Dwi Indria AnggrainiDept. of Pharmacology-Medical Faculty UNILA

Antidiabetic Agents

Diabetes Mellitus

Syndrome characterized by • Blood glucose • Caused by a relative or

absolute deficiency of insulin

Disorders of carbohydrate, protein and lipid metabolisms

TYPE I DM

Defect: cells - destroyed, eliminates insulin prod.

Onset: Childhood/puberty

Nutritional status at onset:

Undernourished

TYPE II DM

Defect: + Inadequate prod.+ Insulin resistance

Onset: 0ver 35 year old

Nutritional status at onset:

Obese

Treatment Type I DM

Exogenous insulin

Good control of Blood Glucose

• Hb1C

less than 9%

2 types:

Treatment Type II DM

Good control of Blood Glucose

Delays long-term complications

Diet and exercise necessities

Treated by Oral Hypoglycemic Agents and/or insulin

Insulin in pregnancy or in severe illness

Insulin

Pork, Beef, Human Parenteral, per oral is preferable but not

yet established Preparation

Rapid action: Regular, lispro Intermediate action: NPH Prolonged action: Ultralente Combination: 30R 70N

ADR: Hypoglycemia

Tachycardi

aConfusion

Vertigo

Diaphoresis

Insulin concentration and binding in normal and overweight subjects

Development of maturity-onset diabetes

ORAL HYPOGLYCAEMICS

Sulphonylureas

Biguanides: Metformin

Thiazolidinediones:

• Rosiglitazone• pioglitazone

Action of oral antidiabetic drugs

Oral Hypoglycemic Agents Sulfonylureas

First Generation : Tolbutamide• Stimulates insulin release• Reduces glucagon release• Increases insulin Binding• Inhibits gluconeogenesis

Second Generation: Glyburide

Mechanisms:

Glipizide and Glyburide have high potency

Drugs Interaction:

• Protein binds• Salicylates, sulfonamides, clofibrate, phenylbutazone

• Metabolized by liver• Dicumarol, MAO inhibitors, phenylbutazone, chloramphenicol,

• Excreted by Kidney• Allopurinol, probenecid, phenylbutazone, salicylates, sulfonamides.

Drug interactions increase the risk of hypoglycemia.

Adverse reactions:

Hypoglycemia, GI dist. Pruritus,

Anemia

Chlorpropamide causes disulfiram

like effects

Chlorpropamide and Glyburide have long T1/2 , especially are likely to cause hypoglycemia

Biguanides

Metformine• insulin release & binding• glucagon release• Inhibits gluconeogenesis and starch & disaccharides absorption

Mechanism:

• - mild-moderate NIDDM diabetes who demonstrate insulin resistance

Reduces hyperlipidemia

Indication:

AR: - GI disturbances

- Lactic acidosis in RF patient

- Long-term used: Vit B12 malabsorption

-Glucosidase InhibitorAcarbose

Inhibits the absorption of strach and disaccharides. control glucose pp

Monotherapy or Combination

NIDDM and IDDM

AR: flatulence, diarrhea, abdominal cramping.

Thiazolidinediones

MOA:• periphe

ral insulin resist insulin act Plasma gluc

Indication: Uncontrolled NIDDM

CI: • Hepatic

impairment

• History of heart dis.

AR: • GI

disturb• Weight

gain• Potential

ly liver failure