Diabetic Drugs Flashcards
(41 cards)
Name a biguanide
Metformin
Mechanism of action of metformin
enhances the effect of insulin
Reduction in insulin resistance via modification of glucose metabolic pathways
Decreases hepatic gluconeogenesis and intestinal glucose absorption
Increases peripheral insulin sensitivity
Lowers postprandial and fasting blood glucose levels
Reduces LDL, increases HDL
Benefits of metformin
Glycemic efficacy: lowers HbA1c by 1.2–2%) over 3 months
Weight loss or weight stabilization
No risk of hypoglycemia
Beneficial effect on dyslipidemia
Studies show metformin reduces the risk of macroangiopathic complications in diabetic patients.
Cost-effective
Common side effects of biguanides
- metformin associated lactic acidosis
- GI- nausea, diarrhoea, flatulance
- B12 deficiency
- metallic taste in mouth
Contraindications to metformin
Renal failure (if creatinine clearance < 30 mL/min)
Severe liver failure
Intravenous iodinated contrast medium
Pause metformin prior to surgery
Chronic pancreatitis, starvation ketosis, ketoacidosis, sepsis
Heart failure (NCYA III and IV), respiratory failure, shock, sepsis
Alcoholism
Interactions with metformin
Sulfonylureas- increase in Cardiovascular mortality
Name some thiazolidinediones
Pioglitazone
Rosiglitazone
Mechanism of action of thiazolidinediones
activation of the transcription factor PPARγ (peroxisome proliferator-activated receptor of gamma type) → ↑ transcription of genes involved in glucose and lipid metabolism → increased storage of triglycerides and subsequent reduction of products of lipid metabolism (e.g., free fatty acids) that enhance insulin resistance → glucose utilization is increased and hepatic glucose production reduced
Benefits of thiazolidinediones
Glycemic efficacy: lowers HbA1c by 1% in 3 months
Favorable effect on lipid metabolism: ↓ triglyceride, ↓ LDL, ↑ HDL
No risk of hypoglycemia
Sid effects of pioglitazone
Fluid retention and oedema
Weight gain
Increased risk of heart failure
Increased risk of bone fractures (osteoporosis!)
Contraindications to pioglitazone
Congestive heart failure (NYHA III or IV)
Liver failure
Pioglitazone: history of bladder cancer or active bladder cancer; macrohematuria of unknown origin
Give some sulfonylureas
Glyburide: the standard substance of this class with a relatively long half-life Glipizide: a short-acting agent Gliclazide
Mechanism of action of sulfonylureas
Sulfonylureas block ATP-sensitive potassium channels of the pancreatic β-cells → depolarization of the cell membrane → calcium influx → insulin secretion
Extrapancreatic effect: decreases hepatic gluconeogenesis and increases peripheral insulin sensitivity
Benefits of sulfonylureas
Glycemic efficacy: lowers HbA1c by 1.2% over 3 months
Long-term experience
Low-cost
Side effects of sulfonylureas
Life-threatening hypoglycemia
Weight gain
Hematological changes: granulocytopenia, hemolytic anemia
Allergic skin reactions
Alcohol intolerance
Compared to metformin, sulfonylureas are associated with more cardiovascular (macrovascular) complications.
Contraindications to sulfonylureas
Severe cardiovascular comorbidity Obesity Sulfonamide allergy (particularly long-acting substances) Severe liver failure Severe kidney failure
Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further. Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!
Give some examples of meglitinides
Repaglinide: the leading agent in the class of meglitinides, which is well tolerated by patients with chronic kidney disease Nateglinide
Mechanism of action of meglitinides
Enhances insulin secretion (similar mechanism of action to that of the sulfonylureas)
Meglitinides should be taken shortly before meals.
Benefits of meglitinides
Glycemic efficacy: lowers HbA1c by 0.75% over 3 months
More expensive than sulfonylureas
Side effects of meglitinides
Life-threatening hypoglycemia (less risky than sulfonylureas)
Weight gain
Hepatotoxicity (rare)
Contraindications to meglitinides
Severe liver failure
Severe renal failure
Interactions: sulfonylureas - same mechanism of action
Examples of GLP-1 agonists
Exenatide
Liraglutide: rapid-release formula that is administered daily
Albiglutide: extended-release formula that is administered once weekly
Dulaglutide
Mechanism of action of GLP-1
Incretin effect: food intake → activation of enteroendocrine cells in the gastrointestinal tract → release of GLP-1 → GLP-1 degradation via the enzyme DPP-4 → end of the GLP-1 effect
Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → increase insulin secretion, decrease glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)
Benefits of GLP-1 agonists
Glycemic efficacy: lowers HbA1c by 0.5–1.5% over 3 months
Subcutaneous injection
Weight loss
No risk of hypoglycemia
