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Tetracyclines - Coggle Diagram
Tetracyclines
Adverse reactions
Gastrointestinal effects
- Nausea, Vomiting, Diarrhea, Anorexia
- suppress normal GI flora causes superinfections with:
- Pseudomonas proteus
- Staphyloccoci
- resistance coliforms
- Clostridia
- Cnadida
- resulting:
1) intestinal functional disturbances
2) anal prutitus
3) vaginal or oral candidiasis,
4) Clostridium difficile associated colitis
Other toxicities
- Impaired hepatic functions
- Renal tubular acidosis & other renal injury
- IV administration - venous thrombosis
- IM injections - painful local irritation
- Systemically administration - sensitive to sunlight or UV light
Bony structure & Teeth
- Young children - bound to calcium deposited in newly formed bone or teeth
- Pregnancy:
- deposited in fetal teeth causes: fluorescence, discoloration, enamel dysplasia
- deposited in bone causes: deformity or growth inhibition
-
MOA
- inhibit bacterial protein synthesis by binding and interfering with ribosomes
- bacteriostatic (mostly) & bactericidal (few)
- 4 rings fused together, side-by-side
- enter microbial cells by: 1) passive diffusion 2) energy-dependent active transport
- bind reversibly to 30S subunit of ribosomes
- block binding of aminoacyl-tRNA
- preventing the addition of amino acids to the peptides, thus, inhibit protein synthesis
- INHIBIT mRNA TRANSLOCATION
Antibacterial spectrum
- broad-spectrum
- active against gram +ve & gram -ve
- including anaerobes, rickettsiae, chlamydiae, mycoplasmas
Mechanism of resistance
- tetracycline-resistance strains: Doxycycline, Minocyclin, Tigecycline (Group3)
- poor substrates for efflux pump that mediate resistance
- Mechanisms:
1) impaired influx or increased efflux by an active transport protein pump
2) ribosome protection due to production of proteins that interfere with tetracycline binding to ribosome
3) enzymatic inactivation
Pharmacokinetics
- oral absorption & renal elimination
- oral absorption:
-30% - Chlotetracycline
-60-70% - Tetracycline, Oxytetracycline, Demeclocycline, Methacycline
-95-100% - Doxycycline, Minoclycline
- tetracycline - poorly absorbed, IV administration & excreted mainly in bile and urine
- drugs remains in gut lumen - alters intestinal flora and excreted in feces
- intestinal absorption is impaired by:
1) food (except Group 3)
2) dairy products
3) divalent cations
4) antacids
5) alkaline pH
- drug excrete in bile is reabsorbed from intestine - contribute to maintenance serum level (enterohepatic circulation)
- Half-life: 36 hours
Clinical uses
- Rickettsial infections
- Mycoplasma pneumonia
- Chlamydiae infections
- Spirochetes infections
- gastric & duodenal infections - Helicobactor pylori
- Gram+ve & -ve infections - Vibro cholera infections
- Gonococcal infection
- prohylaxis for protozoal infections - Plasmodium falciparum, Amoebiasis
- others: Acne, exacerbations of Bronchitis, Community-acquired pneumonia, Lyme disease, relapse fever, Leptospirosis
- as combine drug for - Plague, Tularemia (rabbit fever, deer fly fever), Brucellosis
- eradicate Meningococcal carrier state by Minocycline (200mg OD 5days) or Rifampin