Tolinase
Tolinase - General Information
A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [PubChem]
Pharmacology of Tolinase
Tolinase is an oral blood glucose lowering drug of the sulfonylurea class. Tolinase appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.
Tolinase for patients
Patients should be informed of the potential risks and advantages of TOLINASE and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
Laboratory Tests
Blood and urine glucose should be monitored periodically. Measurement of glycosylated hemoglobin may be useful in some patients.
Tolinase Interactions
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents. When such drugs are administered to a patient receiving TOLINASE, the patient should be closely observed for hypoglycemia. When such drugs are withdrawn from a patient receiving TOLINASE, the patient should be observed closely for loss of control.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympa-thomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving TOLINASE, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving TOLINASE, the patient should be observed closely for hypoglycemia.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal preparations of miconazole is not known.
Carcinogenicity
In a bioassay for carcinogenicity, rats and mice of both sexes were treated with tolazamide for 103 weeks at low and high doses. No evidence of car-cinogenicity was found.
Pregnancy
Teratogenic Effects:
Pregnancy Category C. TOLINASE, administered to pregnant rats at ten times the human dose, decreased litter size but did not produce terato-genic effects in the offspring. In rats treated at a daily dose of 14 mg/kg no reproductive aberrations or drug related fetal anomalies were noted. At an elevated dose of 100 mg/kg per day there was a reduction in the number of pups born and an increased perinatal mortality. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, TOLINASE is not recommended for the treatment of the pregnant diabetic patient. Serious consideration should also be given to the possible hazards of the use of TOLINASE in women of child bearing age and in those who might become pregnant while using the drug.
Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.
Nonteratogenic Effects:
Prolonged severe hypoglycemia (four to ten days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If TOLINASE is used during pregnancy, it should be discontinued at least two weeks before the expected delivery date.
Nursing Mothers
Although it is not known whether tolazamide is excreted in human milk, some sulfonylurea drugs are known to be excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If the drug is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
Safety and effectiveness in children have not been established.
Geriatric Use
Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly. The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions.
Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function.
Tolinase Contraindications
TOLINASE Tablets are contraindicated in patients with:
1) known hypersensitivity or allergy to TOLINASE;
2) diabetic ketoacidosis, with or without coma. This condition should be treated with insulin;
3) Type I diabetes, as sole therapy.
Additional information about Tolinase
Tolinase Indication: For use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.
Mechanism Of Action: Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Tolazamide
Synonyms: Not Available
Drug Category: Hypoglycemic Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Tolazamide: Norglycin; Tolanase; Tolinase;
Absorption: Rapidly and well absorbed from the gastrointestinal tract.
Toxicity (Overdose): Overdosage of sulfonylureas can produce hypoglycemia. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.
Protein Binding: Not Available
Biotransformation: Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.
Half Life: The average biological half-life of the drug is 7 hours.
Dosage Forms of Tolinase: Tablet Oral
Chemical IUPAC Name: 1-(azepan-1-yl)-3-(4-methylphenyl)sulfonylurea
Chemical Formula: C14H21N3O3S
Tolazamide on Wikipedia: https://en.wikipedia.org/wiki/Tolazamide
Organisms Affected: Humans and other mammals
