Flashcard Topics

Overview

• Q: What ribosomal difference allows selective targeting of bacteria? A: Bacteria have 70S ribosomes (30S + 50S); mammals have 80S (40S + 60S).
• Q: Why can some PSIs cause mitochondrial toxicity? A: Mammalian mitochondrial ribosomes resemble bacterial ribosomes, so high doses can inhibit them.

1. Aminoglycosides

• Q: What ribosomal subunit do aminoglycosides target? A: 30S subunit - causing mRNA misreading and faulty ribosome assembly.
• Q: What dosing strategy is preferred and why? A: High-dose extended-interval dosing - exploits concentration-dependent killing and the postantibiotic effect (PAE), and reduces nephrotoxicity.
• Q: Name the 3 major adverse effects. A: Ototoxicity, nephrotoxicity, neuromuscular paralysis.
• Q: How is neuromuscular paralysis treated? A: Calcium gluconate or neostigmine.
• Q: Which aminoglycoside is only given topically/orally, and why? A: Neomycin - severe nephrotoxicity prevents parenteral use.

2. Tetracyclines

• Q: What is the mechanism of tetracyclines? A: Bind reversibly to 30S subunit, blocking tRNA binding to the mRNA-ribosome complex.
• Q: What chelates reduce tetracycline absorption? A: Divalent/trivalent cations - Ca²⁺, Mg²⁺, Al³⁺ (dairy, antacids, iron).
• Q: Which tetracycline is preferred in renal failure? A: Doxycycline - eliminated via bile/feces, not the kidney.
• Q: What is demeclocycline's unique non-antibiotic use? A: Treatment of SIADH (blocks ADH receptor binding).
• Q: Why are tetracyclines avoided in children under 8 and pregnancy? A: Deposit in growing bones/teeth causing discoloration, hypoplasia, and stunted growth.

3. Glycylcyclines (Tigecycline)

• Q: What is tigecycline derived from, and what does it cover? A: Derivative of minocycline; covers MRSA, VRE, MDR streptococci, many anaerobes.
• Q: What serious adverse effect requires dose monitoring with warfarin? A: Tigecycline decreases warfarin clearance - monitor INR closely.

4. Macrolides & Ketolides

• Q: What is the mechanism of macrolides? A: Irreversibly bind the 50S subunit, inhibiting translocation of protein synthesis.
• Q: Which macrolide causes irreversible sensorineural hearing loss? A: Azithromycin.
• Q: What cardiac risk is associated with macrolides? A: QTc prolongation - risk of arrhythmia.
• Q: Why must erythromycin be given as enteric-coated or esterified forms? A: The base is destroyed by gastric acid.
• Q: Name one useful side effect of erythromycin. A: Promotes gastric motility - used off-label for gastroparesis or postoperative ileus.

5. Macrocyclics (Fidaxomicin)

• Q: What is fidaxomicin's mechanism? A: Inhibits the sigma subunit of RNA polymerase, disrupting bacterial transcription.
• Q: What is its primary clinical use? A: C. difficile infection - minimal systemic absorption, stays in the GI tract.

6. Lincosamides (Clindamycin)

• Q: What is the most serious adverse effect of clindamycin? A: Pseudomembranous colitis from C. difficile overgrowth.
• Q: Does clindamycin penetrate the CSF? A: No - poor CSF penetration.

7. Oxazolidinones (Linezolid / Tedizolid)

• Q: What is the mechanism of linezolid? A: Binds 23S rRNA of the 50S subunit, preventing formation of the 70S initiation complex.
• Q: What serious reaction occurs with SSRIs or MAOIs? A: Serotonin syndrome - linezolid has MAO inhibitor activity.
• Q: What long-term toxicities occur with linezolid? A: >10 days: thrombocytopenia; >28 days: peripheral neuropathy and optic neuritis.

8. Streptogramins (Quinupristin/Dalfopristin)

• Q: What is the main clinical indication? A: VRE (Enterococcus faecium) infections when other options fail.
• Q: How do the two components work together? A: Dalfopristin inhibits elongation; quinupristin causes release of incomplete peptide chains. They synergize for bactericidal activity.
• Q: What is a notable drug interaction? A: Inhibits CYP3A4 - can cause toxicity with co-administered CYP3A4-metabolized drugs.

9. Chloramphenicol

• Q: What ribosomal site does chloramphenicol target? A: 50S subunit - inhibits the peptidyl transferase reaction.
• Q: What is Gray Baby Syndrome? A: Neonatal drug accumulation (poor glucuronidation + immature kidneys) causing cardiovascular collapse, cyanosis, and death.
• Q: Name the three types of anemia caused by chloramphenicol. A: Dose-related anemia, hemolytic anemia (G6PD deficiency), and aplastic anemia (dose-independent).
• Q: What drug interactions are clinically important? A: Inhibits hepatic oxidases - potentiates warfarin and phenytoin.