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283 Cards in this Set
- Front
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selective toxicity?
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injury of invading organisms without injury to the host
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concentration-dependent killing?
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the more the drug concentration exceeds the MIC, the greater the rate of killing;
Cmax/MIC or AUC/MIC |
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examples of drugs with concentration-dependent killing?
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fluroquinolones
aminoglycosides |
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time-dependent killing?
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rate of killing is dependent on the length of time the drug concentration remains above the MIC
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example of drug with time-dependent killing?
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β-lactams
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MIC?
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minimum inhibitory concentration
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post-antibiotic effect?
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bacteria do not immediately resume growth once the antibacterial concentration drops below the MIC
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bacteria susceptibility to PAE?
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most antibiotics for Gm(+)
only fluoroquinolones and aminoglycosides fro Gm(-) |
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superinfection and examples?
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secondary infection caused by antibiotic;
oral or vaginal candidiasis; pseudomembranous colitis (c. difficile) |
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intrinsic resistance?
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absence of drug target
inability of drug to penetrate to site of action |
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acquired drug resistance?
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antibiotics help select for drug resistant organisms but do not cause drug resistance
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how do organisms acquire resistance?
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random mutations
transduction transformation conjugation |
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major concern with conjugation?
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transfer of plasmids that code for multiple drug resistance
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transformation?
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acquisition of genetic material from environment coding for drug resistance by competent bacteria
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two major competent pathogens?
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s. pneumoniae
n. meningitides |
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biomechanical mechanisms of drug resistance?
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decreased intracellular concentration
inactivation decreased affinity |
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why not use antibiotics together if their effect is additive?
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not enhance very much but introduces possibilities of more side effects, etc
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synergistic combinations?
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cell wall synthesis inhibitors + aminoglycosides;
trimethoprim-sulfamethoxazole; quinupristin/dalfopristin; amphotericin B + flucytosine |
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breakpoint?
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drug concentration that determines if an organism is susceptible or resistant
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when use combination antibacterial therapy?
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mixed infections
delay emergence of resistance synergism unknown etiology |
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crosslinking of peptidoglycan occurs via which amino acids?
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glycine and D-alanyl-D-alanine
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mechanism of β lactams?
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act on growing bacteria by binding to and irreversibly inactivating several penicillin binding proteins (PBPs);
activate a group of bacterial enzymes, autolysins, causing degradation of the cell wall |
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transpeptidase?
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enzyme responsible for crosslinking the linear glycopeptide strands of the cell wall
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end consequence on bacteria treated with β lactams?
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bactericidal
time-dependent killing weakened cell wall lysis |
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β lactamase?
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multiple families of enzymes that hydrolyze β lactam ring to carboxylic acids without antibacterial activity
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β lactamase in Gm(+)?
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coded by plasmid
most commonly penicillinases secreted |
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β lactamase in Gm(-)?
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coded by genetic elements on chromosome or a plasmid;
can be constitutively expressed or be inducible; broad spectrum that hydrolyze several different substrates; localized to periplasmic space |
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resistance to β lactams?
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β lactamase
decreased pore size [Gm(-)] altered PBPs |
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MRSA and MDRSP method of resistance to β lactams?
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altered PBPs that have either very low or no affinity for β lactam drugs
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all penicillins are derived from?
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6-aminopenicillanic acid
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disadvantages of pharmacokinetics of penicillin?
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destroyed by acid content in stomach;
actively secreted from kidney tubules by anion transport system |
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use of probenecid with penicillin?
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prolongs duration by blocking its active transport in the proximal tubule
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repository forms of penicillin G and benefit?
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procaine and benzathine salts are administered IM into large muscle mass and slowly absorbed
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means of prolonging duration of action of penicillin?
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simultaneous administration of probenecid;
repository forms (procaine and benzathine salts) |
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deficiencies of penicillin?
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low oral bioavailability
β lactamase inactivation narrow therapeutic spectrum |
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natural penicillins?
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penicillin G
penicillin V |
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penicillin V?
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form resistant to acid so more reliable absorption
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pencillinase-resistant penicillins?
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methicillin
oxacillin cloxacillin dicloxacillin nafcillin |
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use of nafcillin?
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chiefly excreted in the bile so useful for renal failure patients to treat penicillinase-producing staphlococci
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amino or extended spectrum penicillins?
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ampicillin
bacampicillin amoxicillin |
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ampicillin effective against?
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e. coli
h. influenzae salmonella shigella some proteus species |
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amoxicillin advantage?
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given po as has good stability and is better absorbed than ampicillin;
not used for shigellosis |
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antipseudomonal penicillins?
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carbenicillin
ticarcillin piperacillin |
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antipseudomonal penicillin spectrum?
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enhanced activity against:
pseudomonas enterobacter indole (+) proteus klebsiella |
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β lactamase inhibitors?
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clavulanic acid
sulbactam tazobactam |
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mechanism of clavulanic acid, sulbactam, and tazobactam?
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irreversibly inactivate some β lactamases
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penicillin plus β lactamase inhibitor combinations available?
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amoxicillin/clavulanic acid
ampicillin/sulbactam piperacillin/tazobactam ticarcillin/clavulanic acid |
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characteristics of hypersensitivity reactions to penicillins?
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cross-sensitivity;
more often = delayed allergic reaction (maculopapular eruptions, fever, or both); less common, more serious = immediate mediated by IgE |
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adverse effects of penicillins?
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hypersensitivity
serum sickness hemolytic anemia allergic interstitial nephritis convulsions at high doses |
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carbenicillin and ticarcillin adverse effects?
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bind ADP receptor on platelets leading to impaired aggregation and coagulation;
electrolyte disturbances |
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which drugs may cause impaired platelet aggregation or electrolyte disturbances?
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carbenicillin
ticarcillin |
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ampicillin and amoxicillin adverse reaction?
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rash that is not immune mediated;
100% incidence in mono patients |
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cause rash that is not immune mediated?
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ampicillin
amoxicillin |
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cephalosporins general mechanism and characteristics?
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bactericidal;
inhibit cell wall synthesis similarly to penicillins and are similarly resisted; intrinsically resistant to Gm(+) penicillinase |
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cephalosporin susceptibility to β lactamases?
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intrinsic resistance to Gm(+) penicillinase;
hydrolyzed by cephalosporinase and broad spectrum β lactamases |
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trends as proceed from 1st to 4th generation cephalosporins?
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increased flux across outer membrane of Gm(-);
increase stability toward Gm(-) β lactamases |
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how does penicillin penetrate cerebrospinal fluid?
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normally poor penetration
meningeal inflammation allows accumulation in CFS |
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cephalosporins penetration of bbb?
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most 1st and 2nd generation do not penetrate even when inflammation is present
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1st generation cephalosporins?
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cephalexin
cefazolin |
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activity of 1st generation cephalosporins?
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active against:
Gm(+) cocci e. coli k. pneumoniae p. mirabilis ineffective against: enterococci MRSA listeria penicillin-resistant streptococci |
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2nd generation cephalosporins?
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cefuroxime
cefaclor |
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spectrum of cefuroxime and cefaclor (2nd)?
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e. coli
klebsiella proteus h. influenzae moraxella catarrhalis |
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cefotetan?
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cephamyin
more resistant to β lactamases similar spectrum as 2nd gen added activity against b. fragilis |
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which has added activity against bacteroides fragilis?
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cefotetan
|
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3rd generation cephalosporins?
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cefotaxime
ceftazidime ceftriaxone |
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spectrum of cefotaxime, ceftazidime, and ceftriaxone?
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expanded Gm(-) specturm and some CNS penetration;
enterobacteriaceae; pseudomonas; serratia; n. gonarrhoeae; s. aureus; strep. pyogenes |
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4th generation cephalosporins?
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cefepime
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spectrum of cefepime?
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similar to 3rd but more resistance to some β lactamases
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adverse effects of cephalosporins?
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hypersensitivity
renal damage local tissue reactions interfere with vitamin K metabolism disulfuram like reaction |
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cephalosporin causing a serum sickness-like reaction in children?
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cefaclor
|
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pseudocholelithiasis as adverse effect?
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ceftriaxone
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contraindication for cephalosporins?
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individuals who have experienced an immediate-type or other serious allergic reaction to penicillin
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carbapenems?
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imipenem
meropenem ertapenem |
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widest spectrum of activity of any β lactam?
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imipenem
held in reserve for resistant infections |
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what is imipenem combined with and why?
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cilistatin to prevent the metabolic inactivation of imipenem by enzyme dehydropeptidase
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adverse reactions of imipenem?
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allergic (some cross sensitivity with penicillins and cephalosporins);
seizures |
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difference between imipenem and meropenem or ertapenem?
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meropenem and ertapenem are resistant to metabolism by dehydropeptidase
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aztreonam class and spectrum?
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monobactam;
Gm(-); excellent stability to β lactamase; main use is treatment of nosocomial Gm(-) pathogens |
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vancomycin class and mechanism?
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glycopeptide antibiotic
binds terminal D-alanyl-D-alanine to inhibit transglycosylase preventing further elongation of peptidoglycan chain and cross-linking |
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resistance to vancomycin?
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substitution of a D-lactic acid for the terminal D-alanine
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'redman' or 'red neck syndrome'?
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flushing of upper body caused by rapid infusion of vancomycin;
vancomycin-induced release of histamine from mast cells |
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vancomycin spectrum?
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narrow Gm(+) antibiotic:
MRSA antibiotic-induced enterocolitis streptococcal endocarditis (+ cephalosporin) MDRSP |
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adverse effects of vancomycin?
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redman or red neck syndrome
nephrotoxicity ototoxicity |
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other miscellaneous inhibitors of cell wall synthesis?
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bacitracin
cycloserine fosfomycin teicoplanin |
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which not approved in us due to treatment failure?
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teicoplanin
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bacitracin?
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peptide antibiotic
used topically due to extreme nephrotoxicity |
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macrolides?
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erythromycin
clarithromycin azithromycin |
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resistance to macrolides?
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efflux pump
mutation of ribosomal binding site methylation of binding site (cross resistance) |
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macrolide mechanism?
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protein synthesis inhibitor that binds the 50S ribosome;
generally considered bacteriostatic |
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erythromycin pharmacokinetics?
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destroyed in stomach;
concentrated in liver and excreted in bile; metabolized by P450; potent inhibitor of CYP3A4 |
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problems with erythromycin?
|
narrow antibacterial spectrum
instability in acid severe abdominal cramping in some inhibition of CYP3A4 |
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clarithromycin?
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broader spectrum than erythromycin;
less likely to produce gi upset; inhibits P450 |
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azithromycin?
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macrolide;
higher tissue concentrations; expanded spectrum from erythromycin |
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adverse effects of erythromycin?
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cholestatic hepatitis;
epigastric distress |
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ketolide mechanism and consequence?
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binds domains II and V of 23S rRNA;
poor ligand for efflux pump; binding to domain II is sufficient for inhibition of protein synthesis |
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telithromycin?
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ketolide;
treatment of community acquired pneumonia |
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telithromycin adverse effects?
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acute hepatic failure and severe liver injury;
not to be used in patients with myasthenia gravis |
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lincosamide mechanism?
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similar to macrolides
|
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clindamycin spectrum?
|
lincosamide:
many Gm(+) community acquired MRSA highly active vs b. fragilis |
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which antibiotic has affinity for osseus tissue?
|
clindamycin
|
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adverse effects of clindamycin?
|
most frequently associated with pseudomembranous colitis
|
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most frequently associated with pseudomembranous colitis?
|
clindamycin
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quinupristin/dalfopristin?
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streptogramin (synercid is combo):
50S ribosome protein synthesis inhibitors; synergistic because bind at different sites that are unrelated |
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which compounds have to cross resistance with other agents that inhibit 50S ribosome?
|
quinupristin
dalfopristin linezolid |
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quinupristin/dalfopristin spectrum?
|
Gm(+)
used for nosocomial infections or those that do not respond to other agents |
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streptogramins adverse effects?
|
metabolized by CYP3A4
venous problems at infusion site arthralgia myalgia |
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linezolid?
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oxazolidinone:
50S ribosome inhibitor Gm(+) spectrum enterococci |
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linezolid pharmacokinetics?
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nearly 100% bioavailability
does not inhibit or induce P450 |
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linezolid adverse effects?
|
myelosuppression
peripheral neuropathy nonspecific monoamine oxidase inhibition |
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which possesses nonspecific monoamine oxidase inhibition?
|
linezolid
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chloramphenicol?
|
nitrobenzene:
50S ribosome inhibitor use is restricted to when no other antibacterial is effective |
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resistance chloramphenicol?
|
due to acetylation that converts to inactive metabolite
|
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chloramphenicol pharmacokinetics?
|
rapidly absorbed and widely distributed;
conjugated by glucuronosyl transferase |
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adverse effects of chloramphenicol?
|
aplastic anemia
blood dyscrasias gray-baby or gray syndrome |
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aplastic anemia and chloramphenicol?
|
not dose related;
symptoms can start as long as 6 months after use; not reversible |
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blood dyscrasias and chloramphenicol?
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dose dependent;
reversible |
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gray syndrome?
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chloramphenicol caused:
cyanosis respiratory irregularities vasomotor collapse abdominal distention loose green stools ashen-gray color (cannot adequately conjugate the drug to eliminate it) |
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tetracyclines mechanism?
|
30S ribosome inhibitor;
bacteriostatic; inhibit both eukaryotic and prokaryotic cells |
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why are tetracyclines somewhat selective for bacteria?
|
susceptible organisms have an active transport system
|
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resistance to tetracyclines?
|
pump that removes drugs from cells
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tetracyclines?
|
tetracycline
minocycline doxycycline |
|
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why has use of tetracyclines declined?
|
increasing bacterial resistance
newer, more effective antibiotics |
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similarities/differences between the tetracyclines?
|
similar structures
similar antibacterial spectrum difference is drug half life |
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why is doxycycline preferred over other tetracyclines?
|
long half life
nearly complete absorption high tissue concentrations excretion in feces (does not accumulate when compromised renal function) |
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use of tetracyclines?
|
rickettsiae
chlamydiae mycoplasmas h. pylori plasmodia amebas |
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adverse effects of tetracyclines?
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hypersensitivity with cross sensitization;
phototoxic reaction; hepatic dysfunction; tooth discoloration and depressed bone growth in children |
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minocycline adverse effects?
|
vertigo and dizziness
hyperpigmentation due to iron complexes in skin |
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tetracyclines drug interactions?
|
antacids, milk, or multivitamins inhibit absorption of tetracyclines
|
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tigecycline?
|
glycylcycline: similar to tetracyclines
|
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resistance to tigecycline?
|
not affected by common mechanisms;
unaffected by tetracycline efflux pumps; exception is efflux pump in pseudomonas); no cross-resistance with other classes |
|
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tigecycline spectrum?
|
activity against variety of multidrug-resistant pathogens
|
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adverse effects of tigecycline?
|
high occurrence of nausea and vomiting (1/3)
|
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aminoglycoside mechanism?
|
bactericidal inhibitors via interference with initiation, cause misreading, produced decreased or abnormal proteins;
taken up by bacteria in energy-dependent oxygen-dependent process |
|
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resistance to aminoglycosides?
|
metabolism by bacteria to inactive species
|
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aminoglycoside specificity for bacteria vs host?
|
large, low lipid solubility, and high polycationic charge allow for poor penetration except to specialized cells (renal tubular, hair cells);
bacteria have an uptake pump |
|
|
aminoglycosides?
|
gentamicin
tobramycin amikacin kanamycin streptomycin neomycin |
|
|
three aminoglycosides most important for treating systemic infections due to Gm(-) enteric bacteria?
|
gentamicin
tobramycin amikacin |
|
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kanamycin use?
|
bowel sterilization prior to surgery
|
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streptomycin use?
|
treatment of TB
|
|
|
neomycin use?
|
topically or in irrigation solutions
|
|
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aminoglycosides dosing?
|
narrow ti
once daily limits side effects requires adjustment for kidney function dose based on lean body mass |
|
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adverse effects of aminoglycosides?
|
ototoxicity
nephrotoxicity neuromuscular blockade |
|
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fluoroquinolone mechanism?
|
inhibit bacterial DNA gyrase Gm(-) and topoisomerase IV Gm(+)
|
|
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resistance to fluoroquinolones?
|
mutation of gyrA
mutation of gyrB (low level) active efflux (cross resistance) |
|
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where do fluoroquinolones accumulate and why might this be beneficial?
|
prostate, kidney, neutrophils, macrophages;
in prostate is good to prevent reseeding following treatment for UTI |
|
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fluoroquinolones?
|
ciprofloxacin
levofloxacin gatifloxacin moxifloxacin |
|
|
fluoroquinolone black box warning?
|
tendon rupture following vigorous exercise
|
|
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adverse effects of fluoroquinolones?
|
gi disturbance
rash headache vertigo excitement visual disturbances tendon rupture not in children to due to possible damage of cartilage |
|
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rifamycins?
|
rifampin
rifabutin |
|
|
rifampin mechanism?
|
inhibits DNA dep RNA polymerase
|
|
|
resistance to rifampin?
|
develops rapidly when used as a single agent
|
|
|
use of rifampin?
|
TB
in combo carriers of n. meningitidis |
|
|
rifampin drug interactions?
|
potent inducer of CYP3A4
|
|
|
sulfonamide selectivity?
|
consequence of fact that source of folic acid is different for humans and bacteria;
humans require dietary folic acid while many bacteria synthesize it de novo |
|
|
sulfonamide mechanism?
|
structural PABA analog and act as competitive inhibitor of dihydropteroate synthetase
|
|
|
resistance to sulfonamides?
|
increased PABA synthesis
altered dihydropteroate synthetase utilize exogenous folic acid |
|
|
sulfonamides pharmacokinetics?
|
oral absorption
renal elimination metabolized by acetylation |
|
|
sulfonamides?
|
sulfisoxazole
sulfamethoxazole sulfacetamide silver sulfadiazine sulfasalazine |
|
|
sulfisoxazole and sulfamethoxazole use?
|
UTIs
|
|
|
sulfacetamide use?
|
ophthalmic infection
topical application |
|
|
silver sulfadiazine use?
|
prevent colonization of burns by bacteria
|
|
|
adverse effects of sulfonamides?
|
mild rash to steven johnsons
drug fever blood dyscrasias eosinophilia crystalluria hepatitis kernicterus in newborns |
|
|
can cause kernicterus?
|
sulfonamides
|
|
|
trimethoprim mechanism and specificity?
|
inhibits dihydrofolate reductase;
greater affinity for bacterial enzyme vs mammalian enzyme |
|
|
trimethoprim + sulfamethoxazole?
|
sequential inhibition of formation of tetrahydrofolate;
synergistic making it bactericidal vs bacteriostatic; bronchitis; otitis media; PCP |
|
|
adverse effects of trimethoprim?
|
potential to interfere with folate metabolism in malnourish individuals
|
|
|
characteristic of urinary tract antiseptic effects?
|
no systemic activity
exert effects entirely in urinary tract |
|
|
why is there no systemic activity with urinary tract antiseptics?
|
rapid elimination
high protein binding requirement for low pH to be effective |
|
|
urinary tract antiseptics?
|
nitrofurantoin
methenamine fosfomycin |
|
|
nitrofurantoin and its adverse effects?
|
urinary tract antiseptic
gi disturbances headache acute allergic pulmonary (chills, cough, pulmonary infiltrations) chronic pulmonary fibrosis |
|
|
why is fosfomycin useful for urinary tract infections?
|
distributed to bladder, prostate, etc
|
|
|
drugs that act at the bacterial cytoplasmic membrane?
|
daptomycin
colistin colistimethate polymyxin B |
|
|
daptomycin mechanism?
|
binds cell membrane of Gm(+) cells in Ca-dependent process that disrupts the membrane potential
|
|
|
daptomycin has activity against?
|
growing or resting bacteria
biofilms MRSA VRSA VRE |
|
|
polymyxins?
|
colistin
colistimethate polymyxin B |
|
|
polymyxin mechanism?
|
surface-active amphipathic agents;
penetrate cell membranes, interact with phospholipids, disrupt the membranes of Gm(-) aerobic bacilli; bactericidal in concentration-dep manner; have post-antibiotic effect |
|
|
use of polymyxins?
|
fell into disuse due to nephrotoxicity;
used as last resort against some Gm(-) organisms |
|
|
metronidazole?
|
reduced to free radical by bacteria ultimately damaging bacterial DNA
|
|
|
metronidazole use?
|
antiprotozoal
anaerobic bacteria c. difficile esp |
|
|
metronidazole adverse effects?
|
headache
metallic taste disulfuram like reaction when consuming alcohol |
|
|
spectinomycin?
|
alternative drug to n. gonnorhea including penicillinase-producing strains in patient allergic to other drugs;
not active against t. pallidum |
|
|
major TB drugs?
|
isoniazid
rifampin ethambutol streptomycin pyrazinamide |
|
|
treatment of TB?
|
multiple drugs with separate MOAs to decrease chance of resistant organisms developing
|
|
|
isoniazid mechanism?
|
inhibits synthesis of mycolic acids;
bactericidal for growing; bacteriostatic for resting; requires a catalase/peroxidase enzyme for activation |
|
|
isoniazid elimination?
|
primarily acetylation - consequence of polymorphisms
|
|
|
consequence of slow acetylator taking isoniazid?
|
no effect on efficacy
more prone to peripheral neuropathy |
|
|
mechanism of peripheral neuropathy with slow acetylators?
|
increased excretion of pyridoxine caused by isoniazid;
can be diminished by supplementing diet with pyridoxine |
|
|
isoniazid side effects?
|
peripheral neuropathy (slow acetylators);
isoniazid-induced hepatitis |
|
|
primary agent for treatment of TB and only drug approved for prophylaxis?
|
isoniazid
|
|
|
rifampin mechanism?
|
inhibits transcription by inactivating DNA dep RNA polymerase
|
|
|
second most important drug in TB treatment?
|
rifampin
|
|
|
adverse effects of rifampin?
|
minor cutaneous, gi, or hepatic reactions;
potent inducer of CYP3A4 |
|
|
ethambutol?
|
major drug used for TB
|
|
|
ethambutol adverse effects?
|
uni or bilateral ocular toxicity
hyperuricemia, may precipitate gout |
|
|
characteristics of uni or bilateral ocular toxicity and associated drug?
|
ethambutol dose related, reversible
gradual loss in visual acuity decrease in visual fields loss of red/green color discrimination |
|
|
streptomycin use and disadvantages?
|
major TB drug
must be injected ototoxic nephrotoxic |
|
|
dapsone use and mechanism?
|
treatment of leprosy
inhibition of folic acid synthesis |
|
|
clofazimine use and mechanism?
|
treatment of leprosy
interfere with replication of bacterial DNA |
|
|
drugs used to treat leprosy?
|
dapsone
clofazimine rifampin |
|
|
polyenes?
|
nystatin
amphotericin B |
|
|
polyenes mechanism?
|
bind to sterols, especially erogsterol, to alter membrane permeability
|
|
|
nystatin use?
|
localized fungal infections
too toxic to be used systemically |
|
|
gold standard for drugs to treat serious systemic fungal infections?
|
amphotericin B
|
|
|
pharmacokinetics of amphotericin B?
|
poor gi absorption, given iv
half-life of 15 days stored in tissues, slowly excreted in urine |
|
|
amphotericin B adverse effects?
|
anaphylaxis
fever chills headache gi disturbances decreased renal function (80% of patients) |
|
|
renal function and amphotericin B?
|
decreased in 80% and typically does not fully recover after therapy is completed
|
|
|
classes of antifungals?
|
polyene
fluorinated pyrimidine azole allyamine echinocandin |
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flucytosine mechanism?
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fluorinated pyrimidine;
taken up by fungus-specific enzyme cytosine permease; converted by cytosine deaminase to 5-fluorouracil; causes RNA miscoding and inhibits DNA synthesis |
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use of flucytosine and why?
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synergistic with amphotericin B;
rapid resistance as single agent |
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flucytosine adverse effects?
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potentially lethal bone marrow depression;
gi upset; rash; hepatic dysfunction |
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bone marrow depression and flucytosine?
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gut bacteria convert to active 5-fluoruracil and body uses
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azole mechanism?
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inhibit fungal P450, lanosterol 14α-demethylase, required for conversion of lanosterol to erogsterol leading to depletion of ergosterol and failure of cytoplasmic membrane;
inhibit mammalian P450s to some degree |
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resistance mechanisms to azoles?
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alterations to target binding site
increased target expression induction of efflux pumps |
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azoles?
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ketoconazole
itraconazole fluconazole voriconazole |
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ketoconazole adverse effects?
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gynecomastia
menstrual irregularities drug interactions need acidic pH for absorption |
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greatest ability to inhibit mammalian P450s?
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ketoconazole
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distribution of itraconazole?
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extensive in lipophilc tissues
accumulates in the stratum corneus |
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most potent of azoles?
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itraconazole
|
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fluconazole pharmacokinetics?
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over 90% oral bioavailability;
widely distributed into body tissues and fluids; urine and skin concentrations = 10x plasma; distributes well into CSF; elimination primarily renal |
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used successfully of invasive fungal infections, including aspergillosis in children refractory or intolerant of conventional antifungal therapy?
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voriconazole
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terbinafine mechanism?
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potent noncompetitive inhibitor of fungal squalene epoxidase (early step in ergosterol synthesis)
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terbinafine + amphotericin B?
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additive or synergistic interactions vs aspergillus
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terbinafine + itraconazole or voriconazole?
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potent syngergistic interactions against aspergillus
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terbinafine + fluconazole?
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additive to synergistic interaction
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caspofungin?
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echinocandin
inhibits synthesis of β-1,3-D-diglucans (essential component of fungal cell wall); approved for invasive aspergillosis in patients that don't respond to other antifungals |
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griseofulvin?
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miscellaneous antifungal
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amantadine and rimantadine mechanism?
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inhibits viral uncoating or disassembly of virion during endocytosis;
inhibit ion channel function of the M2 protein |
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use of amantadine and rimantaine?
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prophylaxis during influenza A virus epidemics
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amantadine adverse effects?
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confusion
hallucination seizure coma |
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antiviral agents for respiratory viruses?
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amantadine
rimantadine oseltamivir zanamivir ribavirin |
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neuraminidase inhibitors?
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oseltamivir
zanamivir |
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oseltamivir and zanamivir mechanism of action?
|
inhibit neuroaminidase (normally removes the sialic acid residues from surface to prevent clumping);
cause clumping of virions making then noninfectious; active against influenza A and B |
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major difference between oseltamivir and zanamivir?
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zanamivir is administered by inhalation;
oseltamivir is taken orally |
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ribavirin mechanism?
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guanosine analogue;
rapidly phosphorylated to compete with guanosine triphosphate-dependent 5'-capping of influenza viral mRNA |
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use of ribavirin?
|
influenza viruses
RSV parainfluenza viruses adenoviruses hepatitis C (+ INF-a) |
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acyclovir mechanism?
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synthetic purine nucleoside analog;
phosphorylated by viral thymidine kinase; competitive inhibitor of viral DNA polymerase; incorporation leads to premature chain termination |
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loss of thymidine kinase activity by a virus causes resistance to what antivirals?
|
acyclovir
valacyclovir famciclovir ganciclovir |
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acyclovir use?
|
iv for serious HSV and VZV infections
|
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valacyclovir?
|
L-valine isomer of acyclovir;
metabolized to acyclovir |
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acyclovir adverse effects?
|
headache
rash gi disturbances crystalline nephropathy |
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spectrum of acyclovir?
|
HSV1, HSV2 > VZV > CMV
|
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famciclovir mechanism?
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inhibits viral DNA polymerase
NO chain termination |
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ganciclovir activity?
|
similar to acyclovir but enhanced activity against CMV;
inhibitor and substrate for viral DNA polymerase |
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ganciclovir adverse effects?
|
granulocytopenia
thrombocytopenia |
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ganciclovir is approved to treat?
|
CMV retinitis, colitis, and esophagitis in AIDS patients;
prevent and treat CMV disease in transplant patients |
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cidofovir?
|
alternative to ganciclovir or to treat ganciclovir resistant CMV
|
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trifluridine use?
|
topic (HSV keratoconjunctivitis)
too toxic for systemic use as causes strand breakage when incorporated into viral or mammalian DNA |
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foscarnet mechanism?
|
binds phosphate binding site of viral DNA or RNA polymerase and HIV reverse transcriptase and inhibits the enzyme
|
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foscarnet use?
|
resistant CMV retinitis and acyclovir-resistant HSV and VZV;
last resort due to high nephrotoxicity |
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what does HAART stand for?
|
Highly
Active Anti Retroviral Therapy |
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purpose of HAART?
|
HIV rapidly becomes resistant when single drug is used;
survivorship is inversely related to circulating level of HIV RNA in the blood; survivorship is positively correlated with CD4 count |
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goals of HAART?
|
reduce blood levels of HIV RNA to undetectable levels (<50 copies RNA/mL blood);
maintain the CD4 count |
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classes of drugs used to treat HIV?
|
nucleoside/nucleotide reverse transcriptase inhibitors (nRTI);
non-nucleoside reverse transcriptase inhibitors (nnRTI); HIV protease inhibitors (PI); fusion inhibitor; entry inhibitor; integrase inhibitor |
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nRTIs mechanism?
|
require intracellular phosphorylation;
competitive inhibitors of normal nucleoside triphosphates for HIV reverse transcriptase; are incorporated and act as chain terminators; lack ribose 3'-hydroxyl group |
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nRTIs?
|
zidovudine
stavudine lamivudine zalcitabine emtricitabine tenofovir didanosine abacavir |
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nRTIs adverse effects?
|
lactic acidosis
hepatic steatosis peripheral neuropathy myopathy lipoatrophy (inhibit mitochondrial DNA polymerase-g and causing mitochondrial dysfunction) |
|
|
nnRTIs mechanism?
|
no intracellular metabolism necessary;
allosteric binding in noncompetitive fashion near active site of reverse transcriptase to lock the enzyme to an inactive state |
|
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nnRTIs?
|
efavirenz
nevirapine |
|
|
nnRTIs adverse effects?
|
cross-resistance is common;
rash that sometimes can be very severe; metabolized by CYP3A4 |
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protease inhibitor mechanism?
|
bind to active site of the enzyme
|
|
|
protease inhibitors?
|
atazanavir
fosamprenavir darunavir lopinavir squinavir |
|
|
ritonavir?
|
protease inhibitor booster;
very potent inhibitor of P450 that metabolizes the PIs |
|
|
protease inhibitor adverse effects?
|
gi intolerance
increase aminotransferase activity increased bleeding in hemophiliacs hyperglycemia new onset or worsening diabetes insulin resistance fat wasting and redistribution metabolized by P450 |
|
|
drug to be avoided with protease inhibitors and why?
|
rifampin due to CYP3A4 inducing action - decreases effectiveness of the protease inhibitors
|
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|
which HIV drugs are used for those that have failed therapy?
|
fusion inhibitor (enfuvirtide)
entry inhibitor (maraviroc) integrase inhibitor (raltegravir) |
|
|
enfuvirtide?
|
fusion inhibitor
binds gp41 preventing fusion |
|
|
maraviroc?
|
entry inhibitor
binds CCR5 (coreceptor) |
|
|
which strains of HIV are resistant to maraviroc?
|
those that use CXCR4 as coreceptor
|
|
|
raltegravir?
|
integrase inhibitor
prevents insertion of HIV DNA into human genome |
|
|
what form is malaria in when it is in the salivary gland of the mosquito?
|
sporozoite
|
|
|
life cycle of malaria in human?
|
sporozoite injected --> invade liver and form an exoerythrocytic or hepatic schizont --> release merozoites by rupturing --> invade erythrocytes to form erythrocytic schizonts --> rupture to release merozoites --> etc
|
|
|
which forms of plasmodium can also remain dormant in liver and what are the dormant form called?
|
p. vivax and p. ovale
hypnozoites later reactivated |
|
|
p. falciparum?
|
most severe form
frequently drug resistant |
|
|
drug of choice for erythrocytic stage of malaria?
|
chloroquine
|
|
|
drug of choice for erythrocytic stage of malaria resistant to chloroquine?
|
mefloquine
|
|
|
for cure of malaria due to p. vivax or p. ovale?
|
primaquine to treat hepatic stage
|
|
|
quinine adverse effects?
|
cinchonism: tinnitus, headache, nausea, visual distrubances
|
|
|
antimalarials?
|
chloroquine
mefloquine quinine primaquine pyrimethamine + sulfadoxine atovaquone/proguanil |
|
|
fansidar?
|
pyrimethamine + sulfadoxine
|
|
|
malarone?
|
atovaquone/proguanil
|
|
|
atovaquone mechanism?
|
disrupts the mitochondrial electric transport
|
|
|
proguanil mechanism?
|
inhibitor of plasmodial dihydrofolate reductase
|
|
|
other antiprotozoals?
|
metronidazole
idoquinol diloxanide furoate pentamidine |
