TETRACYCLINES

  • Doxycycline used as an example here.
Structure/Class  
Pharmacodynamics
  1. Functions by binding to the 30S subunit of bacterial ribosomes.
  2. Spectrum of activity is against Gram+ve bacteria, Gram-ve bacteria and intra-cellular organisms (chlamydia, rickettsia and spirochetes)
    • As such, clinical indications are as follows:
      1. Atypical pneumonia (mycoplasma, chlamydia)
      2. Spirochetes
      3. STIs – chlamydia
      4. May be useful in anti-malarial prophylaxis
  3. Resistance is due to the following mechanisms:
    • Reduced influx/increased efflux
    • Change of the ribosomal binding site
    • Enzymatic inactivation
Absorption/administration
  1. PO – the bioavailability approaches 100% for doxycycline.
  2. Absorption is impaired by food and divalent cations (similar property to fluroquinolones)
Distribution
  1. To tissues widely – but not to CNS.
Metabolism
  1. Hepatic
    • Strong inducers of hepatic enzymes (e.g. carbamazepine, phenobarbital and phenytoin) may decrease the half-life of doxycycline by 50%.
Excretion
  1. Renal. No need for dose adjustment in renal diseases.
Adverse events
  1. Hypersensitivity reactions are uncommon. Most of the adverse effects are due to drug effect/alteration of GIT flora.
  2. GIT effects – nausea, vomiting and diarrhea. The alteration of normal GIT/vaginal flora may lead to candidiasis and C.difficile.
  3. Bone effects
    • May be deposited in teeth/enamel, causing teeth discoloration.
    • May also cause growth inhibition and deformity.
    • Hence, avoid in the pregnant population and children <8yrs.
  4. Other reactions are also possible:
    • Photosensitivity rash
    • Dizziness and vertigo
    • Impaired hepatic function
Dosing/administration  
Toxicology  
Withdrawal syndrome  
Special notes