Endocrine Agents

AGENTS FOR DIABETES MELLITUS

What are the two general categories of drugs that are used to treat diabetes mellitus?

1. Insulin
   
2. 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?

1. β-Hydroxybutyric acid
   
2. Acetoacetic acid
   
3. 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.

1. CHF
   
2. 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?

1. Neurogenic
   
2. 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?

1. Antidiuresis
   
2. 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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