamide quinolones rifampin |
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Which classes of antibiotics are bacteriostatic?
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chloramphenicol
clindamycin ethambutol macrolides nitrofurantoin novobiocin tetracyclines sulfonamides |
bacteriostatic agents CCEMeNNTS them in their tracks
|
|
Which antibiotics have excellent CNS penetrating ability?
|
chloramphenicol
metronidazole rifampin sulfonamides |
|
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Which antibiotics only penetrate the CNS with inflammed meninges?
|
penicillins
3rd-gen cephalosporins |
|
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Which antibiotics are very poor at penetrating the CNS?
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aminoglycosides
clindamycin vancomycin |
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Which antibiotics can get into the prostate?
|
macrolides
trimethoprim ciprofloxacin (fluoroquinolone) doxycycline (tetracycline) |
Many Try but few Can Do it
|
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Which antibiotics require dosage reduction with renal insufficiency?
|
aminoglycosides
vancomycin tetracyclines (except doxycycline) polymyxins most cephalosporins (except cefoperaxone) imipenem |
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Which drugs do not require dosage adjustments with renal insufficiency?
|
macrolides
ceftriaxone chloramphenicol metronidazole clindamycin cefoperazone |
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Which antibiotics cause ototoxicity?
|
aminoglycosides
vancomycin erythromycin clarithromycin minocycline |
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Which antibiotics cause phototoxicity?
|
tetracyclines
quinolones sulfonamides azithromycin |
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Which antibiotics cause phlebitis?
|
naficillin
oxacillin cephalothin cephapirin cefepime vancomycin erythromycin tetracyclines clindamycin |
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Which antibiotics are contraindicated during pregnancy?
|
aminoglycosides
erythromycin clarithromycin quinolones tetracyclines sulfonamides |
Administering Erythromycin Causes Queer Teratogenic Syndromes
|
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Which antibiotics cause hemolysis with G-6-P dehydrogenase deficiency?
|
tetracyclines
sulfonamides quinolones nitrofurantoin azithromycin trimethoprim |
|
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beta-lactam drugs
|
penicillins
cephalosporins carbapenems monobactams inhibitors of beta-lactamase |
|
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What is the mechanism of action for penicillins?
|
covalently binds transpeptidase, preventing cross-linking of peptidoglycan
requires bacteria cell-wall synthesis (growing bacteria) bactericidal |
|
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PBP 1
|
penicillin binding protein 1
involved in cross linking of peptidoglycan inhibition causes rapid lysis (most important site of action of beta-lactam drugs) |
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PBP 2
|
involved in maintaining the "rod" shape
inhibition causes ovoid shape and slow lysis |
|
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PBP 3
|
involved in septum formation
low beta-lactam concentration -> filaments high beta-lactam concentration -> lysis |
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|
autolysins
|
normal component of bacteria
may be required for growth of cell wall or for cells to divide absence or alteration may prevent penicillins from killing bacteria |
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What are the mechanisms of resistance to beta-lactam drugs?
|
1) beta-lactamase
2) reduced permeability of outer membrane 3) altered PBP 4) non-multiplying organisms 5) unknown mechanisms |
|
|
Which is more readily absorbed orally?
Pen V or Pen G |
Penicillin V - ~2/3 absorbed
(Pen G ~1/3 absorbed) |
|
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Do penicillins cross the BBB?
|
Yes; most do when the meninges are inflammed
|
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What is probenecid?
|
a weak acid that competes with other WA for transport (has almost no pharmacologic activity)
increases the half-life of penecillins reduces renal clearance of acyclovir and cidofovir |
|
|
Can a patient allergic to penicillin use cephalosporins?
|
Yes, under most circumstances
<5% cross-allergenicity (probably closer to 2%) |
|
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What is the Jarisch-Herxheimer Reaction?
|
occurs only in patients with syphillis
release of bacterial toxins when they die symptoms: chill, fever, muscle and joint pain with the 1st dose (continue therapy) |
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How is amoxicillin administered?
|
PO
|
|
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How is ampicillin administered?
|
IV
|
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Which penicillins are penicillinase resistant?
|
methicillin (no longer on market)
nafcillin dicloxacillin |
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Which penicillins are effective against pseudomonas?
|
ticarcillin
pipercillin |
|
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What is procaine penicillin G?
|
ester of pen G
procane is a local anesthetic that slows down the rate of absorption -> increased half-life blood levels not very high (good for prophylaxis) |
|
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What is benzathine penicillin G?
|
similar to procaine pen G, but get longer half-life and lower blood levels
(good for prophylaxis) |
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What is the mechanism of action for cephalosporins?
|
covalently binds transpeptidase, preventing cross-linking of peptidoglycan
requires bacteria cell-wall synthesis (growing bacteria) bactericidal |
|
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Which is more stable to hydrolysis?
penicillins or cephalosporins |
cephalosporins
|
|
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What are the adverse effects of cephalosporins?
|
nephrotoxicity
low when used alone, but slightly higher than penicillins slightly more toxic when used w/ aminoglycosides (synergistic toxic effect) |
|
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Which cephalosporins cause bleeding disorders?
|
cephalosporins with MTT side chain
(cefotetan, cefamandole, cefoperazone, cefametazole) these compete w/ vit. K in the liver and reduces synthesis of clotting factors -> bleeding (pts. on these drugs are usually given vit. K) |
|
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Which cephalosporins have a disulfiram-like reaction?
|
cephalosporins w/ MTT side chain
interferes w metabolism of ethanol (acetylaldehyde dehydrogenase), causing an unplesant reaction to ethanol |
|
|
Which causes more superinfections?
penicillins or cephalosporins |
cephalosporins, b/c they have a broader spectrum
|
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Which 1st-gen cephalosporin is administered orally?
|
cephalexin
|
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Which 1st-gen cephalosporin is administered parenterally?
|
cefazolin
|
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Which 2nd-gen cephalosporin is administered orally?
|
cefaclor
cefprozil |
|
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Which 2nd-gen cephalosporin is administered parenterally?
|
cefoxitin
cefuroxime cefotetan |
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Which 3rd-gen cephalosporin is administered orally?
|
cefixime
|
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Which 3rd-gen cephalosporin is administered parenterally?
|
cefotaxime
ceftriaxome ceftazidime cefoperazone |
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Which generation of cephalosporins are most active against gram-positives?
|
1st generation
|
|
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Which generation of cephalosporins are most susceptible to beta-lactamases?
|
1st-generation
|
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Which generation of cephalosporins have the worst penetration into the CSF?
|
1st generation
|
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Which generation of cephalosporins have the shortest half-lives?
|
1st generation
|
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Which generation of cephalosporins have the least activity against gram-positives?
|
3rd generation
(not 4th; 4th has good gram-positive and gram-negitive activity) |
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What are the advantages of 4th-generation cephalosporins?
|
good activity against gram-positives and gram-negatives
very stable to beta-lactamases less induction of resistance in hospital colonizing gram negative organisms? |
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Which cephalosporin is the best penetrator of the CSF?
|
ceftriaxone
|
|
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Which cephalosporin has the longest half-life?
|
ceftriaxone
|
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Which cephalosporins require no adjustment in renally impaired patients?
|
ceftriaxone
cefoperazone |
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Which cephalosporin is the most active against pseudomonas?
|
ceftazidime
cefoperaxone |
|
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Which cephalosporin causes "biliary sludging?"
|
cefoperazone
b/c it attains high levels in the bile -> slows down the ability of the liver to secrete bile |
|
|
What is the parent compound of carbapenems?
|
thienamycin
(unstable) |
|
|
What is the mechanism of action for carbapenems?
|
binds to transpeptidase -> preventing crosslinking of peptidoglycan
especially binds to PBP 2 ("rod shape") |
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Which drug has the broadest antimicrobial spectrum of any antibiotic currently available?
|
imipenem (carbapenem)
good penetration of gram-neg cell membrane high affinity for PBPs stable to most types of beta-lactamases |
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Why does imipenem induce microorganisms to produce beta-lactamases?
|
b/c it is very stable to them
|
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How is imipenem administered?
|
IV
|
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What is dehydropeptidase I?
|
normal enzyme in the brush border of the proximal tubules of the kidney
hydrolyzes imipenem, but not other beta-lactams |
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Why is imipenem always administered with cilastatin?
|
prevent hydrolysis of imipenem by dehydropeptidase I in kidneys
in animal studies, large doses of imipenem alone was more toxic than with cilastatin |
|
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What are the adverse effects of imipenems?
|
1) convulsions - 3%. Not recommended for pts. w/ meningitis
2) superinfections - b/c very broad spectrum (however, lower rate than expected b/c almost never reaches GI) 3) seizures 4) nephrotoxicity |
|
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What part of the body does imipenem almost never reach?
|
GI tract
b/c administered IV and excreted renally |
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What is the difference between imipenem and meropenem?
|
1) not hydrolyzed by dehydropeptidase I -> no need for cilastatin
2) less likely to cause seizures 3) less likely to cause convulsions -> can be used to treat meningitis |
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Can imipenems be used to treat meningitis?
|
no
b/c it can cause convulsions (~3%) |
|
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What are the inhibitors of beta-lactamases?
|
clavulanic acid
sulbactam tazobactam |
|
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Which beta-lactam has only one ring?
|
aztreonam (monobactam)
|
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Which organisms is aztreonam effective against?
|
gram-negative aerobes only
no activity against gram-positive or anerobic bacteria (gram-positive PBP intrinsically do not bind aztreonam) |
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Can aztreonam be used in patients that are allergic to penicillin and/or cephalosporin?
|
yes
no cross-allergenicity, even though allergic reactions w/ beta-lactams occur due to the beta-lactam ring |
|
|
What are aztreonams used for?
|
gram-negative aerobic infections
used as a safer alternative to aminoglycosides (similar spectrum, but safer) used as a substitute for penicillins and cephalosporins in patients allergic to these (no cross allergenicity) |
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How is bacitracin administered?
|
topical only
too toxic |
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What is the mechanism of action for vancomycin?
|
inhibitor of cell wall synthesis
binds terminal D-ala-D-ala -> blocks crosslinking of peptidoglycan activates autolysins |
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What is the mechanism of action for bacitracin?
|
inhibits the dephosphorylation of bactoprenol -> inhibiting transport of precursors out of the cell
|
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What is vancomycin used for?
|
gram-positives (no gram-negative activity)
DOC for MRSA pseudomembranous colitis (C. difficle) - not DOC anymore |
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What was vancomycin originally developed for?
|
as a substitute for penicillin
no cross-allergenicity |
|
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How is vancomycin administered?
|
IV
PO if needed for GI tract (not destroyed by acid, not absorbed orally) |
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How is vancomycin excreted?
|
glomerular filtration only
no tubular secretion b/c it is not a WA (half-life markedly prolonged in renal failure) |
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What are the adverse effects of vancomycin?
|
ototoxicity - damage to CNVIII
Red-man Syndrome - w/ rapid IV infusion nephrotoxicity - increases in combination w/ aminoglycoside |
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Which drug causes the Red-man Syndrome?
|
vancomycin - with rapid IV infusion
(due to displacement of histamines w/o degranulation) |
|
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How is Red-man syndrome prevented?
|
slow down IV infusion
and/or administer anti-histamine |
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What are the components of streptogramin?
|
quinupristin and dalfopristin
30:70 combination (b/c individually, they are only bacteriostatic) |
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What is the mechanism of action for streptogramins?
|
inhibits bacterial protein synthesis
the 2 components bind to separate sites on 50S quinupristin - inhibits synthesis of tRNA and blocks addition of new amino acids to nascent peptide dalfopristin - inhibits peptidyl transferase -> blocks peptide bond formation |
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|
What is streptogamin used for?
|
mainly used for infections caused by vancomycin-resistant strains
used when pt. can't tolerate adverse effects of vancomycin (ex: renally impaired pt.) |
|
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Which bacteria is streptogamin active against?
|
gram-positives
MRSA |
|
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What are the adverse effects of streptogramins?
|
pain, inflammation, phlebitis at site of infusion (~75%)
arthralgia myalgia |
|
|
Why is resistance to streptogramin unlikely?
|
b/c mechanism is due to synergistic combination of 2 drugs with different sites of action
|
|
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What is linezolid active against?
|
bacteriostatic against staphlococci and enterococci
bactericidal against streptococci active against large # of gram-positives - MRSA, enterococcus feacium, enterococcus faecalis |
|
|
What is the mechanism of action for linezolid?
|
inhibits bacterial protein synthesis by binding to 50S
binding site is near the interface w/ 30S -> prevents formation of 70S initiation complex (unique mechanism = no cross allergenicity) same binding site as chloramphenicol and erythromycin -> competition for binding (however, linezolid does not inhibit peptidyl transferase or the translation reaction) |
|
|
What do linezolid, chloramphenicol, and erythromycin have in common?
|
they all bind to the same 50S binding site -> inhibiting protein synthesis
however, linezolid does not inhibit peptidyl transferase or the translation reaction (linezolid prevents the formation of 70S) |
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Aminoglycosides rely on what mechanism to get inside cells?
|
active transport
(thus inactive against anaerobes) |
|
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Why are aminoglycosides inactive against anaerobes?
|
b/c it relys on active transport to get inside cells, which is an oxygen-dependent process
|
|
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What is the mechanism of action for aminoglycosides?
|
irreversibly binds 30S which...
blocks initiation of 70S complex miscodes peptide chain blocks translocation of peptide |
|
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Why are aminoglycosides bactericidal?
|
it has high affinity for 30S of bacterial ribosomes (irreversible binding)
it is rapidly taken up through the membrane |
|
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What antibiotics are aminoglycosides synergystic with?
|
cell-wall inhibitors
theory: disruption of cell wall allows more aminoglycosides to enter the cell |
|
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Are aminoglycosides susceptible to beta-lactamases?
|
no
it is not a beta-lactam drug |
|
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What are aminoglycosides used for?
|
gram-negative, aerobic infections
mainly used for pseudomonas gram-positives - enterococci and strep. viridans (in combination w/ a penicillin or vancomycin, esp. for endocarditis) |
|
|
Which antibiotics have a concentration-dependent effect?
|
aminoglycoside - bactericidal activity increases with increased concentration
quinolones chloramphenicol |
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If aminoglycosides are active against gram-positives, why are they not used to treat gram-positive infections?
|
b/c there are many other drugs that are active against gram-positives and are safer
|
|
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How do microorganisms resist the effects of aminoglycosides?
|
1) decreased ribosomal binding to drug
2) decreased transport of drug into the cell 3) elaboration of drug-metabolizing enzymes (main mechanism)-- ie. acetylation, adenlyation, phosphorylation |
|
|
Which antibiotic exhibits "one-way" cross-resistance?
|
aminoglycosides
order of increasing cross-resistance streptomycin kanamycin gentamicin tobramycin amikacin (resistance to gentamicin = resistance to kanamycin and streptomycin, but not to tobramycin or amikacin) |
|
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How are aminoglycosides administered?
|
PO - steralize GI (no oral absorption)
IV - most common route IM - peak serum levels in 30-60 mins intrathecal - polar, so doesn't cross BBB topical |
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|
Where are aminoglycosides mainly distributed in the body?
|
inner ear (5-10x plasma)
kidneys (50-90x plasma) due to specific transport mechanisms very polar, so small Vd - some distribution to tissues, low deposition in fat |
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|
What are the adverse effects of aminoglycosides?
|
ototoxicity - vestibular and cochlear
initial loss of high frequency sounds vertigo greater with streptomycin and gentamycin nephrotoxicity - 50-90x plasma level neomycin>>gentamicin>>tobramycin=amikacin (half-life prolonged with decreased renal function) neuromuscular blockade - esp. if pt. has myasthenia gravis, hypocalcemia, other nuromuscular blocking agents (curare-like effect) |
|
|
How are aminoglycosides excreted?
|
glomerular filtration (no tubular secretion)
parallels creatinine clearance (CrCl decreases by half, half-life of a.g. increases by 2x) (drug is not metabolized - unchanged) |
|
|
Why are aminoglycosides usually administered via "once-daily-dosing?"
|
1) concentration-dependent activity
2) long post-antibiotic effect 3) active transport of a.g. into cells of renal tubules and inner ear is a saturable process 4) at large doses, a.g. causes down-regulation of active transport into bacterial cells 5) nephrotoxicity and ototoxicity are correlated w/ trough levels of a.g. 6) toxicity less with once-daily dosing b/c of reduced accumulation in inner ear and kidneys |
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What drugs are used to treat endocarditis?
|
combination of streptomycin (aminoglycoside) and vancomycin
|
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Why does the loading dose of aminoglycoside have to be decreased for obese patients?
|
b/c aminoglycosides are very polar (small Vd), and thus are not distributed in fat
|
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Which is the most widely used aminoglycoside?
|
gentamicin
|
|
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When is kanamycin used?
|
used as a 2nd or 3rd line drug in TB
(not used much else) |
|
|
Which aminoglycoside has the broadest spectrum?
|
amikacin
|
|
|
Which aminoglycoside has the least cross-resistance?
|
amikacin
|
|
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Which aminoglycoside is limited to topical use and oral administration to steralize the gut?
|
neomycin
|
|
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Which aminoglycoside is used for TB and endocarditis?
|
streptomycin
|
|
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Which drugs cannot be combined with aminoglycosides due to chemical reaction?
|
antipseudomonal penicillins (ticarcillin, piperacillin)
|
|
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Which class of drugs cannot be combined with ticarcillin/piperacillin due to chemical reaction?
|
aminoglycosides
|
|
|
Why are aminoglycosides preferentially used even though aztreonam has a similar spectrum of activity and is safer?
|
b/c of synergystic effect of a.g. w/ penicillins or cephalosporins
(no synergism b/w aztreonam and penicillin or cephalosporin) |
|
|
What is the mechanism of tetracyclines?
|
binds to 30S to block binding of aminoacyl tRNA to mRNA
|
|
|
Which antibiotics blocks aminoacyl tRNA binding to mRNA?
|
tetracyclines
|
|
|
What is the mechanism of resistance against tetracyclines?
|
1) decreased binding to ribosomes
2) inactivation of enzymes 3) decreased accumulation - increased efflux/pumping out drug (major mechanism) 4) cross resistance - resistance to one tetracycline = resistance to all |
|
|
What are the drawbacks of using tetracyclines?
|
chelates cations (Ca, Mg, Fe) -> thus, not good taken w/ certain foods/vitamins
(binds to teeth and bones -> not used in pregnant women and children) also, increase pH -> increase chelation, thus not good to use tetracyclines w/ antacids |
|
|
What is the number 1 cause of drug-induced renal failure?
|
aminoglycosides
|
|
|
Where is tetracycline distributed in the body?
|
1) teeth and bones - chelates Ca, interferes w/ development of bones (not used in pts. <8 y.o.)
2) prostate (doxycycline) 3) tears and saliva (minocycline) |
|
|
Which tetracycline is most lipid soluble?
|
doxycycline
|
|
|
Which tetracycline is least lipid soluble?
|
tetracycline
|
|
|
Which tetracycline has the greatest oral absorption?
|
doxycycline
|
|
|
Which tetracycline has the lowest oral absorption?
|
tetracycline
|
|
|
Which tetracycline has the longest half-life?
|
doxycycline
|
|
|
Which tetracycline has the shortest half-life?
|
tetracycline
|
|
|
Which tetracycline has the greatest renal excretion?
|
tetracycline
|
|
|
Which tetracycline has the least renal excretion?
|
doxycycline
|
|
|
What are the adverse effects of tetracyclines?
|
1) GI irritation - diarrhea, superinfections (broad spectrum, high concentration in kidneys)
2) espohageal ulceration (if gets stuck in esophagus) 3) hepatotoxicity (pregnant women w/ polynephritis) 4) phototoxicity (drug deposits in skin -> free radicals w/ UV light) 5) nephrotoxicity 6) deposition in teeth and bones 7) vestibular toxicity (minocycline) |
|
|
What drug is Fanconi's Sydrome associated with?
|
tetracyclines
breakdown product of tetracyclines in acid (used to be a problem when citric acid was used as a preservative) |
|
|
What tetracycline is not used as an antibiotic?
|
demeclocycline
an anti-diuretic used to treat SIADH |
|
|
What tetracycline is used to treat SIADH?
|
dimeclocycline
|
|
|
What is dimeclocycline used for?
|
used as an anti-diuretic to treat SIADH
|
|
|
Why does tetracycline turn teeth black?
|
chelates with Ca in teeth
breakdown product of tetracycline is black, and deposits permanently in the teeth |
|
|
Which tetracycline is associated with vestibular toxicity?
|
minocycline
|
|
|
Which antibiotic has the highest incidence of superinfections?
|
tetracyclines (10-20%)
|
|
|
What are tetracyclines used for?
|
gram-positives, gram-negatives, aerobes, anaerobes, non-bacterial microorganisms
DOC for rickettsial infections DOC for chlamydial infections used for gonorrhea and syphillis when beta-lactams cannot be used used for lower respiratory tract infections used for plague, tularemia, brucellosis used to treat acne |
|
|
Which is the most preferred tetracycline?
|
doxycycline
better absorbed longer half-life better tissue levels less GI disturbance non-renal and non-hepatic |
|
|
How does tetracycline affect enterohepatic recirculation?
|
kills bacteria that contain beta-glucronidase -> prevents regeneration of drug -> excretion -> lower blood levels
(drugs that depend on enterohepatic recirculation, such as oral antibiotics, will become ineffective as concentration in the blood decreases) |
|
|
How do tetracyclines prevent acne?
|
1) inhibits bacterial lipase -> no free fatty acid -> no irritation
2) kills bacteria directly |
|
|
Why is doxycycline no longer used for traveller's diarrhea?
|
b/c of high incidence of phototoxicity
|
|
|
What is the mechanism of action for chloramphenicol?
|
blocks peptidyl transferase at 50S
|
|
|
Which antibiotic blocks peptidyl transferase at 50S?
|
chloramphenicol
dalfopristin |
|
|
What is the resistance mechanism of chloramphenicol?
|
acetylation
chloramphenicol acetyl transferase (CAT) |
|
|
Which antibiotic concentrates best in the CNS?
|
chloramphenicol
b/c it is highly lipid soluable -> readily penetrates the BBB |
|
|
How is cloramphenicol metabolized?
|
90% glucuronidation (phase II)
8% unchanged 2% deacetylation/dehalogenation |
|
|
Which drug is associated with Gray Baby Syndrome?
|
chloramphenicol - caused by dosing neonates the same as adults per kg weight
(glucuronidation absent in neonates) (renal function reduced in neonates) |
|
|
What are the adverse effects of chloraphenicol?
|
1) Gray Baby Syndrome
2) bone marrow depression 3) aplastic anemia - appears weeks to months after stopping drug |
|
|
Which drug is associated with aplastic anemia?
|
chloramphenicol
|
|
|
What is the alternative for treating RMSF?
|
chloramphenicol
(usually treat RMSF w/ tetracyclines) |
|
|
What is the mechanism of action for macrolides?
|
binds at 50S to blocks translocation of peptide
|
|
|
Which antibiotics do macrolides compete with?
|
delfopristin (part of streptogramin)
chloramphenicol |
|
|
How are the macrolides selectively toxic?
|
Can't get through mitochondrial membrane -> can only affect bacterial ribosomes
|
|
|
What drugs are part of the macrolides?
|
erythromycin
azithromycin clarithromycin |
|
|
Why are macrolides mainly used for gram-positive infections?
|
gram-positive organisms absorb macrolide 100x better than gram-negatives
|
|
|
Which macrolide has the best bioavailability?
|
clarithromycin
|
|
|
What are the macrolides used for?
|
mainly treating gram-positives
legionella, mycoplasma, chlamydia, some mycobacteria |
|
|
What are the resistance mechanisms against macrolides?
|
1) decreased intracellular concentration (increased efflux)
2) hydrolysis by esterases 3) decreased binding |
|
|
What are the adverse effects of erythromycin?
|
1) cholestatic hepatitis (erythromycin setolate)
2) GI irritation - epigastric pain, nausea, diarrhea -> problems w/ compliance 3) hearing loss (usually w/ IV) - uncommon 4) inhibition of CYP450 (causes arrhythmias when combined w/ terfenadine [antihistamine]; causes seizures and arrhythmias when combined w/ theophylline [asthma medication]) |
|
|
What are macrolides used for?
|
alternative for penicilln-resistant patients (similar spectrum to pen G)
used to treat mycoplasma, chlamydia, legionella |
|
|
How are azithromycin and clarithromycin different from erythromycin?
|
better absorption
higher tissue concentrations less GI upset extended spectrum (MAC and H. influenzae) fewer drug interations (b/c doesn't inhibit CYP450 enzymes) H. pylori (peptic ulcers) - clarithromycin uncomplictated chlamydial infections - azithromycin very expensive compared to erythromycin |
|
|
What is the mechanism of action for clindamycin?
|
binds 50S
|
|
|
How is clindamycin excreted?
|
primarily biliary excretion
(no dosage adjustments required in renal failure) |
|
|
What are the adverse effects of clindamycin?
|
pseudomembranous colitis
(highest incidence of all antibiotics, though amoxicillin causes more b/c of its frequency of use) |
|
|
Which antibiotic has the highest incidence of pseudomembranous colitis?
|
clindamycin
|
|
|
Which antibiotic causes the most pseudomembranous colitis?
|
amoxicillin
|
|
|
What is clindamycin used for?
|
used for gram-positive infections in pts. allergic to penicillin
anaerobic infections (esp. B fragilis), except in endocarditis and CNS infections no effect in gram-negatives |
|
|
Does clindamycin penetrate the CNS?
|
no
|
|
|
What is the mechanism of action for metronidazole?
|
reduction of nitro group by MO -> reactive metabolite -> interacts w/ DNA
(selective toxicity b/c mammalian cells to not convert to active form) |
|
|
Which antibiotic is active against anaerobes?
|
clindamycin
metronidazole reductive metabolite (active form) cannot be formed in aerobic environment |
|
|
What is metronidazole used for?
|
anaerobic bacterial infections
DOC for pseudomembranous colitis (C. difficile) also used for protoza and H. pylori (stomach ulcers) |
|
|
Which antibiotics turns the urine brown?
|
metronidazole
nitrofurantoin |
|
|
Does metronidazole penetrate the CNS?
|
yes
|
|
|
What are the adverse effects of metronidazole?
|
most common - GI disturbances
most severe - CNS and peripheral neuropathies disulfiram-like reaction |
|
|
Why is metronidazole contraindicated during pregnancy?
|
because mechanism of action disrupts DNA (possible mutagen?, carcinogen?)
can possibly cause birth defects, esp. during 1st trimester however, no evidence in human and animal studies |
|
|
Which antibiotics exhibit a disulfuram-like reaction?
|
cephalosporins w/ MTT side chain
metronidazole |
|
|
What is the mechanism of action for rifampin?
|
binds to the beta-subunit of bacterial DNA-dependent RNA polymerase -> blocks initiation of RNA synthesis
|
|
|
What are the drawbacks of rifampin?
|
rapid emergence of resistance -> always used in combination w/ other antibiotics
not reliable by itself hepatotoxicity, red body fluids |
|
|
What are the primary drugs used for treating TB?
|
isoniazid
rifampin streptomycin ethambutol pyrazinamide |
|
|
What is p-glycoprotein?
|
MDR protein that pumps drugs out of the cell
|
|
|
What is the mechanism of action for isoniazid?
|
interferes w/ mycolic acids
inhibits cell wall synthesis of mycobacteria (no activity against gram-positives or gram-negatives) |
|
|
Which antibiotic is associated with causing SLE?
|
isoniazid - rare
|
|
|
What antibiotic is associated with causing SLE-like symptoms?
|
dapsone
|
|
|
What are the adverse effects of isoniazid?
|
1) peripheral neuritis - due to loss of B6
(INH binds B6 -> inteferes w/ formation of pyridoxal phosphate) 2) hepatotoxicity - major problem 3) SLE |
|
|
What are the adverse effects of rifampin?
|
1) hepatotoxicity - not synergystic with INH
2) induction of CYP450 enzymes - interferes w/ oral contraceptives by increasing metabolism of drug (induces CYP450 mechanisms more than any other drug) 3) discoloration of body fluids - turns body fluids red (due to large Vd) |
|
|
What is the mechanism of action for ethambutol?
|
inhibition of arabinosyl transferase -> decreases incorporation of arabinose and interferes w/ cell wall synthesis of mycobacteria
|
|
|
What are the adverse effects of ethambutol?
|
optic neuritis
loss of green color vision |
|
|
What antibiotic is causes loss of green color vision?
|
ethambutol
|
|
|
What is the mechanism of action of pyrazinamide?
|
unknown
Brenner: acts by lowering pH |
|
|
What are the adverse effects pyrazinamide?
|
hepatoxicity - not to extent of INH
hyperuricemia - increase in plasma uric acid levels -> gout |
|
|
When is isoniazid used alone?
|
prophylaxis for TB
(otherwise always used in combination with another drug) |
|
|
Which anti-TB drugs causes liver toxicity?
|
isoniazid
rifampin pyrazinamide - to a lesser extent |
|
|
Which anti-TB drugs causes ototoxicity?
|
streptomycin (aminoglycosides cause ototoxicity)
|
|
|
Which anti-TB drugs causes hyperuricemia?
|
pyrazinamide
(reason why pyrazinamide causes gout) |
|
|
Which anti-TB drugs causes visual toxicity?
|
ethambutol
|
|
|
What is the precursor of sulfonamides?
|
prontosil
|
|
|
What is the mechanism of action for sulfonamides?
|
structural analogs of PABA
competitive inhibitor of dihydropteroate synthetase |
|
|
Why don't the sulfonamides affect mammalian cells?
|
mammalian cells can't synthesize DHFA
(don't contain dihydropteroate synthetase) MO synthesizes DHFA, which is inhibited by sulfonamides |
|
|
What are the resistance mechanisms for sulfonamides?
|
1) increased production of dihydropteroate synthetase
2) alteration of dihydropteroate synthetase so that it's less sensitive to binding and inhibition by sulfonamides 3) decreased penetration of sulfonamides into cells 4) increase PABA |
|
|
How does procaine (local anestetic) reduce the competitiveness of sulfonamides?
|
procaine is metabolized to PABA -> increasing the concentration of PABA which decreases comptitiveness of sulfonamides
|
|
|
What are the adverse effects of sulfonamides?
|
1) crystallurea - w/ high concentrations
2) hypersensitivity rxns - urticaria, photosensitization, serum-sickness, Stevens-Johnson syndrome (destroys mucus membranes, GI tract) 3) cross-sensitivity - allergic to one, allergic to all 4) hemolytic anemia - in pts. w/ G-6-P dehydronase deficiency 5) kernicterus (in neonates) - displacement of bilirubin -> gets into CNS (pts w/ aids have a high incidence of adverse effects) |
|
|
Which antibiotic is associated with Stevens-Johnson syndrome?
|
sulfonamides
|
|
|
What antibiotic is associated with kernicterus?
|
sulfonamides
|
|
|
Which sulfonamide is least likely to cause crystallurea?
|
sulfisoxazole
|
|
|
What is the advantage of triple sulfas compared to other sulfonamides?
|
reduced crystallurea due to solubility of each agent being independent of the others
(thus, can have increased concentrations of drug w/ less crystallurea) |
|
|
What are sulfonamides used for?
|
used for UTI
nocardiosis, chancroid - DOC sulfasoxazole |
|
|
Sulfamethoxazole is often combined with what drug?
|
trimethoprim
|
|
|
How is mafenide administered?
|
topical only
absorbed from burned skin |
|
|
How is silver sulfadiazine administered?
|
topical only
|
|
|
What is the adverse effect of mafenide?
|
1) pain on application
2) skin rashes 3) metabolic acidosis - inhibition of carbonic anhydrase |
|
|
What is the adverse effect of silver sulfadiazine?
|
skin rashes, however lower than mafenide
|
|
|
Does an increase in PABA decrease the activity of silver sulfadiazine?
|
no
different mechanism from other sulfonamides silver is the active compound (known to have antibacterial activity) |
|
|
What is the mechanism of action for trimethoprim/sulfamethoxazole (AKA co-trimoxazole)?
|
trimethoprim is a structural analog of DHFA -> inhibits DHFR
sulfamethoxazole is a sulfonamide (inhibits dihydropteroate synthetase) double-sequential blockade (synergistic) |
|
|
How is trimethoprim selective for bacteria?
|
concentration needed to inhibit mammalian DHFR in much greater than in bacteria (~60000x)
|
|
|
What ratio has the maximum synergistic effect for sulfamethoxazole:trimethoprim?
|
20:1
however, dose is 5:1 (400mg:80mg) |
|
|
What are the adverse effects of trimethoprim?
|
1) folic acid deficiency (SMZ)
2) anemia (TMP) - treat w/ folinic acid |
|
|
What is used to treat anema caused by trimethoprim?
|
folinic acid
bypasses blockade -> reverses anemia doesn't affect activity or TMP b/c MO can't transport it (mammalian cells can) |
|
|
What group of people develop allergy to sulfonamides?
|
AIDS patients (60-90%)
|
|
|
What is trimethoprim:sulfamethoxazole used for?
|
used for UTI, resistant infections, pneumocystitis carinii pneumonia
no anaerobic coverage |
|
|
What drug is used to prevent pneumocystis carinii pneumonia in AIDS patients?
|
trimethoprim/sulfamethoxazole (co-trimoxazole)
|
|
|
What is the mechanism of action for sulfones?
|
structural analogs of PABA
act as antimetabolites in the synthesis of folic acid |
|
|
What is dapsone used for?
|
DOC for leprosy
|
|
|
What is the drug of choice for treating leprosy?
|
dapsone
|
|
|
What are the adverse effects of dapsone?
|
1) nonhemolytic anemia - common
2) acute hemolytic anemia - less frequent 3) SLE-like symptoms 4) erythema nodosum 5) peripheral neuropathy |
|
|
What is the precursor for the fluoroquinolones?
|
nalidixic acid
|
|
|
What is the mechanism of action for fluoroquinolones?
|
binds to A-subunit of DNA gyrase -> interfers with supercoiling and inhibits DNA synthesis
|
|
|
How are the fluoroquinolones selective for bacteria?
|
mammalian topoisomerases are inhibited at a much higher concentration than bacterial topoisomerases
|
|
|
Which antibiotics are selective based on the differences of MIC between bacterial and mammalian cells?
|
trimethoprim
fluoroquinolones methotrexate (anti-cancer) |
|
|
What are fluoroquinolones used for?
|
gram-positive, gram-negative
pesudomonas (PO) resistant infections - due to unique mechanism prophalaxis for traveller's diarrhea - replaced tetracyclines, but still causes phototoxicity UTI, prostatitis (active against some MRSA strains, but not reliable) |
|
|
What are the drawbacks of fluoroquinolones?
|
chelates divalent and trivalent cations
normal amount in the diet is not a problem use of supplements, antacids, vitamins can decrease absorption |
|
|
What are the adverse effects of fluoroquinolones?
|
1) GI irritation - nausea, vomiting, diarrhea
2) CNS - seizures, headache, dizziness, visual disturbances, hallucinations 3) cartilage eroson - evidence from animal studies (not recommended for <18 y.o.) 4) tendinitis w/ occasional rupture of Achilles tendon 5) inhibition of CYP450 system |
|
|
What antibiotic is associated with seizures in patients consuming large quantities of caffeine?
|
fluoroquinolones
|
|
|
What are the quinolones used for?
|
UTIs
achieves theraputic levels only in the urine |
|
|
What is the mechanism of action for quinolones?
|
binds to A-subunit of DNA gyrase -> interfers with supercoiling and inhibits DNA synthesis
|
|
|
What is the mechanism of action for nitrofurantoin?
|
reductive metabolite that causes DNA damage
|
|
|
What is nitrofurantoin used for?
|
UTIs
achieves pharmacological effect only in the urine |
|
|
What are the adverse effects of nitrofurantoin?
|
1) GI disturbances
2) hemolytic anemia in pts. w/ G-6-PDH deficiency 3) pulmonary rxns (nitrofurantoin inhibits the activity of nalidixic acid - don't combine) |
|
|
What drug cannot be combined with nitrofurantoin?
|
nalidixic acid
|
|
|
What drug cannot be combined with nalidixic acid?
|
nitrofurantoin
|
|
|
What is the mechanism of action for methenamine?
|
hydrolyzed under acidic conditions -> releases ammonia and formaldehyde
formaldehyde is bactericidal urea-splitting bacteria (proteus) are resistant (increase ammonia -> increase pH -> decreases hydrolyzation of methenamine -> inactivates drug) |
|
|
What class of antibiotics cannot be combined with methenamine?
|
sulfonamides - mutual antagonism
|
|
|
Which antibiotic cannot be combined with sulfonamides?
|
methenamine
|
|
|
What are the adverse effects of methenamines?
|
1) painful urination due to formaldehyde
2) contraindicated in pts. w/ hepatic insufficiency -> leads to CNS problems (compromised liver -> decreased clearance of ammonia -> ammonia levels build up) |
|
|
What are the inhibitors of p-glycoprotein?
|
Ca-channel blockers
quinidine phenothiazine |
|
|
What is the mechanism of action for nitrogen-mustards?
|
covalently binds N7 on guanine -> cross-links same or differenf DNA strands
|
|
|
Why is cis platinum not a true alkylating agent?
|
b/c it contains no carbons
(not an organic conpound) |
|
|
What is the mechanism of action for 6-mercaptopurine?
|
interferes w/ purine metabolism -> disrupts DNA synthesis
|
|
|
What is the mechanism of action for cis-platinum?
|
covalently cross-links DNA
|
|
|
What is hypoxanthine-guanine phosphoribosyltransferase (HGPTR)?
|
enzyme involved in purine metabolism
also converts 6-mercaptopurine to active form |
|
|
What is the mechanism of 5-fluorouracil?
|
interferes w/ pyrimidine metabolism
inhibits thymidylate synthesase -> interferes w/ production of DNA incorporated into RNA -> dysfunctional RNA |
|
|
What is the mechanism of action for methotrexate?
|
interferes w/ folic acid metabolism
inhibits mammalian DHFR -> inhibits production of FH2 and subsequently FH4 (no FH4, no cofactors for DNA synthesis) |
|
|
What antibiotics inhibit DHFR?
|
trimethoprim - inhibits MO DHFR
methotrexate - inhibits mammalian DHFR |
|
|
What is the difference b/w trimethoprim and methotrexate?
|
trimethoprim binds MO DHFR
MTX binds mammalian DHFR |
|
|
How do trimethoprims and methotrexates stay in the cell for a long period of time?
|
forms polyglutamates
|
|
|
What is the mechanism of action for antracyclines?
|
intercalate b/w adjoining nucleotide pairs of DNA
inhibits topoisomerase disrupts cell membrane function produces free radicals -> toxicity |
|
|
Doxyrubicin and daunorubicin are what class of drugs?
|
anthracyclines
antibiotics used to treat cancer broad spectrum for many different cancers |
|
|
What is the mechanism of action for dactinomycin?
|
binds DNA -> breakup of chain
|
|
|
What is the mechanism of action for bleomycin?
|
causes chain scission and frangmentation of DNA
|
|
|
What is the mechanism of action for mitomycin?
|
forms product that alkylates DNA
|
|
|
What is the mechanism of action for vinca alkaloids?
|
binds to tubulin of microtubules in mitotic spindls and arrests mitosis at metaphase
|
|
|
Vinblastine and vincristine are what type of drugs?
|
vinca alkaloids (from plants)
used to treat cancer binds mictotubules -> arresting mitosis |
|
|
What is the mechanism of action for paclitaxel?
|
stimulates microtubule formation (blocks disassembly of microtubules) -> arrests cell in mitosis
|
|
|
What is the mechanism of action for L-asparaginase?
|
hydrolyzes asparagine
asparagine is a requirement for some cancer cells (destruction of asparagine in blood -> kills certain cancer cells) (normal cells synthesize asparagine) |
|
|
What drugs are cell-cycle specific anti-metabolites used to treat cancer?
|
5-fluorouracil
mercaptopurine methotrexate |
|
|
What drugs are cell-cycle mitotic inhibitors used to treat cancer?
|
vincristine
vinblastine paclitaxel |
|
|
What drugs are cell-cycle non-specific alkylating agents used to treat cancer?
|
mechlorethamine
cyclophosphamide cisplatin (cis-platinum) |
|
|
Whic is more effective in low-growth fraction tumors?
CCS or CCNS |
CCNS b/c acts on both dividing and non-dividing cells
|
|
|
Which drug is better used on high-growth fraction tumors?
CCs or CCNS |
CCS b/c they are less toxic
(larger doses/longer duration possible) they only work on dividing cells |
|
|
What are the adverse effects of anti-cancer drugs?
|
1) acute toxicity - nausea, vomiting (due to chemoreceptor trigger zone)
2) delayed toxicity - bone marrow suppression*, ulceration, alopecia (hair loss), interference w/ reproductive systems (birth defects) *bone marrow suppression -> immunosuppression (main problem) 3) hyperuricemia - elevated uric acid levels -> gout or gouty nephrothapy 4) pulmonary fibrosis (esp. bleomycin, busulfan) 5)hepatotoxicity (esp. cyclophosphamide) -> hemorrhagic cyctitis 6) nephrotoxicity (esp. MTX, cisplain) |
|
|
What anti-cancer drugs are associated with causing pulmonary fibrosis?
|
bleomycin
busulfan |
|
|
What anti-cancer drug is associated with hepatotoxicity leading to hemorrhagic cystitis?
|
cyclophosphamide
caused by acrolein accumulation (mesna inactivates acrolein and reduces toxicity) |
|
|
What is mesna used for?
|
treating hemorrhagic cystitis caused by cyclophosphamide (caused by acrolein accumulation)
(inactivates acrolein and reduces toxicity) |
|
|
What is mannitol and sodium thiosulfate used for?
|
treating nephrotoxicity caused by cisplatin
mannitol (diuretic) -> dilutes urine sodium thiosulfate -> directly inactivates cisplatin |
|
|
What is leucovorin rescue?
|
treat pt. w/ very high levels of MTX
administer leucovorin, citrovorum, or folinic acid (antidote to MTX) before delayed toxicity begins works primary b/c toxicity for MTX is delayed, and cancer cells don't transport in antidote as well as normal cell |
|
|
What is allopurinol used for?
|
inhibitor of xanthine oxidase
used for prolonging the half-life of 6-mercaptopurine by inhibiting metabolism of drug also decreases uric acid levels by inhibiting normal metabolism of purines, preventing gouty nephropathy (however, also decreases body's ability to inactivate 6-MP -> must reduse dose by 50-75%) |
|
|
Which anti-cancer drugs have reduced bone marrow suppression?
|
vincristine
cisplatin bleomycin L-asparagine hormones |
|
|
What is the major dose-limiting toxicity of vincristine?
|
neurotoxicity
|
|
|
What is the major dose-limiting toxicity of cisplatin?
|
nephrotoxicity
|
|
|
What is the major dose-limiting toxicity of bleomycin?
|
pulmonary toxicity
|
|
|
What is the major dose-limiting toxicity of L-asparginase?
|
allergic rxns
(b/c originally isolated from guinea pig serum) |
|
|
What is the major problem with anti-cancer drugs?
|
potent immunosuppressants
|
|
|
Which drug has the longest post-antibiotic effect?
|
aminoglycosides (3-6 hours)
|
|
|
Which antibiotic exhibits a curare-like effect?
|
aminoglycosides
|
|
|
What is the DOC for B. fragilis?
|
clindamycin
|
|
|
What nucleoside analogs are used against HIV?
|
zidovudine
didanosine zalcitabine stavudine lamivudine abacavir |
|
|
What NNTRIs are used against HIV?
|
nevirapine
delavirdine efavirenz |
|
|
What protease inhibitors are used against HIV?
|
saquinavir
indinavir ritonavir nelfinavir amprenavir lopinavir |
|
|
What fusion inhibitor is used against HIV?
|
enfuvirtide
|
|
|
What drugs are used against CMV?
|
ganciclovir
foscarnet cidofovir fomivirsen |
|
|
What drugs are used against hepatitis?
|
interferon alpha-2a
interferon alpha-2b |
|
|
What drugs are used against herpes simplex?
|
acyclovir
famciclovir valcyclovir vidarabine idoxuridine trifluridine foscarnet docosanol |
|
|
What drugs are used against influenza A?
|
amantadine
rimantadine zanamivir oseltamivir |
|
|
What drugs are used against RSV?
|
ribavirin
|
|
|
What drugs are used against VZV?
|
acyclovir
valcyclovir famciclovir foscarnet |
|
|
What is the mechanism of action for zidovudine?
|
analog of deoxythymidine
phosphorylated by cellular kinases -> AZTTP (which has greater affinity for RT than human DNA pol.) inhibitor of HIV RT |
|
|
What is the bioavailability of AZT?
|
65%
|
|
|
What is the half-life of AZT?
|
1 hour
|
|
|
What is the distribution of AZT?
|
brain
liver muscle placenta |
|
|
How is AZT excreted?
|
mostly in urine
|
|
|
What are the adverse effects of AZT?
|
granulocytopeina
anemia headache nausea insomnia |
|
|
What is AZT used for?
|
improve of quality of life
reduce incidence of opportunistic infections reduce transmission of HIV to offspring (given 14-34th week of gestation) |
|
|
When is didanosine used?
|
in patients unresponive/intolerant to zidovudine
|
|
|
What is the mechanism of action for didanosine?
|
analog of inosine
phosphorylated by cellular kinases -> termination of DNA synthesis inhibitor of HIV RT |
|
|
What are the adverse effects of didanosine?
|
abdominal cramps
diarrhea peripheral neuropathy acute pancreatitis hepatic failure |
|
|
Who should not be taking didanosine?
|
pts. w/ history of pancreatitis or alcoholism
|
|
|
What is the mechanism of action for zalcitabine?
|
inhibitor of HIV RT
|
|
|
What are the adverse effects of zalcitabine?
|
rash
stomatitis fever peripheral neuropathy pancreatitis |
|
|
When is zalcitabine used?
|
for pts. refractory to or intolerant of zidovudine
|
|
|
What is the mechanism of action for stavudine?
|
nucleoside analog
inhibitor of HIV RT |
|
|
What is the bioavailability of stavudine?
|
80%
|
|
|
What are the adverse effects of stavudine?
|
peripheral sensory
neuropathy pancreatitis |
|
|
What is the mechanism of action for lamivudine?
|
nucleoside-analog inhibitor of HIT RT
|
|
|
When is lamivudine used?
|
for pts. who have failed or are intolerant to approved drugs
|
|
|
What are the benefits of combining zidovudine and lamivudine?
|
suppresses HIV resistance to zidovudine
decreases viral load increases CD4 cell counts |
|
|
What is the bioavailability of abacavir?
|
95%
|
|
|
What are the adverse effects of abacavir?
|
hypersensitivity
fever nausea vomiting |
|
|
What is the mechanism of reaction for abacavir?
|
nucleoside analog
inhibits HIV RT |
|
|
What are the adverse effects of protease inhibitors for HIV therapy?
|
inhibits of metabolism of other drugs that use CYP3A4 isozyme
GI intolerance nephrotoxicity (indinavir) paresthesia taste perversion elevated triglycerides (ritonavir) diarrhea (nelfinavir) |
|
|
Do the protease inhibitors for HIV penetrate the CNS?
|
no
|
|
|
Which protease inhibitor for HIV has the lowest bioavailability?
|
saquinavir (4%)
|
|
|
Which protease inhibitor for HIV has the greatest bioavailability?
|
ritonavir (80%)
|
|
|
What is the mechanism of action for nevirapine?
|
NNRTI of HIV-1
binds directly to RT and blocks activity by disrupting the catalytic site does not compete with template or nucleoside triphosphate (does not inhibit HIV-2 RT and eukaryotic DNA pol.) |
|
|
What are the adverse effects of nevirapine?
|
severe rash - when occurs -> discontinue therapy
hepatitis |
|
|
What is the bioavailability of nevirapine?
|
90%
|
|
|
What are the adverse effects of delavirdine?
|
rash
|
|
|
What are the adverse effects of efavirenz?
|
rash
dizziness |
|
|
What is the mechanism of action for enfuvirtide?
|
inhibition of the fusion of HIV-1 w/ CD4+ cells
binds to the 1st heptan-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes |
|
|
What is the structure of enfuvirtide?
|
CH3CO-tyr-thr-ser-leu-ile-his-ser-leu-ile-glu-glu-ser-gln-asn-gln-gln-glu-lys-asn-glu-gln-glu-leu-leu-glu-leu-asp-lys-trp-ala-ser-leu-trp-asn-trp-phe-NH2
THIS WILL PROBABLY BE ON THE TEST!!! |
|
|
How is enfuvirtide administered?
|
IM 2x daily
give each injection at a site different from the preceding injection site and only where there is no current injection site rxn from an earlier dose (do not inject into moles, scar tissue, bruises, navel) |
|
|
What are the adverse effects of enfuvirtide?
|
pain at injection site
erythema induration nodules cysts high incidence of bacterial pneumonia (does not affect CYP450) |
|
|
Which anti-HIV drug is associated with high incidences of bacterial pneumonia?
|
enfuvirtide
|
|
|
What is the DOC for HIV infection in adults?
|
2 nucleosides + 1 protease inhibitor
2 nucleosides + 1 non-nucleoside alternatives 2 nucleosides 1 nucleoside + 1 protease inhibitor 2 protease inhibitors +/- nucleoside or non-nucleoside 1 protease inhibitor + 1 nucleoside + 1 non-nucleoside |
|
|
What does HAART therapy usually include?
|
1 nucleoside analog
1 protease inhibitor plus either another nucleoside analog or non-nucleoside RT inhibitor |
|
|
What is acyclovir active against?
|
HSV-1
HSV-2 VZV |
|
|
What is the half-life of acyclovir?
|
3.5 hours
|
|
|
What is the bioavailability of acyclovir?
|
15-20%
|
|
|
What drug reduces the renal clearance of acyclovir?
|
probenecid
|
|
|
What is valacyclovir used for?
|
treatment of VZV in immunocompetent adults
also effective against henital herpes |
|
|
What is the bioavailabilitiy of valacyclovir?
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50%
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What is the difference between acyclovir and valacyclovir?
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valacyclovir is a prodrug of acyclovir and is more rapidly absorbed
valacyclovir is hydrolyzed to acyclovir in the intestinal wall and liver |
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What is the mechanism of action for acyclovir?
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guanosine analog
activated by viral thymidine kinase inhibits herpes virus DNA by interfering w/ the action of viral DNA polymerase |
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What is the mechanism of action for ganciclovir?
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guanosine analog
inhibits herpes virus DNA by interfering w/ the action of viral DNA polymerase 100x more active against CMV than acyclovir |
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What are the adverse effects of gancyclovir?
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bone marrow suppression
neutropenia (40%) headache, psychosis, convulsions, coma (5%) |
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What drugs are used for the treatment of CMV retinitis?
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ganciclovir
cidofovir fomivirsen |
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What is the mechanism of action for cidofovir?
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nucleotide analog
pre-phosphorylated -> does not depend on phosphorylation by CMV enzyme taken up by CMV DNA pol. -> early chain termination |
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What is the mechanism of fomivirsen?
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antisense drug
complimentary to mRNA sequence for the major immediate-early transcriptional region of CMV inhibits CMV replication (active against resistant strains to ganciclovir, foscarnet, cidofovir) |
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What are the adverse effects of fomivirsen?
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iritis
vitritis cataracts increased intraocular pressure (15-20%) vision changes |
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What is the mechanism of action for vidarabine?
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analog of adenosine
inhibits viral DNA pol. -> early chain termination (mammalian DNA pol. inhibited to lesser extent) |
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Why is a large administration volume required for vidarabine?
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b/c of poor solubility
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What are the adverse effects of vidarabine?
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nausea
vomiting diarrhea hallucinations psychoses ataxia tremor pain syndrome dizziness bone marrow suppression |
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What is vidarabine used for?
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HSV
VZV (replaced by acyclovir, which is more effective and less toxic) used topically for superficial keratitis caused by HSV |
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What is the mechanism of action for idoxuridine?
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thymidine analog
incorporated into both viral and mammalian DNA -> DNA susceptable to breakage |
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What is idoxuridine used for?
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HSV infections of cornea
(not effective against genital herpes) |
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What are the adverse effects of idoxuridine?
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irritation
pain pruritus inflammation or edema of eyelids photophobia (not used systemically since it causes hepatic injury and is teratogenic and mutagenic) |
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What is the mechanism of action for trifluridine?
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thymidine analog
incorporated into viral DNA -> early chain termination |
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What is trifluridine used for?
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HSV-1 and 2 (including thymidine kinase deficient strains)
CMV vaccinia adenovirus used to treat keratoconjunctivitis caused by HSV-1 and 2 |
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What are the adverse effects of trifluridine?
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discomfort
irritation edema |
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What is docosanol used for?
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topical treatment of recurrent oral-facial herpes simplex episodes
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What is the mechanism of action for docosonal?
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inhibits fusion b/w the plasma membrane and viral envelope, blocking viral entry
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What are the adverse effects for docosanol?
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headache
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What are the anti-herpes agents?
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acyclovir/valcyclovir/famciclovir
ganciclovir cidofovir fomivirsen virdarabine idoxuridine trifluridine docosanol |
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What is the mechanism of action for ribavirin?
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phosphorylated to RMP by adenosine kinase
RMP inhibits IMP dehydrogenase -> decreasing guanine levels RMP converted to RTP -> inhibits viral RNA polymerase RTP inhibits GTP-dependent enzymes required for "capping" of viral mRNA |
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Where does ribavirin accumlulate?
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RBCs
half-life 40 days in RBCs |
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What are the adverse effects of ribavirin?
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anemia due to hemolysis
increased bilirubin, iron, uric acid levels in plasma teratogenic |
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What viruses is ribavirin active against?
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myxoviruses, paramyxoviruses, arenaviruses, bunyviruss, retroviruses, herpes viruses, adenoviruses, pox viruses, Lassa fever
(wide range of RNA and DNA viruses) |
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What is the mechanism of action for amantadine?
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not fully known
blocks late stage in assembly of influenza A virus acts to buffer pH of endosomes -> blocks fusion of virus envelope w/ endosome membrane blocks viral M2 protein -> blocks acidification of endosome -> blocks fusion |
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What are the adverse effects of amantadine?
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nervousness
confusion hallucinations seizure coma insomnia GI upsets dry mouth pupillary dilation |
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What is amatadine used for?
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treatment of influenza A (not B)
reduce severity and duration of influenza useful in treatment of Parkinsonism |
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What is the mechanism of action for zanamivir?
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neuraminidase inhibitor for influenza A and B -> prevent the release of progeny virons
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What is the mechanism of action for oseltamivir?
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neuraminidase inhibitor for influenza A and B -> prevent the release of progeny virons
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What is the bioavailability of zanamivir?
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<5%
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What is the bioavailability of oseltamivir?
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80%
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What are the adverse effects of zanamivir/oseltamivir?
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diarrhea
nausea headache nasal and throat discomfort (zanamivir) bronchospasm - pts. w/ asthma |
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What is the mechanism of foscarnet?
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inhibits viral DNA pol., RNA pol., and HIV RT by interacting w/ pyrophosphate binding site
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What are the adverse effects of foscarnet?
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reduced renal function
malaise nausea vomiting fatigue anemia |
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What is foscarnet used for?
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herpesviruses
CMV HIV (strains of HSV resistant to acyclovir and gancyclovir are sensitive to foscarnet) |
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What is the mechanism of action for interferons?
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INFs bind to cell surface receptors -> induces 2'-5' oligoadenylates -> activates latent ribonuclease that degrades
major effect: inhibition of viral protein translation |
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What are the adverse affects of interferons?
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chills, headaches, myalgias, nauesa, vomiting (INF-aplha)
bone marrow suppression fatigue, anorexia (long-term Tx) reduces activity of CYP450 system development of antibodies against INF |
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What are interferons used for?
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hairy-cell leukemia
Kaposi's sarcoma condylomata acuminata (genital warts) hepatitis B and C |
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