Oral Hypogylcaemic Drugs : Thiazolidinediones - i. Pioglitazone ii. Ciglitazone iii. Rosiglitazone (Rosicon, Reglit, Rosinorm) iv. α-Glucosidase inhibitors
Thiazolidinediones
Thiazolidinediones
are a new class of oral antidiabetic agents (commercially known as glitazones)
that enhance insulin sensitivity in peripheral tissues. It is relatively safe
in patients with impaired renal function because they are highly metabolized by
the liver and excreted in the faeces.
Mode of action: These drugs produce gene-mediated transcription
for the release of insulin by forming new proteins. They act on the nuclear
peroxisome proliferator activated receptor γ (ppar γ) and elicit the genes. It also inhibits the resistance to
insulin by activating glucose transporters (Glut and Glut 1) in the plasma
membrane.
Metabolism: It is metabolized and gives eight metabolic products. These
products result from oxidation at either carbon adjacent to the pyridine ring.
They are found as various conjugates in the urine and bile. Three metabolites
appear to contribute to the biological activity of pioglitazone (Fig 1.2).
Synthesis
Use: It is used in the treatment of NIDDM.
Synthesis
Metabolism: The primary metabolites consist of sulphate and glucuronic acid
conjugates of hydroxylation and N-demethylation
product. These metabolites contribute to the biological activity of
rosiglitazone (Fig 1.3).
Uses: It is used in the treatment of NIDDM.
Dose: The dosage for type 2 diabetes mellitus for adult is 4 mg daily,
which may be increased after 8–12 week of therapy, according to response and
the maximum dosage is 8 mg daily.
α-Glucosidase
enzyme is responsible for breaking down the complex polysaccharides and sucrose
to monosaccharides, which are then absorbed; α-glucosidase inhibitors decrease
the rate of breakdown. They are also called starch blockers.
Mode of action: These acts on the final enzymes in the digestion
of carbohydrates present in the brush border of small intestine and transport
of polysaccharides and sucrose.
Properties and uses: Acarbose is a white or yellowish amorphous
hygroscopic powder, very soluble in water, soluble in methanol, and practically
insoluble in methylene chloride. It is an alpha-glucosidase inhibitor and used
in the treatment of diabetes mellitus.
Assay: It is assayed by adopting liquid chromatography technique.
i. Acarbose
ii. Miglitol
Properties and uses: It is a crystalline substance, soluble in water.
It is a α-glucosidase inhibitor and used as an antidiabetic agent.
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