Oral hypoglycemic agents

oral hypoglycemic drugs

1. ORAL HYPOGLYCEMIC AGENTS ZAINUL KHAN ASSISTANT PROFESSOR AIPR, LUCKNOW ZAINUL KHAN 1

2. ORAL HYPOGLYCEMIC AGENTS Agents that are given orally to reduce the blood glucose levels in diabetic patients. • Diabetes mellitus type 1 is a disease caused by lack of insulin. Insulin must be used in type 1,which must be injected. • Diabetes mellitus type 2 is a disease of insulin resistance by cells due to several factors. HYPOGLYCEMIC AGENTS WORKS BY :  Increasing the amount of insulin secreted by the pancreas.  Increasing the sensitivity of target organs to insulin  Decreasing the rate at which glucose is absorbed from the gastrointestinal tract . SELECTION OF ANTI DIABETIC DRUGS DEPENDS UP ON: • Nature of the diabetes • Age and situation of the person • Other factors ZAINUL KHAN 2

3. SYMPTOMS OF HYPERGLYCEMIA • Fatigue • Blurred vision • Weight loss • Fast heart beat • Poor wound heeling • Dry mouth • Dry or itchy skin • Sweating • Irritable • headache ZAINUL KHAN 3

4. CLASSIFICATION ZAINUL KHAN 4

5. ORAL HYPOGLYCEMIC DRUGS ZAINUL KHAN 5

6. SULFONYLUREAS: The drugs of this class is divided into two generations:  First Generation:  Second Generation: Tolbutamide Glyburide Chlorpropamide Glipizide Tolazamide Glimepiride MECHANISM OF ACTION : Stimulation of insulin from pancreas. Reduce hepatic glucose production. Increase peripheral insulin sensitivity. ADVERSE EFFECTS :  Hypoglycemia Weight gain  Skin reaction ZAINUL KHAN 6

7. TOLBUTAMIDE Tolbutamide is a first-generation potassium channel blocker,sulfonylurea oral hypoglycemic medication that acts by increasing the pancreatic insulin secretion . Mechanism of action: ZAINUL KHAN 7

8. INDICATION DOSE  INITIAL DOSE : 1 to 2 g orally once a day or in divided doses.  MAINTENANCE DOSE : 0.25 to 3 g orally once a day or in divided doses.  MAXIMUM DOSE: 3 g per day. ZAINUL KHAN 8

9. PHARMACOKINETICS  ABSORPTION : Get absorbed in 30 to 60 minutes but can be altered by increased pH.  ONSET OF ACTION: It is within one hour & lasts for 6-12 Hrs.  DURATION OF ACTION: Short  HALF LIFE: 7 Hrs.  POTENCY: Twice potent as the related second-generation agent Glipizide SIDE EFFECTS  Allergic reactions like itching; red, swollen, blistered, or peeling skin with or without fever , wheezing, tightness in the chest or throat, trouble breathing or talking, unusual hoarseness , or swelling of the mouth, face, lips, tongue, or throat.  Dark urine  Dark urine  Hypoglycemia ZAINUL KHAN 9

10. GLIPIZIDE Glipizide is an oral rapid- and short-acting anti-diabetic medication from the sulfonylurea class. It is classified as a second-generation sulfonylurea . MECHANISM OF ACTION:  Insulin is a hormone secreted from the cells of pancreas. When released into the blood causes cells in the body to remove sugar (glucose) from the blood. It reduces the formation of glucose by the liver. It causes inhibition of hepatic glucose production and reduction in serum glucagon levels. ZAINUL KHAN 10

11. PHARMACOKINETICS : ABSORPTION: Readily absorbed from GI tract ONSET: 15–30 min DURATION: up to 24 h METABOLISM: Metabolized extensively in liver. ELIMINATION: Excreted mainly in urine with some excretion via bile in faeces . HALF LIFE: 3–5 h . DRUGS OF GLINIDES Repaglinide MOA: Stimulation of pancreatic insulin release.  By closing ATP dependent B-cells . INDICATIONS: Type II diabetes mellitus Long term cardiovascular Renal effects CONTRAINDICATIONS: Diabetic ketoacidosis Co-administration with gemfibrozil Known hypersensitivity SIDE EFFECTS: Hypoglycemia Rhinitis Cardiac Ischemia Angina ZAINUL KHAN 11

12. Nateglinide MECHANISM OF ACTION: • Nateglinide has no impact on insulin discharge without glucose or maybe , it potentiates the impact of extracellular glucose on ATP sensitive potassium channel and also has little impact on insulin levels. • Impacts of nateglinide are most elevated at intermediate glucose level (3 to 10 mmo1/L) and it does not expand the insulin discharge effectively stimulated by high glucose fixations. • (It should be greater than 15 mmo1/L) • Nateglinide seems to be specific for pancreatic B-cells and does not seems to be influence skeletal or cardiovascular muscle or thyroid tissue . PHARMACOKINETICS • ABSORPTION : Nateglinide is rapidly absorbed in the intestine. • ONSET: After 30 min of administration. • DURATION: 1 hour • METABOLISM: Nateglinide is extensively metabolised , primarily by cytochrome P450 2C9. • ELIMINATION: eliminated By Urine (83%) and feces (10%). • HALF LIFE: 1.5 hours ZAINUL KHAN 12

13. CONTRAINDICATIONS Nateglinide is contraindicated in patients who:  Hypersensitivity.  Type 1 (namely insulin-dependent) diabetes mellitus . SIDE EFFECT : SERIOUS SIDE EFFECTS: • Seizure (convulsions) • Jaundice (yellowing of the skin or eyes ) LESS SERIOUS SIDE EFFECTS: • Runny or stuffy nose, sneezing, cough,cold or • flu symptoms • Diarrheal, nausea • Back pain • Dizziness or • Joint pain or stiffness ZAINUL KHAN 13

14. THANK YOU! ZAINUL KHAN 14