Anti diabetic drug##treatment of diabetis##metformin hydrochloride##sitagliptin##glikazide###use,side effect,dose deatails......Oral hypoglycemic drug

 Metformin hydrochloride

Indications 

1..type-2 DM 

2.. polycystic ovarian syndrome

 

Dosage & administrations

The usual starting dose is 500 mg twice daily or 850 mg once a day, given with meals. Dosage increase should be made in increments of 500 mg weekly or 850 mg every 2 weeks up to a total of 2000 mg per day, given in divided doses. 

Patients can be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For these patients requiring additional glycaemic control, metformin may be given to a maximum daily dose of 2550 mg per day. 

Doses above 2000 mg may be better tolerated when given three times a day with meals. The usual starting dose of Metformin HCl extended - release tablet is 500 mg once daily with the evening meal. Dosage increase may be made up to a max. of 2000 mg once daily with the evening meal.

Polycystic ovary syndrome Initial: 500 mg/day in the morning for 1 wk, then 500 mg twice daily for 1 wk, then 1.5-1.7 g/day in 2-3 divided doses.

Contraindications

Acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis). Renal failure, severe renal or hepatic impairment, acute conditions which may affect renal function e.g. dehydration, severe infection or shock. Cardiac failure, CHF, IDDM, severe impairment of thyroid function; acute or chronic alcoholism. Acute or chronic diseases which may cause tissue hypoxia e.g. cardiac or respiratory failure, recent MI or shock. Pregnancy, lactation. Adult: PO Type 2 DMInitial: 500 mg 2-3 times/day, may increase slowly. Max:2.25 g/day. Polycystic ovary syndrome Initial: 500 mg/day in the morning for 1 wk, then 500 mg twice daily for 1 wk, then 1.5-1.7 g

Side effects

Anorexia, nausea, vomiting, diarrhoea, wt loss, flatulence, occasional metallic taste; weakness; hypoglycaemia; rash, malabsorption of vit B12. Chest discomfort, flushing, palpitation, chills, headache, lightheadedness, indigestion, abdominal discomfort. Potentially Fatal: Lactic acidosis in presence of renal failure and alcoholism. Patients may experience a metallic taste and there may be weight loss, which in some diabetics could be an advantage.

Precautions & warnings

Caution when used in patients with CHF especially in those with unstable or acute heart failure. Risk of lactic acid accumulation increases with the degree of renal impairment. May need to discontinue treatment in patients with stress-related states e.g. fever, trauma, infection or surgery. Metformin should be temporarily discontinued for 48 hr in patients undergoing radiologic studies involving intravascular admin of iodinated contrast materials. Elderly. Monitor renal function regularly. Because of possibility of hypoglycemia in combination therapy with a sulphonylurea or insulin, diabetic control should be monitored by blood sugar readings.

Pregnancy category

Pregnancy Category - B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

Therapeutic Class

       Biguanides

Mode of Action

Metformin is a biguanide  antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It decreases hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis; delays intestinal absorption of glucose; and enhances insulin sensitivity by increasing peripheral glucose uptake and utilisation.

Interaction

Additive effect  sulfonylureas. Thiazide diuretics, corticosteroids, phenothiazines, OC, sympathomimetics, niacin, Ca channel blockers and isoniazid may exacerbate loss of glycaemic control. ACE inhibitors may reduce fasting blood glucose concentrations. May increase serum level w/ cimetidine.

Potentially Fatal: Concurrent use w/ iodinated contrast agents may increase the risk of metformin-induced lactic acidosis.

            Sitagliptin::

Indications

Type 2 diabetes mellitus 

Dosage & administrations

The recommended dose of Sitagliptin is 100 mg once daily. Sitagliptin can be taken with or without food.     

For patients with mild renal insufficiency ( creatinine clearance [CrCl]>50ml/min), no dosage adjustment is required.     

Renal impairment:

CrCl (ml/min)

30-<50 50 mg daily.

<30 25 mg daily; may be given without regard to the timing of the haemodialysis. 

Pediatric Use:  Safety and effectiveness of Sitagliptin in pediatric patients under 18 years of age have not been established.

Contraindications

Hypersensitivity reactions such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome can occur. Type 1 diabetes. Diabetic ketoacidosis. 

Side effects

Headache, diarrhoea, upper respiratory tract infection, nasopharyngitis. Angioedema, exfoliative dermatitis. Hypoglycemia occurs in patients treated with the combination of Sitagliptin and sulfonylurea, with or without Metformin. Potentially Fatal: Anaphylaxis and/or severe dermatologic reactions such as Stevens-Johnson syndrome.

Precautions & warnings

Discontinue treatment if there are signs of hypersensitivity. Caution when used with sulphonylureas and/or other antidiabetic medications; monitor blood glucose regularly. Renal impairment; dose adjustment may be needed. Children <18 yr. Pregnancy, lactation.

Pregnancy category

Pregnancy Category - B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

Therapeutic Class

Dipeptidyl Peptidase-4 (DPP-4) inhibitor

Mode of Action

Sitagliptin inhibits dipeptidyl peptidase IV (DPP-IV), resulting in prolonged active incretin levels. Incretin hormones increases insulin synthesis and release from pancreatic ?-cells and reduces glucagon secretion from pancreatic ?-cells. Reduced glucagon secretion leads to decreased hepatic glucose production.

Interaction

Increased risk of hypoglycaemia when used in combination w/ sulfonylureas or insulin.

         GliCLAZIDE::

Indications::

       Type 2 DM 

Dosage & administrations

Adult: PO Initial: 40-80 mg/day, increase slowly if needed. Doses >160 mg/day may be given in 2 divided doses.

Contraindications

Type 1 DM, diabetes complicated with ketoacidosis; hypersensitivity; severe renal and hepatic impairment. Pregnancy and lactation.

Side effects

GI disturbances, skin reaction, leucopenia, thrombocytopenia, agranulocytosis, haemolytic anaemia, cholestatic jaundice, vomiting, diarrhoea, gastritis, increased transaminases.

Precautions & warnings

Monitor blood glucose concentration. May require insulin during metabolic stress. Care when transferring from combination therapy. Increased risk of severe hypoglycaemia in elderly, debilitated patients, patients with hepatic or renal impairment. Risk of hypogylcaemia when caloric intake is deficient, after strenuous exercise, when taken with ethanol or when >1 antidiabetic drug is used.

Pregnancy category

Pregnancy Category - C

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks 

Therapeutic Class

       Sulfonylureas

Mode of Action

Gliclazide stimulates insulin secretion from pancreatic  B cells, reduces insulin uptake and glucose output by the liver, and increases insulin sensitivity at peripheral target sites. It decreases microthrombosis by partial inhibition of platelet aggregation and adhesion, and by restoring fibrinolysis w/ an increase in tissue plasminogen activator (t-PA) activity.

Interaction

May increase hypoglycaemic effect w/ phenylbutazone. Potentiation of blood glucose lowering effect w/ other antidiabetics (e.g. acarbose, insulins, metformin), ?-blockers, ACE inhibitors, H2-receptor antagonists, MAOIs, sulfonamides, clarithromycin and NSAIDs. Chlorpromazine, glucocorticoids, ritodrine, salbutamol and terbutaline may cause increases in blood glucose levels. May diminish hypoglycaemic effect w/ danazol. May increase anticoagulant effect of warfarin.

Potentially Fatal: Increased hypoglycaemic effect w/ miconazole