Non-insulin treatment for diabetes Flashcards
Sulfonylureas (mechanism of action, drug names, side effects, and contraindications)
Most useful earlier in the course of type 2 diabetes
Insulin secretagogues that enhance endogenous insulin secretion.
Increase pancreatic β-cell insulin secretion by closing ATP-sensitive potassium channels in the β-cell membrane resulting in depolarization of the membrane, opening of voltage-gated calcium channels and allowing an influx of calcium into the β-cell. This rise in intracellular calcium stimulates the fusion of insulin-containing secretory granules with the cell membrane, resulting in insulin secretion.
glipizIDE (Glucotrol), glyburIDE (Diabeta, Micronase), and glimepirIDE (Amaryl)
Major side effects of sulfonylureas are hypoglycemia and weight gain
Metabolized by the liver and renally excreted so must be used with caution in patients with moderate to severe renal insufficiency or liver disease. Sulfonylureas must not be used in patients with allergy to sulfa drugs, and can cause hemolytic anemia in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency
Metformin (mechanism of action, class of drug, side effects, and contraindications)
Biguanide class
Acts mainly at the liver to potentiate the suppressive effects of insulin on hepatic glucose production. Unlike insulin secretagogues, it does not stimulate insulin secretion or increase circulating insulin levels.
Side effects: Neutral effect on weight, and may even cause mild weight loss in some patients. However, patients who take metformin may develop marked gastrointestinal side effects such as nausea, vomiting, bloating, and diarrhea. No hypoglycemia when used alone.
Patients hospitalized for any reason should stop metformin until their clinical condition improves and stabilizes because of perhaps increased risk for lactic acidosis
Contraindications to metformin use include:
• congestive heart failure, especially unstable or acute
• intravascular iodinated contrast media for radiologic studies
• renal impairment
• metabolic acidosis, acute or chronic, including ketoacidosis
Thiazolidinediones (mechanism of action, drug names, side effects, and contraindications)
TZDs
True insulin sensitizers that enhance insulin action, mainly at the level of skeletal muscle and adipose tissue
Binding of a thiazolidinedione (TZD) to a PPAR-γ receptor leads to heterodimerization with a retinoic X receptor (RXR), which then binds to the promoter region of numerous genes, regulating the transcription of genes involved in adipocyte differentiation, glucose and lipid metabolism, among others
Stimulation of adiponectin production and action
rosiglitaZONE (Avandia) and pioglitaZONE (Actos)
Side effects: fluid retention/edema, hemodilution, and exacerbation of heart failure in a considerable percentage of patients. Bladder cancer and femur fractures.
Contraindications: individuals with active liver disease, moderate or severe congestive heart failure, or significant cardiovascular risk.
GLP-1 (glucagon-like peptide-1) receptor agonists
mechanism of action, drug names, side effects
Exendin-4 (Exenatide), liraglutide
Resistant to cleavage by DPP-4, making it much more potent than endogenous GLP-1
Lowers hemoglobin A1c, it also induces weight loss. T
The main side effects of exenatide are nausea, and hypoglycemia when administered in combination with a sulfonylurea.
DPP-4 (dipeptidylpeptidase-4) inhibitors (mechanism of action, drug names, side effects)
(GLIPTIN): sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina)
administered orally (unlike GLP-1 agonists)
Inhibit enzyme that inactives GLP-1
Lower fasting and postprandial glucose, and are weight-neutral.
Enhance pancreatic insulin secretion and suppress glucagon secretion, but do not alter gastric emptying or affect appetite.
Side effects: nasopharyngitis and headache. Rare Steven’s-Johnson syndrome and acute pancreatitis.
Sodium Glucose Co-transporter-2 (SGLT-2) inhibitors (mechanism of action, drug names, side effects, and contraindications)
FLOZIN: Canagliflozin, dapagliflozin (Farxiga) and empagliflozin (Jardiance)
SGLT-2 is responsible for the reabsorption of glucose in the proximal renal tubule. Inhibition of SGLT-2 leads to a decrease in glucose reabsorption by the kidneys, increased glucose excretion, and reduces circulating glucose levels.
Beneficial effects: weight loss and blood pressure lowering
Adverse effects: increased risk for genital and urinary tract infections, hypovolemia, hyperkalemia, and possible effects on bone metabolism with recent black box warnings added for increased fracture risk and euglycemic diabetic ketoacidosis.
Contraindications: severe renal disease, end stage renal disease, or patients on dialysis
Blood glucose and hemoglobin A1c goals for adults with diabetes
Hemoglobin A1c (HbA1c or A1c):
How and for whom would you adjust the goal HbAC1?
Target A1c of
Describe the routine monitoring and preventive care needed for adults with diabetes
Frequent monitoring of blood glucose at home throughout the day and occasionally at night in all individuals with type 1 diabetes and in individuals with type 2 diabetes who are on insulin therapy.
Individuals are asked to check fingerstick blood glucoses at least twice per day at specific timepoints: fasting, before lunch, before dinner, and at bedtime. They are then asked to record the glucose results, their administered doses of insulin, and in certain cases the specific foods and amounts they eat, as well as the type and duration of physical activity.
Preventive care: HbA1c monitoring Review of home blood glucoses Education about hypo/hyperglycemia and glucose lowering medications oxidation
What are the lifestyle modifications recommended for pts with diabetes?
Less calorie-‐dense, refined carbohydrates
Higher fiber, lean proteins, smaller portions
Increase physical activity
Weight loss if overweight
