Antibugs Flashcards
Which antibiotics affect cell wall synthesis?
B lactams (penicillins, cephalosporins, carbapenems)
Glycopeptides (vanc, teic)
How do b lactams work
Rely on the integrity of the b lactam ring for bacteriocidal activity
Bind to and inhibit the enzyme that catalyzes the cross linking btw polymer chains in the cell wall, causing weakening followed by cell lysis
How do glycopeptides work
Bind the the peptidoglycan chains preventing formation of peptide x linking
WHich antibiotics inhibit protein synthesis
MAcrolides
TEtracyclines
aminoglycosides
Licosamides
Chloramphenicol
What is the difference btw bacterial and mammalian ribosomes
bacterial- 50s + 30s subunits
Mammalian have a 60s and 40s
How do macrolides (erythromycin) work
Bind to the 50s subunit inhibiting peptide chain translocation
How do tetracyclines work
Bind to the 30 s subunit and inhibit binding of aminoacyl-tRNA
How do aminoglycosides work?
Also bind to the 30s subunit and cause misreading of mRNA
Lincosamides MOA ?
eg clindomycin
Disrupt the function of the 50s subunit
How does chloramphenicol work?
Inhibits peptidyl transferase activity of the 50s subunit, stopping transpeptidation
Which abx inhibit nucleic acid synthesis?
Trimethoprim
Quinolones
metronidazole
Rifampacin
HOw does trimethoprim work?
Inhibits dihydrofolate reductase needed in purine/pyrimadine synthesis (bacteriostatic)
How do quinolones work?
Inhibit DNA gyrase, the enzyme that compresses DNA into coils
How does metronidazole work?
INhibits and damages dna synthesis (unclear exact MOA)
How does rifampacin work?
Prevents rna transcripton by inhibiting DNA dependent RNA polymerase
WHen is it important to use a bacteriocidal agent?
In the immunosuppressed
Bacteriostatic drugs?
MAcrolides
licosamides
chloramphenicol
tetracyclines
trimethoprim
Characteristics of penicillins?
Low toxicity, short half life, renal excretion unchanged
HYpersensitivity in 10%, anaphylaxis in 1
Side effects incl encephalopathy and didarrhoea
Tissue penetration good, but meninges need to be inflammed to cross the BBB
CHaracteristics of cephalosporins
Less susceptible to b lactamases
broader spec
Excreted unchanged in urine (bar cefotaxime which is 50% metabolsied in the liver)
What is different about ceftriaxone c.w. other cephalosporins
Highly protein bound (95%) with a long half life (6-12 hr) only given OD
How are cephalosporins divided?
Three generations, increasingly more gram negative cover whilst positive cover is maintained
Second generation cephalosporins examples and use
Cefuroxime
More stable b lactam ring used for prophylaxis in bowel surgery, lack anaerobic cover
Third generation cephalosporins examples
cefotaxime, ceftriaxone, cepftazidime
Carbapenem cover
broad- positive, negative, aerobic and anaerobicUS
Uses of carbapenems
Neutropenic and multiresistant gram neg sepsis.
What do carbapenems not work on
MRSA, E faecalis and some pseudomonas
WHy is imipenem combined with cilastatin
Prevent renal metabolism and increase plasma conc.
S/E of carbapenems
generally well tolerated but can cause convulsions. Excreted unchanged
GLycopeptide cover
gram positive spectrum and used in MRSA + endocarditis.
GRam negative cover limited as large polar molecules cannot penetrate the outer lipd wall
DIfference between teic and vanc?
TEic is more potent, longer duration of action, better tissue penetration and better tolerated. More resistance about
CHaracteristics of glycopeptides
Toxicity common- nephro/oto/neutropenia. monitoring required.
ELimination unchanged in urine
Minimal absorption from gut
Can cause red man syndrome- IV vanc can lead to histamine release
MAcrolide spectrum
SImilar to penicillin, mainly gram positive organisms
SPecific activity against mycoplasma and legionella
What is good about azithromycin
increased gram negative cover with a v long half life (40-60 hrs)
CHaracteristics of macrolides
Well tolerated
metabolised and excreted by the liver
potent inhibitors of the CYP450 enzymes
Side effects of macrolides?
GI (erythromycin is a prokinetic), prolonged QT< thrombophlebitis
Cover of aminoglycosides?
Mainly gram negative, including pseudomonas. First line for serious gram negative infections
Pharmacokinetics of AMinoglycosides?
LArge, polar molecules needing active transport into the cell.
Renally excreted
IV required due to low lipid solubility
Why do aminoglycocides work well with penicillins?
Penicillins break down the cell wall, giving aminoglycosides better cellular access
S/E aminoglycosides
Toxic to kidneys and cn8 with narrow therapeutic range
Impair transmission at NMJ by decreasing prejunctional release and reducing post junctional sensitivity to Ach
Quinolones uses?
Broad spec so often gastroenteritis or multiple resistant infetions
Tends towards covering gram neg, but some pos
Difference between cipro and levofloxacin?
Levo has increased pneumococcal cover, useful for LRTI
Characteristics of quinolones?
Good oral absorption
wide distribution with good cns penetration
excreted unchanges
low toxicity
INhibits cyp450
S/E quinolones
nausea, vomiting, convulsions, prolonged qtc
WHat is metronidazole good for?
Anaerobic bacteria- these predominate in abscesses so useful here
Characteristics of metronidazole
Well tolerated
Distributes in csf, prostate and pleural fluid
Excreted unchanged in urine
Rare side effects of metronidazole
rash
pancreatitis
peripheral neuropathy
Flushing and hypotension with alcohol
Why are quinolones bad in epilepsy?
GABA antagonism
