Lecture 1- beta lactam and glycopeptides Flashcards
beta lactams MOA
interfere with synthesis of bacterial cell wall peptidoglycan
act by binding to active site of enzyme transpeptidase (catalyse cross linking of terminal peptide components) –> weakening of cell wall–> build up of intracellular osmotic pressure–> lysis
types of beta lactam (4)
- penicillin
- cephalosporins/ cephamycins
- carbapenems
- monobactams
types of penicillin (4)
- natural penicillin
- penicillinase resistant penicillins
- aminopenicillins (broad spectrum) + BL inhibitors
- anti pseudomonal penicillins (extended spectrum) + BL inhibitors
which types of penicillin are susceptible to beta-lactamase?
all, thats why they need a beta-lactamase inhibitor as add on
what are the names of natural penicillins (s)
penicillin G, pen V
ROA of penicillin G
IV, IM
ROA of penicillin v
oral coz have better absorption
indication of natural penicillins
- against beta lactamse -ve strains of gram +ve and -ve microbes
how is natural penicillin excreted?
renal, unchanged in urine
why is natural penicillin not effective against S. Aureus?
S. Aureus produces penicillinases– therefore need to use penicillinase resistant penicillin
name of penicillinase- resistant penicillins? (3)
cloxacillin, oxacillin, flucloxacillin
indication for penicillinase resistant penicillins
potent inhibitors of most penicillase producing staphylococci
what are penicillinase resistant penicillins INEFFECTIVE agaisnt? (2)
gram neg org and MO susceptible to penicillin G, only covers MSSA, not MRSA
how is penicillinase resistant penicillin excreted?
renal clearance
why does penicillinase resistant penicillin have narrow spectrum of action
bulky side group- cannot pass through porins on gram neg org
ROA of penicillinase resistant penicillins?
IV, IM, oral
names of aminopenicillins (2)
ampicillin, amoxicillin
what orgs does aminipenicillins cover? gram-___
gram pos and neg
ROA of ampicillin?
oral, IV
ROA of amoxicillin
oral, better absorption thatn ampicillin
indication of aminopenicillins (3)
- treat beta lactamase neg strains of gram neg/pos and anaerobic MO
- in resp inficetions against S. pneumoniae (+) and H. influenzae (-)
- amo: against e coli
- ampi (IV): in bacterial meningitis
what does aminopenicillin NOT cover?
pseudomonas and klebsiella
is it susceptible to beta lactamse production?
yes
name of anti pseudomonal penicillin (1)
piperacillin
ROA of piperacillin?
IV
what is piperacillin given with?
in combi with beta lactam inhibitors eg. clabulanic acid
indication of piperacillin
- greater activity then other penicillins against gram -VE bacteria esp. psesudomonas and proteus app. and klebsiella
- used to treat severe infections caused by GRAM NEG
- incrased anaerobic coverage
what kind of bac does it cover? (gram __)/ aerobic/anaero
both pos and neg
and anaerobic
penetration into CSF of piperacillin?
penetrates fairly well
excretion of piperacillin?
renal. need dose adjustment if hv renal dysfunction
what is piperacillin susceptible to
to inactivation by bacterial beta lactamase– therfore give as combi with beta lac inhibitor
what are beta lactamase inhibitors?
- have week anti-bac properties
how do beta lactamase inhibitors work? MOA
inactivate serine beta lactamases (enzymes that hydrolyse and inactivate beta lactam ring)
- strong affinity for beta lactamases–> can bind and inactivate or bind irreversibly –> protect other beta lactam antibiotics from being targeted by beta lactamses
3 names of beta lactamase inhibitors
clavulate amoxicillin (augmentin) sulbactam ampicillin tazobactam piperacillin (zosyn)
how are beta lactamase inhibitors cleared
renal , excreted unchnaged in urine, dose adjustment needed with renal impairment
MOA of clavulanic acid
suicide inhibitor. covalently binds to beta lactamase and restructures it–> permanently inactivating it
MOA of sulbactam and tazobactam
bind irreversibly to beta lactamase at its active site, protects other beta lactamase antibiotics from beta lactamase catalysis
adverse reactions to penicillins (3)
allergy/ hypersensitivity- 3 types - immediate onset- 2 to 30 mins - accelerated onset - late onset - days to weeks hepatotoxicity neurotoxicity CDAD
how many generations of cephalosporins are there?
5
examples of first gen cephalosporins (2) and their specturm
- cefazolin, cephalexin
- active against gram pos eg. streptococci, staphylococcus aureus
ROA for first gen cephalosporins
oral
example of 2nd gen cephalosporins (1) + specturm
cefuroxime
- against E.coli, klebsiella, proteus
- not as active against gram pos
- better coverage agaisnt gram -ve and those producing beta lactamases
examples of 3rd gen cephalosporins (2) and spectrum
- ceftriaxone , ceftazidime
- activity against s.aureus, streptococcus pneumoniae, enterobacteriaceae…
- can cover pseudomonas
example of 4th gen cephalosporins (1)
- cefepime
- same as 3rd gen but more resistant to beta lactamases and pseudomonas
example of 5th gen cephalosporins (2)
- ceftaroline, ceftobiprole
- can cover MRSA
adverse reaction to cephalosporins (3)
- hypersentivity- freq of cross allergy between cephalosporins and penicillins low chance but dont giev tgt
- GIT eg. diarrhea, CDAD
- thrombophlebitis (can minimise risk by giving diluted form and rotating infusion site)
wat is the indication for carbapenem?
first line for extended spectrum beta lactamse producing bacteria
good coverage agaisnt gram neg and anaerobic spp
exampels of carbapenem (3)
imipenem and cilastatin
meropenem
ertapenem
ROA of carbapenem
IV
carbapenem adverse effects
GIT sx eg. nausea, vomitting
rashed
neurotoxicity (seizures) at high blood conc
cross hypersen with penicillin
example of monobactam (1)
aztreonam
spectrum of activity of aztreonam
- only against gram NEG
- useful against beta lactamase producing gram neg bacteria
aztreonam indication (3)
- UTI caused by enterobacteriaceae
- lower resp tract infection eg. pneumonia, bronchitis
- septicemia and intra abdominal infections
ROA of aztreonam
IV/IM- poor bioavail
excretion of aztreonam?
renal clearance, need dose adjustment if renal impair
aztreonam adverse rxn
generally well tolerated
- skin rahs
types of glycopeptides (1)
vancomycin
Spectrum of vancomycin
gram POS due to large mol size- cannot penetrate gram neg
ROA of vancomycin
IV and oral (only for CDAD)
poor bioavail
how is vancomycin excreted
renal clearance, dose adjust
vancomycin MOA
bind with high affinity to D-ala-d-ala terminus of NAM compoenent of peptidoglycan and interferes with transglycosylation of cell wall–> inhibit cell wall synthesis
spectru of activity of vancomycin
broad spectrum of gram POS
- MRSA and MSSA
what is resistant to vancomycin
all gram neg bacilli and mycobacteria and resistant to
adverse rxn of vancomycin
- thrombophlebitis with fever, chills
- red neck
- nephrotixicity and ototoxicity
