PPT_Chapter_30.ppt - Antidiabetic Drugs Drugs That Affect the Endocrine and Reproductive System Chapter 30 Copyright \u00a9 2013 Wolters Kluwer Health |

PPT_Chapter_30.ppt - Antidiabetic Drugs Drugs That Affect...

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Unformatted text preview: Antidiabetic Drugs Drugs That Affect the Endocrine and Reproductive System Chapter 30 Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Diabetes Mellitus Complicated, chronic disorder characterized by either insufficient insulin production or by cellular resistance to insulin Insulin insufficiency results in elevated blood glucose levels Patients with diabetes are at greater risk for a number of disorders: MI, stroke, blindness, kidney disease, lower limb amputations Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Diabetes Mellitus • Two types: – Type 1 – produce insulin in insufficient amount and therefore must have insulin supplementation to survive • Rapid onset, occurs before the age of 20, produces more severe symptoms than type 1 and is more difficult to control – Type 2 – either a decreased production of insulin by the pancreas or a decreased sensitivity of the cells to insulin Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Diabetes Mellitus Risk factors for type 2: Obesity Older age Family history of diabetes History of gestational diabetes Impaired glucose tolerance Minimal or no physical activity Race/ethnicity Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Insulin Hormone manufactured by the beta-cells of the pancreas Principal hormone required for the proper use of glucose by the body Controls storage and use of amino acids and fatty acids Lowers blood glucose levels by inhibiting liver glucose production Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Insulin Appears to activate a process that helps glucose molecules enter the cells of striated muscle and adipose tissue Stimulates the synthesis of glycogen by the liver Promotes protein synthesis Helps the body store fat by preventing its breakdown for energy Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Insulin Preparations are either synthetic or insulin analogs Classified by onset peak and duration of action Rapid-acting Short-acting Intermediate-acting Long-acting Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Uses of Insulin Necessary for controlling type 1 diabetes More severe and complicated forms of type 2 diabetes Severe diabetic ketoacidosis Diabetic coma In combination with glucose to treat hypokalemia by shifting potassium from the blood into the cells Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Insulin Hypoglycemia Eating too little Dose of insulin wrong and too high Increased physical activity Hyperglycemia Eating too much Dose of insulin wrong, missed, or too low Emotional stress, infection, surgery, pregnancy, illness May become insulin resistant Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Diabetic Ketoacidosis Potentially life-threatening deficiency of insulin resulting in severe hyperglycemia Body breaks down fat for energy and produces ketones in the liver Disrupts the acid-base balance in the body Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypoglycemic Reactions Close observation is important Episodes of hypoglycemia are corrected as soon as the symptoms are recognized Methods of ending reactions: Orange juice or other fruit juice Hard candy or honey Commercial glucose products Glucagon (subcutaneous, IM, or IV) Glucose 10% or 50% (IV) Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Insulin Contraindications: Hypersensitivity, hypoglycemia Precautions: Liver or kidney disease, lactation Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Insulin Drugs that decrease the hypoglycemic effect: Dobutamine AIDS antivirals Epinephrine Albuterol Estrogens Contraceptives, oral Lithium Corticosteroids Diltiazem Diuretics Morphine sulfate Niacin Phenothiazines Thyroid hormones Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Insulin Drugs that increase the hypoglycemic effect: Alcohol ACE inhibitors Antidiabetics, oral Beta-blockers Calcium Clonidine Disopyramide Lithium MAOIs Salicylates Sulfonamides Tetracycline Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Insulin Number of injections, dosage, times of administration, diet, and exercise require continual monitoring. Dosage adjustments may be necessary. Patient should be assessed for signs and symptoms of hypoglycemia and hyperglycemia. Patient needs to frequently monitor blood glucose using a glucometer. No standard dose Must be given parenterally, usually subcutaneously, because it is broken down if given orally Only regular insulin can be given IV. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Insulin Regular insulin is given 30–60 minutes before a meal. Injected into arms, thighs, abdomen, or buttocks Injection sites are rotated to prevent lipodystrophy. Localized allergic reactions, signs of inflammation, or other skin changes must be reported to the health care provider. Some patients inject using a needle and syringe, while others use an insulin pump. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Educating the Patient and Family About Insulin • Noncompliance issues should be discussed. • Educate about proper management of diabetes • Dietary lapses around the holidays • Fasting precautions • Diet is important. • Patient’s self-monitoring of blood glucose levels using a glucometer is important. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Educating the Patient and Family About Insulin Educate on proper use of glucometer Educate on dosage of insulin Store insulin at room temperature and dispose within 1 month of initial puncture Store vials not in use in refrigerator Purchase the same brand and needle size each time Educate on proper withdrawal and injection technique Contact health care provider if become ill and during periods of stress or emotional disturbances Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Educating the Patient and Family About Insulin Follow the prescribed diet Carry an extra supply of insulin and a prescription for needles and syringes Educate on the signs and symptoms of hypoglycemia and hyperglycemia and how to manage both Good skin and foot care is important Frequent dental checkups and routine eye exams are important Follow exercise regimen Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Educating the Patient and Family About Insulin Notify health care provider if: Increase in blood glucose levels Become pregnant Have hypoglycemic episodes Have an illness, infection, or diarrhea Any new problems arise (leg ulcers, numbness of extremities, significant weight loss or gain) Wear identification to inform medical personnel and others about insulin and diabetes Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Antidiabetic Drugs • Sulfonylureas (chlorpropamide, glimepiride, glipizide, glyburide, tolazamide, tolbutamide) • Biguanides (metformin) • α-Glucosidase inhibitors (acarbose, miglitol) • Meglitinides (nateglinide, repaglinide) • Thiazolidinediones (pioglitazone, rosiglitazone) • Amylase analogs (pramlintide) • Dipeptidyl peptidase-4 inhibitors (linagliptin, saxagliptin, sitagliptin) • Glucagon-like peptide 1 receptor agonist (exenatide, liraglutide) Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs • Sulfonylureas – Lower blood glucose by stimulating the beta-cells of the pancreas to release insulin – Not effective if the beta-cells of the pancreas are unable to release a sufficient amount of insulin to meet a patient’s needs – First-generation – not commonly used; long duration of action and higher incidence of adverse reactions and interactions – Second- and third-generation are more commonly used • Glimepiride, glipizide, glyburide Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs • Biguanides – Metformin – only biguanide available – Acts by reducing hepatic glucose production and increasing insulin sensitivity in muscle and fat cells – Sensitizes the liver to circulating insulin levels and reduces hepatic glucose production Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs • α-Glucosidase inhibitors – Lower blood sugar by elevating the digestion of carbohydrates and absorption of carbohydrates in the intestine – Acarbose and miglitol Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs Meglitinides Lower blood glucose levels by stimulating the release of insulin from the pancreas Action depends on the ability of the beta-cell in the pancreas to produce some insulin Examples: nateglinide, repaglinide Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs Thiazolidinediones Also called glitazones Decrease insulin resistance and increase insulin sensitivity by modifying several processes with the end result being decreasing hepatic glucogenesis and increasing insulin-dependent muscle glucose uptake Examples: rosiglitazone, pioglitazone Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs Amylin analogs Pramlintide is only product available Amylin affects the rate of postprandial glucose Acts like amylin in the body, producing several effects that aid in diabetes management Reduces the rate at which food is released from the stomach after eating Decreases secretion of glucagon after a meal in patients using insulin Produces a feeling of satiety that results in decreased caloric intake and possibly in weight loss Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs Dipeptidyl peptidase-4 inhibitors Prevent the breakdown of the incretin hormones resulting in an increase in insulin secretion and decrease in glucagon secretion Examples: linagliptin, saxagliptin, sitagliptin Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Antidiabetic Drugs Glucagon-like peptide 1 receptor agonists Increase in insulin production and secretions from the pancreas in response to increased glucose levels Glucagon secretion is inhibited during periods of hyperglycemia Gastric emptying is delayed, which prolongs the time it takes for glucose to appear in circulation after eating Examples: exenatide, liraglutide Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Uses of Antidiabetic Drugs Treatment of type 2 diabetics whose condition cannot be controlled by diet alone May also be used with insulin in the management of some patients May decrease the required insulin dosage Two antidiabetic drugs with different actions may be used together A number of combination products are available Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Sulfonylureas Hypoglycemia, nausea, vomiting, epigastric discomfort, and heartburn Many, but not all, cause anorexia, headache, and diarrhea Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Biguanides Asthenia, headache, GI upset Self-limiting and can be reduced by starting on a low dose and increasing slowly Hypoglycemia rarely occurs Lactic acidosis may occur Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs • α-Glucosidase inhibitors – GI disturbances: bloating and flatulence – Others: abdominal pain and diarrhea – When used alone, do not cause hypoglycemia Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Meglitinides Upper respiratory infection, back pain, hypoglycemia Nateglinide may also cause flu symptoms and dizziness Repaglinide may also cause headache, nausea, diarrhea, and arthralgia Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Thiazolidinediones Aggravated diabetes mellitus, upper respiratory infections, sinusitis, headache, pharyngitis, myalgia, diarrhea, and back pain When used alone, rarely cause hypoglycemia May cause or exacerbate CHF Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Amylin analogs Headache Nausea Anorexia Vomiting Hypoglycemia Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Dipeptidyl peptidase-4 inhibitors Nasopharyngitis Hypoglycemia Saxagliptin and sitagliptin: headache, upper respiratory infection Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Adverse Reactions of Antidiabetic Drugs Glucagon-Like peptide 1 receptor agonist Nausea Vomiting Diarrhea Constipation Dizziness Hypoglycemia Injection-site reaction Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Antidiabetics are contraindicated in patients with: Known hypersensitivity Diabetic ketoacidosis Severe infection Severe endocrine disease Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Sulfonylureas Contraindications: First-generation: coronary artery disease, liver or renal dysfunction Precautions: renal impairment, severe cardiovascular disease, impaired liver function Cross-sensitivity with sulfonamides Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Sulfonylureas Interactions: Increased hypoglycemic effect: anticoagulants, chloramphenicol, clofibrate, fluconazole, H2 receptor antagonist, methyldopa, MAOIs, salicylates, sulfonamides, TCAs Decreased hypoglycemic effect: beta-blockers, calcium channel blockers, cholestyramine, corticosteroids, estrogens, hydantoins, isoniazid, oral contraceptives, phenothiazines, thiazide diuretics, thyroid agents Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Biguanides Contraindications: heart failure, renal disease, acute or chronic metabolic acidosis, patients over 80, lactation Precautions: during surgery Interactions: iodinated contrast material, alcohol, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, furosemide, glucocorticoids Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs • α-Glucosidase inhibitors – Contraindications: cirrhosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, predisposition to intestinal obstruction, chronic intestinal disease – Precautions: renal impairment, preexisting GI problems – Interactions: digestive enzymes • Acarbose: loop or thiazide diuretics, glucocorticoids, oral contraceptives, calcium channel blockers, phenytoin, thyroid drugs, phenothiazines • Miglitol: ranitidine, propranolol Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Meglitinides Contraindications: type 1 diabetes Precautions: liver or kidney disease Interactions: NSAIDs, salicylates, MAOIs, betablockers, thiazides, corticosteroids, thyroid drugs, sympathomimetics Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Thiazolidinediones Contraindications: severe heart failure Precautions: edema, cardiovascular disease, liver or kidney disease Interactions: oral contraceptives Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Amylin analogs Contraindications: diagnosed gastroparesis, hypoglycemia unawareness Interactions: drugs that affect GI motility, drugs that inhibit absorption of nutrients Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Dipeptidyl peptidase-4 inhibitors Monitor patients on sitagliptin for pancreatitis Interactions: insulin secretagogues (sulfonylureas), rifampin, other antidiabetic drugs Saxagliptin: aluminum and magnesium antacids with simethicone, simvastatin, diltiazem, medications that inhibit cytochrome P450 Sitagliptin: cyclosporine, digoxin Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Glucagon-like peptide 1 receptor agonist Patients should be monitored for pancreatitis Contraindications: Liraglutide: history or a family history of medullary thyroid carcinoma, patients with multiple endocrine neoplasia type 2 Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Contraindications, Precautions, and Interactions of Antidiabetic Drugs Glucagon-like peptide 1 receptor agonist Interactions: other antidiabetic drugs Exenatide: APAP, digoxin, lovastatin, oral antibiotics, oral contraceptives, warfarin Liraglutide: APAP, atorvastatin, digoxin, griseofulvin Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs Patients are observed every 2–4 hours for symptoms of hypoglycemia, particularly during initial therapy or after a dosage change Importance of following the treatment regimen should be emphasized No fixed dosage; the drug regimen is individualized based on the effectiveness and tolerance of the drug(s) used and the maximum recommended dose of the drug(s) Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs Sulfonylureas Chlorpropamide, tolazamide, tolbutamide: take with food Glipizide: 30 minutes before a meal Glyburide and glimepiride: with breakfast or first main meal of the day Secondary failure may occur after long-term therapy Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs Biguanides Taken two to three times a day with meals After 4 weeks, if patient has not responded to maximum dose, then sulfonylurea may be added Extended-release formulation is taken once daily with evening meal Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs • α-Glucosidase inhibitors – Three times per day with first bite of the meal – Start at low dose once daily and gradually increase to minimize GI effects Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs Meglitinides Repaglinide: take 15 minutes before meals, but can be taken immediately or up to 30 minutes before meal Nateglinide: take up to 30 minutes before meals Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs Thiazolidinediones Take with or without food If miss a dose, then take at the next meal Once dose is taken, the meal should not be delayed Delay of a meal for as little as 30 minutes can cause hypoglycemia Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins Patient Management Issues with Antidiabetic Drugs Amylin analogs Given s...
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