Flashcards in Pharm antimicrobials 1 Deck (78):
gram negative organisms vs gram positive
-outer membrane (LPS endotoxin, outer membrane proteins for attachement and virulence, and porins)
-thin cell wall
-thick cell wall cross-linked by transpeptidase
what is the location of beta lactamase for gram negative? gram positive?
gram - : periplasmic space
gram + : secreted outside of cell
which gram - organisms are not covered by your typical drug regimen?
(bacilli -> aerobic -> nonfermenters -> oxidase positive)
what drugs target the peptidoglycan cross-linking of the cell wall?
Beta-lactams (penicillin, penicillinase-sensitive penicillins, penicillinase-resistant penicillins, antipseudomonals, cephalosporins, carbapenems) and monobactams
what is the mechanism of action for beta lactams?
bind to penicillin-binding proteins (PBPs) which catalyze polymerization of the glycan strand
what are mechanisms of resistance to beta lactams?
enzymatic destruction (gram -'s - beta lactamase), reduced permeability (porin channel change), target site alteration (PBP change - gram +s)
what do beta lactams have a lack of activity against?
atypical organisms (mycoplasma pneumoniae and chlymydophilia pneumoniae (no cell wall))
pharmacokinetics of beta lactams
short half lives, polar (go where water is), metabolized in liver, excretion by mostly renal system
side effects of beta lactams
1. hypersensitivity reactions (anaphylaxis, delayed hypersensitivity - rash, drug fever, acute interstitial nephritis, cross-reactivity)
2. seizures (high doeses in patients with renal dysfunction
3. GI effects (nausea, vomiting, diarrhea)
what are the natural penicillins?
penicillin G (IV and IM) and penicillin V (oral)
what spectrum do the natural penicillins cover?
mostly gram-positive aerobic organisms (streptococci, enterococcus, oral anaerobes, clostridium)
also n. meningitidis and t. pallidum (DOC for syphilis)
what are the anti-staphylococcal penicillins (penicillinase-resistant penicillins)
nafcillin, oxacillin, dicloxacillin (DON the STAPH!)
(i met a nasty ox with a beta lactam ring around its neck)
what does the penicillinase-resistant penicillins (anti-staphylococcal penicillins) have that make them penicillinase resistant?
bulky side chain sterically shielding the beta lactam ring (preventing degradation from penicillinase and prevents entry into the gram negative cell)
what is the spectrum of anti-staphylococcal penicillins (penicillinase-resistant penicillins)
MSSA (methicillin susceptible staph aureus)
what is the oral anti-staphylococcal penicillin (penicillinase-resistant penicillin)
side effects of oxacillin
hepatotoxicity and neutropenia
side effects of nefcillin
similar to oxacillin (hepatotoxicity and neutropenia) + thrombophlebitis
amino group increases hydrophilicity causing improved penetration into gram-negative cell membrane
-gram positives: similar to penicillin with ampicillin as drug of choice for enterococci, listeria
-poor activity for gram - (still inhibited by penicillinase) covers e coli (some), proteus, salmonella, shigella, som eh influenza
what is the drug of choice for gram-positive enterococcus
what are the aminopenicillins?
amoxicillin and ampicillin
which aminopenicillin is best given orally?
what are the clinical uses for amoxicillin?
otitis media, upper and lower respiratory tract infections in children, lyme
what are the clinical uses for ampicillin
listeria and enterococcal
adverse effects of aminopenicillins
GI, hypersensitivity (delayed)
what are the antipseudomonal penicillins?
what are antipseudomonal penicillins used in combination with?
beta-lactamase inhibitor to expand spectrum to include beta-lactamase-producing organisms
what are the beta-lactamase inhibitors + anti-pseudomonal penicillins effective against?
broad coverage against the beta-lactamase producing gram-positivies (staph aureus), gram-negatives (h influenza) and anaerobes (bacteroides fragilis)
what are the beta-lactamase inhibitors?
clavulanic acid, sulbactam, tazobactam
what are the penicillins/beta-lactamase resistant combinations?
-amoxicillin and clavulanic acid
-ticarcillin and clavulanic acid
-ampicillin and sulbactam
-piperacillin and tazobactam
what are the drug combinations active against pseudomonas aeruginosa?
piperacillin and tazobactam
ticarcillin and clavulanic acid
what are the extended-spectrum penicillin/beta-lactamase inhibitor combinations used for clinically?
-animal and human bites
which are the only cephalosporins that have activity against pseudomonas aeruginosa?
ceftazidime and cefeprime (cephalosporins)
what do cephalosporins lack activity against?
MRSA, enterococcus (except ceftaroline 5th gen) and b. fragilis
side effects of cephalosporing
hypersensitivity reactions (less common than penicillins), GI, coagulopathy (cefamandole, cefotetan, cefoperazone), disulfiram-like reaction with ethanole), CNS
what advantages do cephalosporins have over penicillins?
1. addition of a new basement makes the beta-lactam ring much more resistant to beta-lactamases
2. new R-group side chain allows for double the manipulations in the lab (more spectrum of activity)
spectrum of cephalosporins by generation
2. even across
4. good against gram-negative like 3rd but also good gram +
what are the first-generation cephalosporins
-cephadroxil, cephalexin, CEFAZOLIN
mechanism to generations 1,2,3,4 cephalosporins
form a complex with a PBP, prevent extracellular transpeptidase activity; broader spectrum than penicillins
spectrum for first-generation cephalosporins
MSSA, streptococci, UTI bugs (e coli, proteus, klebsiella), mouth anaerobes (although activity against enterobacteriaceae shouldn't be assumed)
which first generation cephalosporin can be given IV?
cefazolin (used with surgical prophylaxis and serious MSSA infections)
when is cephalexin used?
pharmacokinetics of first-generation cephalosporins
do not cross BBB
what are the second-generation cephalosporins?
fam, fur, fox, tea
cefamandole, cefuroxime, cefoxitin, cefotetan
what is the spectrum for second-generation cephalosporins?
gram-positive organisms (staph, strep)
gram negative (h flu, m catarrhalis, gonorrheae)
-used above and below diaphragm anaerobes
what are the third generation cephalosporins?
ceftazadime, ceftriazone, cefpodoxime
clinical uses ceftriaxone
-community acquired pneumonia with azithromycin
-intra-abdominal infection with metronidazole
-gonococcal infection and PID
ceftazidime clinical uses
definitive treatment of pseudomonas
-empiric treatment of post-neurosurgical miningitis
side effects of third generation cephalosporins
greatest correlation with c. difficile infection than other drugs
which third generation cephalosporin should not be used in neonates? why?
ceftriaxone (X FOR BABIES!)
biliary sludging, kernicterus, interaction with calcium-containing solutions causing precipitation
third-generation cephalosporins pharmacokinetics
widely distributed (polar) - effective penetration across BBB
what is the fourth generation cephalosporin?
clinical uses of cefepime
nosocomial infections, neutropenic fever, meningitis (CNS*), UTI
3rd generation + staph coverage
cefepime side effects
5th generation cephalosporin
what does ceftaroline cover?
gram + , gram - , MRSA!!!!
lacks activity against pseudomonas
cephalosporins/beta-lactamase inhibitor combinations
ceftazidime/avibactam (more against enterobactericeae!!)
-increased activity against pseudomonas
which cephalosporins have excellent CSF penetration and can cover meningitis causing bacteria?
ceftriaxone (adults) and cefotaxime (children)
what are the carbapenems?
imipenem, meropenem, ertapenem, dorpenem
what is the class of carbapenems? mechanism?
cell wall syntehsis inhibitor
-similar mechanism to penicillins (attacks PBP)
possesses a side chain that acts a "trojan horse" allowing access to PBP2a
broad spectrum excluding MRSA - resistant to beta-lactamases
what drug must be given with imipenem? why?
cilastatin - normal kidney has a dihydropeptidase that breaks imipenem down - cilastatin is a selective enzyme inhibitor of this dihydropeptidase is given
side effect imipenem
higher risk of seizures than other beta-lactams
side effects of carbapenams
renal failure if not dose adjusted
which carbapenam can be given outpatient due to its long half life?
what is the of choice for diabetic foot infections?
ertapenem (not effective against pseudomonas)
clinical uses carbapenems
complicated UTI, complicated intraabdominal infection, healthcare-acquired pneumonia, bone and SSTI, bacterial meningitis
what do carbapenems have significant interaction with?
valproic acid (VPA) - used to treat seizures
what class is aztreonam?
monobactam (cell wall synthesis inhibitor) with similar mechanism to penicillin
what is the spectrum of aztreonam?
gram - aerobic bacilli (if a tree falls on your house, you will feel negative)
NO GRAM + or ANAEROBES!!!
how is aztreonam used clinically?
definitive gram - therapy - not usually used as monotherapy (used with another drug that can cover gram +)
which beta-lactam drug can be used in patients with penicillin allergies?
aztreonam!! (the monobactam)
what are all the penicillin like drugs that are effective against pseudomonas?
pipercillin/tax, ticarcillin/clav, ceftazidine, cefepime, imipenem, aztretam
fourth generation cephalosporin spectrum
excellent activity against enterobacteriaceae (anaerobes) and pseudomonas
fourth generation cephalosporin (cefepime) chemistry and why is it beneficial?
zwitterion: neutral molecule with positive and negative charge that permits rapid entry into outer membrane of gram-negative bacteria
what are the organisms NOT covered by the 1st-4th generation cephalosporins?
MRSA (ceftaroline covers)