Pharmacology Flashcards: Antibiotics, Penicillins, Cephalosporins, Macrolides, Quinolones

Penicillins are beta-lactam antibiotics that kill bacteria by inhibiting the synthesis of the bacterial cell wall. They bind to penicillin-binding proteins and prevent cross-linking of peptidoglycan, the structural component of the cell wall, causing cell lysis and death. Common penicillins include amoxicillin, ampicillin, penicillin G, and piperacillin. They are effective against many gram-positive bacteria and some gram-negative organisms.

Antibiotic resistance occurs when bacteria evolve mechanisms to survive exposure to antibiotics that previously killed them. Common mechanisms include producing enzymes like beta-lactamase that destroy the antibiotic, altering the drug target site, reducing cell wall permeability, and developing efflux pumps that expel the drug. Resistance is accelerated by overprescribing, incomplete treatment courses, agricultural antibiotic use, and poor infection control.

Cephalosporins are beta-lactam antibiotics that work by the same mechanism as penicillins, inhibiting bacterial cell wall synthesis. They are organized into five generations with progressively broader gram-negative coverage. First-generation agents like cefazolin cover gram-positive organisms well. Second-generation agents like cefuroxime add some gram-negative coverage. Third-generation agents like ceftriaxone have strong gram-negative activity. Fourth-generation agents like cefepime cover both. Fifth-generation agents like ceftaroline cover MRSA.

Macrolides are bacteriostatic antibiotics that work by binding to the 50S ribosomal subunit and inhibiting bacterial protein synthesis. Common macrolides include azithromycin, clarithromycin, and erythromycin. Azithromycin is widely used for community-acquired pneumonia, streptococcal pharyngitis in penicillin-allergic patients, sexually transmitted infections like chlamydia, and skin infections. Macrolides can prolong the QT interval on electrocardiogram, increasing the risk of potentially fatal cardiac arrhythmias.

Fluoroquinolones like ciprofloxacin, levofloxacin, and moxifloxacin are broad-spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase four, preventing DNA replication. They treat urinary tract infections, respiratory infections, and abdominal infections. The FDA has issued multiple black box warnings for serious side effects including tendon rupture, especially of the Achilles tendon, peripheral neuropathy, central nervous system effects including seizures, aortic aneurysm, and hypoglycemia.

Bactericidal antibiotics kill bacteria directly, while bacteriostatic antibiotics inhibit bacterial growth and reproduction, relying on the patient's immune system to eliminate the organisms. Penicillins, cephalosporins, fluoroquinolones, and aminoglycosides are bactericidal. Macrolides, tetracyclines, and sulfonamides are generally bacteriostatic. The distinction matters most in immunocompromised patients who may need bactericidal agents because their immune system cannot clear inhibited bacteria. In patients with normal immune function, both types are effective.

Patients with a documented penicillin allergy have approximately a 1 to 2 percent risk of cross-reacting with cephalosporins, much lower than the historically cited 10 percent. The cross-reactivity risk is highest with first-generation cephalosporins that share similar side chains with penicillin and lowest with third, fourth, and fifth-generation agents. Many reported penicillin allergies are not true immunoglobulin E-mediated allergies, and penicillin skin testing can confirm or rule out true allergy.

Aminoglycosides like gentamicin, tobramycin, and amikacin are bactericidal antibiotics that bind to the 30S ribosomal subunit and are effective against serious gram-negative infections. They require monitoring for two dose-limiting toxicities: nephrotoxicity, which causes kidney damage that is usually reversible, and ototoxicity, which causes irreversible hearing loss and vestibular damage. Peak and trough drug levels are monitored to ensure therapeutic efficacy while minimizing toxicity.

Vancomycin is a glycopeptide antibiotic reserved for serious infections caused by gram-positive bacteria resistant to other antibiotics, particularly methicillin-resistant Staphylococcus aureus, or MRSA, and Clostridioides difficile colitis. It works by inhibiting cell wall synthesis at a different site than beta-lactams. The characteristic side effect is "red man syndrome," a histamine-mediated flushing of the face, neck, and trunk caused by rapid intravenous infusion. It is prevented by infusing slowly over at least 60 minutes. ---