nadolol (Rx)

>10%

Drowsiness

Insomnia

Decreased sexual ability

1-10%

Bradycardia (2%)

Dizziness (2%)

Fatigue (2%)

Hypotension (1%)

<1%

Abdominal discomfort

Constipation

Diarrhea

Nausea

Cough

Nasal congestion

Frequency Not Defined

Bronchospasm, depression, decreased exercise tolerance, Raynaud's phenomenon

May increase triglyceride levels and insulin resistance, and decrease HDL levels

Contraindications

Hypersensitivity

2°/3° heart block

Bronchial asthma

Sinus bradycardia

Cardiogenic shock

Overt cardiac failure

Cautions

Anesthesia/surgery (myocardial depression); chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures

Use caution in cerebrovascular insufficiency, well-compensated CHF, liver disease, renal impairment, peripheral vascular disease

Use caution in nonallergic bronchospasm; may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta receptors

Beta-adrenergic blockade may prevent appearance of premonitory signs and symptoms (eg, tachycardia and blood pressure changes) of acute hypoglycemia; this is especially important with labile diabetics; beta-blockade also reduces release of insulin in response to hyperglycemia; dose adjustment of antidiabetic drugs may be necessary

Beta-adrenergic blockade may mask certain clinical signs (eg, tachycardia) of hyperthyroidism; patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blockade which might precipitate thyroid storm

Adequate alpha-blockade required prior to administering beta-blockade in untreated pheochromocytoma

Cardiac Failure

• Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure
• Inhibition by beta-blockade may precipitate more severe failure; although beta-blockers should be avoided in overt congestive heart failure, if necessary, may use with caution in patients with history of failure who are well-compensated, usually with digitalis and diuretics
• Beta-adrenergic blocking agents do not abolish inotropic action of digitalis on heart muscle
• In patients without a history of heart failure, continued use of beta-blockers can, in some cases, lead to cardiac failure
• At the first sign or symptom of heart failure, such patient should be digitalized and/or treated with diuretics, and response observed closely, or nadolol should be discontinued (gradually, if possible)

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal

• Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy
• Exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of therapy
• Gradually reduce dose when discontinuing chronically administered nadolol, particularly in patients with ischemic heart disease, over a period of one to two weeks; patient should be carefully monitored
• If angina markedly worsens or acute coronary insufficiency develops, nadolol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for management of unstable angina should be taken
• Patients should be warned against interruption or discontinuation of therapy without physician's advice
• Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue nadolol therapy abruptly even in patients treated only for hypertension

Pregnancy Category: C

Lactation: concentrated in breast milk, use caution (AAP Committee states compatible w/ nursing)

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Blocks response to beta-adrenergic stimulation to beta1 and beta2 receptors; may reduce portal pressure through beta2 receptor, which reduces portal blood flow

Pharmacokinetics

Half-Life: 10-24 hr

Onset: 3-4 hr

Duration: 17-24 hr

Vd: 1.9 L/kg (1.88-2.02 L/kg)

Peak Plasma Time: 2-4 hr

Bioavailability: 20-40%

Protein Bound: 28-30%

Metabolism: None

Excretion: Urine

Dialyzable: Yes (HD)