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 (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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