Non-Beta Lactam Antibiotics Flashcards
Antifolate drugs MOA
inhibits folic acid (THF acid synthesis)
Cortimoxazole = _ + _
Sulfonamides
Trimethoprim
sulfonamides MOA
inhibits pteridine synthetase (since it is structurally similar to PABA) (PABA + PS)
trimethoprim MOA
inhibits DHF reductase (DHF -> THF)
Cortimoxazole indications
typhoid fever (1st line)
Pneumocystis jirovecii pneumonia
toxoplasmosis
nocardiosis
PK notes Cortimoxazole
wide distribution - crosses PLACENTA
Drugs which inhibit protein synthesis via 30S ribosome
Aminoglycosides
Tetracyclines
Drugs which inhibit protein synthesis via 50S ribosome
Macrolides
Chloramphenicol
Clindamycin
Aminoglycoside MOA (3)
1) inhibits initiation complex formation
2) misread RNA -> wrong protein
3) breaks up polysomes
clinical use of Aminoglycosides ALONE
UTI
//
combine with beta-lactam for other
adverse effects of Aminoglycoside
ototoxicity (irrev)
nephrotoxicity and neuro block (rev)
allergic rxn
given to reverse neuromuscular blockade due to Aminoglycoside
Ca gluconaate, Neostigmine
Tetracycline MOA
binds to 30S, blocks tRNA binding to Acceptor site on the mRNA ribosome complex - no peptide elongation
bacterial resistance mechanisms against tetracycline
1) impaired influx or impaired efflux by active transport protein pump Tet(AE) - G-
2) protects ribosome by producing proteins which interfere with tetracycline binding Tet(M) - G+
How are tetracyclines classified? What are the classifications
By half-life
1) Short-acting (6-8h)
2) Intermediate-Acting (12h)
3) Long-acting (16-18h)
Short-acting tetracycline drugs
Chlortetracycline
Oxytetracycline
Intermediate-acting tetracycline drugs
Democlocycline
Methacycline
Long-acting tetracycline drugs
Doxycycline
Minocycline
Tigecycline
Longest acting tetracycline and half-life
Tigecycline, 36 hours
Difference of route of excretion of long acting tetracyclines
Long-acting by biliary excretion unlike others which are renal
Tetracycline clinical use
Chlamydia
Mycoplasma pneumonia
cholera (short term ok for <8yo)
leptospirosis
tetracycline contraindicated for
pregnant & <8yo
Aminoglycoside and TEtracycline difference in chemical properties
A - not acid stable, irreversibly binds
T - acid stable, reversible
Macrolides MOA
inhibit translocation of tRNA from A to P site
Macrolides examples
Erythromycins
Clarithomycin
Azithromycin
Roxithromycin
Macrolides Pharmacokinetics
wide distribution but poor CSF penetration
Drug interaction with Macrolides
(1) They decrease CYP1A2 and CYP3A3/4 levels -> elevated effects of other drugs
(2) +Terfenadine or Astemizole -> cardiac arrhythmias
advantages of newer macrolides
less GI side effects
macrolide indications
atypical pneumonia whooping cough (Borderella pertussis) Gastroeneteritis Diphtheria Penicillin Hypersensitivity alternative drug
chloramphenicol MOA
binds to 50S ribosomal subunit and inhibits transpeptidation (blocks P-A transfer)
chloramphenicol chemistry
oral - palmitate
IV - succinate
palmitate inactive must be hydrolyzed in s.i. pure chloramphenicol does not dissolve in water
T/F Oral route is preferred than IV route for chloramphenicol
T
succinate is an inactive produg, must be hydrolysed first but process is incomplete losing 30%
Chloramphenicol indications
reserved for serious infections
H. influ - meningitis
1st line for typhoid feer
brain abscess
Adverse effects of Chloramphenicol
Idiosyncratic aplastic anemia
Gray Baby syndrome
Optic Neuritis
