Pharm 101: Gliclazide

Class

Second generation sulphonylurea


Pharmacodynamics of sulphonylureas
  • Increase insulin release from pancreatic beta cells
    • Bind to receptor, cause inhibition of K efflux through a linked ATP-sensitive K channel, leads to extracellular depolarisation
    • This depolarisation opens a voltage-gated calcium channel, causing calcium influx and release of preformed insulin
  • Reduce serum glucagon levels with long term use
    • Unclear mechanism
    • May involve direct inhibition due to enhanced release of insulin and somatostatin which inhibit alpha-cell secretion
  • Other sulphonylureas:
    • 1st generation: tolbutamide, chlopropramide
    • 2nd generation: glipizide, glyburide

Pharmacokinetics
  • PO administration
  • Bioavailability 80%
  • Protein bound
  • Vd 20L
  • Hepatic metabolism to inactive or weakly active metabolites
  • Half-life 10 hours
  • Renal excretion (80%), remainder in bile

Clinical uses
  • Diabetes mellitus

Adverse effects
  • Hypoglycaemia (more common in elderly)
  • Weight gain
  • Flushing after alcohol ingestion
  • Dilutional hyponatraemia
  • Rarely, skin rashes or haematological toxicity (leukopaenia, thrombocytopaenia)
  • GI upset
  • CYP450 enzyme inducer

Further reading

References

Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU Emergency Medicine Trainee with interests in medical education, ECG interpretation, and the use of point-of-care ultrasound in the undifferentiated patient. Co-author of the LITFL ECG Library | Twitter

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