hypoglycemic agents, Insulin

Side effects

• ·            Hypoglycemia
• ·          Lipodystropy: Atropy in subcutaneous fat at site of injection. It is more common with rich        bovine      insulin and rich in proinsulin.
•        Allergic reaction: Urticaria. It is due to non insulin protein contaminants in insulin prepration.
•         Drug interaction: Beta adrenergic blockers promote hypoglycaemia

Lipodystropy and allergic reaction can be minimised by using purified insulin

Oral Hypoglycemic Agents

Oral Hypoglycemic agents

Non insulin dependent diabetes mellitus (NIDDM) is treated with diet modification and exercise. If diet modification and exercise do not control NIDDM then oral hypoglycaemic agents are used. They are effective in recently developed diabetes mellitus. NIDDM not older than 5 years are treated by oral hypoglycemic agents and insulin combination. Oral hypoglycaemic agents are not effective to treat type I diabetes mellitus (IDDM).

Classification:

·         Sulfonylureas

o   First Generation drugs: Tolbutamide, Chlorpropamide, Tolazamide, Acetahexamide

o   Second generation Drugs: Glibinclamide, Glipizide, Gliclazide, Gliquidone

·         Biguanides: Phenformin, Metformin, Buformin

·         Other agents: Glymidine, Ciglitazine, Acarboze

Sulfonylureas: Sulfonamides produce hypoglycaemic effect as an adverse effect. This side effect is clinically used to treat diabetes mellitus. Tolbutamide belongs to sulfonylureas group. Tolbutamide is first sulfonylureas drug to treat type II diabetes mellitus (NIDDM).

Mechanism of action: Sulfonylureas act by producing following side effects

·         Stimulate β-cells of islets of Langerhans of the pancreas to release insulin.

·         Decrease serum glucagon level

·         Increase tissue insulin receptor sensitivity

·         Reduce insulin metabolism in the liver that increases blood insulin liver.

But on prolong use of sulfonylureas, blood insulin level decreases.

First generation sulfonylureas

·         Tolbutamide: It is well absorbed upon oral administration, metabolised in liver by oxidation. Metabolites are weakly active compound. It has comparatively short duration of action i.e. half-life about 8 hours. Thus it has low adverse effects. Thus, It is recommended for elder patients and renal impaired patients. Hyponatremia (low level of sodium in the blood) and hypoglycemia appears s adverse effects. It should be used with caution in patients suffering for liver disease.

·         Tolazamide: It is slowly absorbed from GIT and slowly metabolized in the liver. Metabolites are partially active. It has half-life about 20 hrs. It is excreted through the kidney.

·         Chlorpropamide: It has slow absorption from GIT, slow onset of action and slow metabolism. Half-life is about 30 hrs.  Maximum amounts of the administered drug is excreted unchanged and small amount as metabolites through the kidney. Thus it should be used with caution in renal impairment, liver impairment and in elder patients.

Side effects: prolonged hypoglycemia, hyponatremia, flushing, hypotension  

Sulfonylureas can cross placental barriers. Thus it should not be used during pregnancy. In this condition, it can enter into fetus pancreas. Pregnant women diabetes or hyperglycemia should be treated with insulin.

Second Generation sulfonylureas

·         Glibenclamide: It is the first drug that belongs to second-generation sulfonylureas. It is 200 times more potent than tolbutamide. It is rapidly absorbed from GIT. It has short duration of action about 10 hrs. But it remains biologically active for 24 hrs. Thus it is administered once in a day. Larger dose twice in a day is recommended in severely high blood glucose level. It has low side effects.

Contraindications: hepatic impairment, renal insufficiency.

·         Glipizide: It has rapid absorption and short half-life. Hypoglycemic effects remain for 24 hrs. It is metabolized in the liver and excreted through the kidney.

·         Gliclazide: It has slow duration of action. It is administered once in a day. It is safe for elder patients.   

Biguanides: Biguanides produce following effects

·                                           Increase in insulin action in peripheral tissues

·                                           Inhibit gluconeogenesis to reduce liver glucose output

·                                           Reduce glucose absorption from GIT

They do not produce  hypoglycemic effect. They decrease increased blood glucose level to normal.

Metformin is most widely used biguanide. It also reduces VLDL and LDL in blood and body weight. It is a  drug of choice to treat type II diabetes in the early stage. It is well absorbed from GIT. It does not bind to plasma protein. It is excreted by the kidney. Long-term use produces vitamin B₁₂ deficiency. It is contraindicated in renal and hepatic failure.

Phenformin produces lactic acidosis (It is metabolic acidosis due to metabolism of lactic acid. There will be accumulation of lactate that severely reduces blood pH.) Thus it is not used. Lactic acidosis is fatal in nature.

Acarbose: It is a starch blocker and inhibits carbohydrate digestion in GIT. It is administered with the first bite of the meal. Its effectiveness depends upon the amount of carbohydrate in the meal.

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