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Antidiabetic and A ntilipid drugs and renal failure

Antidiabetic and A ntilipid drugs and renal failure

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Antidiabetic and A ntilipid drugs and renal failure

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  1. Antidiabetic and Antilipid drugs and renal failure DrM.Mortazavi Nephrologist

  2. Goal To understand the use and side effects of anti-diabetic medications and be able to educate patients.

  3. Guidelines for Glycemic, BP, & Lipid Control HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides. ADA. Diabetes Care. 2012;35:S11-63

  4. Nine to Know • Brand & Generic Name • Mechanism of action • Therapeutic effect • Relevant pharmacokinetics and pharmacodynamics • Dosing by route • Adverse reactions and contraindications • Monitoring parameters • Drug-drug and drug food interactions • Comparisons between agents w/in the same class of drugs

  5. Main Pathophysiological Defects in T2DM pancreatic insulin secretion incretin effect pancreatic glucagon secretion ? - gut carbohydrate delivery & absorption HYPERGLYCEMIA - + peripheral glucose uptake hepatic glucose production Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

  6. Type 2 Diabetes High blood glucose Impaired GI motility • Defective beta cell function • Diminished phase 1 insulin release • Delayed phase 2 insulin release 2. Overproduction of glucagon • Tissues less sensitive to insulin • Liver produces excess glucose Type 2 Video from diabetes.com Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

  7. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 3. ANTI-HYPERGLYCEMIC THERAPY • Therapeutic options: • Oral agents & non-insulin injectables • Metformin • Sulfonylureas • Thiazolidinediones • Meglitinides • a-glucosidase inhibitors • Bile acid sequestrants Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  8. Biguanides Indication Type II Diabetes Mellitus, Antipsychotic-induced weight gain MOA Decrease hepatic glucose production, decrease intestinal absorption of glucose and increase insulin sensitivity therefore increasing peripheral glucose uptake

  9. Biguanides (cont) Patient Info • Upset stomach/dyspepsia – take with food • Metallic taste • Minimal Weight Loss • Alcohol may increase likelihood of lactic acidosis • Does not cause hypoglycemia

  10. Biguanides (cont) Special Population Considerations: • Geriatric: limited data suggests starting doses should be 33% lower for geriatric patients than that of an adult dose. Titration should also to a lower limit. Cautions/Severe Adverse Reactions • Black Box Lactic Acidosis: D/C immediately and notify practitioner if: myalgia, malaise, hyperventilation, unusual somnolence. • Alcohol potentiates this reaction

  11. Biguanides (cont) CONTRAINDICATIONS • Renal disease or renal dysfunction (Scr > 1.5 mg/dL in males, >1.4 mg/dL in females) • Abnormal Scr from any cause including: shock, acute MI, or septicemia • Metabolic acidosis (including diabetic ketoacidosis (DKA)) • Heart failure requiring pharmacologic therapy; active liver failure

  12. Sulfonylureas Indications Adjuncts to diet and exercise to lower blood glucose in patients w/ type II diabetes mellitus MOA Stimulating insulin release from beta-cells of pancreatic islets

  13. Where does it work? Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

  14. Sulfonylureas (cont) Patient Info • Hypoglycemia • GI upset/abdominal pain • Dizziness • Weight gain • Heartburn/epigastric fullness • Onset: glucose lowering effect: 30 minutes with peak at 1.5-3 hours lasting 24 hours

  15. Sulfonylureas (cont) Special Population Considerations: • Pediatric: safety and efficacy not established for pts under age 16 • Hepatic/Renal Dysfunction: conservative dosing and titration recommended. Caution/Severe Adverse Reactions • Syndrome of Inappropriate Anti-diuretic Hormone (SIADH) CONTRAINDICATIONS • Diabetes complicated by ketoacidosis • Type I DM • Diabetes w/ pregnancy. Pregnancy Cat: C (except glyburide: B)

  16. Thiazolidinediones (TZD) Indications As adjunct to diet and exercise for type II diabetes MOA Increase insulin sensitivity by affecting PPAR-γ (peroxisome proliferators-activated receptor) at adipose tissue, skeletal muscle and in the liver.

  17. Where does it work? Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

  18. TZD (cont) Patient Info • Weight gain • Edema • Hypoglycemia esp. when used with other antidiabetic medications and insulin (not w/ metformin) • May cause or exacerbate heart failure with risk of fluid retention • Myalgia • Headache

  19. TZD (cont) Cautions/Severe Adverse Reactions • Black Box: Heart Failure (for all thiazolidinediones, mainly due to rosiglitazone) • Hepatic failure • Anemia • Bone loss • Ovulation in premenopausal women • Pregancy Cat: C

  20. TZD (cont) Special Populations Considerations: • Congestive Heart Failure: should be initiated at lowest approved dose with longer intervals between dose increases for NYHA class II. Use is not recommended in patients with NYHA Class III or IV CHF CONTRAINDICATIONS • NYHA Class III-IV heart failure • Active liver disease (ALT > 2.5 upper limit of normal)

  21. Insulin Indications Type I diabetes mellitus, type II diabetes mellitus, hyperkalemia, DKA/diabetic coma MOA Stimulating peripheral glucose uptake and inhibiting hepatic glucose production Patient Info • Hypoglycemia (BG < 70 mg/dL) esp with higher doses • Anxiety, blurred vision, palpitations, shakiness, slurred speech, sweating • Weight gain

  22. Indication for insulin therapy:

  23. Where does it work? Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE Insulin: the Movie from diabetes.org

  24. Insulin (cont) Administration: • Subcutaneous injection • Rotate site • Check blood sugars regularly Storage: • Refrigerate until use • Once vial is punctured, it is good for 28 days and can be left at room temperature (except for glargine which is 90 days)

  25. Insulin (cont) Dosing: • Starting daily dose: 0.5-1 unit/kg/day in divided doses • Adjust according to fasting (premeal) blood glucose of 80-130 mg/dL and peak postprandial blood glucose < 180 mg/dL • Provide 50% as long acting insulin and 50% as prandial insulin • 1 unit of can account for 30 grams of carbohydrate (14-50) • 1 unit can lower 50 mg/dL blood glucose (10-100) Special Population Consderations: • Renal dysfunction • CrCl 10-50 mL/min: 75% of normal dose • CrCl < 10 ml/min: 25-50% of normal dose; monitor closely • Exercise??? ---- Acute Stress???

  26. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 3. ANTI-HYPERGLYCEMIC THERAPY • Therapeutic options: Insulin Rapid (Lispro, Aspart, Glulisine) Short (Regular) Insulin level Intermediate (NPH) Long (Detemir) Long (Glargine) Hours 0 2 4 6 8 10 12 14 16 18 20 22 24 Hours after injection

  27. Long-acting Long-acting & Short-acting Normal insulin secretion 70/30 pre-mixed Insulin Dosing

  28. Insulin Comparison Chart courses.washington.edu/pharm504/Insulin%20Chart.pdf

  29. Table 1. Properties of anti-hyperglycemic agents Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  30. Table 1. Properties of anti-hyperglycemic agents Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  31. Table 1. Properties of anti-hyperglycemic agents Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  32. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 4. OTHER CONSIDERATIONS • Comorbidities • Coronary Disease • Heart Failure • Renal disease • Liver dysfunction • Hypoglycemia • Metformin: CVD benefit (UKPDS) • Avoid hypoglycemia • ? SUs & ischemic preconditioning • ? Pioglitazone & CVD events Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  33. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 4. OTHER CONSIDERATIONS • Comorbidities • Coronary Disease • Heart Failure • Renal disease • Liver dysfunction • Hypoglycemia • Metformin: May use unless condition is unstable or severe • Avoid TZDs Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  34. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 4. OTHER CONSIDERATIONS • Comorbidities • Coronary Disease • Heart Failure • Renal disease • Liver dysfunction • Hypoglycemia • Increased risk of hypoglycemia • Metformin & lactic acidosis • US: stop @SCr ≥ 1.5 (1.4 women) • UK:  dose @GFR <45 & stop @GFR <30 • Caution with SUs (esp. glyburide) Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  35. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 4. OTHER CONSIDERATIONS • Comorbidities • Coronary Disease • Heart Failure • Renal disease • Liver dysfunction • Hypoglycemia • Most drugs not tested in advanced liver disease • Pioglitazone may help steatosis • Insulin best option if disease severe Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  36. ADA-EASD Position Statement: Management of Hyperglycemia in T2DM • 4. OTHER CONSIDERATIONS • Comorbidities • Coronary Disease • Heart Failure • Renal disease • Liver dysfunction • Hypoglycemia • Emerging concerns regarding association with increased mortality • Proper drug selection in the hypoglycemia prone Diabetes Care,Diabetologia. 19April 2012 [Epub ahead of print]

  37. Antilipid Drugs Dr.M.Mortazavi Nephrologist

  38. Lipoproteins • Low-density lipoproteins (LDL): • Elevation of LDL: • Atherosclerotic plaque formation • Increases the risk for heart disease • High-density lipoproteins (HDL): • Take cholesterol from the peripheral cells and transport it to the liver

  39. Cholesterol Levels • HDL cholesterol: Protects against heart diseases • Higher the LDL level: Greater the risk for heart disease • Drugs used to treat hyperlipidemia: • Bile acid sequestrants • HMG-CoA reductase inhibitors • Fibric acid derivatives • Niacin

  40. HMG-CoA Reductase Inhibitors: Actions • Statins** • HMG-CoA reductase: • An enzyme that is a catalyst during the manufacture of cholesterol • Inhibits the manufacture of cholesterol or promotes the breakdown of cholesterol • Lowers the blood levels of cholesterol and serum triglycerides • Increases blood levels of HDLs

  41. HMG-CoA Reductase Inhibitors: Uses • As adjunct to diet in the treatment of hyperlipidemia • For primary prevention of coronary events • MI • For secondary prevention of cardiovascular events • TIA/stroke

  42. HMG-CoA Reductase Inhibitors: Adverse Reactions • Central nervous system reactions: • Headache, blurred vision, dizziness, insomnia • Gastrointestinal reactions: • Flatulence, abdominal pain, cramping, constipation, nausea • Other: • Elevated CPK level, Rhabdomyolysis with possible renal failure • Pharyngitis with use of rosuvastatin/Crestor

  43. HMG-CoA Reductase Inhibitors: Contraindications And Precautions • Contraindicated in patients: • With hypersensitivity to the drugs, serious liver disorders • During pregnancy and lactation • Used cautiously in patients with: • History of alcoholism, acute infection, hypotension, trauma, endocrine disorders, visual disturbances, and myopathy

  44. Nursing alert • Pts taking cyclosporine, Asians and those with severe renal insufficiency are at risk for myopathy/rhabdomyolysis when taking rosuvastatin/Crestor