Oral hypoglycemics

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Oral hypoglycemics

  1. 1. ORALHYPOGLYCEMIC AGENTS
  2. 2. INTRODUCTIONDiabetesTypes – 1, 2, othersPathogenesisDiagnostic criteria
  3. 3. TREATMENT CAREINSULINORAL HYPOGLYCEMICS
  4. 4. ORALHYPOGLYCEMICS
  5. 5. BIGUANIDESSECRETAGOGUESTHIAZOLIDINEDIONESACARBOSEOTHERS
  6. 6. BIGUANIDESPhenformin, MetforminNo hypoglycemiaImprove lipid profileWeight loss
  7. 7. Dose- 500 mg once to max 1000 mg bidSMBG, 2-3 weeks (slow action, gi side effects)Monotherapy effectiveOr combine with others
  8. 8. Mechanism of actionHepatic gluconeogenesis decreasedInsulin mediated glucose disposalRetard intestinal absorptionInterfere with mitochondrial respiratory chain
  9. 9. Adverse effectsNausea, pain abdomen, metallic taste, diarrhoea, anorexiaB12 deficiencyLactic acidosisCareful in alcoholics, renal failure, hepatic disease, hypotensive states, radiographic contrasts, if nil orally
  10. 10. SECRETAGOGUES
  11. 11. Sulfonylureas - MechanismSUR 1 RECEPTORSDecrease conductance of ATP sensitive K+ channelsDepolarization of beta cellsDecrease glucagon release
  12. 12. 1 st generationChlorpropamide, Tolbutamide, TolazamideLonger half-lifeMore hypoglycemiaMore side effects
  13. 13. 2 nd generation Type 2 DM of recent onset Reduce both fasting and PP glucose Start at low doses – increase after 1-2 weeks interval Just before a meal – increase insulin acutely(With chronic therapy – more sustained release)
  14. 14. 2nd generation
  15. 15. Adverse effectsHypoglycemia – may recurWeight gainAvoid in renal/liver diseaseTolbutamide- reduces iodine uptakeChlorpropamide- cholestatic jaundice, hyponatremia
  16. 16. Drug Interactions - positiveProtein binding – salicylates, sulfonamidesDecrease metabolism – warfarin, acute alcoholSynergise – salicylates, lithium, theoph ylline
  17. 17. Drug Interactions - negativeInducers – Phenobarbitone, Phenytoin, Chronic alcohol, rifampicinOpposers – steroids, thiazides, OCPs
  18. 18. Same channel in myocardiumAll except glyburide have a low affinity for thisNO INCREASED CARDIAC MORTALITY
  19. 19. Non-sulfonylureasMeglitinide – RepaglinideD-phenylalanineanalogue – Nateglinide
  20. 20. Rapid onset, short-lasting insulin releaseBefore every mealOmit if skip mealLow risk of hypoglycemiaSide effects – Mild headache, dyspepsia, weight gain, avoid in liver/renal disease, arthralgia
  21. 21. THIAZOLIDINEDIONES
  22. 22. PPAR-gamma receptors (adipocytes)Insulin SENSITISERSLower insulin resistance & requirementRedistribute fat from central to peripheralOvulation in PCOS
  23. 23. Used as supplements with others in type 2Sometimes monotherapy in mild with diet, exercise“Decreased mortality due to MI/Stroke”NON-RESPONDERS – With low baseline insulin
  24. 24. DOSERosiglitazone – 2-8 mg/day once or in 2 divided dosesPioglitazone – 15-45 mg/day once daily
  25. 25. ADVERSE EFFECTS
  26. 26. Troglitazone – Liver failure(monitor LFT)Effect on lipid profilePeripheral edema, CHF,weight gain, ANEMIA, Fractures, macular edemaRosiglitazone – CARDIAC
  27. 27. Pioglitazone – failure of OCP therapyKetoconazole inhibits metabolism of pioglitazoneLess interactions with rosiglitazone
  28. 28. ALPHA-GLUCOSIDASE INHIBITORS
  29. 29. ACARBOSE“REVERSIBLE” inhibitionDecrease post-prandial hyperglycemiaANTI-HYPERGLYCEMIC (NOT HYPOGLYCEMIC)Weight, TG levels decrease with chronic therapy (HbA1c less)Stop-NIDDM trial – in pre- diabetics, REDUCED DM 2, HTN, CARDIOVASCULAR
  30. 30. Role as adjuvant in obese diabeticsStart at 25 mg evening50-100 mg with each meal max doseMiglitol – more potent in inhibiting sucrase
  31. 31. Adverse effectsFLATULENCEABDOMINAL DISCOMFORTLOOSE STOOLS( DUE TO FERMENTATION OF UNABSORBED CARBOHYDRATES)
  32. 32. NOTE:Gradual upward dose titrationAvoid in IBD, gastroparesisIf hypoglycemia from other treatments occurs while taking these agents, use glucose
  33. 33. RECENTADVANCES
  34. 34. BROMOCRIPTINEImproves glycemic control in obese DM2Reduces both fasting and PP glucose levels
  35. 35. INCRETIN EFFECT
  36. 36. GLP-1, GIPDPP 4
  37. 37. DPP 4 inhibitorsSITAGLIPTANVILDAGLIPTANSaxagliptanRitagliptanAlogliptan
  38. 38. AMYLIN EFFECT
  39. 39. COLESEVELAM“Bile acid sequestrant”Mechanism not knownAdverse effects –Constipation, dyspepsia, intestinalobstruction, nausea, painabdomen
  40. 40. RENAL GLUCOSETRANSPORTERINHIBITORSPhlorozinDapagliflozinSergliflozinRemogliflozin
  41. 41. RESVERATROLNatural compound found in grape skinFood sensors activated in shortage of food like IGF & TORMimic effect of dietary restrictionIncrease longeivity
  42. 42. SALSALATEWall Street Journal Health Blog research on using Salsalate to prevent or treat type II diabetes:Fasting glucose levels of those who took salsalate declined 13% compared with those who took a placebo
  43. 43. GLUCOKINASE ACTIVATORSPIRAGLIATINHypoglycemia, fatty liver & hyperlipidemia
  44. 44. THANK YOU

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