Uses

It is used in the treatment of type II diabetes. As of 2007^[update], it is one of only two oral anti-diabetics in the World Health Organization Model List of Essential Medicines (the other being metformin).^[1] As of 2003, in the United States, it was the most popular sulfonyurea.^[2]

Additionally, recent research shows that glyburide improves outcome in animal stroke models by preventing brain swelling. A retrospective study showed that in type 2 diabetic patients already taking glyburide there was improved NIH stroke scale scores on discharge compared to diabetic patients not taking glyburide.

Glibenclamide
Systematic (IUPAC) name
5-chloro-N-(4-[N-(cyclohexylcarbamoyl)sulfamoyl]phenethyl)-2-methoxybenzamide
Identifiers
CAS number	10238-21-8
ATC code	A10BB01
PubChem	3488
DrugBank	APRD00233
Chemical data
Formula	C23H28ClN3O5S
Mol. mass	494.004 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	Extensive
Metabolism	Hepatic hydroxylation (CYP2C9-mediated)
Half life	10 hours
Excretion	Renal and biliary
Therapeutic considerations
Licence data	US FDA:link
Pregnancy cat.	C(AU) B(US)
Legal status	POM(UK) ℞-only(US)
Routes	Oral

Glibenclamide (INN), also known as glyburide (USAN), is an anti-diabetic drug in a class of medications known as sulfonylureas,

It is sold in doses of 1.25 mg, 2.5 mg and 5 mg, under the trade names Diabeta, Glynase and Micronase in the United States and Daonil, Semi-Daonil and Euglucon in the United Kingdom.

It is also sold in combination with metformin under the trade name Glucovance.

Glipizide

Glipizide
Systematic (IUPAC) name
N-(4-[N-(cyclohexylcarbamoyl)sulfamoyl]phenethyl)-5-methylpyrazine-2-carboxamide
Identifiers
CAS number	29094-61-9
ATC code	A10BB07
PubChem	3478
DrugBank	APRD00436
Chemical data
Formula	C21H27N5O4S
Mol. mass	445.536 g/mol
Pharmacokinetic data
Bioavailability	100% (regular formulation) 90% (extended release)
Protein binding	98 to 99%
Metabolism	Hepatic hydroxylation
Half life	2 to 5 hours
Excretion	Renal and fecal
Therapeutic considerations
Pregnancy cat.	C (Au, U.S.)
Legal status	POM (UK), ℞-only (U.S.)
Routes	Oral

Glipizide is an oral medium-to-long acting anti-diabetic drug from the sulfonylurea class. It is classified as a second generation sulfonylurea, which means that it undergoes enterohepatic circulation. The structure on the R2 group is a much larger cyclo or aromatic group compared to the 1st generation sulfonylureas. This leads to a once a day dosing that is much less than the first generation, about 100 fold.

Mechanism of action is produced by blocking potassium channels in the beta cells of the islets of langerhans. By partially blocking the potassium channels, it will increase the time the cell spends in the calcium release stage of cell signaling leading to an increase in calcium. The increase in calcium will initiate more insulin release from each beta cell.

Originally available in 1984, it is marketed by Pfizer under the brand name Glucotrol in the USA, where Pfizer sells Glucotrol in doses of 5 and 10 milligrams and Glucotrol XL (an extended release form of glipizide) in doses of 2.5, 5, and 10 milligrams. Other companies sell generic forms of glipizide, most commonly extended release tablets of 5 and 10 milligrams.

Tolazamide

Tolazamide is an oral blood glucose lowering drug used for people with Type 2 diabetes. It is part of the sulfonamide family (ATC A10BB).

Mechanism of Action

Mechanism of Action

Acetohexamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must produce insulin for this medication to work. For this reason, acetohexamide is not used to treat diabetes mellitus type 1.

Acetohexamide

Acetohexamide (Dymelor) is a first-generation sulfonylurea medication used to treat diabetes mellitus type 2, particularly in people whose diabetes cannot be controlled by diet alone.

Tolbutamide

Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug sold under the brand name Orinase. This drug may be used in the management of type II diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas. Since the pancreas must synthesize insulin in order for this drug to work, it is not effective in the management of type I diabetes. It is not routinely used due to a higher incidence of adverse effects compared to newer second generation sulfonylureas, such as glyburide.

Plasma proteins

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.

Sulfonylureas

Sulfonylurea

Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the K_ATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects. All may cause weight gain.

Insulin

insulin

Insulin is usually given subcutaneously, either by injections or by an insulin pump. Research is underway of other routes of administration. In acute care settings, insulin may also be given intravenously. There are several types of insulin, characterized by the rate which they are metabolized by the body.

Diabetes mellitus type 2

Diabetes mellitus type 2 or type 2 diabetes (formerly called non-insulin-dependent diabetes mellitus (NIDDM), or adult-onset diabetes) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. ^[1] While it is often initially managed by increasing exercise and dietary modification, medications are typically needed as the disease progresses. There are an estimated 23.6 million people in the U.S. (7.8% of the population) with diabetes with 17.9 million being diagnosed^[2], 90% of whom are type 2.^[3] With prevalence rates doubling between 1990 and 2005, CDC has characterized the increase as an epidemic.^[4] Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates.

Diabetes mellitus type1

Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected or inhaled.

Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract.

Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.

Anti-diabetic drug

Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.