RASTINON 500MG TABLET

Indications

• Type 2 diabetes mellitus

Dosage

Children: null

Adults: 0.5–1.5 g daily in divided doses, taken with or immediately after meals.

Mechanism of action

Tolbutamide functions by binding to sulfonylurea receptors on pancreatic beta cells, inhibiting ATP-sensitive potassium channels. This inhibition leads to depolarization of the cell membrane, calcium influx, and subsequent release of insulin. The drug enhances the beta cells' responsiveness to glucose, facilitating insulin release which is crucial for glucose metabolism.

Pharmacodynamics

As a sulfonylurea, Tolbutamide is known to enhance insulin secretion from the pancreatic islets, thus lowering blood glucose levels in individuals with type 2 diabetes. It is considered to be twice as potent as glipizide, another sulfonylurea. The drug's effectiveness depends on the patient's ability to produce insulin, making it unsuitable for type 1 diabetes or in cases where pancreatic function is severely impaired.

Pharmacokinetics

Tolbutamide is absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1-2 hours post-administration. It is metabolized in the liver, primarily through cytochrome P450 enzymes, and has a half-life of about 4-5 hours. The metabolites are excreted in the urine. The onset of action is usually within 30 minutes to 1 hour, and its effects can last for up to 24 hours, necessitating multiple doses throughout the day.

Contra-indications

• Acute porphyrias

Adverse effects

• Hypoglycaemia
• Gastrointestinal discomfort
• Dizziness
• Headache
• Confusion
• Tremor
• Visual disturbances
• Hyponatraemia
• Malaise
• Aplastic anaemia
• Skin reactions (e.g., erythema multiforme, exfoliative dermatitis)
• Photosensitivity
• Weight gain

Interactions

• Mifepristone (increases exposure)
• Nitisinone (increases exposure)

Precautions

• Caution in renal impairment
• Caution in hepatic impairment
• Monitor for signs of hypoglycaemia
• Use with caution in patients with a history of cardiovascular disease

Pregnancy

The use of sulfonylureas in pregnancy should generally be avoided because of the risk of neonatal hypoglycaemia.

Breast-feeding

Avoid-theoretical possibility of hypoglycaemia in the infant.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets (0.5 g, 1 g)
• Oral suspension
• Oral solution

Mechanism of action

Sulfonylureas lower blood glucose in patients with NIDDM by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by an unknown process that involves a sulfonylurea receptor (receptor 1) on the beta cell. Sulfonylureas inhibit the ATP-potassium channels on the beta cell membrane and potassium efflux, which results in depolarization and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis, an effect similar to that of glucose. SULFONYLUREAS STIMULATE ISLET TISSUE TO SECRETE INSULIN. ... SULFONYLUREAS CAUSE DEGRANULATION OF BETA CELLS, A PHENOMENON ASSOC WITH INCR RATE OF SECRETION OF INSULIN. /SULFONYLUREAS/ ALTHOUGH MOLECULAR MECHANISM...NOT UNDERSTOOD, SEVERAL PERTINENT OBSERVATIONS HAVE BEEN MADE. ...TOLBUTAMIDE IS RESTRICTED IN ITS ACTION TO EXTRACELLULAR SPACE & DOES NOT NEED TO ENTER BETA CELL. INVOKED RELEASE OF INSULIN IS IMMEDIATE & INTIMATELY RELATED TO ACTION OF GLUCOSE...MAY SENSITIZE CELL TO NORMAL SECRETAGOGUE. Sulfonylureas are now...thought to act by a number of different mechanisms. 1. ...produce a depolarization of the pancreatic islet beta cell membrane potassium ion permeability. This results in a release of preformed insulin into the circulation and occurs mostly in non-insulin dependent diabetics. 2. ...reduce basal glucose output from the liver... 3. increase insulin receptor binding... 4. ...increasing intracellular levels of AMP... 5. increase insulin secretion by suppressing the release of glucagon and somatostatin from alpha and delta pancreatic cells. /Sulfonylureas/

Pharmacodynamics

Tolbutamide, a first-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Tolbutamide is twice as potent as the related second-generation agent glipizide. Tolbutamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must be able to produce insulin for this drug to work.