indication

Used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension.

pharmacology

Nadolol is a nonselective beta-adrenergic receptor antagonist with a long half-life, and is structurally similar to propranolol. Clinical pharmacology studies have demonstrated beta-blocking activity by showing (1) reduction in heart rate and cardiac output at rest and on exercise, (2) reduction of systolic and diastolic blood pressure at rest and on exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia. Nadolol has no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, nadolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane-stabilizing action.

mechanism of action

Like other beta-adrenergic antagonists, nadolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, nadolol binds at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks beta-2 adrenergic receptors located in bronchiole smooth muscle, causing vasoconstriction. By binding beta-2 receptors in the juxtaglomerular apparatus, nadolol inhibits the production of renin, thereby inhibiting angiotensin II and aldosterone production. Nadolol therefore inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.

toxicity

Oral, mouse: LD₅₀ = 4500mg/kg. Symptoms of overdose include abdominal irritation, central nervous system depression, coma, extremely slow heartbeat, heart failure, lethargy, low blood pressure, and wheezing.

biotransformation

Not metabolized by the liver and excreted unchanged primarily by the kidneys.

absorption

Absorption of nadolol after oral dosing is variable, averaging about 30 percent.

half life

14-24 hours

route of elimination

Unlike many other beta-adrenergic blocking agents, nadolol is not metabolized by the liver and is excreted unchanged, principally by the kidneys. Nadolol is excreted predominantly in the urine.

drug interactions

Acetohexamide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Aminophylline: Antagonism of action and increased effect of theophylline

Chlorpropamide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene.

Dihydroergotoxine: Ischemia with risk of gangrene

Disopyramide: The beta-blocker, nadolol, may increase the toxicity of disopyramide.

Dyphylline: Antagonism of action and increased effect of theophylline

Epinephrine: Hypertension, then bradycardia

Ergonovine: Ischemia with risk of gangrene

Ergotamine: Ischemia with risk of gangrene

Fenoterol: Antagonism

Formoterol: Antagonism

Gliclazide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Glipizide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Glisoxepide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Glycodiazine: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Ibuprofen: Risk of inhibition of renal prostaglandins

Indomethacin: Risk of inhibition of renal prostaglandins

Insulin Glargine: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Isoproterenol: Antagonism

Lidocaine: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Methyldopa: Possible hypertensive crisis

Methysergide: Ischemia with risk of gangrene

Orciprenaline: Antagonism

Oxtriphylline: Antagonism of action and increased effect of theophylline

Pipobroman: Antagonism

Pirbuterol: Antagonism

Piroxicam: Risk of inhibition of renal prostaglandins

Prazosin: Risk of hypotension at the beginning of therapy

Procaterol: Antagonism

Repaglinide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Salbutamol: Antagonism

Salmeterol: Antagonism

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbutaline: Antagonism

Theophylline: Antagonism of action and increased effect of theophylline

Tolazamide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Tolbutamide: The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Verapamil: Increased effect of both drugs