Oral Hypoglycemic Drugs - Sulphonylureas

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simpro

Health & Medicine Technology

CLASSIFICATION

α glucosidase
Sulphonylureas Biguanides Meglitinide Thiazolidinediones inhibitors

I generation
Metformin Repaglinide Rosiglitazone Acarbose
•Tolbutamide
•Chlorpromamide

Nateglinide Pioglitazone Miglitol
II generation
•Glibenclamide
•Glipizide
•Gliclazide
•Glimepiride

PgBlazer.com

Sulphonylureas
• Lower blood glucose in normal persons and
type 2 diabetics
• Not effective in type 1 diabetics

PgBlazer.com

Mechanism of action – Sulphonylureas

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
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Mechanism of action – Sulphonylureas

• Augment 2nd phase of insulin secretion
• At least 30% functional β cells required

PgBlazer.com

Extrapancreatic action – Sulphonylureas
• 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

PgBlazer.com

Pharmacokinetics – Sulphonylureas
• Well absorbed orally
• High plasma protein binding – 90%
• Low volume of distribution – 0.2-0.4 L/kg

PgBlazer.com

Interactions – Sulphonylureas
• Increasing sulphonylurea action
– Displacement from plasma proteins
– Decrease metabolism
– Synergistic action
• Decreasing sulphonylurea action
– Increase metabolism
– Antagonistic action

PgBlazer.com

Interactions – Sulphonylureas
• Increasing sulphonylurea action
– Displacement from plasma proteins
• Phenylbutazone
• Sulphinpyrazone
• Salicylates
• Sulfonamides
• PAS
– Decrease metabolism
– Synergistic action
• Decreasing sulphonylurea action
– Increase metabolism
– Antagonistic action

PgBlazer.com

Interactions – Sulphonylureas
• Increasing sulphonylurea action
– Displacement from plasma proteins
– Decrease metabolism
• Cimetidine
• Sulfonamides
• Warfarin
• Chloramphenicol
• Acute alcohol intake
– Synergistic action
• Decreasing sulphonylurea action
– Increase metabolism
– Antagonistic action

PgBlazer.com

Adverse Effects – Sulphonylureas
• 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

PgBlazer.com

Adverse Effects – Sulphonylureas
• Hypoglycemia
• Non specific side effects
– Nausea
– Vomiting
– Flatulence
– Diarrhoea/constipation
– Headache
– Paresthesias
– Weight gain
• Hypersensitivity

PgBlazer.com

Adverse Effects – Sulphonylureas
• Hypoglycemia
• Non specific side effects
• Hypersensitivity
– Rashes
– Photosensitivity
– Prupura
– Transient leukopenia
– Agranulocytosis (rare)

PgBlazer.com

Adverse Effects – Sulphonylureas
• 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

PgBlazer.com

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