Diabetes Drugs Chapter 32 Student Notes PDF

Chapter- 32 Diabetes Drugs KR by Katie Robinson Pancreas 1 Location 2 Gland Type Located behind stomach. Both exocrine and endocrine gland. 3 Hormone Production 4 Glycogen Storage Exc...

Chapter- 32 Diabetes Drugs KR by Katie Robinson Pancreas 1 Location 2 Gland Type Located behind stomach. Both exocrine and endocrine gland. 3 Hormone Production 4 Glycogen Storage Excess glucose stored in Produces insulin and liver and skeletal muscle. glucagon. Insulin Functions Fat Metabolism Lipogenesis and Lipolysis Direct effect on fat metabolism. Stimulates lipogenesis and inhibits lipolysis. Protein Synthesis Potassium and Magnesium Stimulates protein synthesis. Promotes intracellular shift of potassium and magnesium. Diabetes Mellitus Progressive Diseases Syndrome Diabetes mellitus (DM) is not a single disease. Often regarded as a syndrome rather than a disease. Group of progressive diseases. Diabetes Mellitus Symptoms Elevated fasting blood glucose. Increased urination (polyuria). Excessive thirst (polydipsia). Increased hunger (polyphagia). Type 1 Diabetes Mellitus Insulin Deficiency Exogenous Insulin Prevalence Lack of insulin production or Affected patients need exogenous Fewer than 10% of all DM cases are production of defective insulin. insulin. type 1. Type 2 Diabetes Mellitus Most Common Type Insulin Deficiency and Resistance 90% of all diabetes cases. Caused by insulin deficiency and resistance. Insulin Resistance Insulin Receptor Issues Many tissues resistant to insulin. Reduced number of insulin receptors or less responsive receptors. Type 2 Diabetes Mellitus (Cont.) Several comorbid conditions. Coronary heart disease. Increased risk for thrombotic Collectively referred to as events. metabolic syndrome. Long-Term Complications Macrovascular Microvascular Atherosclerosis plaque buildup. Capillary damage. Coronary arteries Retinopathy Cerebral arteries Neuropathy Peripheral vessels Nephropathy Gestational Diabetes Pregnancy-Related Insulin Treatment Hyperglycemia develops Insulin given to prevent during pregnancy. birth defects. Postpartum Resolution Type 2 Risk 30% may develop type 2 Usually subsides after delivery. DM within 10-15 years. Glycemic Goals 7% 5.7 HbA1C Normal Goal for most patients. HbA1C diagnostic criteria. 6.4 6.5 Prediabetes Diabetes HbA1C diagnostic criteria. HbA1C diagnostic criteria. Types of Antidiabetic Drugs Insulins Oral Hypoglycemic Drugs Injectable Hypoglycemic Drugs Insulin is a hormone that helps Oral drugs help regulate blood sugar. regulate blood sugar. Injectable drugs may be used in addition to insulin or antidiabetic drugs. Human Insulin 1 Recombinant DNA 2 Bacterial and Yeast Production Derived using recombinant DNA Recombinant insulin technologies. produced by bacteria and yeast. 3 Glucose Control 4 Long-Term Complications Goal: tight glucose control. Reduce incidence of long- term complications. Rapid-Acting Insulins Rapid Onset 5 to 15 minutes onset. Peak Action 1 to 2 hours peak. Duration 3 to 5 hours duration. Afrezza Rapid-Acting Insulin Administration Inhaled insulin. Administered within 20 minutes before each meal. Peak of 12 to 15 minutes. Must be given with long-acting insulins or oral diabetic agents. Short duration of action. Short-Acting Insulins Regular Insulin SUBQ Route Humulin R, IV bolus, IV Onset: 30 to 60 minutes, infusion, IM, SUBQ. peak: 2.5 hours, duration: 6 to 10 hours. IV Route Immediate onset, duration: 2 to 6 hours. Intermediate-Acting Insulins Insulin Isophane Suspension Cloudy Appearance Onset, Peak, and Duration Also called NPH. Often combined with regular insulin. Onset: 1 to 2 hours, Peak: 4 to 8 hours, Duration: 10 to 18 hours. Long-Acting Insulins 1 Insulin Glargine 2 Constant Level (Lantus) Provides a constant level Clear, colorless solution. of insulin in the body. 3 Basal Insulin 4 Toujeo Usually dosed once daily, More concentrated U-300 can be dosed every 12 form. hours. Long-Acting Insulins (Cont.) Insulin Detemir (Levemir) Duration of action is dose dependent. Lower doses require twice-daily dosing. Higher doses may be given once daily. Insulin Glargine (Lantus or Basaglar) Biosimilar insulin. U100 Insulin Degludec (Tresiba) Ultra long acting. Once daily. U100 or U200 Fixed-Combination Insulins (Cont.) Two Insulins Intermediate-Acting Rapid-Acting or Short-Acting Each contains two different insulins, One intermediate-acting type. fixed combinations. Either one rapid-acting type (Humalog, NovoLog) or one short- acting type (Humulin). Sliding-Scale Insulin Dosing Rapid-Acting or Short-Acting Hospitalized Patients SUBQ rapid-acting (lispro or aspart) or short-acting Typically used in hospitalized diabetic patients or those (regular) insulins are adjusted according to blood on total parenteral nutrition or enteral tube feedings. glucose test results. Non-Insulin Antidiabetic Drugs Type 2 DM Blood Glucose Monitoring Used for type 2 diabetes mellitus. Careful monitoring of blood glucose levels. Drug Therapy Comorbidities Therapy with one or more Treatment of associated drugs. comorbid conditions. Non-Insulin Antidiabetic Drugs (Cont.) 1 2018 ADA Guidelines 2 Lifestyle Interventions Guidelines for new-onset type 2 DM treatment. Lifestyle modifications are recommended for treatment. 3 Metformin 4 Additional Agents Oral biguanide drug Other antidiabetic agents metformin is are ordered if HbA1C recommended. goals are not met. Biguanides Metformin Type 1 DM First-line drug for type 2 DM. Not used for type 1 DM. Most commonly used oral drug. Biguanides: Mechanism of Action Decreased Glucose Decreased Intestinal Increased Glucose No Insulin Secretion Production Absorption Uptake Increase Liver produces less glucose. Intestine absorbs less Tissues take up more Does not increase insulin glucose. glucose. secretion. Biguanides: Adverse Effects Gastrointestinal Other Effects Effects May also cause metallic Primarily affects GI tract: taste, reduced vitamin B12 abdominal bloating, nausea, levels. cramping, diarrhea, feeling of fullness. Lactic Acidosis Contraindications Rare but lethal if it occurs. Contraindicated in renal or hepatic disease. Sulfonylureas Stimulate Insulin Secretion Improve Insulin Sensitivity Adverse Effects Stimulate insulin secretion from Improve sensitivity to insulin in tissues. Hypoglycemia, hematologic effects, beta cells. nausea, epigastric fullness, heartburn, and many others. Non-Insulin Antidiabetic Drugs: Glinides Glinides Indication Repaglinide (Prandin), Type 2 diabetes mellitus nateglinide (Starlix) Mechanism of Action Increase insulin secretion from pancreas. Thiazolidinediones Adverse Effects Heart Failure Other Adverse Effects Can cause or exacerbate heart failure. Peripheral edema. Contraindicated if HF is present. Weight gain. Decreased bone marrow density. Alpha-Glucosidase Inhibitors Acarbose (Precose) Miglitol (Glyset) Mechanism of Action Type 2 diabetes mellitus. Type 2 diabetes mellitus. Inhibit alpha-glucosidase in the small intestine. Alpha-Glucosidase Inhibitors: Mechanism of Action Enzyme Inhibition Reversibly inhibit alpha glucosidase in small intestine. Delayed Absorption Result in delayed absorption of glucose. Postprandial Control Must be taken with meals to prevent excessive postprandial blood glucose elevations. Alpha-Glucosidase Inhibitors: Adverse Effects Gastrointestinal No Hypoglycemia Effects Do not cause Flatulence, diarrhea, hypoglycemia, abdominal pain. hyperinsulinemia, or weight gain. Non-Insulin Antidiabetic Drugs: Indications Used alone or in combination with other drugs. Diet and lifestyle changes to lower blood glucose. Lower blood glucose levels in patients with type 2 DM. Non-Insulin Antidiabetic Drugs Incretin Mimetics Dipeptidyl Peptidase Glucagon-Like Amylin Agonists IV Inhibitors (DPP-IV) Peptide-1 Receptor Mimic the effects of Mimic the effects of Agonists (GLP-1) incretin hormones. Inhibit the breakdown of amylin, a hormone that incretin hormones. Activate GLP-1 receptors, regulates glucose. promoting insulin release. Incretin Mimetics DPP-IV Inhibitors & Incretin Hormones GLP-1 Receptor Increase insulin synthesis Agonists and lower glucagon Mimic naturally secreted secretion. incretin hormones. Forms Available in oral and injectable forms. Incretin Mimetics Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors Examples Also known as "gliptins". Sitagliptin (Januvia) Saxagliptin (Onglyza) Linagliptin (Tradjenta) Alogliptin (Nesina) DPP-IV Inhibitors: Mechanism of Action 1 1. Delay Breakdown 2 2. Inhibit Enzyme 3 3. Reduce Glucose Delay breakdown of incretin Inhibit the enzyme DPP-IV. Reduce fasting and hormones. postprandial glucose. DPP-IV Inhibitors: Indication Glycemic Control Adjunct Therapy Improve glycemic control Used as an adjunct to diet in patients with Type 2 and exercise. diabetes. GLP-1 Agonists Insulin Secretion Glucagon Secretion Enhance glucose-dependent Suppress elevated glucagon insulin secretion. secretion. Gastric Emptying Insulin Secretion Slow gastric emptying. Increase first and second phase insulin secretion. GLP-1 Agonists (cont.) Combination Products Soliqua (insulin glargine and lizisenatide) Xultophy (insulin degludec and liraglutide) GLP-1 Agonists Indications Type 2 Diabetes Blood Glucose Control Metformin, Sulfonylurea, Glitazone Indicated for patients with type 2 Patients who have not been able to diabetes. achieve blood glucose control. Patients who have not been able to achieve blood glucose control with metformin, a sulfonylurea and/or a glitazone. GLP-1 Agonists: Adverse Effects Black Box Warning Gastrointestinal Effects Risk of developing thyroid C-cell tumors. Nausea, vomiting, and diarrhea. Pancreatitis Weight Loss Rare cases of hemorrhagic Patients may experience or necrotizing pancreatitis. weight loss of 5 to 10 pounds. Amylin Agonist Pramlintide (Symlin) Mechanism of Action Mimics natural hormone Slows gastric emptying amylin. Suppresses glucagon secretion Modulates appetite and satiety Indications Administration Used when other drugs SUBQ injection. have not achieved adequate glucose control. Amylin Agonist: Indications Type 1 or 2 Diabetes Contraindication Patients with Type 1 or Type 2 diabetes who receive Gastroparesis. mealtime insulin. Insulin dose reduced by 50%. Failed to achieve optimal glycemic control with insulin. Amylin Agonist: Adverse Effects Nausea is a common side effect. Vomiting can occur with this medication. Anorexia is a possible side effect. Headache may occur as a side effect. SGLT2 Inhibitors 1 Inhibition of SGLT2 2 New Class of Drugs Decreases blood glucose Oral drugs for treatment by increasing renal of type 2 DM. glucose excretion. 3 Examples 4 Mechanism of Action Canagliflozin, dapagliflozin, Prevent glucose empagliflozin, reabsorption from ertugliflozin. glomerular filtrate. SGLT2 Inhibitors: Other Effects Increase insulin sensitivity and glucose uptake. Glucose uptake in muscle cells. Decrease gluconeogenesis. SGLT2 Inhibitors: Adverse Effects Genital Yeast Urinary Tract Hypotension Hyperkalemia Infections Infections SGLT2 inhibitors can cause Increased potassium Common adverse effect of Increased risk of UTIs with low blood pressure. levels may occur. SGLT2 inhibitors. SGLT2 inhibitors.