抗生素抑制蛋白合成（英文PPT）Antibiotics That Inhibit Protein SynthesisPPT.pptVIP

Antibiotics That Inhibit Protein Synthesis Dr Khalid AlBalushi PHAR4010 Protein Synthesis Inhibitors AMINOGLYCOSIDES: gentamicin, amikacin, streptomycin, neomycin TETRACYCLINES: tetracycline, doxycycline MACROLIDES: erythromycin, clarithromycin, azithromycin CHLORAMPHENICOL CLINDAMYCIN Protein Synthesis Occurs in ribosomes Bacterial cytoplasmic ribosomes is small (70S) and have 50S and 30S subunits. Mammalian cytoplasmic ribosomes is (80 S) and have 60S and 40S subunits. Protein synthesis inhibitors interact with bacterial target and spare the host cells (high levels may interact with mammalian cells). 50S binders - Macrolides, Clindamycin, Chloramphenicol, Streptogramins. 30S binders - Aminoglycosides, Tetracyclines These drugs need to gain entry into the cell (resistance ?) Protein Synthesis Inhibitors TETRACYCLINES: Therapeutic Uses * Infectious diseases: - Rickettesial diseases (eg. Typhus fever) - Trachoma, urethritis, cervisitis - Brucellosis - Cholera - Pneumonia (M. pneumoniae) - Lyme disease -Anthrax Acne: topical or oral for severe acne vulgaris Peptic ulcer disease: H. pylori Periodontal disease: (doxycycline, minocycline) Tetracyclines: structure * TETRACYCLINES: PK Class Drug Effect on Food on absorption Route of Elimination Short acting Tetracycline Oxytetracycline decrease renal Intermediate acting demeclocycline decrease renal Long acting Doxycycline minocycline No change hepatic TETRACYCLINES: PK Food impairs the absorption of tetracyclines (not doxyclycline and minocycline) because they form insoluble chelates with calcium, magnesium, Aluminum and other metals. The use of antacids is not advised when taking tetracycline Widely distributed. Poor CNS penetration Cross placenta and enter fetal circulation Elimination through liver and kidney TETRACYCLINES: resistance Reduced drug accumulation: - decrease uptake - increased efflux increased enzymatic drug inactivation: (rarest)