pharm exam 3 Flashcards
dopamine blockade at mesolimbic-mesocortical pathway
antipsychotic efficacy
DA blockade at nigrostriatal pathway
parkinsonian side effects
DA blockade at tuberoinfundibular pathway
hyperprolactinemia (weight gain, sexual dysfunction)
DA blockade at medullary-periventricular pathway
anti-emetic effects
DA hypothesis
excess DA @ mesolimbic –> + symptoms
deficit DA @ mesocortical –> - symptoms
antipsychotics mechanism
DA D2 receptor antagonists!!
EXCEPT atypical higher affinity for 5-HT2A than D2 (why it’s better at treating - symptoms)
what is the neuroleptic malignant syndrome tetrad?
- mental status change (confusion, stupor)
- hyperthermia
- extreme muscle rigidity (increase CK)
- autonomic dysfunction (tachycardia, HTN, sweating)
high potency antipsychotic characteristics
higher risk EPSE but less sedating
high potency antipsychotic prototype
haloperidol
low potency antipsychotic characteristics
lower risk of EPSE but more sedating
low potency antipsychotic prototype
chlorpromazine
second generation antipsychotic protoype
clozapine
what’s unique about clozapine?
efficacy for recalcitrant schizophrenia & suicidal behavior; reserved for cases where other antipsychotics have failed due to agranulocytosis; nearly absent risk of EPSE/TD
list the four 5-HT2A > D2 antagonists
risperidone
olanzapine
quetiapine
ziprasidone
the partial D2 receptor agonist
aripiprazole (abilify); its partial agonism of D2 receptors blocks full agonist effect of DA
atypical vs typical antipsychotics
atypical better at treating NEGATIVE symptoms, have lower risk EPSE/TD, but higher risk of weight gain & more expensive
MIC definition
lowest conc. of an agent that PREVENTS VISIBLE BACTERIAL GROWTH in 24 hrs
what are innately resistant to aminoglycosides?
anaerobes
what are innately resistant to metronidazole?
aerobes
what are gram negative innately resistant to?
LIPOPHILIC– standard penicillins & high MW hydrophilic– vancomycin
ways a bug can ACQUIRE resistance?
- inactivation of the antibiotic
- decreased uptake of the antibiotic
- increased efflux of the antibiotic
- altered target site (so it can’t bind)
- bypass target process
mechanisms of acquiring resistance
enzyme induction (increasing expression of existing resistance genes), vertical transfer (spontaneous mutation), horizontal transfer (conjugation)
do abx cause mutations?
NO! they promote resistance by exerting selective pressure
classic mech. of MDR
gram neg. doing horizontal transfer (conjugation, plasmid transferring R factor)
highest risk for c dif
clindamycin, cephalosporins (broad spectrum), fluoroquinolones, carbapenems
tx c dif
NOT antidiarrheal agents. abx: metronidazole, vancomycin, fidaxomicin)
downside of bacteriostatics
reliant on competent host immune system (so don’t use in immunocompromised)
what agent would you use for locations that are difficult for abx to penetrate?
bactericidal! esp. in endocarditis, meningitis, osteomyelitis
ideal or actual body weight for aminoglycosides
ideal! bc hydrophilic
abx whose dose should be reduced in pts with decreased kidney fxn
Cephalosporins (1 & 2 gen) Aminoglycosides Vancomycin Ethambutol Sulfonamides/trimethoprim Carbapenems Extended spectrum penicillins
abx whose dose should be reduced in pts with decreased liver fxn
Clindamycin Chloramphenicol Metronidazole Macrolides Rifampin Isoniazid Tetracylclines
category D abx
DON’T USE IN PREGNANT! Aminoglycosides & tetracyclines (and sulfonamide-induced kernicterus during nursing)
most common abx that provoke sensitivity rxn’s
beta lactams
sulfonamides
trimethoprim
erythromycin
significance of gram neg. OM
hinders transport of many abx; small hydrophilic drugs can cross via transport through porins
list the bactericidal agents
aminoglycosides, beta-lactams, daptomycin, fluoroquinolones, isoniazid, metronidazole, polymyxins, pyrazinamide, rifampin, vancomycin
list the bacteriostatic agents
(the CCEMOSTT ones!)
chloramphenicol, clindamycin, ethambutol, macrolides, oxazolidinones, sulfonamides, tetracyclines, trimethoprim
what class inhibits cell wall synthesis?
beta lactams! & glycopeptides (vancomycin), fosfomycin (treats uncomplicated UTIs in women)
beta lactam subclasses
penicillins, cephalosporins, carbapenems, monobactams
which bugs are innately resistant to B lactams and why?
chlamydia, mycoplasma, & legionella! bc they lack a peptidoglycan-based cell wall (b lactam mech. binds PBPs & inhibits cross linking of peptidoglycan)
beta lactam mechanism
irreversibly inhibits PBPs –> inhibits cross-linking of cell wall NAM-NAG polymers & peptidoglycan buildup activates autolysins –> mediate cell wall disassembly
penicillin structure
B-lactam ring fused to a FIVE member thiazolidine ring
4 classifications penicillin
- standard (penicillin G, penicillin V): g +
- anti-staph (nafcillin): protects against B lactamase; MSSA
- aminopenicillins (amoxicillin): adds activity against g - bc + charged R group allows it to get through porins
- anti-pseudomonal (ticarcillin, piperacillin)
which penicillin is orally effective?
pen V! it is acid-stable in stomach (unlike G)
clavulanic acid use?
B-lactamase inhibitor so combine with aminopenicillins & anti-pseudomonals (i.e. amoxicillin, ticarcillin, piperacillin)
what is pen G benzathine used for?
repository preparation; single dose given IM for treatment of syphilis & prevention of rheumatic fever. example of time dependence (absorbed for several weeks & produces persistent but low blood levels)
least toxic of all abx?
penicillins
standard penicillin clinical uses
syphilis–benzathine, group A strep (pharyngitis, endocarditis), oral infections
antistaph penicillins clinical uses
pen G resistant MSSA (endocarditis, skin & soft tissue infections), osteomyelitis; superior to vancomycin
aminopenicillins clinical uses
URI (strep pharyngitis, otitis media); enterococcal infections
antipseudomonal penicillin uses
empiric treatment nosocomial infections, mixed infections, URI with suspected beta lactamase resistance
cephalosporin structure
b lactam ring fused to SIX membered ring
progression of 5 cephalosporin generations
increasing activity against gram negative bacteria, decreasing inactivation by beta lactamases, increasing CNS penetration
first generation cephalosporin
cefazolin–commonly used to prevent surgical site infections
second generation cephalosporin
cefoxitin–prophylaxis in abdominal surgery
third glass cephalosporin
ceftriaxone–widely used; treats gram - meningitis & gonorrhea
fourth generation cephalosporin
cefepime–empiric treatment nosocomial infections
fifth generation cephalosporin
ceftaroline–only cephalosporin active against MRSA
what is imipenem-cilastatin?
beta lactam, very broad spectrum; used in MDR infections, anaerobic & mixed infection
aztreonam structure
beta lactam ring NOT fused with a second ring
aztreonam:
beta lactam, narrow spectrum, GRAM NEGATIVE AEROBES (including pseudomonas); inhaled by CF patients w/ p. aeruginosa
glycopeptide prototype
vancomycin
glycopeptide mech
(vancomycin)–prevents polymerization of cell wall precursors; only active against gram + (strep & staph); reserved for serious resistant infections
vancomycin adverse rxn’s
ototoxic, nephrotoxic, “red man syndrome”
fosfomycin use
cytosol (prevents NAG to NAM); uncomplicated UTIs in females
aminoglycoside required drugs
gentamicin, amikacin
aminoglycoside MOA
bactericidal, conc. dependent; binds to 30s ribosomal subunit which causes misreading of mRNA
aminoglycoside uses
combine w/ beta lactam for serious gram negative infections (septicemia), w/ beta lactam or vancomycin for endocarditis, & plague, TB
adverse rxn aminoglycosides
ototoxicity, nephrotoxicity, neuromuscular blockade (why it’s contraindicated in pts with myasthenia gravis)
how is gentamicin given?
once-daily high doses! bc conc. dependent
tetracyclines required drugs
doxycycline, tigecycline
abx that inhibit protein synthesis
aminoglycosides (gentamicin, amikacin), tetracyclines (doxycycline, tigecycline), macrolides (azithromycin, clarithromycin), clindamycin, chloramphenicol, linezolid, quinupristin-dalfopristin
how are tetracyclines given?
lipid soluble so orally; except tigecycline is given parenterally
tetracyclines form what?
chelates with multivalent cations (don’t administer w/ dairy, pepto bismol, iron supplements)
doxycycline uses
broad spectrum against gram + & -
tigecycline use
IV for highly resistant gram - infections
macrolide required drugs
azithromycin, clarithromycin
macrolide MOA
bacteriostatic; binds 50S subunit & inhibits translocation
COMBO TO AVOID
macrolide w/ clindamycin or chloramphenicol (binding sites overlap so would result in abx antagonism)
macrolide uses
upper & lower respiratory tract infections (pertussis, pneumonias, diphtheria, sinusitis, bronchitis, pharyngitis), atypicals (chlamydia, myco. avium) & PUD (H pylori)
clindamycin MOA & use
binds 50S subunit, most effective against g + & anaerobe; used for skin & soft tissue infections (i.e. gas gangrene)
major concern for clindamycin?
CDAD!
chloramphenicol use
broad spectrum used mainly outside US due to toxicity
isoniazid MOA
prodrug that inhibits synthesis of mycolic acid by inhibiting InhA and KasA enzymes
what would reduce risk of peripheral neuropathy while being treated for TB?
taking vitamin B6!!
what TB drug doesn’t have an effect on the liver?
ethambutol
what can be used as second line for TB treatment?
streptomycin
what would give someone with active TB?
INH + rifampin + pyrazinamide + ethambutol
active TB treatment phases include:
induction: 2 months of INH, rifampin, pyrazinamide, ethambutol
continuation: next 4 months or longer of INH and rifampin
prophylaxis for latent TB consists of:
1st line = daily monotherapy for 9 months with INH
2nd line = daily monotherapy for 4 months with rifampin
drug that can cause unpredictable aplastic anemia
chloramphenicol
what is an adverse effect of fluoroquinolones?
tendon rupture in kids
three drugs that can be used to treat c dif?
metronidazole, vancomycin, fidaxomicin
1 drug for UTI
SMX-TMP
what are the 2 formulations of colistin and how are they given?
- colistin sulfate–topical & oral (GI)
2. colistimethate–parenteral (prodrug)
