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Anti-Diabetic Agents

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Anti-Diabetic Agents CHAPTER © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Anti-Diabetic Agents 2 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Charles Ruchalski, NOTPharmD, FOR BCPS SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Drug Class: Biguanides Introduction • Maintenance dose: © Jones &The Bartlett biguanide Learning, metformin isLLC the drug of choice as initial© Jones °& 2000–2550Bartlett Learning,mg daily in divided LLC doses, or 2000 mg extended-release once daily NOT FORtherapy SALE for OR a newly DISTRIBUTION diagnosed patient with type 2 diabetesNOT FOR SALE OR DISTRIBUTION as an adjunct to diet and exercise. Metformin is contrain- • Renal dosage adjustment: dicated in certain patients to prevent lactic acidosis, a rare ° Not recommended in patients with renal dysfunc- but serious side effect. It is often used in combination with tion (see Contraindications below) other oral antidiabetic agents and/or insulin in patients who do not reach glycemic© Jones goals & Bartletton those therapies.Learning, LLCAdverse Reactions: Most© JonesCommon & Bartlett Learning, LLC • Diarrhea, vomiting, dyspepsia, flatulence, metallic HbA1c reductions withNOT metformin FOR areSALE generally OR betweenDISTRIBUTION NOT FOR SALE OR DISTRIBUTION 1.5% and 2%. taste, weight loss Adverse Reactions: Rare/Severe/Important Mechanism of Action for the Drug Class • Lactic acidosis, megaloblastic anemia Improves glucose tolerance by lowering both basal and © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC postprandial plasma glucose. Decreases hepatic glucose Major Drug Interactions production,NOT FORdecreases SALE intestinal OR DISTRIBUTION absorption of glucose, NOT FOR SALE OR DISTRIBUTION Drugs Affecting Metformin and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. • Alcohol potentiates effect on lactate metabolism • Iodinated contrast media can lead to acute renal failure and metformin toxicity © Jones & Bartlett■■ Metformin Learning, LLC © Jones & Bartlett Learning, LLC Contraindications Brand Names NOT FOR SALE OR DISTRIBUTION NOT FOR• Renal SALE disease OR (males: DISTRIBUTION SrCr >1.5 mg/dl; females: SrCr Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet >1.4 mg/dl), heart failure requiring pharmacologic therapy, acute or chronic metabolic acidosis, active Generic Names liver disease Metformin, metformin extended-release © Jones & Bartlett Learning, LLCCounseling Points © Jones & Bartlett Learning, LLC Dosage Forms NOT FOR SALE OR DISTRIBUTION• Discontinue immediatelyNOT and promptlyFOR SALE notify ORhealth- DISTRIBUTION Tablets, extended-release tablets, oral solution care practitioner if unexplained myalgia, malaise, hyperventilation, or unusual somnolence because Usage these are symptoms of lactic acidosis • Type 2 diabetes mellitus*, PCOS, antipsychotic-induced ©weight Jones gain. & Bartlett Learning, LLC Key Points© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • TemporarilyNOT FOR withhold SALE in patients OR DISTRIBUTION undergoing radio- Dosing logic procedures involving the parenteral administra- • Initial dose: tion of iodinated contrast media because it may result ° 500 mg twice daily with morning and evening in acute alteration of renal function. Do not restart meals, 850 mg once daily with a meal, or 500 mg for at least 48 hours or until renal function appears © Jones & Bartlettextended Learning, release once LLC daily with a meal © Jones adequate.& Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 15 © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. 81170_CH02_PASS02.indd 15 9/10/10 3:19:51 PM Drug Class: Di-Peptidyl Peptidase-4 Inhibitor © Jones & Bartlett Learning, LLC © Jones Introduction& Bartlett Learning, LLC Generic Name NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Sitagliptin is the first di-peptidyl peptidase-4 (DPP-4) Sitagliptin inhibitor available. It inhibits the breakdown of active GLP-1 to inactive GLP-1 through the inhibition of the Dosage Forms enzyme DPP-4. Active GLP-1 is released from the α cells Tablets of the pancreas in response© Jones to food & intake. Bartlett GLP-1 Learning, plays a LLC © Jones & Bartlett Learning, LLC role in regulating blood glucose by increasing the secre- Usage tion of insulin from theNOT pancreas FOR in SALE a glucose-dependent OR DISTRIBUTION • Type 2 diabetes mellitusNOT FOR SALE OR DISTRIBUTION manner. GLP-1 also helps regulate glucagon secretion and Dosing decreases hepatic glucose production. Sitagliptin is used • 100 mg once daily with or without food as monotherapy as an adjunct to diet and exercise or in • Renal dosage adjustment: combination with other oral antidiabetic agents in patients 50 mg once daily: CrCl >30 to <50 ml/minute who do© Jonesnot reach & glycemic Bartlett goals. Learning, Average HbA1c LLC reduc- ° © Jones & Bartlett Learning, LLC 25 mg once daily: CrCl <30 ml/minute tions NOTare between FOR 0.7%SALE and OR 1%. DISTRIBUTION ° NOT FOR SALE OR DISTRIBUTION Mechanism of Action for the Drug Class Adverse Reactions: Most Common • Nasopharyngitis, nausea, diarrhea, vomiting, hypo- Inhibition of DPP-4 enhances the activity of active GLP-1, glycemia, weight loss thus increasing glucose-dependent insulin secretion and © Jones &decreasing Bartlett levels Learning, of circulating LLC glucagon and hepatic© JonesAdverse & Bartlett Reactions: Learning, Rare/Severe/Important LLC glucose production. NOT FOR SALE OR DISTRIBUTION NOT FOR• Acute SALE pancreatitis, OR DISTRIBUTION rash (Stevens–Johnson syndrome) Members of the Drug Class Major Drug Interactions In this section: Sitagliptin Other: Saxagliptin Sitagliptin’s Effect on Other Drugs • Digoxin: Increased levels © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC ■■ Sitagliptin NOT FOR SALE OR DISTRIBUTIONCounseling Points NOT FOR SALE OR DISTRIBUTION Brand Name • Discontinue immediately and promptly notify health- Januvia care practitioner if unexplained persistent nausea and vomiting occur (signs of acute pancreatitis) © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Drug Class: Insulin © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORIntroduction SALE OR DISTRIBUTION NOT MechanismFOR SALE ofOR Action DISTRIBUTION for the Drug Class The hormone insulin is endogenously released from the β Insulin lowers blood glucose by stimulating peripheral cells of the pancreas. Patients with type 1 diabetes mellitus glucose uptake, especially in skeletal muscle and fat, and have an absolute deficiency of insulin, and patients with by inhibiting hepatic glucose production. type 2 diabetes mellitus may also have a decreased produc- tion of endogenous insulin.© Jones Insulin & is Bartlett required in Learning, all type LLCUsage for the Drug Class© Jones & Bartlett Learning, LLC 1 diabetic patients as aNOT lifelong FOR treatment. SALE Insulin OR DISTRIBUTIONis com- • Type 1 diabetes mellitus*,NOT type FOR 2 diabetes SALE mellitus*, OR DISTRIBUTION monly used in type 2 diabetic patients as either adjunct hyperkalemia, DKA*/diabetic coma therapy to oral antidiabetic agents or as monotherapy as the disease progresses. Various substitutions on the insulin Dosing for the Drug Class molecule and other modifications have led to multiple • Initial dose: types© of Jones insulins. & These Bartlett are characterized Learning, andLLC adminis- © Jones & Bartlett Learning, LLC ° 0.5 to 1 unit/kg per day Sub-Q (high interpatient teredNOT based FORon their SALE pharmacodynamic OR DISTRIBUTION and pharmacoki- variability)NOT FOR SALE OR DISTRIBUTION netic characteristics such as onset, peak, and duration of • Maintenance dose: action. Most significantly, they are classified as rapid-acting, ° Adjust doses to achieve premeal and bedtime short-acting, intermediate-acting, or long-acting types of blood glucose levels of 80–140 mg/dl insulin. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 16 FREQUENTLY PRESCRIBED MEDICATIONS: DRUGS YOU NEED TO KNOW © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. 81170_CH02_PASS02.indd 16 9/10/10 3:19:52 PM • Renal dosage adjustment: Drugs Affecting Insulin (Increased Hypoglycemic ° CrCl 10–50 ml/minute: Administer 75% of normal Effect) © Jones & Bartlettdose Learning, LLC © Jones• Alcohol& Bartlett Learning, LLC CrCl <10 ml/minute: Administer 25–50% of normal NOT FOR SALE° OR DISTRIBUTION NOT FOR• Fluoxetine SALE OR DISTRIBUTION dose; monitor closely • Anabolic steroids Adverse Reactions for the Drug Class: Most • Lithium β• -Blockers Common TY • Sulfonamides P E • Hypoglycemia (anxiety, blurred vision, palpitations, • Clonidine S © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, OF IN LLC shakiness, slurred speech, sweating), weight gain NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Contraindications for the Drug Class S Adverse Reactions for the Drug Class: Rare/ UL • Use during severe hypoglycemia Severe/Important I • Allergy or sensitivity to any ingredient of the product N • Severe hypoglycemia (seizure/coma), edema, lipoat- rophy or lipohypertrophy at injection site © Jones & Bartlett Learning, LLC Counseling© Jones Points &for Bartlett the Drug
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