Treatment of diabetes mellitus
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Treatment of diabetes mellitus

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Treatment of diabetes mellitus Treatment of diabetes mellitus Presentation Transcript

  • Treatment of Diabetes Mellitus Dr. Salman Iftikhar Department of Pharmacology UHS
  • Diabetes Mellitus
    • Type 1 (IDDM):
      • Early onset
      • Loss of pancreatic B cells  absolute dependence on insulin
      • Ketoacidosis – prone
    • Type 2 (NIDDM)
      • Usually adult onset
      •  response to insulin
      • Not Ketoacidosis – prone
  • Insulin
  •  
  •  
  • Oral Hypoglycemic Agents
  • Sulfonylureas
  •  
  • Sulfonylureas
    • Mechanism
      • The acute action of sulfonylureas is to block K + channels  depolarization  insulin release
    • Effects of increased insulin
      •  glucagon release from pancreatic  cells
  • Sulfonylureas
    • Acetohexamide (active metabolite,  dose in renal dysfunction)
    • Tolbutamide (appropriate in renal dysfunction)
    • Chlorpropamide (long acting, SIADH/disulfiram reaction)
    • Glipizide (  dose in hepatic dysfunction)
    • Glyburide (active metabolite,  dose in renal dysfunction)
  • Sulfonylureas
    • Adverse effects:
      • Hypoglycemia
      • Weight gain
      • Hypersensitivity (possible cross allergy with sulfonamides)
      • Drug interactions mainly with first-generation drugs  hypoglycemia with cemetidine, insulin, sulfonamides, salicylates
  • Metformin
    • “ Euglycemic”,  postprandial glucose levels but does not cause hypoglycemia or weight gain
    • May involve  tissue sensitivity to insulin and/or  hepatic gluconeogenesis
    • Adverse effects: possible lactic acidosis; gastrointestinal distress is common
  • Acarbose
    • No hypoglycemia
    • Mechanisms: inhibits  glucosidase in brush borders of small intestine   formation of absorbable carbohydrate   postprandial glucose   demand for insulin
    • Adverse effects: GI discomforts, flatulence and diarrhea; recent concerns over potential hepatotoxicity
  • Thiazolidinediones Pioglitazone & Rosiglitazone
    • Mechanism:
      • Bind to nuclear peroxisome proliferator-activating receptors (PPARs) involved in transcription of insulin responsive genes  sensitization of tissues to insulin, plus  in hepatic gluconeogenesis and triglycerides and  insulin receptor numbers
      • Adverse effects: less hypoglycemia than sulfonylureas, but weight gain and edema reported
  • BLOOD
  • New Drugs
  • PRAMLINTIDE
    • Synthetic analog of amylin
    • Injectable: modulates postprandial glucose levels
    • Suppresses glucagon release via undetermined mechanisms, delays gastric emptying, and has central nervous system-mediated anorectic effects
    • Administered in addition to insulin in those who are unable to achieve their target postprandial blood sugars
    • Renal metabolism and excretion
    • Always be injected by itself with a separate syringe; it cannot be mixed with insulin
    • Adverse effects: hypoglycemia and gastrointestinal symptoms including nausea, vomiting, and anorexia.
    PRAMLINTIDE
  • EXENATIDE
    • A synthetic analog of glucagon-like-polypeptide 1 (GLP-1), exenatide is the first incretin therapy to become available for the treatment of diabetes
    • Approved as an injectable, adjunctive therapy in persons with type 2 diabetes treated with metformin or metformin plus sulfonylureas who still have suboptimal glycemic control
    • Multiple actions
      • potentiation of glucose-mediated insulin secretion
      • Suppression of postprandial glucagon release through as-yet unknown mechanisms
      • slowed gastric emptying, and a central loss of appetite
      • The increased insulin secretion is speculated to be due in part to an increase in beta-cell mass
    • Adverse effects are nausea (about 44% of users) and vomiting and diarrhea. The nausea decreases with ongoing exenatide usage
    • Weight loss is reported in some users, presumably because of the nausea and anorectic effects. A serious and, in some cases, fatal adverse effect of exenatide is necrotizing and hemorrhagic pancreatitis.
    • Safety issues, however, may deter future use.
    EXENATIDE
  • SITAGLIPTIN
    • Inhibitor of dipeptidyl peptidase-4 (DPP-4), the enzyme that degrades incretin and other GLP-1-like molecules
    • Its major action is to increase circulating levels of GLP-1 and GIP.
    • Decreases postprandial glucose excursions by increasing glucose-mediated insulin secretion and decreasing glucagon levels
    • Adverse effects include
      • nasopharyngitis, upper respiratory infections, and headaches. Rarely, severe allergic reactions
    • Dosage should be reduced in patients with renal impairment. Sitagliptin can be given as monotherapy or combined with metformin or Tzds.