INSULIN & ORAL HYPOGLYCEMIC DRUGS

TRULY SITORUS
Depart. of Pharmacology & Therapy Faculty Of Medicine Padjadjaran University

It is a heterogeneous group of syndromes all characterized by an elevation of blood glucose caused by a relative or absolute deficiency of insulin. Symptom:

DM
A. TYPE I (INSULIN DEPENDENT DIABETES MELLITUS, IDDM)
Absolute deficiency of insulin Caused by massive -cell lesions or necrosis Treatment: exogenous insulin

B. TYPE II (NON INSULIN DEPENDENT DIABETES MELLITUS, NIDDM)

Inability of -cell to produce appropriate quantities of insulin Insulin resistance Other unknown defects Treatment: Hypoglycemic oral drugs insulin

INSULIN
Insulin exogen
Beef Pork Human (by. E.colli, OOA <<, DOA <<)

Effect
Hyperglycemia Normal

MECHANISM OF ACTION

PHARMACOKINETICS
Insulin p.o degradation subcutaneous IV: in hyperglycemic emergency

ADVERSE EFFECT & OVERDOSE TOXICITY

Hypoglycemia Hypoglycemia brain damage ! Symptom of hypoglycemia
Tachycardia Confusion Vertigo Diaphoresis

Lipodystrophy Hypersensitivity

INDICATION
1. All patients with type I DM regardless of age 2. Patient who have ketoacidosis or hyperosmolar coma 3. Patient with type II DM when diet restriction, exercise and oral hypoglycemic agent have failed to maintain satisfactory blood glucose concentration 4. Patient with type II DM in presence of surgery fever, infections, serious renal or hepatic dysfunction, and other metabolic disturbances 5. Pregnant diabetic women

CONTRAINDICATION
There are no contraindications if the proper indication exists. Patients must be well educated regarding the role of diet, exercise and illness in modifying their insulin requirements.

INSULIN PREPARATIONS
A. RAPID ACTION INSULIN PREPARATION
Zinc insulin: sc
iv (in emergencies)

B. INTERMEDIATE ACTION INSULIN PREPARATION

1. 2. 3. 4. Semilente insulin suspension Isophane insulin suspension Lente insulin Insulin incombination

C. PROLONGED ACTION INSULIN PREPARATION

ORAL HYPOGLYCEMIC AGENTS

I.

SULFONILUREAS
First generation Tolbutamide, Chlorpropamide, Tolazamide Second generation Glipizide, Glyburide

II. III.

BIGUANIDES
Metformin

GLUCOSIDASE INHIBITORS
Acarbose

IV. REPAGLINIDE (?)

Repaglinide

V.

THIAZOLIDINEDIONES
Troglitazone

SULFONILUREAS
Mechanism of action 1. Stimulation of insulin release from the cells 2. Reduction of serum glucagon levels 3. Increased binding of insulin to target tissues Pharmacokinetics Oral, bind to serum proteins Metabolized by liver
1st G : inactive, less active, active 2nd G: inert

Excreted by kidney or liver

 Side effect Hypoglycemia (especially: chlorpropamide, Glyburide) Contraindication: Renal or hepatic insufficiency Pregnancy Elderly

INTERACTION

METFORMIN
Used alone or in combination with sulfonilurea, others Drugs of choice in newly diagnosed type II DM Decreasing hepatic glucose output Reduced hyperlipidemia (LDL, VDL, cholesterol, HDL) Oral, unbound to serum protein Not metabolized Side effect: GI disturbance, hypoglycemic <<

ACARBOSE
Inhibits glucosidase in intestinal decreased the absorption of starch and disaccharides Taken with meals Not cause hypoglycemia Side effects: flatulence diarrhea abdominal cramping

REPAGLINIDE
Binds to the ATP- sensitive potassium channels of cells release of insulin Metabolized inactive

TROGLITAZONE
Decreases insulin resistance

BIGUANIDES
METFORMIN Inhibiting gluconeogenesis Reduce hyperlipidemia (LDL, VDL, cholesterol, HDL) Not bound to serum protein Is not metabolized SE: hypoglycemic <<