Tetracycline

• What are tetracyclines classified as?

  A group of antibiotics
• How are tetracyclines obtained?

  They are obtained naturally by fermentation from Streptomyces spp. or by chemical transformation of natural products
• What is the chemical structure of tetracyclines?

  • Nucleus of 4-fused cyclic rings
• Name one example of a tetracycline.

  Tetracycline
• What is the mechanism of action of tetracyclines?

  They bind to the 30S ribosomal subunit
• What effect do tetracyclines have on protein synthesis?

  They block aminoacyl-tRNA from binding at the Acceptor (A) site on the 50S ribosomal subunit
• What is the result of tetracyclines binding to the ribosomal subunit?

  It prevents the addition of new amino acids to the growing peptide chain
• What type of bacteria do tetracyclines primarily target?

  Gram-negative bacteria
• What are the mechanisms of penetration for tetracyclines into Gram-negative bacteria?

  1. Passive diffusion through hydrophilic porins

  2. Through lipid bilayer of outer membrane

  3. Protein-carriers on inner membrane transport drugs to ribosomes (energy-dependent mechanism)
• What are the mechanisms of resistance to tetracyclines?

  1. Alteration in transport proteins

  2. Development of "efflux" mechanism (except for doxycycline & minocycline)

  3. Alteration on ribosomal binding sites

  4. Enzymatic inactivation of drugs

  5. Decreased entry of drugs into bacterial cells
• How does natural selection contribute to tetracycline resistance?

  Through subtherapeutic use of antibiotics
• What is the antimicrobial activity of tetracyclines?

  • Bacteriostatic
  • Broad spectrum
  • Effective against G+ve, G-ve, chlamydia, rickettsia, mycoplasma, antiplasmodium, and some amoeba
• What is the bioavailability of doxycycline and minocycline?

  90-100% bioavailable
• How does food affect the absorption of tetracyclines?

  Generally, food impairs absorption
• What minerals can chelate tetracyclines and decrease their absorption?

  Ca++, Mg++, Fe, and Al
• What is the distribution pattern of tetracyclines?

  • Variable distribution depending on the drug
  • Minocycline & doxycycline (lipid soluble) have large volume of distribution
  • Oxytetracycline (lipid soluble) is poorly distributed
• How do tetracyclines affect fetal development?

  They cross the placenta and bind to growing bone and teeth
• What are the metabolic pathways for tetracyclines?

  They undergo hepatic and renal mechanisms
• What is the elimination route for tetracyclines?

  Excreted in bile and urine
• Which tetracycline is totally broken down in the liver?

  Doxycycline
• What are the classifications of tetracyclines based on their duration of action?

  • Short acting: Tetracycline, Oxytetracycline
  • Intermediate acting: Demeclocycline, methacycline
  • Long acting: Doxycycline, Minocycline
• What are the clinical uses of tetracyclines?

  They are used for a broad range of infections not treated by B-lactam antibiotics
• Why is doxycycline preferred for renal-impaired patients?

  It has a longer half-life, hepatic metabolism, and lack of renal toxicity
• What are some specific infections treated with tetracyclines?

  • Trachoma (Chlamydia trachomatis)
  • Lymphogranuloma (Chlamydia trachomatis)
  • Psittacosis (Chlamydia psittaci)
  • Brucellosis (Brucella spp)
  • Acne vulgaris
• What is a common adverse reaction of tetracyclines?

  Yellowish-brown discoloration of growing teeth
• Why should tetracyclines not be used in pregnant or lactating women and children under 8 years?

  They impair long bone development
• What are some adverse reactions associated with tetracyclines?

  • GIT irritation (nausea, vomiting, diarrhea)
  • Enterocolitis (overgrowth of Clostridium difficile)
  • Liver damage
  • Kidney damage (except doxycycline)
  • Hypersensitivity (skin rash, urticaria)
  • Photosensitization