Oral hypoglycemia drugs(OHA)

Classification:

1.Secretogouge	a.Sulforamide derivatives:Sulfonylureas b.Meglitinide:Nateglinide	1st generation:Old ·         Tolbutamide(Safest) ·         Chlorpromide ·         Acetohexamide ·         Tolazamide. 2nd generation:New ·         Glyburide. ·         Glipizide. ·         Glibenclamide.
2.Biguanide derivatives		·         Phenformin(Banned) ·         Metformin(Used) ·         Buformin.
3.Thiazolidindion		·         Troglitazone. ·         Rosiglitazone. ·         Pioglitazone.
4.α glucosidase inhibitors		·         Acarbose. ·         Migilitol.

Mechanism of action of Sulfouylureas:

[A]Pancreatic functions:

(a) Enhance insulin release from β cells by inhibting the  channel.

Sulfouylurea + Receptor

↓

S-R complex

↓ (-)

 efflux(outflux)

↓

 accumulation in cell

↓

↑Positivity of cell

↓

Depolarization

↓

 channels open

↓

 influx

↓

Degranulation

↓

Insulin release

At least 30% of total β cells must be present(active) for getting the effect of sulfouylureas.In the absence of β cells the drugs are totally inactive.So OHA cannot be used in IDDM.

(b)Reduction of serum glucagon level:

a)      Direct action:Inhibition of α cells.

b)      Indirect action:↑ insulin→↓Glucagon release.

Limitations of Sulphonylureas/Tolbutamide:

1)      To get the hypoglycaemic effect,30% of the total β cells of pancreas must be functioning.

2)      Can only given in NIDDM.

3)      It cannot synthesize new insulins but can release the stored insulin.

4)      Cannot be given in to pregnant woman due to teratogenic effect.

5)      Cannot be given where more than 40 IU/day of insulin is needed.

6)      These drugs are not adequate in diabetic complications(e.g diabetic gangrene), major surgery,shock etc.

7)      Cannot be given in hepatic & renal insufficiency.

Adverse effects Sulphonylureas/Gilbenclamide:

1)      Hypoglycemia.

2)      GIT upset:Nausea,Vomiting,Diarrhoea.

3)      Allergic reaction:Rash.

4)      Blood disorders:Agranulocytosis,Aplastic anemia.

5)      Teratogenesis(So strictly contraindicated in pregnancy,During pregnancy,only insulin is indicated is DM pt)

6)      Cholestatic jaundice.

7)      Alcohol intolerance:Sulfonylurea causes alcohol intolerance.It inhibits metabolism of alcohol & produces disulfurum like action(i.e the pt can not tolerate)

Indications of OHA:

1)      Type II or NIDDM.

2)      Insulin resistance case.

3)      In obese person.

Contraindications of Sulphonylureas:

1)      Type-I.

2)      Pregnancy.

3)      Lactation.

4)      Hepatic & renal insufficiency.

Treatment of DM:

1)      D→Diet:Regular diet.-Fixed quantity.Fixed time.

2)      D→Discipline:Regular exercise,wt reduction.

3)      D→Drug:Type I DM→Insulin.Type II DM→OHA,if fail insulin.