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

• Buttner R. Pharm 101: Metformin. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 758-760