Term
| half life of penicillin G (30 min) can be prolonged when injected IM with ? |
|
Definition
|
|
Term
| narrow spectrum, penicillinase resistant |
|
Definition
1) methicillin
2) nafcillin
3) dicloxacillin
4) oxacillin |
|
|
Term
| are penicillinase resistant drugs resistant vs. gram (-) ? |
|
Definition
| no, b/c they are hydrophobic and the porins are hydrophillic |
|
|
Term
| vancomycin + ? vs. MRSA when foreign body involved |
|
Definition
|
|
Term
|
Definition
| by IV due to poor oral and IM absorption |
|
|
Term
| dicloxacillin and oxacillin administered? |
|
Definition
| absorbed well orally but inhibited by food, should be administered IV in life threatening situations. |
|
|
Term
| narrow-spectrum penicillinase resistant elimination? |
|
Definition
| by liver as well as kidney so dosage doesn't have to be adjusted in renal failure |
|
|
Term
| extended spectrum aminopenicillins |
|
Definition
1) ampicillin
2) amoxicillin |
|
|
Term
| an amino side group increases the ability of these drugs to penetrate gram (-) porins |
|
Definition
1) ampicillin
2) amoxicillin |
|
|
Term
| ampicillin and amoxicillin are susceptible to ? |
|
Definition
| B-lactamases so generally not useful vs. staph |
|
|
Term
| IV ampicillin is drug of choice for? |
|
Definition
1) Listeria
2) enterococci
3) anaerobes |
|
|
Term
| amoxicillin (AMOXIL) is used empirically for ? |
|
Definition
| respiratory tract infections |
|
|
Term
| amoxicillin or ampicillin is better absorbed orally? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| clavulanic acid administered with amoxicillin (orally, AUGMENTIN) or with ticarcillin (injected, TIMENTIN)can extend their spectrum to include? |
|
Definition
| penicillinase producing staph and H. influenza |
|
|
Term
| ticarcillin (TICAR) active against? |
|
Definition
1) pseudomonas aeruginosa
2) some ampicillin-resistant Proteus strains |
|
|
Term
| Piperacillin (PIPRACIL)active vs. ? |
|
Definition
1) Pseudomonas aeruginosa
2) some ampicillin-resistant proteus strains
3)Klebsiella
(basically, same as ticarcillin but also kills klebsiella) |
|
|
Term
| ? used with a B-lactamase inhibitor has the broadest spectrum of all penicillins |
|
Definition
|
|
Term
| extended-spectrum anti-pseudomonal penicillins |
|
Definition
1) Ticarcillin
2) Pipercillin |
|
|
Term
| administration of extended-spectrum antipseudomonal penicillins |
|
Definition
| injection b/c oral absorption is poor |
|
|
Term
| clearance of exteended spectrum anti-pseudomonal penicillins |
|
Definition
|
|
Term
| most important side effects of penicillin |
|
Definition
| hypersensitivity rxn , including anaphylactic rxns (can be fatal, allergy to one means risk of allergy to another) penicillins are the most likely to cause an anaphylactic ir aaphylactoid rxn |
|
|
Term
| difference in geneerations of cephalosporins |
|
Definition
| classified 1st to 4th gen. Later gen having broader spectra and greater resistance to B-lactamases |
|
|
Term
| mech of action of cephalosporins |
|
Definition
| inhibit transpeptidase like penicillins |
|
|
Term
| general indications of cephalosporins |
|
Definition
| w/ aminoglycosides for serious infections wiith: 1)klebsiella 2)enterobacter 3)proteus 4)serratia 5)haemophilus |
|
|
Term
| side effects of cephalosporins |
|
Definition
| hypersensitivity; cross allergenicity b/w these and penicillins so just in case dont give pt a cephalosporin after a recent severe, immediate rxn to penicillins |
|
|
Term
| excretion of cephalosporins |
|
Definition
| by kidney so must adjust dose in MOST cases |
|
|
Term
| first gen cephalosporins are effective against? |
|
Definition
| aerobic gram (+) bacteria, oral cavity anaerobes and S. aureus (unlike penicillin G) |
|
|
Term
| 1st generation cephalosporin with the longest half life |
|
Definition
| cefazolin (ANCEF, KEFZOL) |
|
|
Term
| first generation cephalosporins |
|
Definition
1) cefazolin (ANCEF, KEFZOL)
2) cephalexin (KEFLEX) |
|
|
Term
|
Definition
1) E. coli
2) klebsiella
3) s. aureus
(resistant to some B-lactamases) |
|
|
Term
| cephalexin (KEFLEX)active vs. |
|
Definition
similar in spectrum to cefazolin but less active vs. penicillinase producing s. aureus
1)e. coli
2)klebsiella
3)s. aureus |
|
|
Term
| 2nd generation cephalosporins |
|
Definition
1)cefoxitin (MEFOXIN)
2)cefprozil (CEFZIL) |
|
|
Term
|
Definition
| given IV for anaerobic and mixed aerobic-anaerobic infections such as PID and lung abcesses |
|
|
Term
|
Definition
| better than 1st generation vs. streptococci. administer orally to treat respiratory tract infections |
|
|
Term
| 3rd generation cephalosporin |
|
Definition
1)ceftriaxone (ROCEPHIN)
2)ceftazidime (FORTAZ)
3)cefdinir (OMNICEF) |
|
|
Term
| third generation cephalosporins in comparison to 1st and 2nd |
|
Definition
1)penetrates CSF
2)better vs. gram (-) bacteria (including enteric bacilli)
3)least effective vs. gram (+) bacteria
4)more resistant to B-lactamases |
|
|
Term
|
Definition
| long half life, administered IV. twice a day for meningitis, once/day for pneumonia. Drug of choice for gonorrhea, meningitis and late stages of Lyme disease. |
|
|
Term
| drug of choice for late stages of lyme disease, meningitis and gonorrhea |
|
Definition
| ceftriaxone (ROCEPHIN) a 3rd generation cephalosporin |
|
|
Term
|
Definition
| in urine and bile so don't have to lower dose in renal failure |
|
|
Term
|
Definition
| anitpseudomonal activity, often used in combo with aminoglycoside |
|
|
Term
|
Definition
administered orally to treat respiratory tract and skin infections from:
1)s. pyogenes
2)h. influenza
3)m. catarrhalis
4)s. aureus (not MRSA) |
|
|
Term
| fourth generation cephalosporins |
|
Definition
widest spectrum due to higher restance to B-lactamases
1)cefepime (MAXIPIME) |
|
|
Term
| cefepime (MAXIPIME)active vs. |
|
Definition
| nosocomial infections where ab resistance is anticipated due to extended spectrum B-lactamases. good anti-pseudomonal activity like ceftazidime (FORTAZ) |
|
|
Term
|
Definition
| inhibits transglycosylase and chain elongation by binding to the D-Ala-D-Ala terminus of cell wall precursors attached to bactoprenol (a lipid carrier) |
|
|
Term
|
Definition
|
|
Term
| vancomycin is synergistic with ? |
|
Definition
|
|
Term
| primary indication for vancomycin |
|
Definition
|
|
Term
| penicillin resistant pneumococcal infections, endocarditis caused by e. faecalis may be treated by |
|
Definition
| vancomycin in combo with aminoglycoside |
|
|
Term
| preferred treatment for pseudomembraneous colitis from c. difficile |
|
Definition
| metronidazole then vancomycin (to minimize resistance to vancomycin) |
|
|
Term
| Drug of last resort, widespread emergence of resistance to this drug would be a public health crisis |
|
Definition
|
|
Term
|
Definition
| IV except for pseudomembranous colitis (orally?) |
|
|
Term
|
Definition
| renally so dosage must be reduced dramatically in cases of renal insufficiency |
|
|
Term
| side effects of vancomycin |
|
Definition
1) red man syndrome: rapid flushing from rapid IV infusion (prevent by slow infusion)
2)phlebitis at injection site
3)ototoxicity and nephrotoxicityunusual at normal doses but risk increased when used in combo with aminoglycosides |
|
|
Term
|
Definition
|
|
Term
|
Definition
| most gram (+) and (-) including P. aeruginosa and enterobacter |
|
|
Term
| carbapenems are not useful vs. |
|
Definition
1)MRSA
2)e. faecium
3)c. difficile |
|
|
Term
| imipenem must be administered with ? |
|
Definition
| cilastatin, an inhibitor of renal dipeptidase (combo= PRIMAXIN) |
|
|
Term
|
Definition
| cilastatin (inhibitor of renal dipeptidase) + imipenem |
|
|
Term
|
Definition
| renal so dosages must be reduced when renal insufficiency |
|
|
Term
| indications for carbapenems |
|
Definition
| 1)mixed infections with nosocomial infections. In particular cephalosporin-resistant bacteria. 2)empiric therapy of pts recently treated with other B-lactam abs as cephalosporin or penicillin resistance may be present |
|
|
Term
| side effects of carbapenems |
|
Definition
1)possible cross allergenicity with penicillins
2)imipenem more likely than others to cause irritation at site of infusion
3)imipenem mor elikely than others to cause seizures in pts with renal failure |
|
|
Term
| 2 carbapenems that do not require inhibitor of renal dipeptidase |
|
Definition
|
|
Term
| only monobactam licensed in US |
|
Definition
|
|
Term
|
Definition
| similar to that of penicillins and cephalosporins, but highly resistant to B-lactamases |
|
|
Term
| spectrum for monobactams (aztreonam) |
|
Definition
| gram (-) bacteria including 1)pseudomonas and 2)serratia |
|
|
Term
| elimination of monobactams (aztreonam) |
|
Definition
| renal elimination, so dose for renal failure |
|
|
Term
| side-effects of monobactams (aztreonam) |
|
Definition
| no cross-allergenicity woth cephalosporins or penicillins |
|
|
Term
| mechanism of action of aminoglycosides |
|
Definition
| binds to 30s ribsome so get abnormal reading of mRNA. get defective proteins which leads to insertion of these pretins into the cell membrane disrupting the cell envelope causing death. Bactericidal (unlike most other protein synthesis inhibitors) |
|
|
Term
|
Definition
| gram (-) (they pass through their porins) in an energy and oxygen dependent manner so they are vs. aerobes |
|
|
Term
| mechanism of resistance to aminoglycosides |
|
Definition
1)modification (acetylation, adenylation or phosphorylation) of amino or hydroxyl groups by bacterial enzymes. 2)mutations in ribosomes
3) reduced ability totransport drug into the cell |
|
|
Term
| spectrum of aminoglycosides |
|
Definition
aerobic gram (-) bacteria; 1)enterobacter
2)e.coli
3)k. pneumonia
4)proteus
5)serratia
6)pseudomonas |
|
|
Term
| indications for use of aminoglycosides |
|
Definition
| serious, life threatening infections with gram-negative enteric bacteria, especially when drug resistance or sepsis is present |
|
|
Term
| aminoglycosides are synergistic with ? extending its coverage to gram (+) bacteria |
|
Definition
|
|
Term
| why are B-lactam drugs and aminoglycosides synergistic |
|
Definition
| theoretically, B-lactam drugs are thought to make the cells more permeable to the aminoglycoside even when the bacteria switches to anaerobic metabolism |
|
|
Term
| aminoglycosides used with B-lactams to treat? |
|
Definition
| UTIs, bacteremias, peritonitis, infected burns, gram (+) endocarditis. Also, for nosocomial pneumonia when p. aeruginosa may be involved. |
|
|
Term
| could treat gram (+) endocarditis with? |
|
Definition
| Penicillin + aminoglycoside |
|
|
Term
| P.aeruginosa could be treated with? |
|
Definition
| antipseudomonal penicillin + aminoglycoside |
|
|
Term
| aminoglycosides administered? |
|
Definition
| IV or IM but IV preferred for extremely ill pts due to possible poor perfusion at IM sites. |
|
|
Term
| drawback of aminoglycoside |
|
Definition
|
|
Term
| excretion of aminoglycoside |
|
Definition
| large renal su must be VERY CAREFUL to reduce dosage |
|
|
Term
| aminoglycoside display what kind of killing? |
|
Definition
| concentration dependent killing = bacteria killed in higher portions and at a higher rate with higher drug concentrations (so one large daily dose may be more effective than multiple small doses) |
|
|
Term
| aminoglycosides have residual therapeutic effects called |
|
Definition
| postantibiotic effect = serum levels stay elevated after withdrawing the drug as it is released from its tissue binding sights |
|
|
Term
| side effects of aminoglycosides |
|
Definition
same doses can give different plasma levels
1)ototoxicity
2)nephrotoxicity |
|
|
Term
| ototoxicity may be caused by ? |
|
Definition
aminoglycosides; vestibular and auditory dysfunction occurs in up to 25% of patients, tinitus may be the first sign of hearing loss, then headaches precede nausea and vertigo as symptoms of vestibular toxicity. (could cause fetal hearing loss during pregnancy)
LARGELY IRREVERSIBLE |
|
|
Term
| nephrotoxicity may be caused by ? |
|
Definition
| aminoglycosides; usually reversible, but could lead to ototoxicity b/c of decreased excretion |
|
|
Term
| first choice aminoglycoside |
|
Definition
| gentamicin generally preferred due to more experience with this drug and lower cost |
|
|
Term
|
Definition
1)gentamycin
2)tobramycin
3)amikacin
4)streptomycin |
|
|
Term
| commonly prescribed with dexamethasone to topically treat conjunctivitis |
|
Definition
|
|
Term
| broadest prectrum aminoglycoside and most resistant to aminoglycoside modifying enzymes |
|
Definition
|
|
Term
|
Definition
| not used as much now b/c of lower effectiveness, higher toxicity and pain on injection. (drug of choice only for specific infections, i.e. drug-resistant tuberculosis) |
|
|
Term
| tetracycline mechanism of action |
|
Definition
| diffuse through porins in gram (-) and gets into both gram (+) and gram (-) through active transport. inhibit protein synthesis by binding to 30S subunit and blocking binding of aminoacyl tRNA. (bacteriostatic) |
|
|
Term
| mechanism of resistance to tetracycline |
|
Definition
1)efflux pump
2)enzymatic inactivation
3)ribosome protection proteins |
|
|
Term
| spectrum of tetracyclines |
|
Definition
| VERY BROAD: gram (+) and (-), aerobic and anaerobic; overuse has led to emergence of widespread resistance |
|
|
Term
| indications for tetracyclines |
|
Definition
1)chlamydia
2)acne
3)rickettsial diseases such as lyme disease or RMSF
4)effective vs. spirochetes |
|
|
Term
| absorption of tetracyclines inhibited by |
|
Definition
1)dairy products
2)antacids |
|
|
Term
| elimination of tetracycline |
|
Definition
| mostly renal excretion so must be dosed accordingly; EXCEPT doxycycline which is tetracycline of choice in renal failure. |
|
|
Term
| tetracycline of choice during renal failure |
|
Definition
|
|
Term
| side effects of tetracycline |
|
Definition
| teeth staining so don't use in kids or pregnant women; photosensitivity, hepatotoxicity, nephrotoxicity. Also, potential superinfection and pseudomembranous colitis from c. difficile (like any broad spectrum ab) |
|
|
Term
| mechanism of action of chloramphenicol |
|
Definition
| binds 50s ribosome preventing peptidyl transferase activity (can affect mitochondrial ribosomes as well) generally bacteriostatic but can be bacteriocidal |
|
|
Term
| resistance to chloramphenicol: |
|
Definition
| mediated by chloramphenicol acetyltransferase |
|
|
Term
| spectrum of chloramphenicol |
|
Definition
| (BROAD) gram (+) and (-), aerobic and anaerobic |
|
|
Term
| Indications for chloramphenicol |
|
Definition
| (rarely used b/c availability of less toxic alternatives) used for serious rickettsial infections of tetracycline is contraindicated (due to hypersensitivity or use in young children) |
|
|
Term
| chloramphenicol is administered: |
|
Definition
| orally or through IV (good penetration, including CSF) |
|
|
Term
| elimination of chloramphenicol is through: |
|
Definition
| hepatic metabolism and renal excretion, plasma conc. is variable and must be closely monitored, so reduce dosage in case of hepatic insufficiency and in newborns. |
|
|
Term
| side effects of chloramphenicol: |
|
Definition
1)hematopoietic disorders (including aplastic anemia)
2)inhibition of cyt P-450 causing drug interactions.
3)Gray baby syndrome: can be fatal to neonates (especially premies), vomiting, abdominal distention, cyanosis, turn ashen gray and become hypothermic. (may be observed in older children) |
|
|
Term
|
Definition
1)erythromycin
2)azithromycin
3)clarithromycin |
|
|
Term
| mechanism of action of macrolides |
|
Definition
| reversible binding to 50s ribosomal subunit preventing translocation of peptidyl tRNA from acceptor to donor site. Generally BACERIOSTATIC but can be bacteriocidal |
|
|
Term
| mechanism of resistance to macrolides |
|
Definition
1) plasmid mediated: decreased permeability or active efflux
2)methylase that modifies the ribosome
3)drug-hydrolyzing esterases
4)ribosomal mutations |
|
|
Term
|
Definition
| aerobic gram (+) cocci and bacilli (gram + b/c the peptidyl tRNA accumulates faster there than gram - ) some activity towards gram -, mycobacteria and protozoa |
|
|
Term
| drug of choice for treating legionnaire's disease |
|
Definition
|
|
Term
| alternative to doxycycline for treating chlamydial infections |
|
Definition
|
|
Term
| drug of choice for treating diptheria and pertussis |
|
Definition
|
|
Term
| what macrolides are most active vs. mycobacterial infections and useful for treating community-acquired pneumonia |
|
Definition
|
|
Term
| administration of macrolides |
|
Definition
| generally administered orally but IV azithromycin is available for severe legionella infections |
|
|
Term
|
Definition
| metabolism is mostly hepatic via CYP3A so dosage DOES NOT have to be adjusted in renal failure |
|
|
Term
| this drug is destroyed by stomach acid so enteric coating is used to allow absorption from duodenum |
|
Definition
|
|
Term
| elimination of clarithromycin (BIAXIN) |
|
Definition
| renal clearance; dosage reduced only in severe renal insufficiency |
|
|
Term
| elimination of azithromycin (ZITHROMAX) |
|
Definition
| biliary clearance is the major route of elimination |
|
|
Term
| side effects of erythromycin |
|
Definition
1)severe abdominal pain
2)cholestatic hepatitis
3)drug interactions due to inhibition of cytochrome P450 3A enzymes (CYP3A);
erythromycin can cause a long QT syndrome (prolongation of cardiac repolarization) other inhibitors of cyp3a can increase erythromycin increasing the risk for ventricular arrhythmias |
|
|
Term
| side effects of clarithromycin |
|
Definition
| some abdominal pain but less frequent than erythromycin |
|
|
Term
| side effects of azithromycin |
|
Definition
| unlike the other macrolides, little effect on cytochrome P450 |
|
|
Term
| mechanism of action of clindamycin (CLEOCIN) |
|
Definition
| binds to the same 50s ribosomal site as macrolides with similar action |
|
|
Term
| never use clindamycin with ? and ? |
|
Definition
1)macrolides
2)chloramphenicol; b/c binding of one drug to 50s subunit can inhibit binding of others |
|
|
Term
| indications for clindamycin (CLEOCIN) |
|
Definition
| severe anaerobic and mixed GI infections |
|
|
Term
| drug of choice for lung abscesses and anaerobic lung infections |
|
Definition
|
|
Term
| ? used topically with peroxide (BENSACIN)to treat acne |
|
Definition
|
|
Term
| administration for clindamycin |
|
Definition
| IV or IM for severe infections but may be administered orally |
|
|
Term
| elimination of clindamycin |
|
Definition
| hepatic clearance; dosage must be adjusted in hepatic failure |
|
|
Term
| side effects of clindamycin (CLEOCIN) |
|
Definition
| diarrhea; thought to be most likely drug to cause pseudomembranous colitis from c. difficle |
|
|
Term
| mechanism of action of linezolid (ZYVOX) |
|
Definition
| prevents formation of 70s ribosomal complex by binding the 50s subunit. NO CROSS RXN WITH OTHER DRUGS DUE TO UNIQUE BINDING SITE |
|
|
Term
| spectrum of linezolid (ZYVOX) |
|
Definition
|
|
Term
| indications for use of linezolid (ZYVOX) |
|
Definition
| vancomycin resistant strains of enterococcus faecium and VRSA |
|
|
Term
| administration of linezolid (ZYVOX) |
|
Definition
|
|
Term
| elimination of linezolid (ZYVOX) |
|
Definition
| no dose adjustment for renal or hepatic impairment |
|
|
Term
| drug interactions with linezolid (ZYVOX) |
|
Definition
| adrenergic and serotinergic agents |
|
|
Term
| resistance to linezolid (ZYVOX) |
|
Definition
| mutation of 23s rRNA of 50s subunit. should be a drug of last resort since it is a back up for vancomycin and widespread resistance could cause serious problem |
|
|
Term
| side effects of linezolid (ZYVOX) |
|
Definition
1)mild reversible thrombocytopenia
2)neutropenia |
|
|
Term
|
Definition
1)dalfopristin(streptogramim A)
2)quinupristin(streptogramim B) |
|
|
Term
| mechanism of action of streptogramim |
|
Definition
| quinupristin and dalfopristin act synergistically at 2 different sites on the 50s ribosomal subunits to inhibit protein synthesis |
|
|
Term
| mechanism of reistance of streptogramims |
|
Definition
1)acetylation of dalfopristin
2)efflux pumps removing it from cells
3)modification of quinupristin |
|
|
Term
| spectrum of streptogramims |
|
Definition
|
|
Term
| indications for streptogramims |
|
Definition
| combo of quinupristin and dalfopristin (SYNERCID) is used to treat vanc resistant strains of enterococcus faecium and VRSA (like linezolid) also, a drug of last resort |
|
|
Term
| what drug other than linezolid is used to treat vanc resistant enterococcus faecium and VRSA |
|
Definition
| (SYNERCID) combo of dalfopristin and quinupristin |
|
|
Term
| administration of streptogramins |
|
Definition
|
|
Term
| elimination of streptogramims |
|
Definition
| hepatic clearance so reduced dosage for hepatic insufficiency |
|
|
Term
| side effects of streptogramims |
|
Definition
1)pain and phlebitis at infusion site
2)drug interactions due to inhibition of cytochrome P450 |
|
|
Term
| CDC recommends therapy with 4 drug combo of first line agents for TB until clinical isolate determined |
|
Definition
1)isoniazid
2)rifampin
3)pyrazinamide
4) ethambutol or streptomycin |
|
|
Term
| isoniazid-resistant strains of TB treated with |
|
Definition
6 month regimen of 1)rifampin 2)ethambutol 3)pyrazinamide or
12 month regimen of 1)rifampin and 2)ethambutol |
|
|
Term
| isoniazid-sensitive strains of TB treated with |
|
Definition
| 6 month regimen of 1)isoniazid 2)rifampin 3)pyrazinamide or 9 month regimen of 1)isoziazid 2)rifampin |
|
|
Term
| rifampin-resistant strains of TB treated with |
|
Definition
| 18 month regimen of 1)isoniazid 2)ethambutol |
|
|
Term
| sulfonamides are structurally related to what compound? |
|
Definition
| paraaminobenzoic acid (PABA) |
|
|
Term
| what enzyme do sulfonamides inhibit? |
|
Definition
| dihydropteroate synthase - critical enzyme in synthesis of folic acid |
|
|
Term
| Are sulfonamides bacteriocidal or bacteriostatic? |
|
Definition
| bacteriostatic- bacteria depend on folate synthesis for growth while humans don't because they get it through their diet |
|
|
Term
| mechanisms of resistance to sulfonamides |
|
Definition
| 1) mutation in dihydropteroate synthase so it has less affinity for sulfonamides 2) increased production of PABA so it can outcompete sulfonamides for enzyme active site |
|
|
Term
| what is the spectrum of sulfonamides? |
|
Definition
| gram negative and positive bacteria, some protozoa |
|
|
Term
| What is silver sulfadiazine used to treat? |
|
Definition
| Used topically to prevent infection of burn wounds |
|
|
Term
| What is sulfacetamide used to treat? |
|
Definition
|
|
Term
| when does dosage need to be reduced if giving sulfonamides? |
|
Definition
| with significant renal impairment |
|
|
Term
| side effects of sulfonamides |
|
Definition
| 1)crystalluria and renal toxicity - keep hydrated 2)kernicterus in newborns 3) hypersensitivity reactions |
|
|
Term
| Who should not be perscribed sulfonammides and why? |
|
Definition
| pregnant women near term and infants- it displaces bilirubin from albumin causing kernicterus in newborns |
|
|
Term
| When is hypersensitivity seen due to sulfonamides? |
|
Definition
| usually seen in AIDS patients- can range from rash to Stevens-Johnson syndrome and exfoliative dermatitis |
|
|
Term
| What is the target of trimethoprim? |
|
Definition
| bacterial dihydrofolate reductase |
|
|
Term
| Why do bacterial need tetrahydrofolate? |
|
Definition
| it is needed to synthesize purines for DNA |
|
|
Term
| What is trimethoprim used in combination with and why? |
|
Definition
| sulfamethoxazole - synergistic action because they inhibit sequential steps in the same pathway (folate metabolism) and resistance is less common when used together |
|
|
Term
| specturm of trimethoprim-sulfamethoxazole |
|
Definition
| gram negative and positive bacteria |
|
|
Term
| What infections are trimethorpim-sulfamethoxazole used to treat? |
|
Definition
| 1)UTI 2)respiratory tract infection 3) prostatitis |
|
|
Term
| Why is trimethoprim used with sulfamethoxazole instead of other sulfonamides? |
|
Definition
| because sulfamethoxazole has a very similar half-life so last about the same amount of time when taken together |
|
|
Term
| When should you reduce the dosage if giving trimethoprim-sulfamethoxazole? |
|
Definition
|
|
Term
| what are the side effects of trimethoprim-sulfamethoxazole? |
|
Definition
| same as sulfonamides - 1)kernitcterus in newborns 2) hypersensitivity reactions in AIDS, 3)crystalluria |
|
|
Term
|
Definition
| ciprofloxacin, levofloxacin, moxifloxacin |
|
|
Term
| fluoroquiniolones are fluorinated derivatives of which compound? |
|
Definition
|
|
Term
| what are the targets of fluoroquinolones? |
|
Definition
1) DNA gyrase - introduces neg. supercoils in DNA
2)topoisomerase IV - separates concatenated DNA during replication |
|
|
Term
| Whatdo fluoroquinolones prevent from occur during replication? |
|
Definition
| They prevent relaxation of positively supercoiled DNA which is required for replication |
|
|
Term
| Are fluoroquinolones bacteriocidal or bacteriostatic? |
|
Definition
|
|
Term
| What enzyme in humans can fluoroquinolones inhibit at very high concentrations? |
|
Definition
|
|
Term
| mechanism of resistance to flurooquinolones |
|
Definition
| muations in topoisomerase or gyrase |
|
|
Term
| What is the spectrum of fluoroquinolones? |
|
Definition
1) aerobic gram neg bacteria that cause UTI - Pseudomonas aeriginosa and Enterobacter
2)intracellular pathogens- Chlamydia, Legionella, mycobacteria
3)gram positive bacteria (levofloxacin and moxifloxacin) |
|
|
Term
| what are the drugs of choice for treating Legionella pneumoniae? |
|
Definition
| fluoroquinolones along with azithromycin |
|
|
Term
| What infections are fluoroquinolones used to treat? |
|
Definition
| UTI, traveler's diarrhea, bone/joint/soft tissue infections, broad spec fluoroquinolones for resp tract infection , topical cipro for ear infections |
|
|
Term
| What fluoroquinolone is used to treat ear infections? |
|
Definition
| topical ciprofloxacin with dexamethasone |
|
|
Term
| What inhibits the basorption of fluoroquinolones? |
|
Definition
| divalent cations such as those found in antacids - not effective with milk/antacids |
|
|
Term
| What fluoroquinolone doesn't have to be dosed for renal insufficiency? |
|
Definition
| moxifloxacin - it is cleared non-renally |
|
|
Term
| side effects of fluoroquinolones |
|
Definition
1) damage to growing cartilage/ reversible arthropathy in kids
2)seizures due to interaction with NSAIDS
3)**rare tendonitis with possible rupture in adults
4) photosensitiivity
5) QT prolongation |
|
|
Term
| ho should not be given fluoroquinolones and why? |
|
Definition
| pregnant women, children, nursing mothers - causes damage to growing cartilage and reversible arthropathy in children |
|
|
Term
| What is nitrofurantoin used for? |
|
Definition
| urinary tract antispetic - used for prophylaxis of recurrent UTI |
|
|
Term
| When is nitrofurantoin contraindicated? |
|
Definition
| In renal insufficiency because therapeutic levels not reached in the urine and could cause toxic blood levels |
|
|
Term
| Is nitrofurantoin bacteriostatic or cidal? |
|
Definition
| bacteriostatic for E. coli and entercocci |
|
|
Term
| what is the spectrum of nitrofurantoin? |
|
Definition
| gram positive and negative bacteria |
|
|
Term
| Why does nitrofuratoin not have systemic effects? |
|
Definition
| because it is rapidly metabolized and excreted renally |
|
|
Term
| what are the side effects of nitrofurantoin? |
|
Definition
1) common - nausea, vomiting, diarrhea, brown urine
2) less common - nueropathies, hemolytic anemia in G6PD deficiency,
3)rare - hepatitis, pulmonary fibrosis |
|
|
Term
| What is the mechanism of action of metronidazole? |
|
Definition
| the reduction of its nitro group produces a reactive compound that reacts with DNA to inhibit its synthesis - bactericidal |
|
|
Term
| what is the spectrum of metronidazole? |
|
Definition
| primarily ANAEROBES (Bacteroides, Clostridium, Helicobacter, Peptococcus) - perform the reduction that causes its toxicity |
|
|
Term
| What infections are treated with metronidazole? |
|
Definition
1)**anaerobic infections
2)abdominal infections
3) brain abscesses
4)**pseudomembranous colitis
5) orally for protozoal infections |
|
|
Term
| When should you avoid giving metronidazole? |
|
Definition
| during the 1st trimester -teratogenicity |
|
|
Term
| When shold the dosage be reduced for methonidazole? |
|
Definition
| severe hepatic or renal impairment |
|
|
Term
| what are the side effects of metronidazole? |
|
Definition
1)** Disukfiram reaction if alcohol consumed - severe nausea , vomiting
2) rare CNS toxicity or peripheral neuropathy |
|
|
Term
| what is the spectrum of mupiprocin? |
|
Definition
| gram positive cocci - MRSA and non-reistant staph |
|
|
Term
| what is mupiprocin used to treat? |
|
Definition
topical treatment of impetigo and minor skin infections
** temporary removal of nasal staph aureus in health care workers/patients |
|
|
Term
| How are fluoroquinolones administered? |
|
Definition
| orally or through IV - excellent oral bioavailability (absorption inhibited by divalent cations) |
|
|
Term
| How is nitrofurantoin administered? |
|
Definition
| orally- absorbed well and metabolized/excreted rapidly |
|
|
Term
| How is metronidazole administered? |
|
Definition
IV for bacterial infections
Orally for protozoal infections - absorbed well |
|
|
Term
| What drugs are classified as cell wall inhibitors? |
|
Definition
1) penicillins
2) cephalosporins
3) vancomycin
4) carbapenems
5) monobactams |
|
|
Term
| What is the major constituent of bacterial cell walls? |
|
Definition
| peptidoglycan or murein = polymer of glycan chains crosslinked by peptide chains |
|
|
Term
| What is the final step in the synthesis of peptidoglycan? |
|
Definition
|
|
Term
| What drugs inhibit the transpeptidase reaction? |
|
Definition
| penicillins, cephalosporins, carbapenems, monobactams |
|
|
Term
| What do most drugs mimic to inhibit the transpeptidase reaction? |
|
Definition
| the D-alanine dipeptide found on monomers that are substrates for transpeptidase |
|
|
Term
| What plays a mjor role in drug susceptibility in gram negative bacteria? |
|
Definition
| porins in the outer membrane - must be able to get through to kill or stop growth |
|
|
Term
| What do cell walls look like in gram pos vs neg bacteria? |
|
Definition
positive- several layers of petidoglycan
negative- only 1-2 layers, has an outer membrane |
|
|
Term
| What compund is used to make semisynthetic penicillins by adding different side chains? |
|
Definition
|
|
Term
| What is the mechanism of action od penicillins? |
|
Definition
| inhibition of transpeptidase reaction by acetylating transpeptidase (AKA PBP) - bactericidal |
|
|
Term
| What ring is found in the structure of penicillins and cephalosporins? |
|
Definition
|
|
Term
| What are the four mechanisms of reistance to penicillins? |
|
Definition
1)inactivation by beta-lactamases
2)expression of PBPs with lower affinity for penicillin
3)reduction in # and size of porins in gram (-) bacteria (only sufficient in beta lactamases present)
4)active efflux pumps |
|
|
Term
|
Definition
| enzyme produced by bacteria that hydrolyzes beta-lactam rings thus inhibiting some antibiotics (different spectrums- some specific for penicillin, other more broad spec for cephalosporins) |
|
|
Term
| What are the narrow spectrum, penicillinase-sensitive drugs? |
|
Definition
|
|
Term
| What bacteria are almost all resistant to peniciillin G and V? |
|
Definition
|
|
Term
| Penicillin G is the drug of choice for what infections? |
|
Definition
**meningococcal disease
syphilis
actinomycosis
anthrax
listeria
clostridial inf (except for C. difficle) |
|
|
Term
| Penicillin G is used as a prophylactic drug of choice for: |
|
Definition
1) contacts with syphilis
2) recurrence of rheumatic fever
3) prevention of endocarditis following dental procedure |
|
|
Term
| what gram positive bacteria is usually susceptible to penicillin G and V? |
|
Definition
| streptococci- drug of choice for treatment of bacterial pharyngitis and other infections caused by s. pyogenes |
|
|
Term
| what is the spectrum of pencillin G and V? |
|
Definition
susceptible gram-pos aerobis bacteria, most anaerobes
streptococci usally sensitive
s. aureus usually resistant |
|
|
Term
| when must the dosage be adjusted for penicillin G or V? |
|
Definition
| impaired renal function - clearance is primarily renal |
|
|
Term
| What are the narrow-spectrum, penicillinase-resistant drugs? |
|
Definition
methicillin
nafcillin
dicloxacillin
oxacillin |
|
|
Term
| What makes methicillin and the other drugs resistant to pencillinase? |
|
Definition
| bulky side group blocks the action of beta-lactamases so can't perform cleavage of the ring |
|
|
Term
| What bacteria are not susceptible to narrow-spectrum, penicillinase-resistant drugs? |
|
Definition
1)gram negative bacteria - drugs are too hydrophobic to pass through the hydrophilic porins
2)MRSA |
|
|
Term
| when are narrow-spectrum, penicillinase-resistant drugs used? |
|
Definition
staphylococcal meningitis and infections with penicillinase-producing staph
NOT used for MRSA |
|
|
Term
| How are narrow-spectrum, peniclliniase-resistant drugs eliminated? |
|
Definition
by the liver and the kidney
DOSAGE DOESN'T HAVE TO BE ADJUSTED IN RENAL FAILURE** |
|
|
Term
| How is nafcillin administered? |
|
Definition
| IV ONLY! poor oral and IM absorption |
|
|
Term
| What inhibits oral absorption of oxacillin and dicloxacillin? |
|
Definition
Food
Administer IV in life-threatening situations! |
|
|
Term
| What are the extended-spectrum aminopenicillins? |
|
Definition
|
|
Term
| What is the function of the amino group in ampicillin and amoxicillin? |
|
Definition
| it makes them more hydrophilic thus increases their ability to penetrate porins of fram negative bacteria |
|
|
Term
| Are ampicillin/amoxicillin susseptible to beta lactamase? |
|
Definition
| Yes so not useful against staph |
|
|
Term
| Is amoxicillin or ampicillin absorbed better? |
|
Definition
| amoxicillin is better absorbed orally so used more often |
|
|
Term
| When do you need to reduce dosage for ampicillin/amoxicillin? |
|
Definition
|
|
Term
|
Definition
| inhibitor of beta-lactamase |
|
|
Term
| What penicillin is clavulanic acid typically administered with? |
|
Definition
1)amoxicillin
2)ticarcillin
increases their spectrum to staph and other beta lactamase-producing bacteria |
|
|
Term
| What are the extended-spectrum antipseudomonal penicillins? |
|
Definition
|
|
Term
| Which penicillin is active against Klebsiella? |
|
Definition
|
|
Term
| What type of infections are antipseudomonal penicillins effective against? |
|
Definition
| Pseudomonas aeruginosa, Proteus, Enterobacter |
|
|
Term
| How are antipseudomonal penicillins administered? |
|
Definition
| MUST be injected - usually hospital acquired infections so given by IV |
|
|
Term
| What are antipseudomonal penicillins used in cmobination with and why? |
|
Definition
| aminoglycosides to prevent emergence of resistance |
|
|
Term
| What are the most important side effects of penicillins? |
|
Definition
| hypersensitivity reactions (includes anaphylactic rxns) |
|
|
Term
| What is the best way to avoid allergic reactions to penicillins? |
|
Definition
| **Evaluate patient's history |
|
|
Term
| What cephalosporin was priginally derived from a fungal source? |
|
Definition
|
|
Term
| What is the mechinism of action for cephalosporins? |
|
Definition
| interfere with cell wall synthesis by inhibiting transpeptidase |
|
|
Term
| How are cephalosporins classified? |
|
Definition
| by generation - more recent generations have broader spectra and greater resistance to beta-lactamase |
|
|
Term
| What are the side effects of cephalosporins? |
|
Definition
hypersensitivity = cross allergenicity with penicillins
patients with severe reaction to penicillin shouldnt be given cephalosporins, okay if only had a mild reaction |
|
|
Term
| Which generations of cephalosporins penetrate the CSF? |
|
Definition
|
|
Term
| How are cephalosporins excreted? |
|
Definition
primarily by the kidney
adjust dosage for renal impairment in most cases |
|
|
Term
| What first generation cephalosporin is given orally? |
|
Definition
|
|
Term
| What first generation cephalosporin is given IV? |
|
Definition
| cefazolin - has a long half life |
|
|
Term
| What second generation cephalosporin is administered by IV? |
|
Definition
|
|
Term
| What second generation cephalosporin is given orally? |
|
Definition
|
|
Term
| What is cefoxitin used to treat? |
|
Definition
| pelvic infammatory diseases, lung abscesses (anaerobic and mixed aerobic-anaerobic infections) |
|
|
Term
| What is cefprozil used to treat? |
|
Definition
| respiratory tract infections and strep |
|
|
Term
| what is ceftriaxone used as drug of choice to treat? |
|
Definition
| meningitis, gonorrhea, Lyme disease |
|
|
Term
| What drig is a fourth generation cephalosporin? |
|
Definition
|
|
Term
| What generation of cephalosporins is the least effective against treating gram positive bacteria? |
|
Definition
|
|
Term
| What are the third generation cephalosporins? |
|
Definition
ceftriaxone and ceftazidime - IV
Ceftdinir- oral |
|
|
Term
| Which third generation cephalosporin is used for antipseudomonal activity? |
|
Definition
|
|
Term
| Which third generation cephalosporin doesn't have to have dosage adjusted for in renal impairment? |
|
Definition
| ceftriaxone - gets into CSF, has a long half life |
|
|
Term
| What is the spectrum of vancomycin? |
|
Definition
| gram positive bacteria ONLY |
|
|
Term
| What is the mechanism of action of vancomycin? |
|
Definition
| inhibits transglycosylase and chain elongation by binding to D-Ala terminus of cell wall precursors attached to bactoprenol |
|
|
Term
| what is synergistic when used with vancomycin? |
|
Definition
|
|
Term
| What is the drug of choice for MRSA? |
|
Definition
|
|
Term
| What is the drug of choice for pseudomembranous colitis cause by C difficle? |
|
Definition
Metronidazole
Vancomycin can be used but as a last resort |
|
|
Term
| What bugs have developed resistant to vancomycin? |
|
Definition
| E. faecalis and E.faecium |
|
|
Term
| Mechanism of action of isoniazid? |
|
Definition
| inhibits synthesis of mycolic acid |
|
|
Term
| How is vancomycin administerd? |
|
Definition
| IV except when treating pseudomembranous colitis |
|
|
Term
| What drug is very specific for mycobacteria? |
|
Definition
| isoniazid b/c it inhibits the synthesis of mycolic acid |
|
|
Term
| What infections can vancomycin be used to treat? |
|
Definition
1)MRSA
2)pseudomemnbranous colitis
3)meningitis -only penetrates CSF when there is a meningeal infection |
|
|
Term
| When should vancomycin dosage be reduced? |
|
Definition
| renal impairment- reduce dramatically |
|
|
Term
| What are the side effects of vancomycin? |
|
Definition
1)**Red man syndrome
2)ototoxicity
3)nephrotoxicity
4)phlebitis at injection site |
|
|
Term
|
Definition
| extreme flushing of the skin caused by rapid infusion of vancomycin |
|
|
Term
| What increases the risk of oto and nephrotoxicity with vancomycin? |
|
Definition
| using in combo with aminoglycosides or renal function not adjusted for |
|
|
Term
| 2 mechanisms of resistance to isoniazid treatment? |
|
Definition
1) mutation in katG (catalase-peroxidase) gene
2)mutation in inhA gene |
|
|
Term
| mutation of KatG gene does what? |
|
Definition
| prevents conversion of the prodrug, isoniazid, to its active metabolite. |
|
|
Term
| Mutation of inhA gene does what? |
|
Definition
| inhA is a carrier protein involved in mycolic acid biosynthesis, so a mutation in it contributes to resistance. |
|
|
Term
| what drugs are most resistant to beta-lactamases? |
|
Definition
|
|
Term
| What type of drug is Imipenem? |
|
Definition
|
|
Term
| What drug causes increased excretion of pyridoxine? |
|
Definition
|
|
Term
| What must be adminstered IV with Imipenem? |
|
Definition
| **cilistatin - inhibitor of renal dipeptidase which will degrade imipenam |
|
|
Term
| Isoniazid must be adjusted for hepatic or renal insufficiency? |
|
Definition
|
|
Term
| How is isoniazid administered? |
|
Definition
|
|
Term
| What are carbapenams used to treat? |
|
Definition
| cephalosporin resistant bacteria |
|
|
Term
| What are the side effetcs of carbapenams? |
|
Definition
1)cross-allergenicity with penicillins
2)irritation at infusion site
3)seizures in patients with renal failure |
|
|
Term
| Side effects of isoniazid? |
|
Definition
1)Hepatotoxicity
2)peripheral neuritis (not normally a problemat normal doses) |
|
|
Term
| What is the only monobactam licensed for use in the US? |
|
Definition
|
|
Term
| What is the mechanism of action of aztreonam? |
|
Definition
|
|
Term
| It is important to use pyridoxine with __________ to avoid side effect of peripheral neuropathy? |
|
Definition
|
|
Term
| What is the spectrum of aztreonam? |
|
Definition
| gram negative bacteria ONLY |
|
|
Term
| How is aztreonam administered? |
|
Definition
|
|
Term
| What beta-lactam drug is safest to use if patient is allergic to penicillin? |
|
Definition
| ** Aztreonam - no cross allergenicity with penicillins or cephalosporins |
|
|
Term
| What type of bacteria are aminoglycosides active against? |
|
Definition
| aerobic gram negative bacteria - transported into cell in an oxygen dependent manner |
|
|
Term
| Mechanism of action of rifampin? |
|
Definition
| inhibits the B subunit of bacterial RNA polymerase |
|
|
Term
|
Definition
Bactericidal for
1)gram +
2)gram -
3)some enterics
4)chlamydia
5)mycobacteria |
|
|
Term
| What is the mechanism of action of the aminoglycosides? |
|
Definition
| ** inhibit protein synthesis by binding the *30S* ribosomal subunit and causing *ABNORMAL READING OF mRNA* |
|
|
Term
| what causes resistance to rifampin? |
|
Definition
| mutations in bacterial RNA polymerase. |
|
|
Term
| Cross-resistance occurs between rifampin and other rifamycin derivatives such as _________ that act by the same mechansim. |
|
Definition
|
|
Term
| Are aminoglycosides bacteriostatic or cidal? |
|
Definition
| bactericidal - cause insertion of aberrant proteins into cell membrane which disrupts envelope causing death |
|
|
Term
| side effects of rifampin? |
|
Definition
1)red body fluids
2)induction of cyt P450 decreasing efficacy of oral contraceptives, protease inhibitors, anticonvulsants and methdaone.
3)rare hepatotoxicity in pts with liver disease |
|
|
Term
| what are the three effects of aminoglycosides on protein synthesis |
|
Definition
1) blocks initiation
2) causes premature termination
3) causes incorporation of incorrect amino acids so abnormal protein made |
|
|
Term
| What are the mechanism of resistance to aminoglycosides? |
|
Definition
1) mutation in ribosome
2) enzymes that alter the drug (acetylation, adenylation, phosphorylation)
3) reduced ability to transport drug into cell |
|
|
Term
| What are aminoglycosides often used in combination with and why? |
|
Definition
| beta-lactam drugs because work synergistically and extend coverage to gram positive bacteria - sometimes work on bacteria when neither drug alone would |
|
|
Term
| How do beta-lactam drugs and aminoglycosides work synergistically? |
|
Definition
| beta lactams make the cells more permeable to aminoglycosides |
|
|
Term
| mechanism of action of pyrazinoic acid? |
|
Definition
| must be metabolized to pyrazinoic acid, the active drug but the target of the compound is unknown |
|
|
Term
| what causes resistance to pyrazinamide? |
|
Definition
1)mutations in pyrazinamidase prevents conversion of the drug to its active form
2)also, decreased uptake |
|
|
Term
| When should aminoglycosides be used? |
|
Definition
| ONLY for life threatening conditions and when a less toxic antibiotic is less effective - they can be very toxic |
|
|
Term
| How is pyrazinamide administered? |
|
Definition
|
|
Term
| How are aminoglycosides administered? |
|
Definition
|
|
Term
| Why do you have to monitor the concentrations of aminoglycosides daily? |
|
Definition
| because they have a **very narrow therapeutic window - want to prevent toxicity |
|
|
Term
| How are aminoglycosides elminated? |
|
Definition
| renally - must be very careful about dosage in renal impairment |
|
|
Term
| What is concentration-dependent killing? |
|
Definition
| bacteria killed in higher proportions and at a higher rate with higher drug concentrations |
|
|
Term
| side effects of pyrazinamide? |
|
Definition
1)hepatotoxicity is the most common (don't give to pts with hepatic dysfunction)
2)hyperuricemia (see in almost all pts) with possible gout |
|
|
Term
| Why is a single dose of aminoglycosides more effective than multiple small doses? |
|
Definition
| concentration-dependent killing |
|
|
Term
| Mechanism of action of ethambutol? |
|
Definition
| inhibits synthesis of arabinogalactan (component of mycobacterial cell wall) by inhibiting arabinosyl transferase. |
|
|
Term
| resistance to ethambutol is mediated by? |
|
Definition
| overexpression or mutation of the arabinosyl transferase |
|
|
Term
| How is ethambutol administered? |
|
Definition
|
|
Term
| ethambutol must be dosed for ________ insufficiency> |
|
Definition
|
|
Term
| Side effects of ethambutol? |
|
Definition
| **reversible optic neuritis with loss of visual acuity and red/green color blindness. (do baseline test to monitor vision during treatment, not recommended for kids under 5 due to difficulty testing visual acuity) |
|
|
Term
| Why do serum levels stay elevated and have some therapeutic effect after withdrawal of aminoglycosides? |
|
Definition
| they exhibit a postantibiotic effect because they bind tissues and are gradually released after withdrawal of the drug |
|
|
Term
| What are the side effects of aminoglycosides? |
|
Definition
1)ototoxicity - IRREVERSIBLE
2)nephrotoxicity - reversibe |
|
|
Term
| what drug is the least used first-line agent for TB? and why? |
|
Definition
| streptomycin b/c it doesn't penetrate cells so only suppresses TB in vivo rather than being bactericidal like it is in vitro. |
|
|
Term
| When should you avoid using aminoglycosides? |
|
Definition
| during pregnancy to prevent fetal hearing loss |
|
|
Term
| What is usually the first sign of hearing loss due to aminoglycosides? |
|
Definition
|
|
Term
| 2nd line drugs for therapy for TB? (4) |
|
Definition
1)cycloserine
2)ethionamide
3)p-aminosalicylic acid
4)amikacin, capreomycin |
|
|
Term
| what are the signs of vestibular toxicity with aminoglycosides? |
|
Definition
| headaches which usually precede nausea and vertigo |
|
|
Term
| What is the aminoglycoside of first choice? |
|
Definition
|
|
Term
| What is Tobramycin used to treat? |
|
Definition
| Used with dexamethasone for topical treatment of conjunctivitis |
|
|
Term
| What is the broadest spectrum aminoglycoside? |
|
Definition
| Amikacin - has the most resistance to modifying enzymes |
|
|
Term
| Why is streptomycin not used much anymore except for TB? |
|
Definition
| lower effectiveness, higher toxicity, and pain on injection |
|
|
Term
| Mechanism of action of cycloserine? |
|
Definition
| inhibits cell wall synthesis |
|
|
Term
| how is cycloserine administered? |
|
Definition
|
|
Term
| Cycloserine is cleared ________ so must be dosed for ________ failure. |
|
Definition
|
|
Term
| side effects of cycloserine? |
|
Definition
1)CNS effects including: depression and psychotic rxns
2)peripheral neuropathy |
|
|
Term
| What is the mechanism of action of tetracyclines? |
|
Definition
| inhibit protein synthesis by binding to the 30S subunit and blocking binding of aminoacyl-tRNA (BACTERIOSTATIC) |
|
|
Term
| cycloserine is contraindicated in __________. |
|
Definition
|
|
Term
| What are the mechanisms of resistance to tetracyclines? |
|
Definition
1)efflux pumps - decreases drug accumulation
2)ribosome protection proteins - enzymatic inhibition |
|
|
Term
| Ethionamide has possible cross-resistance with? |
|
Definition
|
|
Term
| Ethionamide is administered orally with _________ to avoid ___________ |
|
Definition
| pyridoxine, neurological effects |
|
|
Term
| side effects of ethionamide? |
|
Definition
1)gastric irritation
2)hepatotoxicity |
|
|
Term
| p-aminosalicylic acid (PAS) mechanism? |
|
Definition
| mechanism of action and side effects are similar to sulfonamides |
|
|
Term
| What are tetracyclines used for as the drugs of choice? |
|
Definition
Chlamydia
acne
**Rickettsial diseases - Lyme, Rocky Mountain Spotted Fever |
|
|
Term
| What is the tetracycline of choice in renal failure? |
|
Definition
|
|
Term
| Which tetracyclines have long half lives? |
|
Definition
| minocycline and doxycycline |
|
|
Term
| What inhibits the absorption of tetracyclines? |
|
Definition
|
|
Term
| What is mycobacterium avium complex? |
|
Definition
| disseminated infection with both M. avium and M. intracellulare. |
|
|
Term
| What are the side effects of tetracyclines? |
|
Definition
1)**dental staining
2)**photosensitivity
3)hepatotoxicity
4)nephrotoxicity
5)potential superinfection and pseudomembranous colitis with C. difficle |
|
|
Term
| When is the use of tetracyclines contraindicated? |
|
Definition
| in prepubertal children and pregnant women - due to dental staining |
|
|
Term
|
Definition
1)clarithromycin or azithromycin
2)ethambutol
(ciprofloxacin may be added as a 3rd drug)
Isoniazid and pyrazinamide are ineffective |
|
|
Term
| Prophylaxis for MAC in AIDS? (3) |
|
Definition
1)rifabutin
2)clarithromycin
3)azithromycin
(use one of these three for prophylaxis) |
|
|
Term
| How do you treat leprosy (m. leprae) ? |
|
Definition
1)dapsone
2)clofazimine
3)rifampin
all administered orally as combo therapy to prevent resistance |
|
|
Term
| Mechanism of action of Dapsone? |
|
Definition
| inhibits folate synthesis by same mechanisma s sulfonamides. (structurally related to PABA) |
|
|
Term
| Mechanism of action of Clofazimine? |
|
Definition
| action unknown but may bind to DNA and inhibit its replication. |
|
|
Term
| Mechanism of action of amphotericin B? |
|
Definition
| binds more strongly to ergosterol in fungal cell membranes than to cholesterol in mammalian cell membranes. It is amphipathic binding to ergosterol and water eventually assembling enough to form pores in the CM leading to protein and ion leakage and cell death |
|
|
Term
| Toxic effects of amphotericin B may be caused by? |
|
Definition
| some binding to cholesterol |
|
|
Term
| What causes resistance to amphotericin B? |
|
Definition
| resistance is uncommon, but may be mediated by decreases in CM concentration of ergosterol or favoring ergosterol precursors in the CM rather than ergosterol |
|
|
Term
| What is the spectrum of amphotericin B? |
|
Definition
|
|
Term
| Indications for amphotericin B? |
|
Definition
| all life-threatening systemic fungal infections |
|
|
Term
| How do you treat cryptococcal meningitis in AIDS pts? |
|
Definition
| amphotericin B followed by life-long prophylaxis with fluconazole (decreases morbidity) |
|
|
Term
| What is the mechanism of action of chloramphenicol? |
|
Definition
| binds to 50S subunit of ribosome and inhibits the peptidyl transferase reaction - usually bacteriostatic but can be bactericidal |
|
|
Term
| Why is chloramphenicol considered a toxic drug? |
|
Definition
| it binds to our mitochodrial ribosomes |
|
|
Term
| What is the indicated use of chloramphenicol? |
|
Definition
| used for rickettsial infections if tetracycline is contraindicated |
|
|
Term
| When should the dosage of chloramphenicol be reduced? |
|
Definition
1) hepatic insufficiency
2) newborns |
|
|
Term
| What are the side effects of chloramphenicol? |
|
Definition
1)aplastic anemia
2)drug interactions due to cyt 450 inhibition
3)**Gray Baby Syndrome |
|
|
Term
| What is Gray Baby Syndrome? |
|
Definition
due to chloramphenicol- toxic to newborn
characterized by vomiting, abdominal distention, cyanosis- within a day turn a gray color and become hypothermic |
|
|
Term
| How is amphotericin B administered? |
|
Definition
| IV or intrathecally for meningitis (b/c doesn't penetrate the CSF) |
|
|
Term
| What is the mechanism of action of the macrolides? |
|
Definition
| reversibly bind 50S subunit and inhibit translocation of peptidyl-tRNA from acceptor to donor site - usually *bacteriostatic* but can be bactericidal |
|
|
Term
| What bacteria are macrolides active against? |
|
Definition
| aerobic gram positive cocci and bacilli |
|
|
Term
| Is Amphotericin metabolism and excretion affected by hepatic or renal impairment? |
|
Definition
| No, so dosage does not have to be adjusted |
|
|
Term
| What are the mechanisms of resistance to macrolides? |
|
Definition
1)plasmid-med. decreased permeability
2)active efflux
3)drug-hydrolyzing esterases
4)modification of ribosome by methylase
5)ribosomal mutation |
|
|
Term
| What is azithromycin the drug of choice for? |
|
Definition
|
|
Term
| Side effects of amphotericin B? |
|
Definition
1)fever and chills (pretreat wil acetominoohen or hydrocortisone)
2)renal impairment |
|
|
Term
| Azithromycin can be used as an alternative drug for what type of infection? |
|
Definition
| chlamydia -alternative to doxycycline |
|
|
Term
| How can nephrotoxicity of amphotericin B be attenuated? |
|
Definition
| with sodium loading: administration of normal saline with the daily dose of the drug |
|
|
Term
| What is erytromycin the drug of choice for? |
|
Definition
|
|
Term
| What kind of amphotericin B preps are used in pts intolerant to or unresponsive to conventional treatment? |
|
Definition
| liposomal preps of amphotericin B (may be moderately less toxic than standard complex with glucose and deoxycholate) |
|
|
Term
| hat macrolides are active against mycobacterial infections? |
|
Definition
| clarithromycin and azithromycin |
|
|
Term
| How are the macrolides administered? |
|
Definition
usually orally because painful to inject
IV azithromycin for legionnaire's |
|
|
Term
| what is the mechanism of action of Nystatin (MYCOSTATIN, NILSTAT)? |
|
Definition
| same mechanism of action as amphotericin B (binds ergosterol) but too toxic for systemic use |
|
|
Term
| How is absorption increased for erythromycin? |
|
Definition
1) tablets coated becaue destroyed by stomach acid
2)synthesized as an ester to another compund to increase acid stability |
|
|
Term
| Indications for Nystatin? |
|
Definition
topical treatment of candidiasis (i.e. oropharyngeal thrush)
BAD taste can limit compliance |
|
|
Term
| What is responsible to erythromycin metabolism? |
|
Definition
liver via CYP3A
* dosage does not have to be adjusted in renal failure! |
|
|
Term
| which macrolide has a very short half life? |
|
Definition
| erythromycin - must be administered every 6 hours |
|
|
Term
| How id clarithromycin eliminated? |
|
Definition
| renal clearance - must reduce dosage in severe renal impairment |
|
|
Term
| Mechanism of action of Flucytosine? |
|
Definition
| metabolized by fungal cells to form 5-fluorodeoxyuridine monophosphate (inhibits DNA synthesis) and fluorouridine triphosphate (inhibits RNA synthesis) |
|
|
Term
| which macrolide will have increased compliance? |
|
Definition
| azithromycin - half life of 3 days so only administered once daily for a short period of time(5 days) |
|
|
Term
| How is azithromycin eliminated? |
|
Definition
|
|
Term
| Flucytosine is specific for fungal cells because? |
|
Definition
| human cells lack cytosine deaminase needed to metabolize flucytosine to active metabolites |
|
|
Term
| What is cytosine deaminase? |
|
Definition
| it is part of the cascade that metabolizes flucytosine to active metabolites in fungal cells |
|
|
Term
| Mechanism of resistance to flucytosine? |
|
Definition
1)loss of cytosine permease
2)reduced activity of cytosine deaminase |
|
|
Term
| What are the side effects of erythromycin? |
|
Definition
severe abdominal pain
cholestatic hepatitis
drug interactions due to inhibition on CYP3A
**prolongation of QT interval
**sudden cardiac death - risk further increased if taking another CYP3A inhibitor |
|
|
Term
| What are the side effects for clarithromycin? |
|
Definition
| less abdominal pain and drug interactions than with erythromycin |
|
|
Term
|
Definition
(narrow)
1)cryptococcus neoformans
2)candida species
3)molds that cause chromobastomycosis |
|
|
Term
| Which macrolide has little effect on cytochrome p450s? |
|
Definition
|
|
Term
| What is the mechanism of action of Clindamycin? |
|
Definition
| binds to 50S ribosomal subunit |
|
|
Term
| What drugs should clindamycin NOT be used in combination with? |
|
Definition
| macrolides and chloramiphenicol - bind to 50S as well so interfere with each other |
|
|
Term
| Indications for use of Flucytosine? |
|
Definition
1)cryptococcal meningitis in AIDS pts (combo therapy with amphotericin B to reduce toxicity)
2)chromoblastomycosis (combo with itraconazole) |
|
|
Term
| Administration of flucytosine? |
|
Definition
|
|
Term
| Flucytosine dose must be adjusted for decreased _________ function. |
|
Definition
|
|
Term
| What are the side effects of clindamycin? |
|
Definition
1)diarrhea
2)**pseudomembranous colitis with C. difficle - one of the most common antibiotics to cause this! |
|
|
Term
| When should dosage of clindamycin be adjusted? |
|
Definition
|
|
Term
| How is clindamycin administered? |
|
Definition
| usually IV or IM, but can be oral |
|
|
Term
| Side effects of flucytosine? |
|
Definition
1)bone marrow toxicity w/ anemia, leukopenia and thrombocytopenia.
2)(less common)hepatotoxicity
3)(less common)severe enterocolitis |
|
|
Term
| When is clindamycin use indicated? |
|
Definition
| serious anaerobic and mixed GI infections |
|
|
Term
| What is clindamycin the drug of choice for? |
|
Definition
lung abscesses
anaerobic lung infections |
|
|
Term
| What may the side effects of flucytosine be attributed to? |
|
Definition
| conversion to 5-fluorouracil by intestinal flora |
|
|
Term
| What is clindamycin used topically with peroxide for? |
|
Definition
|
|
Term
| What is the mechanism of action of Linezolid? |
|
Definition
| prevents formation of 70S complex that initiates protein synthesis by **binding to 50S |
|
|
Term
| Does linezolid cross react with other drugs that bind to 50S? |
|
Definition
| No because it binds to a different site |
|
|
Term
| What is linezolid used to treat? |
|
Definition
| vancomycin-resistant staph and enterococcus faecium |
|
|
Term
| What is the spectrum of linezolid? |
|
Definition
| aerobic gram positive bacteria |
|
|
Term
| mechanism of action of caspofungin? |
|
Definition
inhibits synthesis of B(1-3)glucan
(disrupting cell wall and resulting in death) |
|
|
Term
| what is the first drug of the echinocandins? |
|
Definition
|
|
Term
| How is linezolid administered? |
|
Definition
| orally or IV -good bioavailability |
|
|
Term
| Is linezolid dosage adjusted for hepatic or renal impairment? |
|
Definition
|
|
Term
| Indications for caspofungin? |
|
Definition
| Licensed only for aspergillosis unresponsive to amphotericin B (also active vs. candida species) |
|
|
Term
| How is caspofungin administered? |
|
Definition
|
|
Term
| What is the mechanism of resistance to linezolid? |
|
Definition
| mutation of the 23S ribosomal RNA of the 50 S subunit |
|
|
Term
| For caspofungin administration, the dosage must be adjusted for? |
|
Definition
| severe hepatic insufficiency |
|
|
Term
| What are the side effects of linezolid? |
|
Definition
1)neutropenia
2)thrombocytopenia
both reversible |
|
|
Term
| Side effects of caspofungin? |
|
Definition
| possible liver toxicity when combined with cyclosporine |
|
|
Term
| What is the mechanism of action of the streptogramims? |
|
Definition
| combo of streptogramims used to bind 50S subunit and inhibit protein synthesis |
|
|
Term
| Due to possible liver toxicity do not combine caspofungin with ___________ |
|
Definition
|
|
Term
| What combo of streptogramims are used for vancomycin-resistant bacteria? |
|
Definition
| quinupristin (streptogramim B) and dalfopristin (A) |
|
|
Term
| What is the streptogramim combo primarily used to treat? |
|
Definition
| vancomycin- resistant E. faecium and S. aureus/epidermidis |
|
|
Term
| Mechanism of action of azoles? |
|
Definition
inhibits ergosterol synthesis by interfering with fungal cyt P450 enzyme, sterol 14-a-demethylase.
(inhibits fungal cyt P450 more so than human cyt P450) |
|
|
Term
| How are streptogramims eliminated? |
|
Definition
| hepatic clearance - reduce dosage in hepatic insufficiency |
|
|
Term
| How are streptogramims administered? |
|
Definition
|
|
Term
| What are the side effects of streptogramims? |
|
Definition
1)pain/phlebitis at infusion site
2)drug interaction due to inhibition of CYP450s |
|
|
Term
| What type of therapy is recommended for TB? |
|
Definition
| directly observed therapy - observe patient taking pills several times a week because compliance is very important for effective treatment |
|
|
Term
| What has to be taken into consideration for therpy of TB? |
|
Definition
1) TB is slow growing so killed slowly - requires longer treatment period
2)lipid rich cell wall is impermeable to most antibiotics
3)many organisms found intracellularly
4)directly observed therapy to ensure compliance |
|
|
Term
| The first oral azole, use decreasing due to lack of selectivity for fungal cyt P450 |
|
Definition
|
|
Term
| What are the first line agents used for TB? |
|
Definition
isoniazid
rifampin
pyrazinamide
ethambutol
streptomycin |
|
|
Term
| side effects of ketoconazole? |
|
Definition
Nausea, anorexia and vomiting
Effects due to cyt P450 inhibition include: gynecomastia, infertility and menstrual irregularities due to interference with steroid hormone synthesis
(may also see drug interactions due to the cyt p450 inhibition) |
|
|
Term
| When are second line drugs used to treat TB? |
|
Definition
used for strains with mutliple resistances
used in more aggressive therapy for HIV patients |
|
|
Term
| Indications for itraconazole? |
|
Definition
1)histoplasmosis
2)blastomycosis
(does not replace amphotericin B in case of CNS or rapidly progressing infections) |
|
|
Term
| What drug is used as a maintenance drug for prophylaxis of histoplasmosis in AIDS pts after amphotericin B treatment? |
|
Definition
|
|
Term
| CDC recommends what our drug therapy for TB until susceptibility is determined? |
|
Definition
1)rifampin
2)isoniazid
3)pyrazinamide
4)ethambutol or streptomycin |
|
|
Term
| How do you administer itraconazole? |
|
Definition
| Orally or IV. Loading dose for several days is required to reach steady state levels due to protein and tissue binding |
|
|
Term
| Side effects of itraconazole? |
|
Definition
| metabolism of other drugs with hepatic clearance is reduced (drug interactions, but less than with ketoconazole) |
|
|
Term
| what is the drug of choice for invasive aspergillosis? |
|
Definition
|
|
Term
| How do you administer voriconazole? |
|
Definition
| orally or IV (90% bioavailability) |
|
|
Term
| Side effects of voriconazole? |
|
Definition
| visual disturbances including blurring, changes in color vision and brightness. (usually resolve within 30 minutes of taking the drug) |
|
|
Term
| Drug of choice for treatment and prophylaxis of cryptococcal meningitis AFTER treatment with amphotericin B |
|
Definition
|
|
Term
| Indications for Fluconazole? |
|
Definition
1)Cryptococcal meningitis
2)Mucocutaneous candidiasis
3)candidemia |
|
|
Term
| can administer single dose of __________ for vaginal candidiasis |
|
Definition
|
|
Term
| How do you administer fluconazole? |
|
Definition
|
|
Term
| This drug has the widest therapeutic index of all the azoles and has less drug interactions |
|
Definition
|
|
Term
| What has caused the emergence of azole-resistant fungi? |
|
Definition
| prophylactic use of fluconazole in immunocompromised pts |
|
|
Term
| Indications for Clotrimazole (Lotrimin) and Miconazole (Monistat) |
|
Definition
topical treatment for candidiasis and dermatophytes
(oral clotrimazole better tasting than nystatin for oral thrush) |
|
|
Term
| Spectrum of griseofulvin ? |
|
Definition
|
|
Term
| Indications for griseofulvin? |
|
Definition
| mycoses of skin, hair and nails. (don't use for infections that respond to topical treatment) |
|
|
Term
| Griseofulvin has largely been replaced by _____________ |
|
Definition
|
|
Term
| How do you administer griseofulvin? |
|
Definition
| orally, better absorption with food |
|
|
Term
| mechanism of action of griseofulvin |
|
Definition
| binds to keratin in cells forming new skin, hair and nails and protects them from infection. (up to 6 weeks for skin and hair and up to 12 months for nails) |
|
|
Term
| Side effects of griseofulvin? |
|
Definition
1)allergic rxns similar to serum sickness
2)hepatitis |
|
|
Term
| griseofulvin may have drug interactions with? (2) |
|
Definition
1)warfarin
2)phenobarbital |
|
|
Term
| Mechanism of action of terbinafine? |
|
Definition
| blocks fungal enzyme, squalene epoxidase, interfering with ergosterol synthesis. |
|
|
Term
| Indications for terbinafine? |
|
Definition
1)fungal nail infections (orally for 3 months)
2)dermatphytoses (topically)
3)onchyomycosis |
|
|
Term
| Drug of choice for onchyomycosis? |
|
Definition
|
|
Term
| terbinafine is contraindicated in __________ |
|
Definition
|
|
Term
| Side effects of terbinafine? |
|
Definition
1)rare hepatotoxicity
2)neutropenia
3)Hypersensitivity
4)GI upset
5)headache |
|
|
Term
| Acyclovir is an ________________ derivative |
|
Definition
|
|
Term
| Mechanism of action of acyclovir? |
|
Definition
| Acyclovir is selectively phosphorylated by viral thymidine kinase and then further phosphorylated to a triphosphate. The acyclovir triphosphate then competes with dGTP binding irreversibly to the viral DNA polymerase inhibiting viral nucleic acid synthesis |
|
|
Term
| Acyclovir is highly selective for _________ infected cells |
|
Definition
|
|
Term
| what causes resistance to acyclovir? |
|
Definition
1)Mutations in thymidine kinase
2)Mutations in DNA polymerase |
|
|
Term
| Oral acyclovir shortens the duration of symptoms for __________ |
|
Definition
| Herpes simplex viruses 1 and 2 |
|
|
Term
| IV acyclovir is the treatment of choice for ? |
|
Definition
1)HSV encephalitis
2)neonatal HSV infections
3)serious HSV or VZV infections
(also, prevents reactivation of HSV in transplant pts) |
|
|
Term
| Treat VZV with _____________ if within 24 hrs of rash onset in varicella and 72 hrs in zoster. |
|
Definition
|
|
Term
| This drug has a very short have life and is administered 5 times daily for most indications |
|
Definition
|
|
Term
| what are the side effects of acyclovir? |
|
Definition
| side effects are rare even with long term use, but IV use can be associated w/ transient renal insufficiency or neurological toxicity (minimize with hydration and avoid rapid infusion) |
|
|
Term
| what is the mechanism of action of valacyclovir? |
|
Definition
| valacyclovir is a prodrug that is converted to acyclovir in the body so the mechanism of action is identical to acyclovir. (phosphorylated to triphosphate and terminates chain elongation) |
|
|
Term
| Treatment of HSV with _________ has been shown to decrease risk of sexual transmission |
|
Definition
|
|
Term
| Describe the pharmacokinetic difference b/w acyclovir and valacyclovir |
|
Definition
| valacyclovir has a much higher oral bioavailability leading to levels similar to IV acyclovir. It has a much longer half life and is usually administered twice daily |
|
|
Term
| The addition ______________ group in ganciclovir enhances its anti-CMV activity and hematopoeitic toxicity |
|
Definition
|
|
Term
| Ganciclovir's specificity is based on its need to be phosphorylated by this viral kinase |
|
Definition
|
|
Term
| 2 mechanisms of resistance to ganciclovir |
|
Definition
1)mutations in the viral kinase (UL97)
2)mutations in the viral DNA polymerase |
|
|
Term
| gancyclovir is used to treat/prophylaxis? |
|
Definition
1)CMV retinitis
2)CMV infecions in transplant pts |
|
|
Term
| Dual therapy of ________ and ________ is most effective in slowing the progression of CMV retinitis. |
|
Definition
|
|
Term
| ganciclovir is administered how? |
|
Definition
1)orally
2)iv
3)intraocular implant |
|
|
Term
| Side effects of ganciclovir? |
|
Definition
myelosuppression, particularly neutropenia
(20-40% of pts) |
|
|
Term
| name 2 acyclic guanosine analogs: |
|
Definition
|
|
Term
| Mechanism of action of Cidofovir |
|
Definition
| It is an acyclic cytosine nucleotide whose diphosphate form competitively inhibits viral DNA polymerase by inhibiting binding of dCTP. (does not terminate chain but gets incorporated) |
|
|
Term
| Cidofovir is used to treat ? |
|
Definition
|
|
Term
| cidofovir has a poor oral bioavailability due to? |
|
Definition
|
|
Term
| cidofovir must be administered with _________ to increase serum levels of cidofovir and reduce nephrotoxicity |
|
Definition
|
|
Term
| probenecid does what to increase serum levels of cidofovir? |
|
Definition
|
|
Term
| what metabolite of cidofovir has a half life of 87 hours and may serve as an intracellular reservoir of active drug? |
|
Definition
|
|
Term
| What is the mechanism of action of isoniazid? |
|
Definition
| inhibits synthesis of mycolic acids which are important for synthesizing the mycobacterial cell wall - BACTERICIDAL |
|
|
Term
| When is the only time isoniazid is used alone? |
|
Definition
| prophylactic therapy except for during pregnancy of hepatic disease |
|
|
Term
| what is the limiting toxicity of cidofovir? |
|
Definition
| dose-dependent nephrotoxicity |
|
|
Term
| What is the mechanism of action of foscarnet? |
|
Definition
| It directly inhibits viral RNA and DNA polymerase, including HIV reverse transcriptase. (blocks the pyrophosphate binding site, blocking cleavage of pyrophosphate from dNTPs) |
|
|
Term
| What two genes can be mutated in order to develop resistance to isoniazid? |
|
Definition
1)katG-will prevent conversion of the prodrug into an active metabolite
2)inhA-encodes a carrier protein in mycoloic acid biosynthesis |
|
|
Term
| What is the mechanism of resistance to foscarnet? |
|
Definition
| mutations in viral DNA polymerase (associated w/ prolonged use of drug) |
|
|
Term
| How are first line drugs for TB administered with the exception of streptomycin? |
|
Definition
|
|
Term
| When must isoniazid dosage be adjusted? |
|
Definition
| hepatic insufficiency only |
|
|
Term
| Indications for foscarnet? |
|
Definition
1)CMV retinitis
2)CMV colitis
3)CMV esophagitis
4)ganciclovir resistant infections
5)acyclovir-resistant HSV and VZV
(more effective in combo w/ ganciclovir) |
|
|
Term
| What molecule does isoniazid cause to be excreted leading to a deficiency? |
|
Definition
|
|
Term
| why is it important to administer pyridoxine along with isoniazid? |
|
Definition
| to prevent peripheral neuropathy caused by a pyridoxine deficiency |
|
|
Term
| What are the side effects of isoniazid? |
|
Definition
1)peripheral neuropathy
2)hepatotoxicity |
|
|
Term
| What should be monitored while taking isoniazid? |
|
Definition
| liver function to check for signs of hepatitis |
|
|
Term
| What is the mechanism of action of rifampin? |
|
Definition
| inhibits the beta subunit of RNA polymerase- BACTERICIDAL |
|
|
Term
| How do bacteria develop resistance to rifampin? |
|
Definition
| mutations in RNA polymerase |
|
|
Term
| Foscarnet is deposited in ___________ |
|
Definition
|
|
Term
| Foscarnet is administered by ? |
|
Definition
| IV (poor oral bioavailability) |
|
|
Term
| What are the side effects of rifampin? |
|
Definition
1) red bodily fluids
2) hepatotoxicity
3) drug interactions via induction of CYP450s - decreases efficacy of *oral contraceptives*, anticonvulsants, methadone, protease inhibitors |
|
|
Term
| There is cross resistance between isoniazid and ____________ |
|
Definition
|
|
Term
| Use of an infusion pump to avoid nephrotoxicity, hyper/hypocalcemia, and hypo/hyperphosphatemia is necessary for what dryg? |
|
Definition
|
|
Term
| What are the side effects of pyrazinamide? |
|
Definition
1) hepatotoxicity
2) **hyperuricemia which can lead to gout |
|
|
Term
| When is pyrazinamide contraindicated? |
|
Definition
| when there is any sort of liver dysfunction |
|
|
Term
| What are the dose-limiting toxicities for foscarnet? |
|
Definition
1)Nephrotoxicity
2)hypocalcemia (can lead to arrhythmias, seizures, tetany and other CNS disturbances) |
|
|
Term
| What is the mechanism of resistance to pyrazinamide? |
|
Definition
1)mutations in pyrazinamidase which prevent conversion to its active form, pyrazinoic acid
2) decreased uptake |
|
|
Term
| what should be monitored during treatment with pyrazinamide? |
|
Definition
|
|
Term
| What is the mechanism of action of Fomivirsen? |
|
Definition
| It is an anti-sense oligonucleotide that hybridizes specifically to CMV immediate early region 2 mRNA. This inhibits synthesis of CMV proteins/viral replication |
|
|
Term
| what is the mechanism of action of ethambutol? |
|
Definition
| inhibits mycobacterial cell wall synthesis by inhibiting arabinosyl transferase which is responsible for the synthesis of arabinogalactan - BACTERIOSTATIC |
|
|
Term
| Fomivirsen is used to treat? |
|
Definition
| CMV retinitis that is resistant to other therapies |
|
|
Term
| How is reisstance developed to ethambutol? |
|
Definition
| overexpression or mutation in arabinosyl transferase |
|
|
Term
| When must the dosage be reduced for ethambutol? |
|
Definition
|
|
Term
| fomivirsen is administered by ? |
|
Definition
| intravitreal injection (into eye) every 2-4 weeks |
|
|
Term
| What are the side effects of ethambutol? |
|
Definition
| **optic neuritis - loss of visual acuity, and red/green color blindness |
|
|
Term
| how is fomivirsen eliminated by the body? |
|
Definition
| local metabolism by exonucleases |
|
|
Term
| What should be monitored while taking ethambutol? |
|
Definition
|
|
Term
| Who should not be treated with ethambutol and why? |
|
Definition
| children under 5 - difficult to test their visual acuity |
|
|
Term
| what are the side effects of fomivirsen? |
|
Definition
| no side effects directly from the drug actions, but effects from injection itself. (iritis, vitreitis, increased ocular pressure) |
|
|
Term
| Which first line TB drug doesn't penetrate cells? |
|
Definition
| streptomycin -only suppresses TB |
|
|
Term
| What is very important to do PRIOR to starting treatment for TB? |
|
Definition
| **take a sample of bacteria for drug susceptibility testing |
|
|
Term
| What are the second line drugs used to treat resistant strains of TB? |
|
Definition
cycloserine
ethionamide
p-aminosalicylic acis (PAS)
amikacin
capreomycin |
|
|
Term
| What is the mycobacterium avium complex (MAC)? |
|
Definition
| disseminated infection with both M.avium and M. intracellulare - common in AIDS |
|
|
Term
| Where is MAC found in non-HIV patients? |
|
Definition
| usually limited to the lungs |
|
|
Term
| What is used to treat MAC? |
|
Definition
ethambutol and clarithromycin or azithromycin
Ciprofloxacin can be used as a 3rd drug |
|
|
Term
| what Tb drugs are ineffective against MAC? |
|
Definition
| isoniazid and pyrazinamide |
|
|
Term
| When should prophylaxis for MAC be administered? |
|
Definition
| in AIDS patients once their CD4 levels drop below a certain point |
|
|
Term
| What is used for the prophylaxis of MAC? |
|
Definition
**rifabutin
macrolides(clarithromycin and azithromycin) no longer used because want MAC to be susceptible to them if prophylaxis doesn't work! |
|
|
Term
| What three drug combo is used to treat M. leprae? |
|
Definition
1)dapsone
2)clofazimine
3)rifampin |
|
|
Term
| What is the mechanism of action of dapsone? |
|
Definition
| inhibits folate synthesis by inhibiting dihydropteroate synthase (same mech as sulfonamides) - BACTERIOSTATIC |
|
|
Term
| what is the mechanism of action of amphotericin B? |
|
Definition
| it binds ergosterol and forms pores in the membrane of fungal cells allowing leakage of proteins and ions which leads to cell death |
|
|
Term
| what are the toxic effects of amphotericin B due to? |
|
Definition
| binding to cholesterol in human cell membranes |
|
|
Term
| what part of amphotericin B is responsible for the binding of ergosterol? |
|
Definition
| the hydrophobic double bond-rich side |
|
|
Term
| what is the mechanism of resistance to amphotericin B? |
|
Definition
1) decresing ergosterol membrane concentration
2)changing membrane composition to favor ergosterol precursors over ergosterol |
|
|
Term
| what is the drug of choice for all life-threaning fungal infections? |
|
Definition
|
|
Term
| cryptococcal meningitis is initially treated with _________ followed by lifelong prophylactic treatment with _________ |
|
Definition
| amphotericin B ; fluconazole |
|
|
Term
| how is amphotericin B administered? |
|
Definition
|
|
Term
| what are the side effects of amphotericin B? |
|
Definition
fever and chills
renal impairment |
|
|
Term
| what can be given prior to amphotericin B to minimize fever and chills? |
|
Definition
| acetaminophen or hydrocortisone |
|
|
Term
| what must be monitored while taking amphotericin B? |
|
Definition
|
|
Term
| what is the standard preparation of amphotericin B? |
|
Definition
| in a complex with deoxycholate and glucose |
|
|
Term
| when should liposomal preparations of amphotericin B be given? |
|
Definition
| only if the patient is intolerant or unresponsive to the standard prep |
|
|
Term
| when taking amphotericin B, nephrotoxicity can be attenuated with _________ |
|
Definition
| sodium loading - normal saline administered with daily dose of the drug |
|
|
Term
| what is the mechanism of Nystatin? |
|
Definition
| same as amphotericin B - binds ergosterol and forms pores in fungal membrane resulting in cell death |
|
|
Term
| what is Nystatin used to treat? |
|
Definition
| topical treatment of Candidiasis (oral thrush) |
|
|
Term
| How does flucytosine get into fungal cells? |
|
Definition
| transported in by cytosine permease |
|
|
Term
| what is the echanism of action of flucytosine? |
|
Definition
| it is transported into fungal by cytosine permease then metabolzed to 5-fluorouracil by cytosine deaminase ----it is then phosphorylates to form two metabolites which will inhibit DNA and RNA synthesis |
|
|
Term
| what metabolite of flucytosine inhibits DNA synthesis? |
|
Definition
| 5-fluorodeoxyuridine monophosphate (5-FdUMP) - equivaent of thymidine so inhibits synthesis of thymidine monphosphate |
|
|
Term
| what metabolite of flucytosine inhibits RNA synthesis? |
|
Definition
| fluorouridine triphosphate (5-FUTP) |
|
|
Term
| How do fungi develop resistance to flucytosine? |
|
Definition
1)loss of cytosine permease
2)reduced activity of cytosine deaminase |
|
|
Term
| What make flucytosine specific for fungal cells and not human cells? |
|
Definition
| humans lack cytosine deaminase enzyme |
|
|
Term
| what is flucytosine used in combination with to treat crytococcal meningitis of AIDS? |
|
Definition
|
|
Term
| what combination therapy is used for the treatment of chromoblastomycosis? |
|
Definition
| flucytosine + itraconazole |
|
|
Term
| when is flucytosine indicated for use? |
|
Definition
| ONLY in combination therapy for cryptococcal meningitis or chromoblastomycosis |
|
|
Term
| when should the dosage of flucytosine be adjusted? |
|
Definition
| for decreased renal function |
|
|
Term
| flucytosine is active against what 3 infections? |
|
Definition
Cryptococcus neoformans
Candida species
molds causing chromoblastomycosis |
|
|
Term
| howis flucytosine administered? |
|
Definition
|
|
Term
| what are the side effects of flucytosine? |
|
Definition
bone marrow toxicity - anemia, leukopenia, thrombocytopenia
hepatotoxicity, enterocolitis |
|
|
Term
| what probably causes the side effects seen in flucytosine? |
|
Definition
| conversion of flucytosine to 5-fluorouracil by intesinal flora which gets into human cells |
|
|
Term
| what is the mechanism of action of caspofungin? |
|
Definition
| inhibits the synthesis of beta glucan which disrupts the fungal cell wall causing death |
|
|
Term
| what is the side effect of caspofungin? |
|
Definition
| liver toxicity when combined with cyclosporine |
|
|
Term
| what is caspofungin liscensed to be used for? |
|
Definition
| invasive aspergillosis that is unresponsive to amphotericin B |
|
|
Term
| how is caspofungin administered? |
|
Definition
|
|
Term
| when should dosage be adjusted for caspofungin? |
|
Definition
| severe hepatic insufficiency |
|
|
Term
| what is the mechanism of action of the azoles? |
|
Definition
| inhibit ergosterol synthesis by interfering with the function of a fungal **cytochrome P450 enzyme, **sterol 14-alpha-demethylase** - disrupts membrane synthesis |
|
|
Term
| what are the side effects if ketoconazole? |
|
Definition
1)nausea, vomiting, anorexia
2)**gynecomastia, infertility, and menstrual irregularities due to inhibition of human CYP450s which interferes with hormone synthesis
3)drug interactions |
|
|
Term
| what is the azole of choice for treament of histoplasmosis and blastomycosis? |
|
Definition
| itraconazole - used when infection is not rapidly progressing/life-threatening |
|
|
Term
| what is used as a maintenance drug for prophylaxis of histoplamosis in AIDS patients after amphotericin B treatment? |
|
Definition
|
|
Term
| how is itraconazole administered? |
|
Definition
|
|
Term
| what is the drug of choice for invasive aspergillosis? |
|
Definition
|
|
Term
| what are the side effects of voriconazole? |
|
Definition
| visual disturbances - blurring, changes in color vision, brightness (resolves within 30 min) |
|
|
Term
| what azole is the drug of choice for treatment and prophylaxis of cryptococcal meningitis of AIDS after treatment with amphotericin B? |
|
Definition
|
|
Term
| what is fluconazole used to treat? |
|
Definition
1)mucocutaneous candidiasis/candidemia
2)vaginal candidiasis
3)coccidioidal meningitis |
|
|
Term
| which azole has the widest therpeutic index? |
|
Definition
|
|
Term
| what should be measured when adminstering flucytosine? |
|
Definition
| plasma concentration bc has a narrow therapeutic window |
|
|
Term
| what are clotrimazole and miconazole used ot treat? |
|
Definition
| topical treatment of candidiasis and dermatophytes |
|
|
Term
| what is a better tasting alternative to nystatin for oral thrush? |
|
Definition
|
|
Term
| what is griseofulvin used to treat? |
|
Definition
| mycoses of the skin, hair and nails |
|
|
Term
| what is the spectrum of griseofulvin? |
|
Definition
|
|
Term
| what is the mechanism of action of terbinafine? |
|
Definition
| interferes with ergosterol synthesis by blocking the fungal enzyme, **squalene epoxidase - accumulation of squalene kills the cell =FUNGICIDAL |
|
|
Term
| what should griseofulvin not be used for? |
|
Definition
| infections that will respond to topical treatment |
|
|
Term
| is griseofulvin fungistatic or cidal? |
|
Definition
| static - binds keratin in cells forming new skin, hair, nails and prevents them from infection but doesn't eliminate existing infection |
|
|
Term
| what are the side effects of griseofulvin? |
|
Definition
1)allergic reaction similar to serum sickness
2)hepatitis
3)drug interactions with warfarin, phenobarbital |
|
|
Term
| when is terbinafine contraindicated? |
|
Definition
|
|
Term
| what is the spectrum of terinafine? |
|
Definition
|
|
Term
| what is terbinafine used to treat? |
|
Definition
1)orally for fungal nail infection
2)topically for dermatophytoses
3) DOC for onchymycosis |
|
|
Term
| what is the drug of choice for onchyomycosis? |
|
Definition
|
|
Term
| what are the side effects of terbinafine? |
|
Definition
| hepatotoxicity, neutropenia, hypersensitivity reactions, GI upset, headache |
|
|
