Antimicrobials Flashcards
MOA of PCNs
bind PBPs–> inhib. transpeptidation–> inhib. crosslinking of bacterial cell walls
Mech. of Resistance for PNCs
penicillinases (B lactamases); structural change in PBP, change in porin structure
how do you treat MRSA?
vancomycin
how do you treat syphillis?
PCN G or V
what are the narrow spectrum PCNs?
PCN G and V
*B lactamase sensitive
List the lactams
PCNs, cephalosporins, imipenem, meropenem, aztreonam
what are the very narrow spectrum PCNs? what do they treat?
methicillin, nafcillin, oxacillin
staph aureus (not MRSA)
*B lactamase resistant
what are the broad spectrum PCNs?
amoxicillin, ampicillin
tx: gram + cocci, not staph, listeria, E. coli, H influenza, borrelia, H. pylori
* B lactamase sensitive
what are the extended spectrum PCNs?
ticarcillin, piperacillin, azlocillin
tx: gram neg rods, pseudomonas
* B lactamase sensitive
* *synergy with aminoglycosides
how are most PCNs excreted?
kidney
*dose reduction in kidney disease
What two PCNs are NOT excreted in the kidney?
nafcillin, oxacillin (bile excretion)
If a person is allergic to one PCN, can you give them a different one?
NO, assume allergy to all PCNs
What is the most unique side effect of PCNs?
Jarish-herxheimer rxn - when tx syphilis
What part of a PCN tends to cause hypersensitivity?
sulfur group
What is a side effect of methicillin?
interstitial nephritis
What is a common side effect of PCNs?
GI distress
how do you enhance PCN activity?
add Clavulanic acid or sulbactam
they are B lactamase inhib.
what drug increases PCN and cephalosporin concentration?
probenecid
What is the MOA of cephalosporins?
same as PCNs: bind PBPs–> inhib. transpeptidation–> inhib. crosslinking of bacterial cell walls
same resistance mech too.
first generation cephalosporins
cefazolin
cePHalexin
what are first generation cephalosporins used for?
surgical prophylaxis gram + E. coli klebsiella proteus
second generation cephalosporins
cefotetan, cefaclor,
cefuroxime–> crosses BBB
What are second generation cephalosporins used for?
gram neg.
third gen. cephalosporins
ceftriaxone, cefotaxime, cefdinir, cefixime, cefoperazone
what do you use third gen. cephalosporins for?
empirical tx of sepsis and meningitis
NO ACTIVITY AGAINST LAME: listeria, atypicals, MRSA, enterococci
How do you treat listeria?
amoxicillin
How do you treat atypicals?
macrolides or tetracyclines
How do you treat enterococci?
amoxicillin with aminoglycosides
4th gen. cephalosporins
cefepime IV only!
- wider spectrum
- B lactamase resistant
- *enters CNS
What is the mode of excretion for most cephalosporins?
Kidney
What cephalosporins are not excreted through the kidney?
cefoperazone, ceftriaxone –> bile
Cephalosporin Side Effects
hypersensitivity, GI distress, Disulfiram-like effect
What drug should you use if a pt is allergic to cephalosporins?
macrolides (gram+), or aztreonam (gram-)
MOA of imipenem and meropenem?
same as PCN but resistant to B lactamases
What doe you use imipenem and meropenem for?
gram + cocci, gram - rods, empiric use in nosocomial infections
What drug must you give with imipenem? Why?
cilastatin
prevent kidney from metabolizing it too quickly
SE of imipenem and meropenem?
GI distress, drug fever, CNS
**1/2 of pts have seizures with imipenem
MOA for aztreonam? Use? SE?
same as PCNs + B lactamase RESISTANT
ONLY IV
use: gram neg. rods
**no cross allergenicity with cephalosporins and PCNs
MOA vancomycin
binds d-ala-d-ala muramyl pentapeptide–> blocks transglycosylation–> prevents elongation of peptidoglycan cell wall
What do you use vancomycin for?
MRSA
enterococci
c. diff
What is the first line tx for C. difficile?
metronidazole
What are VRSA and VRE microbes? how do they develop resistance?
vancomycin resistant staph aureus
vancomycin resistant enterococci
*change in muramyl pentapeptide target to d-lactate
how do you treat VRSA and VRE?
linezolid and streptogramins
How is vancomycin delivered?
IV
orally only for colitis
SE of vancomycin?
Red man syndrome (histamine induced vasodilation)
ototoxicity
nephrotoxicity
MOA of aminoglycosides
inhibits initiation of protein synthesis (30S subunit)–> BACTERIOSTATIC
can also cause misreading of genetic code-> BACTERIOCIDAL
Name the aminoglycosides
gentamycin, tobramycin, amikacin, streptomycin
What do you use aminoglycosides for?
TB, bubonic plague, tularemia
gram neg rods: pseudomonas
CANT BE USED ON ANAEROBES
Excretion of aminoglycosides?
water soluble–> KIDNEY
Side effect of aminoglycosides?
nephrotoxicity, ototoxicity, neuromuscular blockade
What is neomycin and what is it known for?
aminoglycoside in neosporin, known for contact dermatitis (hypersensitivity)
How are aminoglycosides given?
1xday dosing: bacteriocidal so only need a spike once a day
decreases SE
aminoglycosides resistance?
conjugating enzymes–> eliminates it too fast to be effective
MOA of chloramphenicol?
inhibits peptides transferase (50S)
bacteriostatic
What is chloramphenicol used for?
backup for salmonella, b. fragillis, rickettsia, bacterial meningitis
Where is chloramphenicol broken down?
LIVER; does reduction in liver dysfunction and in neonates
INHIBITS CYP450
SE of chloramphenicol?
dose dependent bone marrow suppression (hypersensitivity), grey baby syndrome and kernicterus
Resistance of chloramphenicol?
changes in peptidyl transferase
Macrolides MOA?
inhibit translocation (50S) **inhib. CYP450
Names of Macrolides?
erythromycin, azithromycin, clarithromycin, clindamycin
What are the Macrolides used for?
gram pos. cocci: staph aureus and anaerobes
also goes into bones for osteomyelitis
atypicals (chlamydia, mycoplasma, ureaplasma)
legionella
campylobacter
mycobacteria avium-intracellular
SE of Macrolides?
GI distress, reversible deafness
how do you treat macrolide resistant s. pneumo?
telithromycin
Macrolides resistance?
methylation of rRNA by methyltransferase of bug–> unable to recognize binding site
Tetracylines MOA?
inhibits elongation (30S) bacteriostatic
What abx cannot be used in pregnant women?What do you use tetracyclines for?
aminoglycosides, fluoroquinolones, sulfonamides, tetracylcines
What do you use tetracyclines for?
chlamydia, mycoplasma, H. pylori, rickettsia, borrelia burgdorferi, brucella, vibrio, treponema
name the tetracyclines
doxycycline, minocycline, demeclocycline
what do you use doxycycline for?
prostatitis
what do you use minocycline for?
gingivitis
what do you use demeclocycline for?
SIADH (blocks ADH receptors)
SE of tetracyclines
tooth enamel dysphagia, decreased bone growth, phototoxicity, GI distress, superinfection with candidiasis, vestibular dysfunction
tetracycline resistance
pumps drugs out of cells
excretion of tetracyclines
most through kidneys, doxycyline goes through liver
What is unique about the tetracyclines in regard to divalent cations?
they are chelators
so they shouldn’t be taken with food or with vitamins
streptogramins moa?
inhibit elongation 50S by blocking acceptor site and decreases release of completed peptide
what are the streptogramins?
quinipristin and dalfopristin
What do you use streptogramins for?
VRE and VRSA
Linezolid MOA?
inhibits initiation (50S)
What do you use Linezolid for?
VRE, VRSA, drug resistant pneumococci
SE of Linezolid?
bone marrow suppression
Fluoroquinolones MOA?
inhib. NA synthesis by inhib. topoisomerase 2 and 4 (DNA gyrase)
Name the Fluoroquinolones?
norfloxacin, ciprofloxacin, ofloxacin
What do you use Fluoroquinolones for?
UTI, STD (chlamydia, gonorrhea), skin and soft tissue infection with gram neg., shigella, salmonella, E. coli, campylobacter, drug resistant pneumo
Why do you have to take Fluoroquinolones without food?
it binds to iron and calcium which inhibits its absorption
Excretion of Fluoroquinolones
kidney
SE of Fluoroquinolones
tendonitis, tendon rupture, phototoxicity, rash, CNS effects (increase QT interval, Seizures with IV), contraindicated in kids and preg
MOA of sulfonamides?
inhib. dihydropteroate synthetase (indirectly inhib. NA synth.)
SE of sulfonamides?
hypersensitivity, Stevens-Johnson syndrome (aka exfoliating dermatitis), hemolysis in G6PD deficiency, phototoxicity
MOA of trimethoprim and pyrimethamine?
inhib. dihydrofolate reductase (also in humas) - indirectly inhib NA synth.
How does trimethoprim and pyrimethamine have anti-neoplastic activity?
because its inhib. dihydrofolate reductase, which is in the microbe and human!
SE of trimethoprim and pyrimethamine?
bone marrow suppression
*worrisome because it is used for tx in HIV pts and can worsen leukoplakia
What is trimethoprim-sulfamethoxazole used for?
nocardia, listeria, gram neg. and gram pos., pneumocystis jiroveci (prophylaxis in HIV)
Pyrimethamine-sulfadiazine use?
toxoplasma gondii (prophylaxis in HIV)
Metabolism of trimethoprim and pyrimethamine?
acetylation by liver, excreted in kidney–> can cause kidney stones because its conjugate is less water soluble
Why do trimethoprim and pyrimethamine cause drug interactions?
high protein binding, causes kernicterus in neonates
Metronidazole MOA?
produces free radicals, bactericidal
What is Metronidazole used for?
drug of choice for giardia, trich, entamoeba, C. diff, gardernella, H. pylori
SE of Metronidazole?
metallic taste!
disulfiram-like effect
What combos are usually used for H. pylori?
BMT= bismuth + metronidazole + tetracycline OR
clarithromycin + amoxicillin + omeprazole
Antitubercular drugs
isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin
How do you prevent resistance in antitubercular drugs?
combination therapy
isoniazid MOA?
cell wall synth inhib. - mycolic acid synth.
isoniazid is a prodrug, what allows it to become activated?
conversion by catalase
isoniazid resistance?
if the microbe is missing the catalase gene
isoniazid use?
mycobacterium only
SE of isoniazid?
hepatitis, peripheral neuritis, sideroblastic anemia (B6 def., increased iron), SLE, hemolysis in G6PD def.
Rifampin MOA?
inhib. DNA dependent RNA polymerase (transcription)
SE of Rifampin?
hepatitis, induction of P450, red-orange metabolites in urine, saliva, tears
Ethambutol MOA?
inhib. cell wall synth. by blocking arabingalactan
SE of Ethambutol?
dose dependent optic neuritis –> loss of color vision
Pyrazinamide MOA?
UNKOWN, prodrug
SE of Pyrazinamide?
hepatitis, hyperuricemia
Streptomycin MOA?
inihib protein synthesis
SE of Streptomycin?
deafness, vestibular dysfunction, nephrotoxicity, neuromuscular blockade vie decreased ach release
