Pharmacological Management of Diabetes Flashcards
What’s the most important incretin in humans? What does it do? Where are its receptors located? How is it metabolized? Is release affected in T2DM?
GLP-1: Glucagon-Like Hormone 1 – Enhances glucose-dependent insulin secretion, slows gastric emptying,
suppresses glucagon secretion, promotes satiety. Receptors are in the islet cells, CNS, elsewhere. Metabolized rapidly (half-life 2-3 min) by DPP-4 (dipepetidyl peptidase-4). Yes, release is reduced in T2DM.
What class is metformin? MOA? Advantages/Disadvantages? Cost?
Class: Biguanides. MOA: Activates hepatic AMP-kinase & inhibit mitochondrial glyceroP dehydrogenase, decreasing hepatic glucose production. Adv: First-line therapy in diabetes due to no weight gain or hypoglycemia, reduction in cardiovascular events and mortality. Disadv:Gastrointestinal side effects (diarrhea, abdominal cramping, anorexia), Lactic acidosis (rare), Vitamin B12 deficiency, contraindications if reduced kidney function. Cost: Low.
What are the sulfonylureas? MOA? Advantages/Disadvantages? Cost?
Sulfonylureas: Glibenclamide/Glyburide, Glipizide, Gliclazide, Glimepiride. MOA: Closure of ATP-sensitive K+ channels on β- cell plasma membrane –> stimulation of insulin release. Adv: Generally well-tolerated. Disadv: Hypoglycemia (this is glucose-independent stimulation of insulin secretion), Weight gain, Blunt myocardial ischemia preconditioning. Cost: Low.
What are the meglitinides? MOA? Advantages/Disadvantages? Cost?
Meglitinides: Repaglinide, Nateglinide. MOA: Closure of ATP-sensitive K+ channels on β- cell plasma membrane –> stimulation of insulin release (same as Sulfonylureas) – BUT, much shorter-acting, and thus these are used with meals. The advantage is accentuated effects around meal ingestion w/o the increased risk of hypoglycemia later (although hypoglycemia is still a risk). Disadvantages: Weight gain, Blunt myocardial ischemia preconditioning, Dosing frequency. Cost: Generics available.
What class is pioglitazone? MOA? Advantages/Disadvantages? Cost? Is this used much?
Class: Thiazolidinediones (Glitazones). MOA: Binds PPAR-γ, a nuclear transcription factor, increasing peripheral insulin sensitivity (decreasing peripheral insulin resistance). Advantages: No hypoglycemia; increase HDL cholesterol while decreasing triglycerides, possible reduction in MI. Disadvantages: Weight gain (subQ, not visceral); edema; heart failure; bone fractures; macular edema; bladder cancer. Cost: Expensive. This is not used much anymore.
What class is rosiglitazone? MOA? Advantages/Disadvantages? Cost? Is this used much?
Class: Thiazolidinediones (Glitazones). MOA: Binds PPAR-γ, a nuclear transcription factor, increasing peripheral insulin sensitivity (decreasing peripheral insulin resistance). Advantages: No hypoglycemia. Disadvantages: Weight gain; edema; heart failure; bone fractures; increased cardiovascular events; increased LDL cholesterol; contraindicated in cardiac disease. Cost: Expensive. This is almost never used anymore.
What are the a-glucosidase inhibitors? MOA? Advantages/Disadvantages? Cost?
a-Glucosidase Inhibitors: Acarbose, Miglitol. MOA: Competitively inhibit enzymes that break down carbohydrates into simple sugars, delaying GI carbohydrate absorption & reducing postprandial glucose levels. Advantages: Nonsystemic, weight neutral, no hypoglycemia. Disadvantages: GI side effects, dosing frequency (taken with any carbohydrate meal), modest reduction in A1c. Cost: Medium.
What are the incretin mimetics (GLP-1 receptor agonists) MOA? What is the dosing frequencies? Advantages/Disadvantages? Cost?
Incretin mimetics (GLP-1 receptor agonists): Exenatide (2X daily or weekly), Liraglutide (daily), Albiglutide (weekly), Dulaglutide (weekly). ("Al's Big Dulag -- i mean Lirag -- Exenatide"). MOA: Activates GLP-1 receptor in β-cells, endocrine pancreas, and brain, Increases insulin secretion, Decreases glucagon
secretion (glucose-dependent), Slows gastric emptying, Increases satiety. Advantages: Weight reduction, improved B-cell mass and function. Disadvantages: Acute pancreatitis; GI (nausea, vomiting, diarrhea);
hypoglycemia (though less than sulfonylureas); Injection only; Caution with renal insufficency; C-cell Hyperplasia/Medullary Carcinoma?, Long-term safety unknown. Cost: High.What are the incretin enhancers (DPP-4 inhibitors)? MOA? Advantages/Disadvantages? Cost?
Incretin Enhancers (DPP-4 inhibitors): Sitagliptin, Alogliptin, Saxagliptin, Linagliptin (“Alo blac Sits and does Lines while playing a Sax and drinking Liptin tea”). MOA: Inhibit DPP-4. Advantages: Increases insulin, decrease glucagon secretion, Increase [GLP-1 & GIP] (incretins), No hypoglycemia, Weight neutrality. Disadvantages: Urticaria/Angioedemia, URIs, HAs, Pancreatitis, Long-term safety unknown. Cost: Expensive.
What are the SGLT2 inhibitors? MOA? Advantages/Disadvantages? Cost?
SGLT2 inhibitors: Canagliflozin, Dapagliflozin, Empagliflozin. (“Cana Da pEmp -agliflozin”) MOA: Redfuces glucose resorption in the kidney, increasing urinary glucose excretion. Adv: No hypoglycemia, Weight loss possible. Disadv: UTIs; Genital mycotic infections; Volume depletion; Hyperkalemia; Hypersensitivity; Increased LDL; Long-term safety unknown. Cost: High.
Which bile acid sequestrant can be used in the tx of diabetes? MOA? Advantages/Disadvantages? Cost?
Colesevelam. MOA: Binds bile acids & cholesterol and decreases hepatic glucose production. Adv: No hypoglycemia; decreased LDL. Disadv: Increase in triglycerides; Constipation; May interfere with
absorption of other medications. Cost: High.
What is the recommendation for therapy at the diagnosis of T2DM? What if at the diagnosis the patient is markedly symptomatic and/or has elevated blood glucose levels or A1c? If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain the A1c target over three months, what actions should be taken?
Initiate metformin therapy with lifestyle interventions unless metformin is contraindicated. Consider insulin therapy with or without additional agents from the outset. Add a second oral agent, a GLP-1 receptor agonist, or insulin.
Which drugs are commonly associated with hypoglycemia, and which type is hypoglycemia more common in? What are other RFs for hypoglycemia?How should this be treated? What should be prescribed for all T1DM patients and for T2DM with previous hypoglycemic episodes? These patients should also do what and consider use of what? What is administered in a hospital setting?
Most common with treatment with sulfonylurea drugs and insulin; More common in type 1 vs. type 2 diabetes
Increased risk if over 60 years old, impaired renal function, poor nutrition, liver disease, increased physical activity, longer duration of diabetes. Glucose (15–20 g) preferred treatment for conscious individual with hypoglycemia. Glucagon should be prescribed for all T1 and for T2 with previous episodes. These patients shoul also raise glycemic targets and/or use CGMS to reduce risk of future episodes. In the hospital, IV dextrose is administered.
What is pramlintide? MOA? How is this used? Side effects?
Amylin analog – Mimics amylin: slows gastric emptying, suppresses postprandial glucose secretion, may reduce appetite. Used (injected) with short or rapidly acting insulin with meals. Side effect: Hypoglycemia (significant risk), GI side effects (especially nausea).
Insulin is used in ___ patients with T1DM and ___ patients with T2DM. In patients with T1DM, insulin is a ___ treatment. When is insulin indicated in T2DM patients? All insulins have what side effects?
All. Many. Essential, Life-Sustaining! Significant hyperglycemia at presentation, Hyperglycemia on maximal doses of oral agents, Decompensation:
acute injury, stress, infection, myocardial ischemia, Severe hyperglycemia with ketonemia and/or ketonuria,
Uncontrolled weight loss, Use of diabetogenic medications (eg, corticosteroids), Surgery, Pregnancy, Serious renal or hepatic disease. SIde effects: Hypoglycemia, weight gain, lipoatrophy, lipohypertrophy, allergic reaction.
