Endocrine Agents
AGENTS FOR DIABETES MELLITUS
What are the two general categories of drugs that are used to treat diabetes mellitus?
- Insulin
- Oral hypoglycemic agents
Which type of diabetes mellitus is each of the following statements referring to?
Loss of pancreatic β-cells
Type 1
Usually early onset
Type 1
Decreased response to insulin
Type 2
Ketoacidosis prone
Type 1
Usually adult onset
Type 2
Not ketoacidosis prone
Type 2
Absolute dependence on insulin
Type 1
May be controlled by diet and oral hypoglycemics alone
Type 2
Usually thin
Type 1
Usually obese
Type 2
Islet cell antibodies
Type 1
Near 100% concordance in monozygotic twins
Type 2
What types of drugs can elevate blood glucose concentrations?
Alcohol; β-adrenergic blockers; calcium channel blockers; combination oral contraceptives; diazoxide; diuretics; corticosteroids; lithium; niacin; phenytoin; sympathomimetics
What are the signs and symptoms of diabetic ketoacidosis?
Kussmaul respirations; fruity breath; abdominal pain; nausea; vomiting; polyuria; polydipsia; dehydration; fatigue
What chemical is responsible for causing “fruity breath” during ketoacidosis?
Acetone
What are the three ketones made during ketoacidosis?
- β-Hydroxybutyric acid
- Acetoacetic acid
- Acetone
What is the term used to describe a rise in blood glucose usually between 4 and 11 AM due to the release of growth hormone, cortisol, glucagons, and epinephrine?
Dawn phenomenon. To determine the cause of elevated morning blood sugars, the patient must measure their glucose levels throughout the night. Then alterations in diet, medication doses, or medication choice may be made.
What is the term used to describe a rebound rise in morning blood glucose secondary to a low overnight blood glucose?
Somogyi effect. This usually results from hyperinsulinemia which decreases blood glucose. Glucagon is released when the patient becomes hypoglycemic, which causes a rebound spike in blood glucose levels. Decreasing the evening insulin dose is first-line therapy.
For each of the following types of insulin give the time of onset, peak effect, and duration:
Aspart
0.17 to 0.33 hours; 1 to 3 hours; 3 to 5 hours
Lispro
0.25 hours; 0.5 to 1.5 hours; 6 to 8 hours
Regular
0.5 to 1 hours; 2 to 3 hours; 8 to 12 hours
NPH (isophane insulin suspension)
1 to 1.5 hours; 4 to 12 hours; 24 hours
Lente (insulin zinc suspension)
1 to 2.5 hours; 8 to 12 hours; 18 to 24 hours
Ultralente (extended insulin zinc suspension)
4 to 8 hours; 16 to 18 hours; > 36 hours
Glargine
No peak; duration is 24 hours
Can insulin glargine be mixed with other insulins?
No
What is the most common side effect of insulin?
Hypoglycemia
What are the signs and symptoms of hypoglycemia?
Confusion; diaphoresis; tremors; tachycardia; seizures; coma; lethargy
Which sign/symptom of hypoglycemia is not masked by β-adrenergic antagonists?
Diaphoresis
What is the name of the incretin mimetic that increases insulin secretion, slows gastric emptying, and decreases food intake?
Exenatide
What is the name of the human amylin analog that is cosecreted with insulin and reduces postprandial glucose by prolonging gastric emptying time, reduces postprandial glucagon secretion, and suppresses appetite?
Pramlintide
What hypoglycemic agent is not contraindicated in a pregnant woman with diabetes mellitus?
Insulin
Other than blood glucose reduction, regular insulin can also be used for what condition?
Hyperkalemia. Insulin causes an intracellular shift of potassium. Insulin is given in combination with glucose to prevent hypoglycemia in this situation.
For each of the following oral hypoglycemic agents, state which drug class it belongs to?
Chlorpropamide
First-generation sulfonylurea
Tolazamide
First-generation sulfonylurea
Tolbutamide
First-generation sulfonylurea
Glyburide
Second-generation sulfonylurea
Glipizide
Second-generation sulfonylurea
Glimepiride
Second-generation sulfonylurea
Nateglinide
D-phenylalanine derivative
Rosiglitazone
Thiazolidinedione
Pioglitazone
Thiazolidinedione
Acarbose
α-Glucosidase inhibitor
Miglitol
α-Glucosidase inhibitor
Metformin
Biguanide
Repaglinide
Meglitinide
Nateglinide
Meglitinide
Pramlintide
Amylin analog
Exenatide
Incretin
For each of the following drug classes, give the mechanism of action:
Sulfonylureas
Block adenosine triphosphate (ATP)-dependent potassium channels, thereby depolarizing pancreatic β-cells which lead to insulin release (release mediated via calcium influx); insulin secretagogue
Thiazolidinediones
Bind to nuclear peroxisome proliferator activating receptor-gamma (PPAR-γ) which leads to increased sensitization of cells to insulin; decrease hepatic gluconeogenesis; upregulate insulin receptors
D-phenylalanine derivatives
Newest insulin secretagogue which closes the potassium channels on the β-cells leading to a rapid but short-acting release of insulin
α-Glucosidase inhibitors
Inhibit intestinal amylase and α-glucosidase causing a delay in the breakdown of complex carbohydrates into glucose which subsequently delays glucose absorption, thereby lowering postprandial glucose levels
Biguanides
Decrease hepatic gluconeogenesis; increase tissue sensitivity to insulin
Meglitinides
Nonsulfonylurea insulin secretagogue
Amylin analogs
Suppresses glucagon release, delays gastric emptying, decreases hunger
Incretins
Synthetic glucagon-like-polypeptide (GLP-1) analogs which potentiates glucose-mediated insulin release, decreases postprandial glucagon release, decreases gastric emptying, decreases hunger
What are the side effects of the sulfonylureas?
Hypoglycemia; cross-reaction with sulfonamide allergy; weight gain
What is the longest acting sulfonylurea?
Chlorpropamide
Which sulfonylurea can cause disulfiram-like reactions?
Chlorpropamide
Which sulfonylurea can cause syndrome of inappropriate secretion of antidiuretic hormone (SIADH)?
Chlorpropamide
The dose of what second-generation sulf onylurea should be decreased in patients with renal dysfunction?
Glyburide
The dose of what second-generation sulf onylurea should be decreased in patients with hepatic dysfunction?
Glipizide
What are the side effects of the thiazolidinediones (TZDs)?
Edema; congestive heart failure (CHF) exacerbation; weight gain; hepatotoxicity; macular edema (rare); increased bone fractures in women due to diminished osteoblast formation
Name two concomitant health conditions in which TZDs may not be used in a diabetic patient.
- CHF
- Liver failure
What are the side effects of the biguanides?
Diarrhea; lactic acidosis; decreased vitamin B12; abnormal taste
What are the side effects of the meglitinides?
Hypoglycemia; upper respiratory tract infection
What are the side effects of the α-glucosidase inhibitors?
Abdominal cramping; diarrhea; flatulence
What drug with positive inotropic and chronotropic activity can be used to stimulate the heart during a β-blocker overdose?
Glucagon
Based on liver function test (LFT) results, when should therapy with a thiazolidinedione be withheld?
When LFTs rise above 2.5 times the upper limit of normal
What oral hypoglycemic should be withheld when the serum creatinine is above 1.5 for males and 1.4 for females?
Metformin
When used alone, can TZDs cause hypoglycemia?
No, TZDs do not cause hypoglycemia.
When used alone, can biguanides cause hypoglycemia?
No, biguanides do not cause hypoglycemia.
What time of day should meglitinides be given?
15 to 30 minutes before each meal
Would oral sucrose be effective in a hypoglycemic patient who is currently taking an α-glucosidase inhibitor?
No, it would not because sucrose is a disaccharide whose absorption is competitively blocked by the α-glucosidase inhibitors.
Would oral glucose be effective in a hypoglycemic patient who is currently taking an α-glucosidase inhibitor?
Yes, it would since glucose is a monosaccharides. α-Glucosidase inhibitors do not block intestinal transporters for monosaccharides.
AGENTS FOR DIABETES INSIPIDUS
What are the two types of diabetes insipidus?
- Neurogenic
- Nephrogenic
Which type of diabetes insipidus is characterized by insensitivity to vasopressin in the collecting ducts?
Nephrogenic diabetes insipidus
Which type of diabetes insipidus is characterized by inadequate secretion of vasopressin from the posterior pituitary gland?
Neurogenic diabetes insipidus
What types of drugs can cause a nephrogenic diabetes insipidus?
Lithium; demeclocycline; vincristine; amphotericin B; alcohol
What two effects does vasopressin have on the body?
- Antidiuresis
- Vasopressor
Where is theV1receptor found?
Vascular smooth muscle (causes vasoconstriction)
Where is the V2receptor found?
Renal collecting ducts (increases water permeability and reabsorption)
What is the drug of choice for neurogenic diabetes insipidus?
Desmopressin
What is desmopressin?
Synthetic analog of vasopressin with longer half-life and no vasopressor activity (antidiuresis properties only)
What is another name for desmopressin?
l-Deamino-8-D-arginine vasopressin (DDAVP)
How is desmopressin administered?
Intranasally; orally
What are the side effects of vasopressin?
Water intoxication; hyponatremia; tremor; headache; bronchoconstriction
What is vasopressin also used for?
Esophageal varices
What is desmopressin also used for?
Hemophilia A; von Willebrand disease; primary nocturnal enuresis
How is nephrogenic diabetes insipidus treated?
Thiazide diuretics in combination with amiloride; chlorpropamide; clofibrate
What drug that can cause nephrogenic diabetes insipidus is used to treat SIADH?
Demeclocycline
AGENTS FOR THYROID DISORDERS
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