Mechanism of Action: Inhibits bacterial protein synthesis by binding with the 30S ribosomal subunit. Pharmacodynamics: Tetracyclines produce a combination of concentration and time-dependent killing (AUC:MIC ratio). Pharmacokinetics: Dose of 500mg PO: Cmax: 1.5-5 mcg/mL; Tmax: 2-4 hours; Half-life: 6-12 hours; Volume of distribution: 108 L/kg; Table 3 Adverse Effects: GI: epigastric burning, abdominal discomfort, nausea, vomiting, anorexia, diarrhea, esophagitis, esophageal ulcers, dysphagia, candidal superinfections Teeth and bone: (dose/duration related) yellow discoloration of teeth, which turns into a gray- brown permanent discoloration, hypoplasia of enamel, teeth demineralization, skeletal growth retardation Hepatotoxicity: rare, but fatal; intrahepatic cholestasis, jaundice, azotemia, acidosis, irreversible shock Renal Toxicity: hyperphosphatemia, acidosis, polyuria, polydipsia Photosensitivity and hyperpigmentation: red rash to blistering on sun-exposed areas; photoallergic reactions manifested by paresthesias of hands, feet, nose, photo-onycholysis Auditory: tinnitus, hearing loss Vision: visual disturbances CNS: lightheadedness, dizziness, ataxia, drowsiness, headache Dosage: Oral: 250mg, 500mg capsules Adult dosing (common indications): Acne vulgaris: 250 mg PO q other day to 500 mg PO q24h Bartonellosis: 1-2 g/day divided PO in 2-4 doses Brucellosis: 500 mg PO q6h 4 x 3 plus streptomycin Chlamydia psitacci infection: 1-2 g/day divided PO in 2-4 doses Rickettsial disease: 1-2 g/day divided PO in 2-4 doses Nongonococcal urethritis: 500 mg PO q6h x 7 days
Pediatric dosing: 25-50mg/kg/day in 2 to 4 divided doses OR 0.6-1.2g/m2 in 2 – 4divided doses Table 4 Disease state based dosing: Renal failure: CrCl > 50mL/min: 250mg to 500mg q6h
CrCl 10-50 mL/min: 250mg to 500mg q12h to q24h
Hepatic failure: No dosing changes recommended at this time. Contraindications/Warnings/Precautions: Contraindications: Hypersensitivity to tetracycline antibiotics. Precautions: Usage in newborns, infants, and children less than 8 years of age; risk for tooth discoloration; Renal or liver impairment; Phototoxicity; Veneral disease with suspected coexistent syphilis Drug Interactions: Oral contraceptives: Decreased contraceptive effectiveness Warfarin: Increased warfarin effect Barbiturates, phenytoin, carbamazepine: Decreased serum concentrations of doxycycline Ethanol: Decreased doxycyline serum concentrations Antacids, didanosine, sucralfate, multivitamins: decreased tetracycline absorption Kaolin, bismuth subsalicylate: decreased absorption of tetracycline Food: Decreased absorption of tetracycline Milk: Decreased absorption of tetracycline Table 6 Pregnancy: Category D: Risk established, but benefits may outweigh risk. Monitoring Requirements: Therapeutic: Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count Toxic: Hypersensitivity syndrome reaction, serum sickness like reaction or single organ dysfunction – Monitor: CBC, LFTs, urinalysis, urea, creatinine, chest radiograph; Drug-induced lupus: monitor antinuclear antibody and hepatic transaminases; General long-term therapy: Liver and renal function tests, Hematopoietic studies Brand names/Manufacturer: Available by many names and manufacturers
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