Hyperglycemia

Hyperglycemia is the specialized term for high blood (glucose). High glucose happens when the body has too little insulin or when the body can't utilize insulin appropriately.

1. Topic :- Hyperglycemia Presented By Tuhin Samanta B.Pharm

2. Introduction The pancreas contains at least four different types of endocrine cells, including A (alpha, glucagon-producing), B (beta, insulin-producing), D (delta, somatostatin-producing), and F (PP, pancreatic polypeptide-producing). Of these, the B cells are predominant. Type-I diabetes occurs when the pancreas cannot produce insulin, a hormone essential for moving glucose from the blood into cells. Type-II diabetes is the most common disorder. In this, either the body does not produce enough insulin or the cells ignore the insulin . Gestational diabet es is a form of diabetes that appears only during pregnancy and occurs in women with no previous history of diabetes. Some diabetic symptoms are frequent urination, excessive thirst, extreme hunger, unusual weight loss, increased fatigue, irritability and blurred vision.

3. ORAL HYPOGLYCAEMIC AGENTS CLASSIFICATION Sulphonyl Ureas Example - Tolbutamide 2 . Biguanides Example - Metformin 3 . Substituted benzoic acid derivatives (meglitinides) Example - Meglitinide 4. Thiazolidinediones (glitazones) Example - Ciglitazone

4. SULPHONYL UREAS Mechanism of action : Sulphonyl ureas bind to an ATP- dependent k + channel on the cell membrane of pancreatic β cell. This inhibits a tonic, hyperpolarizing outflux of potassium, which cause the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca 2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and, therefore, increased secretion of (pro)insulin. Tolbutamide

5. Biguanides Mechanism of action : Biguanides are antihyperglycaemic, not hypoglycemic. The exact mode of action of biguanides is not fully elucidated. However, in hyperinsulinmia, biguanides can lower fating levels of insulin plasma. Their therapeutic used derive from their tendency to reduce gluconeogenesis in the liver, and as a result, reduce the level of glucose in the blood. Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and thereby reduce the level of glucose in the plasma. Metformin

6. Thiazolidinediones Mechanism of action :- These compounds act by binding to peroxisome poliferator-activated receptors, a group of receptor molecules inside the cell nucleus, specifically PPARγ. The normal ligands for these receptor are free fatty acids and eicosanoids. When activated, the receptor migrates to the DNA, activating transcription of a number of specific genes. By activating PPAR γ: (a) insulin resistance is decreased; (b) adipocyte differentiation is modified; © VEGF-induced angiogenesis is inhibited; (d) leptin levels decrease; (e) levels of certain interleukins; and (f) adiponectin levels rise. Ciglitazone

7. RECENT development DRUG N-acetyl- β- D'Glucopyranosyl Amine 6. spiro-thiohydantoin 18. isofagomine 45 DAB 56

8. REFERENCE Giugliano D, Marfella R, Coppola L, et al. (1997). "Vascular effects of acute hyperglycemia in humans are reversed by L- arginine . Evidence for reduced availability of nitric oxide during hyperglycemia". Circulation 95 (7): 1783–90. Cetin M, Yetgin S, Kara A, et al. (1994). "Hyperglycemia, ketoacidosis and other complications of L- asparaginase in children with acute lymphoblastic leukemia". J Med 25 (3–4): 219–29 Sriram D., Yogeeswari P., “ Medicinal Chemistry”, Pearson India Education Services Pvt Ltd., Second Edition, Chennai, 2015, Page :- 381-391

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