Insulin

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Insulin

  1. 1. INSULIN AND ORAL HYPOGLYCEMIC AGENTS
  2. 2. DIABETES <ul><li>Diabetes Insipidus (DI) </li></ul><ul><li>Diabetes Mellitus (DM) </li></ul><ul><li>Metabolic disorder – </li></ul><ul><li>Hyperglycemia </li></ul><ul><li>Glycosuria </li></ul><ul><li>Hyperlipemia </li></ul><ul><li>Negative nitrogen balance </li></ul><ul><li>Ketonaemia </li></ul>
  3. 3. <ul><li>Pathological changes </li></ul><ul><li>Thickening of capillary basement membrane </li></ul><ul><li>Increase in vessel wall matrix </li></ul><ul><li>Cellular proliferation </li></ul><ul><li>Complications </li></ul><ul><li>Early atherosclerosis </li></ul><ul><li>Retinopathy </li></ul><ul><li>Neuropathy </li></ul>
  4. 4. Types of DM <ul><li>Type I insulin dependent diabetes mellitus( IDDM ), </li></ul><ul><li>juvenile onset diabetes mellitus. </li></ul><ul><li>Type IA(autoimmune) </li></ul><ul><li>Type IB(idiopathic) </li></ul><ul><li>Type II noninsulin dependent diabetes mellitus( NIDDM ), </li></ul><ul><li>maturity onset diabetes mellitus </li></ul>
  5. 5. Insulin <ul><li>Two chain polypeptide- 51 amino acid </li></ul><ul><li>A- chain- 21 amino acids </li></ul><ul><li>B-chain- 30 amino acids </li></ul>
  6. 6. Regulation of Insulin Secretion <ul><li>Chemical </li></ul><ul><li>Hormonal </li></ul><ul><li>Neural </li></ul><ul><li>ACTION OF INSULIN </li></ul><ul><li>Carbohydrate </li></ul><ul><li>Protein </li></ul><ul><li>Fat metabolism </li></ul>
  7. 7. Mechanism of action Tyrosin kinase receptor <ul><li>Fate of insulin </li></ul><ul><li>Orally- degraded in g.i.t </li></ul><ul><li>i.v- metabolised in liver </li></ul>Types of insulin preprations Conventional Highly purified
  8. 8. According to purification method <ul><li>Single peak insulin </li></ul><ul><li>Monocomponent insulins </li></ul><ul><li>HUMAN INSULINS </li></ul><ul><li>rDNA technology in E.coli </li></ul><ul><li>Enzymatic modification of porcine insulin </li></ul>
  9. 9. Indication of Human insulin <ul><li>Insulin resistance </li></ul><ul><li>Allergy to conventional preprations </li></ul><ul><li>Injection site lipodystrophy </li></ul><ul><li>Short term use of insulin in diabetics </li></ul><ul><li>During pregnancy </li></ul>
  10. 10. Reactions of insulin <ul><li>Hypoglycaemia </li></ul><ul><li>Local reactions </li></ul><ul><li>Allergy </li></ul><ul><li>Edema </li></ul><ul><li>Drug interactions </li></ul><ul><li>USES OF INSULIN </li></ul><ul><li>DM </li></ul><ul><li>Diabetic ketoacidosis(Diabetic Coma) </li></ul>
  11. 11. Insulin lack Hyperglycaemia Ketosis Glycosuria Acidosis ketonuria Impairment of glucose entry into brain Loss of electrolytes Intracellular K + depletion Loss of fixed cations in urine Loss of water Hyperosmolarity of blood Intracellular dehydration Osmotic diuresis Vomiting Hyperventilation Dehydration Hypotension, Shock, tachycardia Impairment of consciousness
  12. 12. Hyperosmolar (Non ketotic hyperglycaemia) <ul><li>Insulin Resistance </li></ul><ul><li>Acute </li></ul><ul><li>Chronic </li></ul>Infection,trauma,surgery,emotional stress ketoacidosis Conventional preprations
  13. 13. ORAL HYPOGLYCAEMIC DRUGS <ul><li>Drugs lower the blood glucose level </li></ul><ul><li>Effective orally </li></ul>
  14. 14. <ul><li>Sulfonyl Ureas </li></ul><ul><li>Biguanides </li></ul><ul><li>Meglitinide Analogues </li></ul>First generation Tolbutamide chlorpropamide Second generation Glibenclamide(glyburide) Glipizide Gliclazide Glimepiride Phenformin Metformin Repaglinide Nateglinide
  15. 15. Thiazolidinediones Rosiglitazone Pioglitazone α -Glucosidase Inhibitors Acarbose Miglitol
  16. 16. <ul><li>SULFONYLUREAS </li></ul><ul><li>These agents promote the release of insulin from β-cells (secretogogues); </li></ul><ul><li>Mechanism: </li></ul><ul><ul><li>These agents require functioning β-cells, they stimulate release by blocking ATP-sensitive K + channels resulting in depolarization with Ca +2 influx which promotes insulin secretion. </li></ul></ul><ul><ul><li>They also reduce glucagon secretion and increase the binding of insulin to target tissues. </li></ul></ul><ul><ul><li>They may also increase the number of insulin receptors </li></ul></ul>
  17. 17. BIGUANIDES (Insulin Sensitizers) <ul><li>work by improving insulin target cell response; the biguanides & thiazolidinediones. </li></ul><ul><li>Biguanides: </li></ul><ul><li>it increases glucose uptake and utilization by target tissues </li></ul><ul><li>Mechanism: </li></ul><ul><li>Metformin reduces plasma glucose levels by inhibiting hepatic gluconeogenesis. </li></ul><ul><li>It also slows the intestinal absorption of sugars. It also reduces hyperlipidemia (↓LDL & VLDL cholesterol and ↑ HDL). </li></ul><ul><li>It is the only oral hypoglycemic shown to reduce cardiovascular mortality. </li></ul>
  18. 18. <ul><li>THIAZOLIDINEDIONES (Glitazones) </li></ul><ul><li>These agents are insulin sensitizers, they do not promote insulin secretion from β-cells but insulin is necessary for them to be effective </li></ul><ul><li>Mechanism of Action : </li></ul><ul><li>These agents act through the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ). </li></ul><ul><li>Agents binding to PPAR-γ result in increased insulin sensitivity is adipocytes, hepatocytes and skeletal muscle. </li></ul><ul><li>Accumulation of subcutaneous fat occurs with these agents. </li></ul>
  19. 21. MEGLITINIDE ANALOGUES <ul><li>Mechanism: </li></ul><ul><li>These agents bind to ATP sensitive K+channels like sulfonylureas acting in a similar fashion to promote insulin secretion however their onset and duration of action are much shorter. </li></ul><ul><li>They are particularly effective at mimicking the prandial & post-prandial release of insulin . </li></ul>
  20. 22. α-Glucosidase Inhibitors oligosaccharides monosaccharides Acarbose also inhibits pancreatic amylase. hydrolyses
  21. 23. Glucagon Single chain polypeptide- 29 amino acid MW- 3500 Regulation ↑ glucose level FFA and ketone bodies Action- opposite to insulin (hormone of fuel mobilization) Secretion ↑ during fasting
  22. 24. MOA Activates adenylyl cyclase ↓ ↑ cAMP USES - hypoglycaemia due to insulin or oral hypoglycaemics -cardiogenic shock -diagnosis of pheochromocytoma Liver Fat cells heart

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