Sulfonylureas – Presentation Transcript

1. Sulfonylureas
2. Introduction – Sulfonylureas • Lower blood glucose in normal persons and type 2 diabetics • Not effective in type 1 diabetics
3. Mechanism of action – Sulfonylureas SUR1 receptors on pancreatic β cell membrane Binding to receptor Reduced conductance of ATP sensitive K+ channels Depolarization of membrane Enhanced Ca2+ influx Degranulation of insulin vesicles
4. Mechanism of action – Sulfonylureas • Augment 2nd phase of insulin secretion • At least 30% functional β cells required
5. Extrapancreatic action – Sulfonylureas • Chronic administration – downregulation of sulphonylurea receptors – Insulin release decreased • But control of blood sugar is maintained • Tissues are sensitized to insulin – By Increase in insulin receptors and/or postreceptor action
6. Pharmacokinetics – Sulfonylureas • Well absorbed orally • High plasma protein binding – 90% • Low volume of distribution – 0.2-0.4 L/kg
7. Interactions – Sulfonylureas • Increasing sulfonylurea action – Displacement from plasma proteins – Decrease metabolism – Synergistic action • Decreasing sulfonylurea action – Increase metabolism – Antagonistic action
8. Interactions – Sulfonylureas • Increasing sulfonylurea action – Displacement from plasma proteins • Phenylbutazone • Sulphinpyrazone • Salicylates • Sulfonamides • PAS – Decrease metabolism – Synergistic action • Decreasing sulfonylurea action – Increase metabolism – Antagonistic action
9. Interactions – Sulfonylureas • Increasing sulfonylurea action – Displacement from plasma proteins – Decrease metabolism • Cimetidine • Sulfonamides • Warfarin • Chloramphenicol • Acute alcohol intake – Synergistic action • Decreasing sulfonylurea action – Increase metabolism – Antagonistic action
10. Interactions – Sulfonylureas • Increasing sulfonylurea action – Displacement from plasma proteins – Decrease metabolism – Synergistic action • Salicylates • Propranolol • Sympatholytic antihypertensives • Lithium • Theophylline • Alcohol (inhibits gluconeogenesis) • Decreasing sulfonylurea action – Increase metabolism – Antagonistic action
11. Interactions – Sulfonylureas • Increasing sulfonylurea action – Displacement from plasma proteins – Decrease metabolism – Synergistic action • Decreasing sulfonylurea action – Increase metabolism • Phenobarbitone • Phenytoin • Rifampicin • Chronic alcoholism – Antagonistic action
12. Interactions – Sulfonylureas • Increasing sulfonylurea action – Displacement from plasma proteins – Decrease metabolism – Synergistic action • Decreasing sulfonylurea action – Increase metabolism – Antagonistic action • Corticosteroids • Diazoxide • Thiazides • Furosemide • Oral contraceptives
13. Adverse Effects – Sulfonylureas • Hypoglycemia – Commonest – More in elderly, liver+kidney disease – More with Chlorpropamide – long action – Least with Tolbutamide – low potency, short action • Non specific side effects • Hypersensitivity
14. Adverse Effects – Sulfonylureas • Hypoglycemia • Non specific side effects – Nausea – Vomiting – Flatulence – Diarrhoea/constipation – Headache – Paresthesias – Weight gain • Hypersensitivity
15. Adverse Effects – Sulfonylureas • Hypoglycemia • Non specific side effects • Hypersensitivity – Rashes – Photosensitivity – Prupura – Transient leukopenia – Agranulocytosis (rare)
16. Adverse Effects – Sulfonylureas • Chlorpropamide – Cholestatic jaundice – Dilutional hyponatremia (sensitise kidney to ADH) – Disulfuram like reactions • Tolbutamide – Reduce iodine uptake by thyroid • Does not cause hypothyroidism • Should changeover to insulin during pregnancy!

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