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Tetracycline
Tetracyclines are a class of broad-spectrum bacteriostatic antibiotics that work by binding to the 30S subunit of bacterial ribosomes and inhibiting protein synthesis. They are effective against many gram-positive and gram-negative bacteria, as well as anaerobes, rickettsiae, chlamydiae, mycoplasmas, and protozoa. Tetracyclines have a range of pharmacokinetic properties from short-acting to long-acting drugs. They are subject to resistance via efflux pumps, ribosomal protection proteins, and enzymatic inactivation. Common adverse effects include gastrointestinal issues, staining of teeth and bones, and photosensitivity.
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Tetracycline
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- 2. Bacterial Protein Synthesis Inhibitors •Tetracyclines • Macrolides • Clindamycin • Chloramphenicol • Streptogramins
- 3. Tetracyclines Inhibit bacterial proteinsynthesis by binding to and interfering with ribosomes 1) Short-acting (6-8 hours) Chlortetracycline, Tetracycline, Oxytetracycline 2) Intermediate-acting (12 hours) Demeclocycline and Methacycline 3) Long-acting (16-18 hours) Doxycycline and Minocycline
- 4. Antimicrobial Activity • Broad-SpectrumBacteriostatic Antibiotics • Active against many gram-positive and gram-negative bacteria, including Anaerobes Rickettsiae Chlamydiae Mycoplasmas Protozoa, e.g. amebas
- 5. Pharmacodynamics(MOA) The Tetracyclines bindto the 30S subunit and prevent binding of the incoming charged tRNA unit (Inhibit step 1 in bacterial protein synthesis). Tetracyclines enter microorganisms Susceptible cells concentrate the drug intracellularly Tetracyclines bind to 30S subunit of the bacterial ribosome Blocking the binding of tRNA to the acceptor site on the mRNA- ribosome complex This prevents addition of amino acids to the growing peptide
- 7. RESISTANCE Three mechanism ofresistance to tetracycline analogs (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 the ribosome (3) Enzymatic inactivation
- 8. • Tet (AE)efflux pump-expressing gram-negative species Resistant to Older Tetracyclines Doxycycline Minocycline. Susceptible to Tigecycline • Tet (K) efflux pump of staphylococci Resistance to Tetracyclines Susceptible to Doxycycline, Minocycline, Tigecycline • Tet (M) ribosomal protection protein expressed by gram-positives Resistance to Tetracyclines, Doxycycline, Minocycline, Susceptible to Tigecycline,
- 9. PHARMACOKINETICS Absorption • 60-70% tetracycline,oxytetracycline, demeclocycline, and methacycline • 95-100% doxycycline and minocycline • Tigecycline is poorly absorbed orally and must be administered intravenously. Absorption occurs in upper small intestine and is impaired by • Food (except doxycycline and minocycline) • Divalent cations (Ca2+, Mg2+, Fe2+) or Al3+ • Dairy products • Antacids
- 10. PHARMACOKINETICS • 40-80% boundby serum proteins • Distributed widely to tissues and body fluids except for CSF(10-25%) • Tetracyclines cross the placenta to reach the fetus and are also excreted in milk Chelation with calcium, damage growing bones and teeth • 10 – 50 % excreted into the urine 10 - 40 % excreted in feces • Doxycycline and Tigecycline eliminated by nonrenal mechanisms do not accumulate in renal insufficiency
- 11. DRUG INTERACTION • AntacidImpaired absorption • Carbamazepine • Phenytoin • Barbiturates • Chronic alcohol ingestion • Diuretics Nitrogen retention Decreases the half-life of Doxycycline
- 12. INDICATIONS ( Clinicaluses) Tetracycline • Drug of choice in infection with Mycoplasma pneumoniae Chlamydiae Rickettsiae Some spirochetes • Used in PEPTIC ULCER caused by H.pylori • Vibrio infections( Cholera) • Chlamydial infections, including sexually transmitted diseases • In combination with an aminoglycoside, indicated for plague, tularemia, and brucellosis
- 13. • Treatment ofacne • Exacerbations of bronchitis • Community-acquired pneumonia • Lyme disease • Relapsing fever • Leptospirosis • Nontuberculous mycobacterial infections (e.g., Mycobacterium marinum) Minocycline Meningococcal carrier state Demeclocycline Inhibits the action of ADH So used in inappropriate secretion of ADH
- 14. Tigecycline • Tetracycline-resistant strainsare susceptible to Tigecycline. • Methicillin& Vancomycin-resistant Staphylococci • Penicillin-susceptible and – resistant streptococci • Vancomycin-resistant enterococci • Gram-positive rods • Enterobacteriaceae • Multidrug-resistant strains of Acinetobacter sp • Gram-positive and gram-negative anaerobes • Rickettsiae, chlamydia, and legionella • Rapidly growing mycobacteria • Proteus and P aeruginosa, are intrinsically resistant.
- 15. ADVERSE EFFECTS 1) GASTROINTESTINALADVERSE EFFECTS • Nausea, vomiting, anorexia and diarrhea • Anal Pruritus • Vaginal or oral candidiasis • Enterocolitis 2) BONY STRUCTURES AND TEETH When a tetracycline is given during pregnancy Deposited in the fetal Teeth& Bones Fluorescence, Discoloration, and Enamel Dysplasia; Bone deformity or Growth inhibition
- 16. 3) LIVER TOXICITY •Impair hepatic function • Hepatic necrosis (4 g) 4) KIDNEY TOXICITY Administration of outdated tetracycline Damage to renal proximal tubule Renal tubular acidosis (Fanconi-like syndrom)
- 17. 5) LOCAL TISSUETOXICITY I/V injection Venous Thrombosis I/M injection Painful local irritation 6) PHOTOSENSITIZATION Demeclocycline Sensitivity to sunlight or ultraviolet light 7) VESTIBULAR REACTIONS Dizziness Vertigo Nausea Vomiting