Broad-spectrum antibiotics – Chloramphenicol

MOA: Chloramphenicol prevents mRNA from binding to the 50S ribosome. Chloramphenicol also depresses the activity of peptidyltransferase. Net result is small incomplete fragments of protein. Bacteriostatic.

Selective toxicity: Inhibits protein synthesis in prokaryotes and eukaryotes.

Spectrum: Drug of choice only for S. typhii carrier state.

Resistance: R factor-mediated. May be due to acetylation of hydroxyl group.

Pharmacokinetics: Well absorbed from GI tract; hepatic metabolism is rapid; inactive conjugates are excreted in the urine (decreased renal function is no problem, decreased live function needs reduction in dose); excellent CSF diffusion as well as excellent diffusion intraocularly.

Toxicity: Dose-related bone marrow depression; dose-independent aplastic anemia; GI irritation; neurological problems; superinfection; gray baby syndrome

Drug interactions

Erythromycin-Clindamycin – Antagonism

Erythromycin-Penicillin – Synergism, antagonism, or antagonism.

Doxycycline-Carbamazepine/Phenobarbital/Phenytoin – Reduction in half-life of doxycycline due to induction of liver enzymes.

Chlortetracycline-Penicillin – Tetracycline derivatives may antagonize the bactericidal action of penicillin G under such conditions such as meningitis.

Tetracycline-Aluminum hydroxide/ferrous sulfate – Combination decreases absorption of tetracycline.

Tetracycline-oral contraceptives – Contraceptive failure.

Category: Pharmacology Notes