Page 838 - Basic _ Clinical Pharmacology ( PDFDrive )

824 SECTION VIII Chemotherapeutic Drugs

SUMMARY Tetracyclines, Macrolides, Clindamycin, Chloramphenicol,
Streptogramins, & Oxazolidinones

Pharmacokinetics, Toxicities,
Subclass, Drug Mechanism of Action Effects Clinical Applications Interactions
TETRACYCLINES
• Tetracycline Prevents bacterial protein Bacteriostatic activity Infections caused by Oral • mixed clearance (half-life 8 h) • dosed
synthesis by binding to the against susceptible mycoplasma, chlamydiae, every 6 h • divalent cations impair oral
30S ribosomal subunit bacteria rickettsiae, some spirochetes absorption • Toxicity: Gastrointestinal upset,
• malaria • H pylori • acne hepatotoxicity, photosensitivity, deposition in
bone and teeth
• Doxycycline: Oral and IV; longer half-life (18 h) so dosed twice daily; nonrenal elimination; absorption is minimally affected by divalent cations; used to treat community-
acquired pneumonia and exacerbations of bronchitis
• Minocycline: Oral and IV; longer half-life (16 h) so dosed twice daily; frequently causes reversible vestibular toxicity
• Tigecycline: IV; unaffected by common tetracycline resistance mechanisms; very broad spectrum of activity against Gram-positive, Gram-negative, and anaerobic
bacteria; nausea and vomiting are the primary toxicities

MACROLIDES
• Erythromycin Prevents bacterial protein Bacteriostatic activity Community-acquired Oral, IV • hepatic clearance (half-life 1.5 h)
synthesis by binding to the against susceptible pneumonia • pertussis • dosed every 6 h • cytochrome P450 inhibitor
50S ribosomal subunit bacteria • corynebacterial and • Toxicity: Gastrointestinal upset, hepatotoxicity,
chlamydial infections QT c prolongation
• Clarithromycin: Oral; longer half-life (6 h) so dosed twice daily; added activity versus M avium complex, toxoplasma, and M leprae
• Azithromycin: Oral, IV; very long half-life (68 h) allows for once-daily dosing and 5-day course of therapy of community-acquired pneumonia; does not inhibit cytochrome
P450 enzymes
• Telithromycin: Oral; unaffected by efflux-mediated resistance so is active versus many erythromycin-resistant strains of pneumococci; rare cases of fulminant hepatic
failure
LINCOSAMIDE
• Clindamycin Prevents bacterial protein Bacteriostatic activity Skin and soft tissue infections Oral, IV • hepatic clearance (half-life 2.5 h)
synthesis by binding to the against susceptible • anaerobic infections • dosed every 6–8 hours • Toxicity:
50S ribosomal subunit bacteria Gastrointestinal upset, C difficile colitis
STREPTOGRAMINS
• Quinupristin- Prevents bacterial protein Rapid bactericidal Infections caused by IV • hepatic clearance • dosed every 8–12 h
dalfopristin synthesis by binding to the activity against most staphylococci or vancomycin- • cytochrome P450 inhibitor • Toxicity: Severe
50S ribosomal subunit susceptible bacteria resistant strains of E faecium infusion-related myalgias and arthralgias
CHLORAMPHENICOL
Prevents bacterial protein Bacteriostatic activity Use is rare in the developed IV • hepatic clearance (half-life 2.5 h) • dosage is
synthesis by binding to the against susceptible world because of serious 50–100 mg/kg/d in four divided doses
50S ribosomal subunit bacteria toxicities • Toxicity: Dose-related anemia, idiosyncratic
aplastic anemia, gray baby syndrome

OXAZOLIDINONES
• Linezolid Prevents bacterial protein Bacteriostatic activity Infections caused by Oral, IV • hepatic clearance (half-life 6 h) • dosed
synthesis by binding to the against susceptible methicillin-resistant twice-daily • Toxicity: Duration-dependent bone
23S ribosomal RNA of 50S bacteria staphylococci and vancomycin- marrow suppression, neuropathy, and optic
subunit resistant enterococci neuritis • serotonin syndrome may occur when
co-administered with other serotonergic drugs
(eg, selective serotonin reuptake inhibitors)
Tedizolid: Oral and IV; longer half-life (12 h) so dosed once daily; increased potency versus staphylococci; approved for use in skin and soft tissue infections.