Antibiotics- Cell wall synthesis inhibitors Flashcards
Beta-lactam antibiotics include:
Penicillins, cephalosporins, Carbapenems, Monobactams, Glycopeptides and “other drugs”
Classes of penicillins and mechanism of action:
Mechanism of action: irreversible inhibition of transpeptidation step of cell wall synthesis in bacteria.
Beta-lactam is structurally similar to D-ala and forms a stable product with transpeptidase enzyme and therefore inhibited the transpeptidation process.
Natural penicillins, Lactamase stable, Broad spectrum, and extended-spectrum
broad and extended-spectrum are combined with lactamase inhibitors.
Natural penicillins:
Benzylpenicillin- I.V. Phenoxymethylpenicillin- Oral Use: gram +, Gram - (only Neisseria) , anaerobes and Spirochetes significant resistance use for : gram + diseases which are skin/wound infections RTI endocarditis Dental inf gram - : first-line for syphilis (Spirochetes)
Lactamase stable penicillins
Methicillin - I.V.
Use: obsolete due to MRSA
however, before used for lactamase resistant staphylococcus aureus infections i.e endocarditis and skin/wound infections
Broad-spectrum penicillins
Amoxicillin, Ampicillin- oral and I.V.
More effective on Gram -
so spectrum includes : gram +, Gram - including Neisseria, hemophilia, and coliform. only NOT including pseudomonas.
diseases:
skin/wound infections
RTI (S.pneumoniae and neiss. and hemoph.)
endocarditis
UTI ( Coliform)
abdominal and pelvic infections (coliform, anaerobes)
also syphilis
meningitis
Broad-spectrum penicillins used with:
Beta-lactamase inhibitors : (irreversible inhibition of beta lactam)
Amoxicillin- Clavulanic acid
Ampicillin- Sulbactam
Extended Spectrum Penicillin:
Ureidopenicillins- piperacillin- I.V.
the spectrum includes ALL including Pseudomonas
Use: Nosocomial infections (due to Pseudomonas)
Extended Spectrum Penicillin used with:
Beta-lactamase inhibitors : (irreversible inhibition of beta-lactam)
Piperacillin- Tazobactam combination
Side Effects of penicillin
Allergy (anaphylaxis, rash, fever) -> IgE mediated
Seizure
Interstitial nephritis
<10% cross reactivity w/ cephalosporins
drug induced autoimmune hemolytic anemia -> IgG binds to RBCs
safe during pregnancy
Cephalosporins: first gen
Cefazolin - I.V.
Cefalexin- oral
not used anymore.
spectrum: Gram +, Gram negative (only neisseria), Spiro
UTI’s (PEK: Proteus, E.coli, Klebsiella)
NO ANEROBES ( so no dental inf. or pelvic/stomach infec)
Cephalosporins: second gen
Cefuroxime- I.V. Cefaclor, Cefuroxime axetil- Oral Spectrum: gram +, gram - except pseudomonas, Spirochetes Use: gonorrhoea (neisseria) RTI UTI surgical prophylaxis against HENS: H.infl., Neisseria, Serratia
Cephalosporins: third gen
Cefotaxime , Ceftriaxone, - I.V. spectrum: gram +, common gram - GI bugs, RTI, gono (IM CEFTRIAXONE), meningitis, lyme disease, surgical prophylaxis Ceftazidime - I.V. Mostly gram - INCLUDING pseudomonas so nosocomial infections , UTI RTI etc Cefixim- oral gram -, not as widely used.
Cephalosporins - fourth gen
Cefepime - I.V.
balanced gram + and -
spare antibiotics- use in severe infections
broad spectrum
used in Pseudomonas & bacterial meningitis
Cephalosporins - fifth-gen
Ceftaroline- I.V.
broad spectrum
usually: MRSA (skin/wound infections)
PRSP( RTI)
3rd, 4th gen used for:
First-line for meningitis!
pass the BBB
side effects of cephalosporins
Allergy, kidney damage (rare), <10% cross reactivity w/ PENICILLINS
Carbapenems include:
Imipenem (-cilastatin)
Meropenem
Ertapenem
Spectrum: Gram -, gram -, anaerobes, spiro
Imipenem used with:
degraded via dehydropeptidase enzyme rapidly (human enzyme) so we use it with DHP inhibitor: cilastatin
Use of carbapenems
severe infections:
skin/wound
RTI, UTI, abdominal/pelvic, and meningitis
nosocomial inf. (Pseudomonas)
glycopeptides
MOC: covers D-ala, D-ala
so inhibits both transglycosylation and transpeptidation
Drugs: Vancomycin, I.V. and oral
Use: ONLY gram + (including gram + anaerobes)
used for severe infections that are resistant to Beta lactams (MRSA, PRSP)
such as: endocarditis, skin/tissue, RTI, meningitis
and pseudomembrane colitis (C.dificile)
“Other drugs” include:
Fosfomycin- intracellular
irreversibly inhibit MurA enzyme and inhibit the synthesis of muramic acid.
Spectrum: both gram + and gram -
fosfomycin is hydrophilic that’s why it inhibits gram -
Use: non complicated UTI
safe in pregnancy
Bacitracin-
spectrum: gram +
topical use for skin infections
nephrotoxicity
SE of glycopeptides
Red man syndrome (rashes)
thrombophlebitis on the site of injection
ototoxicity
nephrotoxicity
monobactams
AZTREONAM
USE:
Pseudomonas (nosocomial inf.)
Gram - (meningitis, pneumonia, sepsis)
No SE
not used in Europe (yet) only in the USA
used in case a patient is allergic to PENICILLIN
resistant to beta-lactamases
Membrane damaging antibiotics
COLISTINE (target gram +): polycationic, interacts w/ bacterial outer membrane by displacing Ca & Mg ions from the polysaccharide lipids -> disruption of outer cell membrane -> leakage -> bacterial death
POLYMIXIN (target gram -): bind to polysaccharides in outer membrane
