oral hypoglycemic drugs.pptx this ppt is related to oral hypoglycemic drugs their classification

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1. Oral hypoglycemic drugs

2. Oral hypoglycemic drugs are medications designed to help manage high blood sugar levels in individuals with diabetes when lifestyle changes such as diet and exercise alone are insufficient. These drugs are taken by mouth and work through various mechanisms to improve insulin sensitivity, increase insulin production, or reduce glucose absorption in the intestines or its production by the liver . They are primarily used in the treatment of type 2 diabetes, either alone or in combination with other medications or insulin therapy, and are prescribed based on factors such as the individual's medical history, glucose levels, and other health considerations. Regular monitoring of blood sugar levels and ongoing medical supervision are essential when using oral hypoglycemic drugs to optimize their effectiveness and minimize the risk of side effects.

3. classification

4. Insulin secretagogues Are drugs which increase the amount of insulin secreted by the pancreas Include: Sulfonylureas Meglitinides DPP-4 inhibitors

5. Stimulate insulin release from functioning β cells by blocking of ATP-sensitive K channels which causes depolarization and opening of voltage- dependent calcium channels, which causes an increase in intracellular calcium in the beta cells, which stimulates insulin release. Mechanism of action of sulfonylureas:

6. Mechanism of Insulin Release

7. Pharmacokinetics of sulfonylureas: Orally, well absorbed. Reach peak concentration after 2-4 hr. All are highly bound to plasma proteins. Duration of action is variable. Second generation has longer duration than first generation . Metabolized in liver excreted in urine (elderly and renal disease) Cross placenta, stimulate fetal β -cells to release insulin → fetal hypoglycemia at birth.

8. Tolbutamid short-acting Acetohexamide intermediate-acting Tolazamide intermediate-acting Chlorpropamide long- acting Absorption Well Well Slow Well Metabolism Yes Yes Yes Yes Metabolites Inactive Active Active Inactive Half-life 4 - 5 hrs 6 – 8 hrs 7 hrs 24 – 40 hrs Duration of action Short (6 – 8 hrs) Intermediate (12 – 20 hrs) Intermediate (12 – 18 hrs) Long ( 20 – 60 hrs) Excretion Urine Urine Urine Urine First generation sulfonylureas

9. Tolbutamide : safe for old diabetic patients or pts with renal impairment. Second generation sulfonylureas Glipizide - glyburide ( Glibenclamide ) More potent than first generation Have longer duration of action. Less frequency of administration Have fewer adverse effects Have fewer drug interactions First generation sulfonylureas

10. Glipizide Glibenclamide (Glyburide) Glimepiride Absorption Well Well Well Metabolism Yes Yes Yes Metabolites Inactive Inactive Inactive Half-life 2 – 4 hrs Less than 3 hrs 5 - 9 hrs Duration of 10 – 16 hrs 12 – 24 hrs 12 – 24 hrs action short long long Doses Divided doses 30 min before meals Single dose Single dose Excretion Urine Urine Urine Second generation sulfonylureas

11. Unwanted Effects: 1. Hyperinsulinemia & Hypoglycemia: Less in tolbutamide . More in old age, hepatic or renal diseases. 2. Weight gain due to increase in appetite 3. GIT upset . CONTRAINDICATIONS: Hepatic impairment or renal insufficiency Pregnancy & lactation Type I diabetes

12. Repaglinide are rapidly acting insulin secretagogues Mechanism of Action: Stimulate insulin release from functioning β cells via blocking ATP-sensitive K-channels resulting in calcium influx and insulin exocytosis . Meglitinides

13. Pharmacokinetics of meglitinides Orally, well absorbed. Very fast onset of action, peak 1 h. short duration of action (4 h). Metabolized in liver and excreted in bile. Taken just before each meal (3 times/day).

14. Type II diabetes: monotherapy or combined with metformin ( better than monotherapy ). Specific use in patients allergic to sulfur or sulfonylureas . Adverse effects of Meglitinides Hypoglycemia. Weight gain. Uses of Meglitinides

15. Mechanism of DDP-4 inhibitors Inhibits DPP-4 enzyme, which metabolizes the naturally occurring incretin hormones thus increase incretin secretion ( gastrointestinal hormones secreted in response to food ). Incretin hormones decreases blood glucose level by : Increasing insulin secretion Decreasing glucagon secretion.

16. Mechanism of action of DPP-4 inhibitors

17. Clinical uses Type 2 diabetes mellitus as a monotherapy or in combination with other oral antidiabetic drugs when diet and exercise are not enough. Orally Given once daily half life 8-14 h Dose is reduced in pts with renal impairment Adverse effects Nausea, abdominal pain, diarrhea.

18. Are drugs which increase the sensitivity of target organs to insulin. Include Biguanides ( AMPk activator) AMP K stands for AMP-activated protein kinase . It's a crucial enzyme in cells that functions as a metabolic master switch. AMP K is activated in response to low energy levels, signaled by high levels of AMP compared to ATP. When activated, AMPK promotes processes that generate energy (such as glucose uptake and fatty acid oxidation) while inhibiting energy-consuming pathways (such as protein and lipid synthesis). Insulin sensitizers

19. Does not require functioning β cells. Does not stimulate insulin release. Increases peripheral glucose utilization ( tissue glycolysis ). Inhibits hepatic gluconeogenesis . Impairs glucose absorption from GIT. Reduces plasma glucagon level.  LDL &VLDL.  HDL Mechanism of action of metformin

20. GIT disturbances: nausea, vomiting, diarrhea Long term use interferes with vitamin B 12 absorption. Lactic acidosis: in patients with renal, liver, pulmonary or cardiac diseases. Metallic taste in the mouth . Contraindications of metformin Pregnancy. Renal disease. Liver disease. Alcoholism. Conditions predisposing to hypoxia as cardiopulmonary dysfunction. Adverse effects of metformin

21. Thiazolidinediones ( glitazones ) Mechanism of action Activate PPAR- ( peroxisome proliferator -activated receptor - ). PPAR-gamma is a protein in our cells that helps control how our bodies use and store fats and sugars. When activated, it improves insulin sensitivity, making cells better at using glucose for energy. Decrease insulin resistance. Increase sensitivity of target tissues to insulin. Increase glucose uptake and utilization in muscle and adipose tissue.

22. Pharmacokinetics of pioglitazone Orally (once daily dose). Highly bound to plasma albumins (99%) Slow onset of activity Half life 3-4 h Metabolized in liver . Excreted in urine 64% & bile Uses of pioglitazone Type II diabetes with insulin resistance. Used either alone or combined with sulfonylurea, biguanides . No risk of hypoglycemia when used alone.

23. Hepatotoxicity (liver function tests for 1st year of therapy). Fluid retention (Edema). Precipitate congestive heart failure Mild weight gain . Contraindications of pioglitazone Congestive heart failure. Pregnancy. Lactating women Significant liver disease. Adverse effects of pioglitazone

24. Acorbose Are reversible inhibitors of intestinal - glucosidases in intestinal brush border that are responsible for carbohydrate digestion. decrease carbohydrate digestion and glucose absorption in small intestine . Decrease postprandial hyperglycemia. Taken just before meals. No hypoglycemia if used alone. -Glucosidase inhibitors

25. effective alone in the earliest stages of impaired glucose tolerance . Combined with sulfonylurea in treatment of Type 2 diabetes to improve blood glucose control . Kinetics of - glucosidase inhibitors Given orally, poorly absorbed. Metabolized by intestinal bacteria. Excreted in stool and urine. Adverse effects GIT: Flatulence, diarrhea, abdominal pain Uses of - glucosidase inhibitors

26. An amylin analogue is a synthetic version of the hormone amylin , assisting in blood sugar regulation by slowing glucose absorption and suppressing glucagon secretion, commonly used in diabetes management to improve glycemic  control. Dopamine D2 receptor agonists , such as bromocriptine , are used in diabetes management to improve glycemic control by modulating central nervous system pathways involved in glucose metabolism, insulin sensitivity, and circadian rhythm regulation. They work by enhancing dopamine signaling, which can lead to decreased hepatic glucose production, improved insulin sensitivity, and reduced postprandial hyperglycemia.

27. SGLT-2 inhibitors are a class of medications used in the treatment of type 2 diabetes. They work by blocking the sodium-glucose co-transporter 2 (SGLT-2) in the kidneys, which is responsible for reabsorbing glucose back into the bloodstream. By inhibiting this transporter, SGLT-2 inhibitors promote the excretion of glucose in the urine, leading to lower blood sugar levels. Additionally, they may also have other beneficial effects such as reducing blood pressure and body weight.

28. SUMMARY Class Mechanism Site of action Main advantages Main side effects Sulfonylureas Tolbutamide Glipizide Glibenclamide (glyburide) Stimulating insulin production by inhibiting the KATP channel Pancreatic beta cells Effective Inexpensive Hypoglycemia Weight gain Meglitinides repaglinide Stimulates insulin secretion Pancreatic beta cells Sulfa free Hypoglycemia Weight gain Biguanides Metformin Decreases insulin resistance Liver mild weight loss No hypoglycemia GIT symptoms, Lactic acidosis Metallic taste Thiazolidinediones pioglitazone Decreases insulin resistance Fat, muscle Hepatoxicity Edema -Glucosidase inhibitors Acarbose Inhibits α -glucosidase GI tract Low risk GI symptoms, flatulence DPP-4 inhibitor Sitagliptin Increase secretin GI tract