Diabetes Mellitus

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Presentation Transcript

Diabetes Mellitus: 

Diabetes Mellitus Brooke Y. Patterson, PharmD, BCPS NU 7080 Advanced Pharmacology Research College of Nursing

Epidemiology: 

Epidemiology 7% of the United States population has either Type 1 or Type 2 diabetes 14.6 million have diabetes 1/3 do not know that they have it Diabetes prevalence increasing in all patient groups Minority Children

Pathophysiology: 

Pathophysiology Type 1 Beta-cell destruction Absolute lack of insulin Type 2 Progressive insulin secretory defect Insulin resistance Relative lack of insulin Gestational Glucose intolerance during pregnancy

Clinical Presentation: 

Clinical Presentation Obesity or unexplained weight loss Polyuria Polydipsia Blurry vision Fatigue Neuropathy of hands or feet Asymptomatic

Diagnosis of Non-Pregnant Adults: 

Diagnosis of Non-Pregnant Adults Random plasma glucose ≥200 mg/dL with symptoms OR Fasting plasma glucose ≥126 mg/dL Fasting = no caloric intake X 8 hours OR 2-hour-post glucose ≥200 mg/dL after an oral glucose tolerance test (OGTT) ALL tests should be confirmed by repeat testing on a different day

Therapeutic Goals: 

Therapeutic Goals Glycemic control Individualized Less intense goals for certain patient populations HgbA1C, preprandial, and post-prandial goals ADA recommendations www.diabetes.org

ADA Guidelines for Glycemic Control: 

ADA Guidelines for Glycemic Control *Some clinicians may prefer HgbA1C <6.5% (AACE)

Therapeutic Goals: 

Therapeutic Goals Blood Pressure <130/80 mmHg Treat with ACE inhibitor or Angiotensin Receptor Blocker (ARB) Lipids LDL <100 mg/dL TGs <150 mg/dL HDL >40 mg/dL

General Approach To Type 2 DM Treatment: 

General Approach To Type 2 DM Treatment

General Approach To Type 2 DM Treatment: 

General Approach To Type 2 DM Treatment

Sulfonylureas (SFU): 

Sulfonylureas (SFU) Stimulate insulin secretion Improve insulin sensitivity at the receptor Decrease hepatic glucose output HgbA1C decreases 1-2% on average

Sulfonylureas: 

Sulfonylureas

Sulfonylureas: 

Sulfonylureas Hepatic Impairment Give reduced dose Renal impairment Active metabolite and parent drug stay active Decrease dose in renal impairment Side Effects Hypoglycemia Photosensitivity Rash Weight gain GI discomfort

Biguanides: 

Biguanides Metformin Decreases hepatic glucose output Increases peripheral glucose uptake and utilization Decreases HgbA1C by 1-2% Additive effect when combined with SFU

Metformin: 

Metformin Advantages No hypoglycemia Weight loss Decreases TGs Improve glycemic control in >90% patients Better CV outcomes (UKPDS) Adverse Effects Anorexia Nausea Flatulence and GI discomfort Lactic acidosis (rare)

Biguanides: 

Biguanides Metformin Decreases hepatic glucose output Increases peripheral glucose uptake and utilization Decreases HgbA1C by 1-2% Additive effect when combined with SFU

Metformin: 

Metformin Advantages No hypoglycemia Weight loss Decreases TGs Improve glycemic control in >90% patients Better CV outcomes (UKPDS) Adverse Effects Anorexia Nausea Flatulence and GI discomfort Lactic acidosis (rare)

Metformin: 

Metformin Contraindicated in renal impairment Males SrCr ≥1.5 mg/dL Females SrCr ≥1.4 mg/dL Hepatic impairment Hypoxic states CHF EtOH abuse Patients >80 yo

Metformin: 

Metformin Initial dose 500mg PO BID Titrate dose up gradually to avoid GI effects 1500-2000mg/day Drug interactions Alcohol Iodinated contrast dye Cimetidine

Thiazolidinediones: 

Thiazolidinediones PPAR agonist to promote glucose uptake into target cells Decreases insulin resistance Increases insulin sensitivity No effect on insulin secretion Decreases HgbA1C 0.6-1.3% Addictive effect when used with metformin Adverse Effects Hepatotoxicity (monitor LFTs often) Edema (contraindicated in CHF) Resumption of ovulation

Thiazolidinediones: 

Thiazolidinediones Rosiglitazone (Avandia®) 4-8mg PO QD or divided BID Pioglitazone (Actos®) 15-45mg PO QD Delayed onset of activity; may take several weeks to see maximal effect

Repaglinide (Prandin®): 

Repaglinide (Prandin®) Meglitinide Monotherapy or in combination with metformin Stimulate insulin secretion Decrease HgbA1C by 0.5-1.0% Take immediately before meals 0.5mg-1 mg PO before meals 2-3X/day Hypoglycemia, weight gain

Nateglinide (Starlix®): 

Nateglinide (Starlix®) Stimulates rapid release of insulin from pancrease Reduces HgbA1C by 0.6-0.8% 120mg PO TID with meals Rarely used

Alpha-Glucosidase Inhibitors: 

Alpha-Glucosidase Inhibitors Potent competitive inhibitors of brush border alpha-glucosidases necessary in breakdown of complex carbohydrates Decreases HgbA1C minimally Adjunct therapy Acarbose (Precose®) and Miglitol (Glyset®) Adverse Effects Abdominal pain Flatulence Diarrhea Treatment of hypoglycemia: glucose tablets ONLY Rarely used

Exenatide (Byetta®): 

Exenatide (Byetta®) Stimulation of the glucagons-like-peptide-1 (GLP-1) receptor Production of insulin in response to high glucose levels Inhibition of release of glucagons after meals Slows rate of gastric emptying Adjunctive therapy for type 2 DM no adequately controlled with metformin, SFUs, or combination. 5 mcg SQ BID within 60 minutes of morning and evening meals Prefilled syringe pens May increase dose to 10 mcg SQ BID Decrease SFU dose

Exenatide (Byetta®): 

Exenatide (Byetta®) Adverse Effects Hypoglycemia (when combined with SFU) Nausea Diarrhea NOT a substitute for insulin in Type 1 Decreases HgbA1C 0.5-1.0% in combination therapy Weight loss (?)

Pramlinitide (Symlin®): 

Pramlinitide (Symlin®) Synthetic analog of human neuroendocrine hormone amylin Modulates gastric emptying Decreases post-prandial glucagons release Increased satiety Type 1 and Type 2 DM Type 1: adjunctive therapy to meal time insulin Type 2: adjunctive therapy to meal time insulin with or without metformin/SFU

Pramlinitide (Symlin®): 

Pramlinitide (Symlin®) Type 1 15 mcg SQ prior to major meals Titrate by 15 mcg increments up to 60 mcg Decrease rapid acting insulin by 50% Type 2 Initiate at 60 mcg prior to major meals May increase to 120 mcg in 3-7 days Decrease preprandial or short acting insulin by 50%

Pramlinitide (Symlin®): 

Pramlinitide (Symlin®) Adverse Effects Severe hypoglycemia (Black Box Warning) Nausea

Insulin: 

Insulin Total daily dose of insulin is based on actual body weight Type 1: Initial dose 0.5-0.8 units/kg/day Type 2: Variable; usually start with long acting HS insulin at low dose. Insulin adjustment in Type 1 DM requires expertise CDE Endocrinologists Titrate slowly!

Insulin: 

Insulin

Adjusting Insulin: 

Adjusting Insulin

Case: 

Case PR is a 35 yo AAM with a history of Type I DM and HTN. His current regimen is lisinopril 20 mg, regular insulin 10 units before meals and NPH insulin 30 minutes at breakfast. He brings his blood glucose log with him to the visit. The log shows fairly good glycemic control with pre-dinner blood glucose consistently in the 200-250 range.

Prevention of DM Complications: 

Prevention of DM Complications ASA therapy Prevention of CV risk ASA 81 mg QD Hypertension ACE inhibitors Hyperlipidemia Statin therapy Vaccinations Influenza annually Pneumococcal vaccine

Slide33: 

Part of the secret of success in life is to eat what you like and let the food fight it out inside. -Mark Twain