Drugs Flashcards
block cell wall synthesis by inhibition of peptidoglycan cross-linking
penicillin, methicillin, ampicillin, pipercillin, cephalosporins, aztreonam, imipenem
block peptidoglycan synthesis
bacitracin, vancomycin
block nucleotide synthesis by inhibiting folic acid synthesis
sulfonamides, trimethoprim
block DNA topoisomerases
fluoroquinolones
block mRNA synthesis
rifampin
damage DNA
metronidazole
block protein synthesis at 50S ribosomal subunit
chloramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
block protein synthesis at 30S ribosomal subunit
aminoglycosides, tetracyclins
structural analog of D-ala D-ala
penicillin
penicillin MOA
bind transpeptidases, block transpeptidase cross-linking of peptidoglycan, activate autolytic enzymes
penicillin use
gram + (S. pneumonia, S. pyogenes, Actinomyces), N. meningitidis, Treponema pallidum, bactericidal for gram+ cocci, rods, gram - cocci, spirochetes
penicillin toxicity
hypersensitivity, hemolytic anemia
penicillin resistance
beta lactamases cleave beta lactam ring
D-ala D-ala
a.a. sequence on peptidoglycan precursor molecules that is recognized by enzyme transpeptidase
oxacillin, nafcillin, dicloxacillin MOA
narrow spectrum, penicillinase resistant )bulky R group blocks access of beta-lactamase to beta lactam ring)
oxacillin, nafcillin, dicloxacillin use
S. aureus (except MRSA–>altered penicillin-binding protein target site)
oxacillin, nafcillin, dicloxacillin toxicity
hypersensitivity, interstitial nephritis
ampicillin, amoxicillin MOA
wider spectrum, penicillinase sensitive; combine with clavulanic acid to protect against beta-lactamase; amoxicillin has greater oral bioavalability
ampicillin, amoxicillin use
HELPSS kill enterococci
H. influenza, E. coli, Listeria, Proteus, Salmonella, Shigella, enterococci
ampicillin, amoxicillin toxicity
hypersensitivity, ampicillin rash, pseudomembranous colitis
ampicillin, amoxicillin resistance
beta-lactamases cleave beta-lactam ring
ticarcillin, pipercillin MOA
extended spectrum
ticarcillin, pipercillin use
pseudomonas, gram - rods, susceptible to penicillinase, use with clavulanic acid
ticarcillin, pipercillin toxicity
hypersensitivity
beta-lactamase inhibitors
CAST
clavulanic acid, sulbactam, tazobactam
cephalosporins MOA
inhibit peptidoglycan synthesis through blockage of transpeptidation enzymes; bactericidal
organisms not covered by cephalosporins
LAME
Listeria, atypicals (chlamydia, mycoplasma), MRSA, enterococci. ceftaroline covers MRSA
1st generation cephalosporins
cefazolin, cephalexin
1st generation cephalosporins use
gram + cocci;
PEcK
proteus, e. coli, klebsiella.
cefazolin used prior to surgery to prevent S. aureus infection of wound
2nd generation cephalosporins
cefoxitin, cefaclor, cefuroxime
2nd generation cephalosporins use
gram + cocci
HEN PEcKS
H. influenza, enterobacter, neisseria, proteus, e. coli, klebsiella, serratia
3rd generation cephalosporins
ceftriaxone, cefotaxime, ceftazidime
3rd generation cephalosporins use
gram - infections resistant to other beta-lactams
ceftriaxone: meningitis and gonorrhea
ceftazidime: pseudomonas
4th generation cephalosporins
cefepime
4th generation cephalosporins use
increased activity against pseudomonas and gram +
cephalosporins toxicity
hypersensitivity, vitamin K deficiency, low cross-reactivity with penicillins, increase nephrotoxicity of aminoglycosides
aztreonam MOA
monobactam resistant to beta-lactamases
prevents peptidoglycan cross-linking by binding PBP3, synergistic with aminoglycosides, no cross-allerginicity with penicillins
aztreonam use
gram - rods only
for penicillin-allergic pts and those with renal insufficiency who can’t tolerate aminoglycosides
aztreonam toxicity
occasional GI upset
imipenem/cilastatin, meropenem MOA
imipenem: broad-spectrum, beta-lactamase resistant cerbapenem, always administered with cilastatin (inhibitor of renal dehydropeptidase I)
imipenem/cilastatin, meropenem use
gram + cocci, gram - rods, anaerobes
meropenem: reduced risk of seizures, stable to dehydropeptidase I
imipenem/cilastatin, meropenem toxicity
GI distress, skin rash, CNS (seizures)
vancomycin MOA
inhibits cell wall peptidoglycan formation by binding D-ala D-ala; bactericidal
vancomycin use
gram + only; MRSA, enterococci, C. difficile
vancomycin toxicity
NOT (does not have many problems)
nephrotoxicity, ototoxicity, thrombophlebitis, red man syndrome (pretreat with antihistamines and slow infusion rate)
vancomycin resistance
D-ala D-ala change to D-ala D-lac
daptomycin MOA
lipopeptide antibiotic limited to gram + (including MRSA)
causes depolarization of bacterial cellular membrane and inhibition of DNA, RNA, amd protein synthesis
daptomycin toxicity
increased CPK levels and increased incidence of myopathy
30S inhibitors
aminoglycosides (bactericidal), tetracyclines (bacteriostatic)
50S inhibitors
chloramphenicol, clindamycin (bacteriostatic)
erythromycin (bacteriostatic)
linezolid (s.e. thrombocytopenia, optic neuritis)
aminoglycosides MOA
bactericidal; inhibit formation of initiation complex and cause misreading of mRNA; block translocation; require O2 for uptake (ineffective against anaerobes)
aminoglycosides use
severe gram - rod infections; synergistic with beta-lactams
neomycin for bowel surgery
aminoglycosides toxicity
nephrotoxicity (especially with cephalosporins), neuromuscular blockade, ototoxicity (especially with loop diuretics), teratogen
aminoglycosides resistance
transferase enzymes: acetylation, phosphorylation, adenylation
tetracyclines MOA
bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA, limited CNS penetration
doxycycline for pts with renal failure
do not take with milk, antacids, iron-containing preps because divalent cations inhibit absorption
demeclocycline use
ADH antagonist; diuretic in SIADH
tetracyclines use
borrelia burgdorferi, M. pneumonia; ability to accumulate intracellularly–<effective against rickettsia and clamydia
tetracyclines toxicity
GI, discoloration of teeth, inhibition of bone growth in children, photosensitivity. contraindicated in pregnancy
tetracyclines resistance
decreased uptake into cells or increased efflux by plasmin-encoded transport pumps
macrolides MOA
inhibit protein synthesis by blocking translocation; bind to 23S rRNA of 50S; bacteriostatic
macrolides use
atypical pneumonia (mycoplasma, chlamydia, legionella), chlamydia, gram + cocci (strep infections in pts allergic to penicillin)
macrolides toxicity
MACRO
motility issues, arrhythmia (prolonged QT), acute cholestatic hepatitis, rash, eosinophilia; increase serum concentration of theophyllines, oral anticoagulants
macrolides resistance
methylation of 23S rRNA
chloramphenicol MOA
blocks peptidyltransferase at 50S; bacteriostatic
chloramphenicol use
meningitis (H. influenza, neisseria, strep pneumonia)
chloramphenicol toxicity
anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (lack liver UDP-glucuronyl transferase)
chloramphenicol resistance
plasmid-encoded acetyltransferase
clindamycin MOA
blocks peptide transfer at 50S; bacteriostatic
clindamycin use
anaerobic infections (bacteroides fragilis, C. perfringens) in aspiration pneumonia or lung abscess, gram + cocci
clindamycin toxicity
pseudomembranous colitis, fever, diarrhea
sulfonamides MOA
PABA antimetabolites inhibit dihydropteroate synthase; bacteriostatic
sulfonamides use
gram +, gram -, nocardia, chmamydia; triple sulfas or SMX for simple UTI
sulfonamides toxicity
hypersensitivity, hemolysis of G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (warfarin)
sulfonamides resistance
altered bacterial dihydroproteroate synthase, decreased uptake, increased PABA synthesis
trimethoprim MOA
inhibits bacterial dihydrofolate reductase; bacteriostatic
trimethoprim use
in combo with sulfonamides causing sequential block of folate synthesis; combo used for UTI, shigella, salmonella, pneumocystis jirovecii
trimethoprim toxicity
TMP: treats marrow poorly
megaloblastic anemia, leukopenia, granulocytopenia (may alleviate with supplemental folinic acid: leucovorin rescue)
fluoroquinolones MOA
inhibit DNA gyrase (topoisomerase II) and topoisomerase IV; bactericidal; must not be taken with antacids
fluoroquinolones use
gram - rods of urinary and GI tracts (pseudomonas), neisseria, some gram +
fluoroquinolones toxicity
GI, superinfections, skin rashes, headaches, dizziness, tendonitis, myalgias; contraindicated in pregnant women and children; prolonged QT; may cause tendon rupture in pts taking prednisone
fluoroquinolone resistance
chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pump
metronidazole MOA
forms free radical toxic metabolites that damage DNA; bactericidal; antiprotozoal
metronidazole use
GET GAP
giardia, entamoeba, trichomonas, gardenella vaginalis, anaerobes, with proton pump inhibitor and clarithromycin against H. pylori
metronidazole toxicity
disulfiram-like reactions with alcohol (inhibits alcohol oxidizing enzymes), headache, metallic taste, GI
M. TB prophylaxis
isoniazid
M. TB treatment
RIPE
rifampin, isoniazid, pyrazinamide, ethambutol
M. avium intracellulare prophylaxis
azithromycin
M. avium intracellulare treatment
azithromycin, rifampin, ethambutol, streptomycin
M. leprae treatment
tuberculoid form: dapsone and rifampin
lepromatous form: add clofazimine
isoniazid MOA
decreased synthesis of mycolic acids; bacterial catalase peroxidase (KatG) needed to convert INH to active metabolites
isoniazid use
M. TB; different half-lives in fast vs slow acetylators
isoniazid toxicity
neurotoxicity, hepatotoxicity. Pyridoxine can prevent neurotoxicity, lupus
rifampin MOA
inhibits DNA-dependent RNA polymerase
rifampin use
M. TB, delays resistance to dapsone, meningococcal and H. influenza type B prophylaxis
rifampin toxicity
hepatotoxicity; enhances P-450, orange body fluids
pyrazinimide MOA
acidify intracellular environment via conversion of pyrazinoic acid
pyrazinimide use
M. TB
pyrazinimide toxicity
hyperuricemia, hepatotoxicity
ethambutol MOA
decrease carbohydrate polymerization of mycobacterial cell wall by blocking arabinosyltrabsferase
ethambutol use
M. TB
ethambutol toxicity
optic neuropathy (red-green color blindness)