BMS161: Chemotherapy Pharmacology - Protein Synthesis Inhibitors

Flashcards covering key aspects of protein synthesis inhibitors, including chloramphenicol, tetracyclines, macrolides, and clindamycin.

Chloramphenicol

Protein synthesis inhibitor with adverse effects including gastrointestinal disturbance, hemolytic anemia, aplastic anemia, and gray baby syndrome. It is a LME inhibitor.

Pharmacokinetics of Chloramphenicol

Lipophilic, completely absorbed orally, widely distributed (enters normal CSF), eliminated via liver conjugation with glucuronide and renal tubule secretion.

Uses of Chloramphenicol

Restricted due to toxicity. Intravenous uses: Bacterial meningitis (alternative to 3rd generation cephalosporin), anaerobic brain abscess. Oral use: Typhoid fever. Topical use: Eye infections.

Tetracyclines

Broad-spectrum antibiotics including doxycycline and minocycline. Effective against Mycoplasma pneumonia, Chlamydia, Rickettsia, Gram +Ve bacilli (Anthrax), Gram –ve rods (Brucella / Cholera), and Anaerobic clostridium.

Pharmacokinetics of Tetracyclines

Incompletely absorbed orally (decreased with Ca2+, iron, antacids, dairy). Doxycycline is almost totally absorbed orally. Binds to calcifying tissues, crosses the placenta. Metabolized and conjugated with glucuronides. Doxycycline is excreted via bile into feces.

Adverse Effects of Tetracyclines

Gastric discomfort, GIT disturbance, deposition in bone/teeth (discoloration, hypoplasia), hepatotoxicity, phototoxicity. Contraindicated in renally impaired patients (except doxycycline), pregnant/breast-feeding women, and children < 8 years.

Macrolides

Examples include erythromycin, clarithromycin (+H. pylori), and azithromycin. Alternative to tetracycline and penicillin. Used in atypical pneumonia.

Pharmacokinetics of Macrolides

Food decreases the absorption of erythromycin and azithromycin. Concentrates in the liver. Azithromycin concentrates in WBCs (long half-life). Eliminated mainly by the liver.

Adverse Effects of Macrolides

Epigastric pain, hepatotoxicity (cholestatic jaundice), ototoxicity (high dose erythromycin). Contraindicated in patients with hepatic dysfunction. All except azithromycin are LME inhibitors (risk of drug interactions).

Clindamycin

Used in anaerobic bacteria, bone infections (osteomyelitis), and beta-lactamase producing organisms. Adverse effect: pseudomembranous colitis caused by overgrowth of C. difficile. Treatment: oral metronidazole or oral vancomycin.