diabetes mellitus drugs Flashcards
Hormones other than insulin involved in diabetes
glucagon, cortisol, and growth hormone (the so-called counterregulatory hormones); Serum potassium levels also play a role, because adequate levels of extracellular potassium are key in the ability of insulin to drive glucose into the cell.
sequelae
acute or longterm complications
Pharmacotherapeutic agents for diabetes can be divided into the following categories:
- Agents that stimulate insulin release
- Agents that stimulate insulin receptors
- Agents that decrease/delay glucose absorption
- Insulin replacement
- Agents that suppress glucagon
- Glucagon to counteract excess insulin
- Agents to prevent complications of diabetes
- Agents to treat complications of diabetes
Agents that stimulate insulin release include:
- Sulfonylureas: first and second generations
* Meglitinides: repaglinide (Prandin) and nateglinide (Starlix)
Glycogenolysis
- the breakdown of glycogen to glucose
Sulfonylureas
- chemically related to sulfonamide antibiotics (“sulfa drugs”). They increase beta-cell insulin release and decrease glycogenolysis. When taken for a long time, they may also increase insulin receptor sensitivity.
Advantages of second-generation sulfonylureas:
- Longer duration of action (once-daily dosing convenience)
- Less likely to cause disulfiram-like reactions with alcohol
- Less likely to be involved in cross-sensitivity in people allergic to sulfonamides
- Less potential for fluid retention (they have diuretic properties)
- Less risk of UVA/UVB photosensitivity
potential adverse effects of all sulfonylureas:
- Hypoglycemia
- Displacement from plasma proteins by other drugs
- Inhibition of hepatic metabolism by other drugs
- Decreased action from drugs that cause hypokalemia
- Decreased action from drugs that cause hyperglycemia
- Reduced efficacy with long-term use
the meglitiniedes - Repaglinide (Prandin) and nateglinide (Starlix) - differ from sulfonylureas in the following ways
- Short half-life (1 hour)
- Less likely to cause hypoglycemia
- Less likely to cause pancreatic burnout
- Metabolized by CYP 3A4
Metformin (glucophage)
- a Biguanide related to a naturally occurring substance called guanidine. Plants containing guanidine were used in medieval times to treat diabetes. Metformin requires sufficient levels of insulin to exert its action, so it is used to treat only type 2 diabetes; has been shown to prevent impaired glucose tolerance in patients taking corticosteroids. Other studies suggest that metformin can prevent type 2 diabetes in patients at high risk for the disease when combined with lifestyle changes (exercise, diet, weight control).
Metformin’s actions
Increases the number of insulin receptors
•Increases insulin receptor sensitivity
•Increases cellular uptake of glucose
•As a result of increased hepatic insulin receptor sensitivity, reduces hepatic gluconeogenesis (formation of glycogen from fatty acids and proteins)
•Reduces gastrointestinal (GI) glucose absorption
Metformin’s advantages
- Does not cause hypoglycemia
- Decreases plasma lipids (low-density lipoprotein [LDL], triglycerides)
- Decreases blood pressure in obese patients (about 2%)
- Decreases weight in obese patients
- Not bound to plasma proteins; no drug displacement interactions
- Not metabolized in the liver; no CYP–drug interactions
Medtiformin’s adverse reactions
- Metformin increases risk of lactic acidosis.
- Metformin should be avoided with renal impairment.
- Alcohol potentiates the effect of metformin on lactate metabolism.
- Metformin decreases absorption of folate and vitamin B12.
- Metformin is withheld before administration of a contrast agent.
- Metformin causes GI distress and metallic taste.
Glitazones
“get in the zone” with “glitazones”) activate a gene that decreases insulin resistance in patients with type 2 diabetes. They increase insulin receptor number and sensitivity. They also decrease hepatic gluconeogenesis. They have none of the side effects of metformin and have no effect on hepatic liver enzymes.
