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Diabetes Mellitus: Pharmacotherapy-Sulfonyl Ureas!

 


PHARMACOTHERAPY

Oral and injectable agents are available to treat patients with T2DM who are unable to achieve glycemic control through meal planning and physical activity.

Medications classifications include:

  1.  Sulfonyl Urea's
  2. Nonsylfonylurea Secretagogues (a-Glinides)
  3. Biguanides
  4. Thiazolidinediones
  5. a-Glucosidase Inhibitors
  6. Dipeptidyl Peptidase-4 Inhibitors(Gliptins)
  7. Sodium-glucose co-transporter (SGLT) Inhibitors 
  8. Central-Acting Dopamine Agonists
  9. Bile Acid Sequestrants
  10. Insulin therapy

SULFONYL UREAS

  • Sulfonylureas represent the first class of Oral blood glucose lowering agents approved by the United States.
  • These drugs are classified as either First- or Second-Generation drugs.
  • Both classes of sulfonyl ureas are effective when given at equipotent doses.

Mechanism of Action

  • Sulfonyl ureas enhance insulin secretion by blocking ATP-sensitive potassium channels in the cell membranes of pancreatic beta cells. This action results in membrane depolarization, allowing the influx of calcium to cause the translocation of secretory granules of Insulin to the cell surface and enhances insulin secretion in a non-glucose dependent manner.

Metabolism

  • All sulfonyl ureas undergo hepatic biotransformation with most agents being metabolized by Cytochrome-P450 2C9 Pathway. 
  • The first-generation sulfonyl ureas are most likely to cause drug interaction than the second-generation ones.
  • All sulfonyl ureas except Tolbutamide require dose adjustment or are not recommended for renal impairment.

Clinical Use

  • Sulfonyl ureas blood-glucose lowering agents can be observed in both Fasting and post-prandial levels.

Therapy

  • Monotherapy with these agents generally produce a 1.5-2% decline in A1c levels. and a 60-70mg/dL reduction in Fasting blood glucose levels (FBG).

Adverse Drug Reactions

  • Hypoglycemia
  • Weight Gain
  • Sulfa allergy


**ONLY SULFONYL UREAS THAT DOESNOT REQUIRE DOSE ADJUSTMENTS IS TOLBUTAMIDE**

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