Antidiabetic agents

drugs used for diabetics mellitus

1. Unit-1: Drugs used in endocrine disorder Antidiabetic Agents Dr Muslim Abbas

2. Personal Information Name: Muslim Abbas Current Affiliation: Jinnah Medical and Dental College Current Position: Assistant Professor of Pharmacology I practice general dentistry at my own clinic in evening since 2013 Qualification: B.D.S (Jinnah Medical and Dental College)-2012 M.Phil. (University of Karachi) -2018

3. Diabetes Mellitus Diabetes mellitus is a chronic systemic disease characterized by metabolic and vascular abnormalities A major clinical manifestation of disordered metabolism is hyperglycemia. Clinical manifestations of vascular disorders may include hypertension, myocardial infarction, stroke, retinopathy, blindness, nephropathy, and peripheral vascular disease.

4. Types of Diabetes Mellitus There are two types of Diabetes Mellitus- type 1 & 2 Type 1 diabetes is a common chronic disorder of childhood which results from an autoimmune disorder that destroys pancreatic beta cells. Type 2 is caused by decrease release and resistance of insulin. Insulin resistance means that higher-than usual concentrations of insulin are required

5. Sign and Symptoms-Diabetes Mellitus Hyperglycemia Polydipsia- thirst Polyuria- urine Dehydration Polyphagia- appetite

6. EFFECTS OF INSULIN ON METABOLISM Insulin increases glucose transport into the liver, skeletal muscle, adipose tissue, the heart, and some smooth muscle organs, such as the uterus. Insulin promotes transport of glucose into fat cells, where it is broken down When insulin is lacking, fat is released into the bloodstream as free fatty acids. Blood concentrations of triglycerides, cholesterol, and phospholipids are also increased

7. EFFECTS OF INSULIN ON METABOLISM Insulin increases the total amount of body protein by increasing transport of amino acids into cells and synthesis of protein within the cells

8. Drugs Used For the Treatment of DM Insulin: Exogenous insulin used to replace endogenous insulin Insulin and its analogs lower blood glucose levels by increasing glucose uptake by body cells, especially skeletal muscle and fat cells Decreasing glucose production in the liver Insulin is the only effective treatment for type 1 The only clear-cut contraindication to the use of insulin is hypoglycemia

9. Insulin and its types Human insulin means that the synthetic product is identical to endogenous insulin Insulin cannot be given orally because it is a protein that is destroyed by proteolytic enzymes in the GI tract. It is given only parenterally, most often SC Short acting, Intermediate acting or long acting.

10. Insulin and its types Short-acting insulins have a rapid onset and a short duration of action. Intermediate- and long-acting insulins (except for insulin glargine) are modified by adding protamine (a large, insoluble protein), zinc, or both to slow absorption and prolong drug action. Several mixtures of an intermediate- and a short-acting insulin are available and commonly used

11. Short Acting Insulin Regular insulin Hypoglycemic drug of choice for diabetics experiencing acute or emergency situations, diabetic ketoacidosis, hyperosmolar nonketotic coma, severe infections or other illnesses, major surgery, and pregnancy Only insulin preparation that can be given IV

12. Intermediate-acting Insulins NPH Commonly used for long-term administration Modified by addition of protamine (a protein) and zinc Given only SC

13. Long-acting Insulin Ultralente Modified by addition of zinc and formation of large crystals, which are slowly absorbed Given SC

14. Insulin Analogs Lispro , aspart and Glargine Lispro and aspart have faster onset and a shorter duration of action than human regular insulin and given 15 minutes before meal Glargine is long acting All are given SC

15. Oral Hypoglycemic drugs Sulfonylureas- Glipizide, Glyburide and Glimepiride Alpha glucosidase inhibitors- Acarbose Biguanides - Metformin Glitazones - Pioglitazone and rosiglitazone Meglitinides - Nateglinide and repaglinide

16. Sulfonylureas Called as insulin secretogogues MOA : Stimulates release of insulin from beta cell of pancreas by blocking ATP sensitive K channels resulting in depolarization Ca influx and insulin exocytosis Reduce hepatic glucose production Increase peripheral insulin sensitivity

17. Sulfonylureas AE: Weight gain, hyper insulinemia , hypoglycemia Should be used with caution in renal impaired patients Glyburide can be used in pregnancy

18. Glinides Called insulin secrotogogues Stimulates insulin secretion by binding to distinct sites on beta cells closing ATP sensitive K channels Rapid onset and short duration of action is main difference from sulfonylureas Can not be used with sulfonylureas as hypoglycemia can occur Also called post prandial glucose regulators

19. Glinides AE: Hypoglycemia, weight gain Less chances as compared to sulfonylureas

20. Biguanides Called as insulin sensitizer Increases glucose uptake and use by target tissues there by decreasing insulin resistance Do not promote release of insulin so no problem of hyperinsulinemia and no hypoglycemia MOA : Decrease hepatic gluconeogenesis , Slows intestinal absorption of sugars and improves peripheral glucose uptake and utilization

21. Biguanides AE: Mostly gastrointestinal, interfere with vit B12 absorption Contraindicated in renal impairment as it can cause lactic acidosis Also used in the treatment of PCOD by lowering insulin resistance it promotes ovulation and possibly pregnancy

22. Thiazolidinediones (TZDs) Called as insulin sensitizers MOA: Agonist of Peroxisome proliferator activated receptor (PPAR). Activation of this receptor regulates transcription of several insulin responsive genes resulting in increase insulin sensitivity in adipose tissue, liver and skeletal muscles ADA recommends pioglitazone as second or third line drug for diabetes

23. Thiazolidinediones (TZDs) Rosiglitazone is less used due to cardiac problems Should be avoid in nursing mothers AE: Liver toxicity, Weight gain due to deposition of fat and fluid retention Osteopenia and fractures Also used in PCOD

24. Alpha glucosidase inhibitor Alpha glucosidase enzyme complex glucose into simpler form so it can absorbed Results in lower postprandial glucose level AE: flatulence, diarrhea and abdominal cramping CI: Inflammatory bowel disease,colonic ulceration, intestinal obstruction

25. Principle of therapy T he goals of treatment are M aintain blood glucose at normal or near-normal levels P romote normal metabolism of carbohydrate, fat, and protein P revent acute and long-term complications P revent hypoglycemic episodes.

26. Principles of therapy S trict control of blood sugar delays the onset and slows progression of complications of diabetes L imited intake of dietary protein P rompt treatment of urinary tract infections A voidance of nephrotoxic drugs when possible.