Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
112 Cards in this Set
- Front
- Back
name the groups and subgroups of the Beta lactams
|
penecillins - native penecillins, antistaphs, extended spectrum, antipseudemonals
carbapenams monobactams cephalosporins |
|
name the native penicililns
|
pen G
Pen V - probenecid |
|
name the antistaphylococcal penicillins
|
nafcillin
oxacillin cloxicillin dicloxicillin |
|
name the extended spectrum penicillins
|
ampicillin
amoxacillin antipseudomonal penicillins |
|
name the antipseudemonal penicillins
|
ticarcillin
piperacillin |
|
name the first generation cephalosporins
|
cefazolin
cephalexin |
|
name the 2nd gen cephalosporins
|
cefoxitin
cefaclor cefprozil |
|
name the 3rd gen cephalosporins
|
ceftriaxone
ceftazidime cefotaxime cefdinir |
|
name the 4th gen cephs
|
cefepime
|
|
name the B-lactamase inhibitors
|
clavulanic acid
sulbactam tazobactam |
|
name the carbapenem we have to know
|
imipenem (+cilastatin)
|
|
name the monobactam we have to know
|
aztreonam
|
|
name the 2 "other cell wall/membrane inhibitiros we need to know
|
vancomycin
bacitracin |
|
what are the 4 steps in which beta mactams work
|
1. bind to PBP
2. PBP is unable to crosslink peptidoglycan chans 3. bacteria are unable to sythesize stable cell wall 4. weakened cell wall leads to lysis of bacteria from osmotic pressure |
|
describe difference between gram pos and gram neg
|
gram pos- cell wall composed of many sheaths of peptidoglycan layers - they have peptide cross -links, also have teichoic acid and lipoteichoic acid
Gram NEG - small peptidoglycan layer with outer cell wall composed ofporins and other proteins - lipid rich- target the periplasmic space |
|
what does the structure of gram positive peptidoglycan layers have that gram negative does NOT
what do both have that are important |
gram positive - (gly)5
both have ala-ala |
|
what does vancomycin bind to ?
|
ala-ala of the NAM side chain
|
|
what does cycloserine do?
|
blocks the formation of alanine-alanine before it is added to the N-acetylmuramic acid (NAM)
it is a 2nd line agent for TB |
|
describe the formation of the cell wall
|
NAM is formed with its tetrapeptide side chain
combined with bactoprenox then combined with NAG + (gly)5 Moves out of cell Bactoprenol is removed and brought back into cell to be recycled |
|
what drug binds to the Ala-Ala structure?
what does this prevent |
vancomycin
prevents cross linking and elongation of peptidoglycan layer, i.e. blocks transglycosylase |
|
what is bactoprenol?
what does it connect to? |
carrier protein that carries the NAG-NAM peptidoglycan piece outside of bacterial cell
Connects to NAM 1st. then NAG and gly5 are added it is brought back in and recycled |
|
what inhibits bactoprenol recycling?
|
bacitracin
|
|
How do penecillins work?
|
they are structurally similar to Ala-Ala structure on NAM,
and bind to transpeptidase this blocks the cross linking of peptidoglycan chains |
|
what is a penicillin binding protein?
what are the different types of PBP, as in their function? |
anything that binds penicillins
-there are several types, can be membrane bound or cytoplasmic functions - catalyze transpeptidase rxn, maintain shape, form septum during division, inhibit autolytic enzyme |
|
what is autolysis in bacteria?
how can we effect with drugs? |
it is the normal breakdown of the bacterial cell wall in order for the cell to grow
if we inhibit the autolysis inhibitors --> chews up cell wall |
|
what is the most important thing to know about pharmacokinetics of penicillins
|
they are TIME DEPENDENT killers!!!
effect is directly proportional to amount of time the drug concentraion at site of infection is above minimal inhibitory concentration |
|
what is the major chemical structure in all the beta lactams?
what is the product of its breakdown? |
beta lactam ring
penilcilloic acid |
|
what part of B-lactam structures defien their spectrum of antibacterial activity?
how can we change the spectrum of B-lactams by changing these? (5) |
R groups
increase acid stability resist beta-lactamases improve psectrum to include G- increase activity against pseudomonas iomprove activity against anaerobes |
|
describe the characteristics of Pen G
what does it target? |
acid labile - poor oral, ioavailability, low cost, safe - large thx index
Targets Gram +, few Gram _ (nisseria meningococci), Some anaerobes and spirochetes (syphillis) |
|
Characteristics of pen V
used to treat what? |
more acid stable, can be taken orally "V is not IV"
used ot treat resp tract infections, otitis media, sinusitis, skin, UTI Also prophylaxis in rheum fever |
|
what is Pen G used to treat?
|
infections - sepsis, pnemonia, pericarditis, endocarditis, menengitis, anthrax - which are caused by susceptible orgamisms - Gram +, bu tusually not staph aureus, Some gram Neg like nisseria gonorhea, some anaerobes some spirocehetes
|
|
what bugs have acquired resistance to Pen G
|
Staph Aureus (90)%
streptococci (5%) most of neisseria gonococci is resistant - PenG no long DOC |
|
what parts of the body does Pen G not readily reach?
|
prostate
ocular CSF - does not cross BBB, but inflammation causes leaky membrane which allows for penicillin tx |
|
How is Pen G cleared and what is half life?
what must we watch for? and what drug must we be careful in using? |
via active transport pump in kidneys, very quickly HL=~30min
probenecid (gout tx) |
|
what are the two Pen G drugs that are given as "repository penicillins"
|
Pen G procaine
Pen G benzathine |
|
most common adverse effect of Pen G
|
allergic Rxn - can be any types of the 4 hypersens rxns
most ppl that say they are allergic are not. |
|
name the 4 types of hypersens rxns
|
1. anaphylaxis
2. antibody-dependent cyto toxicitiy 3. immune complex disase 4. cell mediated or delayed hypersens. |
|
breakdown product of penecillins
what can it act as? |
penicilloic acid
can act as a hapten --> to cause a hypersens rxn |
|
what are the non-allergic side effects of penecillin G
|
diahrrea and GI intolerance
NEUROTOX - seizures, coma, hyper-reflexia Super infections (more common with broader spectrum) |
|
what are common superinections and what do they cause?
|
clostridium difficile - pseudomembranous collitis
staph aurerus - enterocolitis candida albicans - vaginal, oral thrush |
|
what are the general 5 modes of resistance to Pen G?
|
1. gram neg's are generally resistant - thick outer cell wall
2. penicillinase production (B-lactamse - most common_ 3. cell lysis cascade is not activated (streph, staph, listeria) 4. mycoplasma - no cell wall 5. transpeptidase is altered (MRSA) |
|
what is the major mode of resistance against B- lactams?
what are the different kinds |
bacterial production of B-lactamase
chromosome encoded - inducible plasmid encoded - constitutively expressed - most mediate resistance to pens and 1st and 2nd gen cephs |
|
what is the attack point of the B-lactamase
beta lactamases of what types of bacteria chew up pens and cephs well |
beta lactam ring - essential for PBP binding
pseudomonas, enterobacter |
|
what are ESBLs? expain them
what are most common producers of ESBLs |
extended spectrum beta-lactamases
certain B lactamases that hydrolyze pens, cephs (ALL) monobactams primarily seen in gram Negs most common - klebsiella pneumonia and e. coli |
|
what is special about the antistaphylococcal penicillins
extends spectrum to what? |
they are resistant to the beta lactamases - their side chains don't fit in B-lactamase active site
extends spectrum to include B-lactamase producting Staphylococci - NOT MRSA DOC for MSSA |
|
adverse effects of antistaphylococcal pens?
|
same as Pen G
also: blood dyscrasia - agranulocytosis acute interstitial nephritis Oxacillin - hepatotoxicity! |
|
deescribe the spectrum of extended spectrum penicillins?
what are they , and how are they administered |
ampicillin &amoxicililn &antipseuds
penetrate gran negative more readily - E Coli, N. meningitidis not effective against B-lactamase producers - use B-lacatamase inhibitors amoxicillin - better bioavailability than Amp amox: one of oral pens tha tFOOD DOES NOT INTERFERE with absorption |
|
what is one of the only penecillins that food does NOT effect with its absorption
|
amoxicillin
O in the amox is for ORAL |
|
what is the spectrum of the extended spectrum pens?
|
Same as Pen G + extends to :
HELPS Haemophilus influenza E. Coli Listeria Proteus Salmonella |
|
what are clinical uses of Extended specturm penicillins
what is one of the drugs often used in combo with? why? |
sinusitis, otitis, UTIs, pneumonia SOUP
HELPS FOR SOUP amox used with aminoglycoside (gentamicin) - synergism for broad range of coverage in serious infections |
|
what is ampicililn a DOC for?
|
listeria meningitis
|
|
wht are the antipseudomonal pens and what is their spectrum??? what are they sensitive to?
|
ticarcillin and piperacillin.
they are sensitive to B-lactamase - so we use with B-lactamase inhibitors spectrum similar to ampicillin but extends to include other gram Negatives - Pen G + HELPS + Pseudomonas, klebsiella and Serratia |
|
if we have an ifection of klebsiella, pseudomonas, or serratia... what penecillin do we use to treat it?
|
antipseudomonas - they are all gram negs
PEN G + HELPS + kleb, pseud, serratia |
|
how are the antipseudomonal pens given? why?
|
with aminoglycoside... because of increasing emergence of resistance
|
|
what are clinical uses of the antipseudomonal pens?
what kind of px do we treat in? |
pneumonia, UTI, peritonitis, skin and soft tissue infections with susceptible organism
immunocompromised pxs |
|
what is the broadest spectrum penecillin we can give
|
piperacillin with tazobactam - a beta lactamase inhibitor
|
|
what are the adverse effects of antipseudomonal penicililns? name them again
|
liek that of Pen G but most importantly....
Super infection b/c so broad spectrum Can potentiate aminoglycoside-associated nephrotoxicity Sodium overload |
|
what kind of px must we be careful with when giving antipsuedomonal pens? why?
|
pts with CHF or renal insufficiency... sodium overload, the drug is given with sodium formula
|
|
what are the resistance mechanisms involving antipseudomonal pens? why?
|
since they target Gram Neg and gram Pos -
Pos- beta-lactamase outside cell wall & changes in PBP Neg- change in entry though porins, beta lactamases in periplasmic space, EFFLUX PUMP |
|
why and how do beta lactamase inhibitors work
name them again |
they contain a beta lactam ring so it fits in their binding site and INACTIVATES THEM
clavulanic acid sulbactam tazobactam |
|
what kind of beta lactamase are beta lactamase inhibitors effective for?
|
plasmid encoded beta lectamases, NOT CHROMOSOMAL (induced by gram NEG bacilli by 2nd and 3rd gen cephs)
|
|
what are the 4 main combo preps with beta lactamase inhibitors
|
amoxicillin + clavulanic acid (augmentin) only ORAL one!!!!
ampicillin+sulbactam Ticarcillin + clavulinic acid Piperacillin + tazobactam |
|
what is the MOA of cephalosporins
|
same as penecillins, b-lactams that block cell wall cynthesis. resemble the structure of NAG-NAM and attract transpeptidase
BACTERICIDAL |
|
how are cephs cleared by the body?
|
via the kidneys
|
|
what is the spectrum of cephs?
|
like ampicillin
G+ & HELPS H. flu, ecoli, lissteria, proteus, salmonella |
|
what are cephalosporins not active against? (2)
|
enterococcus or MRSA
|
|
what are the extended spectrum B-lactamases?
what can they break down? |
E.coli, Klebsiella, pseudomonas, enterobacter
|
|
discuss the role of allergic reaction about cephalosporins
|
cephs seem to cause less allergic reactions, some cross sensitivity (~10%)
good alternative to pxs who are allergic to pens |
|
describe the coverage of cephalosporins against gram positives vs gram negs
|
as you go up in generation 1->4
decrease in Gram+ coverage and increase in Gram- coverage |
|
how do cephs compare to penecillins in resistance to Beta-lactamases
Describe each generation |
cephs are more resistant to B-lactamases
they all act on MSSA resistance to b-lactamases increases with higher generation |
|
describe half life differences in each generation of cephalosprins
|
half life increases with generation 3>2>1
renal elimination goes down in higher gens |
|
what drugs can penetrate CSF
|
3rd and 4th Generation cephalosporins only
|
|
what are the major adverse effects of cephalosporins
what is it due to? Which drugs specifically??? |
hypoprothrombinemia - coagulation prob
alcohol intolerance dude to MTT group on R- Cefotetan(2nd) Cefoperazone(3rd) |
|
Genearl primary uses of 1st fgeneration cephalosporins
|
Rarely DOC for any infection
Maybe- UTIs caused by Klebsiella and Pen/sulf resistant organisms. staphylococcal or streptococcal infections; cellulutis or soft tissue infections ******PROPHYLAXIS FOR SURGERY (cefazolin) |
|
what are 1st generation cephs active against, what are they not active against
|
active against G+ and Proteus, E.coli, Klebsiella
PenG+ PEcK not effective agaisnt MRSA, enterococcus, or pseudomonas |
|
what are what are the 2nd gen cephs and what are their coverage?
|
cefoxitin, cefaclor, cefprozil
Active: G+, H. influenza, enterobacter, neisseria, proteus, e.colii, klebsiella G+ HEN PEcK Not active: enterococci, MRSA or pseudomonas |
|
what are primary uses for 2nd generation cephs?
|
sinusitis, bronchitis, otitis media
lower respiratory tract infections mixedd anaerobic infections, eg peritonitis, diverticulitis Lyme dz - but 3rd gen better |
|
what are adverse reactions of 2nd generation cephalosporins
|
allergic rxns
blood dyscrasias - anemia, eosinophilia Pseudomembranous colitis - due to superinfection |
|
what happens as you move up in ceph classes
|
increase in Gram neg and anaerobe coverage
increase in ability to cross BBB increase in B-lactamase resistance |
|
compare halflives of 3rd gen to others, specific
|
Generally they have longer halflives
|
|
what is excretion of 3rd gen cephs
what is the exception |
all renally
EXCEPT ceftriaxone - liver!!! |
|
3rd gen ceph coverage
|
less against G+
more G-: PSEUDOMONAS, kleb, E. coli, Proteus, serratia |
|
describe serratia
|
gram negative
facultataive anaerobe enterobacter family rod shaped tend to colonize respiratory and UTI |
|
what is the general clinical use of 3rd gen cephs? specifically what type or presentation
how administered? |
SERIOUS Gram (-) infections!
with aminoglycoside Gram neg. sepsis, pneumonia, meningitis nosocomial infections complicated UTI IMMUNOCOMPROMISED host ghonnoreah and lyme disease DOC |
|
what does nosocomial mean?
|
hospital acquiered
|
|
when is a 3rd gen ceph a DOC? that we have learned so far (5)
|
klebsiella pneumoniae (ceftazidime)
E.coli - wound Gonorrhea - ceftriaxone lyme dz - ceftriaxone hospitalized pneumonia pxs! |
|
a person is being treated for Community acquired pneumonia as an outpatient, what drug?
|
NOT a 3rd gen ceph,
azithromycin, clindamycin, or doxycycline |
|
describe 4th gen ceph spectrum
|
wider spectrum, more resistant to beta-lactamases
|
|
describe the uses of 4th gen ceph
clinical uses |
more effective against PSEUDOMONAS than 3rd
also against Staph and Strep pneumoniae And Haemophilis and neisseria |
|
describe neisseria
what disesases and strands what do we use against this? |
gram negative diplococci bacteria
n. ghonorrhea n. meningitidis 4th gen ceph |
|
describe cefapime the drug
|
not oral
renally eliminated crosses BBB No disulfram side effects, but similar to all other cephs otherwise |
|
name the carbapenem and its MOA and spectrum
|
imipenem
MOA - same as pens and cephs - has Ala-ala to attract transpeptidase specturm - broader than B-lactams - bactericidal to almost ALL bacteria except enterococcus faecium, MRSA and c. difficil |
|
what is resistant to imipenem
|
MRSA
c. difficile enterococcus faecium |
|
what is special about imipenems action
|
it has post antibiotic effect after it falls below minimum inhibitory concentration
|
|
what is primary use for carbapenems
(lots to know) and when do we use it? |
treatment of tough drugs
ESBL-producing microbes (kleb and ecoli) Alt tx for G- pneum and bacteremia, compilcated UTI, serious pseudomonas infections emprical tx of nosocomial and mixed infections caused by MDR LAST RESORT KINDA THING |
|
what are the two most common ESBL-producing bugs
|
e.coli and klebsiella
|
|
when is carbapenem DOC?
|
enterobacter infections
ESBL producing klebsiella |
|
what is carbapenem always used with?
what does it do? |
cilastatin
blocks carbapenem being rapidly BROKEN down in renal proximal tubule, by dehydropeptidase |
|
characteristics of carbapenems
distribution and limitations |
Crosses BBB
gram neg porins may resis entry hydrolyzed by metallo-B-lactamases pseudomonas develops resistance quickly not effective against MRSA, c. difficile, enterococcus faecium |
|
side effects of iminpenem
|
NVD - only one we've seen
seizures!! especially in renal insufficiency - spikes drug hypersensitivity - cross reactive with pens - 10-50%? |
|
what is the monobactam we need to know?
MOA? |
aztreonam
MOA same as other B-lactams, but only to Gram neg PBP |
|
Spectrum of aztreonam?
|
GRAM NEG ANAEROBES ONLY****
|
|
what are the gram negative aerobes?
what is not? |
serratia
pseudomonas enterobacter neisseria not - enterobacter, kleb, etc |
|
what is aztreonam not effective against?
|
gram positive and anearobes
|
|
when do we use aztreonam?
specific px? |
SERIOUS gram neg infections
Useful in MDR infections in px's allergic to pens and cephs - no cross reactivity |
|
vancomycin MOA
|
binds tightly to ala-ala structure of NMG-NAG complex to inhibit transglycosylse activity
|
|
how is vancomycin administered?
special cases? |
paretnally
except in GI infection - C. difficile, and enterocollitis (s. aureus) - not orally bioavailable |
|
spectrum of vancomycin
when do we use? when DOC? |
GRAM POSITIVE ONLY
used only in SERIOUS infections: MRSA (DOC) enterococci (DOC) c. difficile (alt to metronidazole) |
|
what is DOC for collitis due to C. difficile
|
metronidazole
alternate is vanc |
|
Side effects of vanc?
when to use caution? |
ototoxicity
nephrotoxicity extreme flushing due to histamine relase - not a type I allergic rxn use cautiously with aminoglycosides (other agents with oto and nephro tox) |
|
what do we sometimes give with vancomycin to increase effect
|
aminoglycoside for synergistic effect
|
|
bacitracin MOA and coverage?
|
MOA - binds bactoprenol - doesnt allow the carrier protein for NAG-NAM to re-enter cell
coverage - GRAM POSITIVE ONLY |