Pharm 101: Doxycycline

Class

Tetracycline antibiotic

Pharmacodynamics

• Long-acting tetracycline antibiotic
• Broad spectrum
• Bacteriostatic
• Inhibits protein synthesis by binding reversibly to the 30S ribosomal subunit

Pharmacokinetics

• PO or IV administration
• Well absorbed orally
  • Absorption is mainly in upper small intestine and is impaired by multivalent cations (Ca2+, Fe2+), dairy products and antacids
• 40-80% protein bound
• Well distributed to body tissues, except for CSF where concentrations are 10-25% of serum
• Cross placenta and are excreted in breast milk
• Serum half life 16-18 hours
• Non-renal elimination:
  • Concentration in bile is 10x serum
  • Enterohepatic circulation may contribute to maintenance of serum levels
  • No dose adjustment required in renal failure

Antimicrobial activity

• Effective against various gram positive and gram negative bacteria
  • Ricketssiae
  • Chlamydiae
• Mycoplasma pneumoniae
• Combination therapy to treat H Pylori
• Clinical uses:
  • Acne
  • Community-acquired pneumonia
  • Exacerbation of COPD
  • Malaria treatment/prophylaxis (Plasmodium falciparum)

Adverse effects

• Gastrointestinal upset
  • Due to direct local irritation
  • Rarely, can cause oesophageal ulceration
  • Alteration in intestinal flora can result in intestinal functional disturbances, pruritus and candidiasis
• Readily binds to calcium in newly formed bone or teeth in young children (and fetus), therefore can cause:
  • Enamel dysplasia and teeth discolouration
  • Growth inhibition or deformity of bone
• Deranged LFTs
  • Especially in pregnancy or high doses IV
• Photosensitivity

Precautions/contraindications

• Pregnancy and young children
• Hepatic failure
• Drug interactions:
  • Carbamazepine, phenytoin, barbiturates, chronic alcohol ingestion shorten half-life by 50% due to hepatic enzyme induction

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 815-818