Brands, Medical Use, Clinical Data
Drug Category
- Sympatholytics
- Antihypertensive Agents
- Anti-Arrhythmia Agents
- Adrenergic beta-Antagonists
Dosage Forms
- Tablets (20 mg, 40 mg, 80 mg, 120 mg, and 160 mg)
Brands / Synonyms
Anabet; Corgard; Corzide; Nadolol; Solgol
Indications
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.
Absorption
Absorption of nadolol after oral dosing is variable, averaging about 30 percent.
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.
Biotrnasformation / Drug Metabolism
Not metabolized by the liver and excreted unchanged primarily by the kidneys.
Contraindications
Nadolol is contraindicated in bronchial asthma, sinus bradycardia and greater than first degree conduction block,
cardiogenic shock, and overt cardiac failure.
Drug Interactions
When administered concurrently, the following drugs may interact with beta-adrenergic receptor blocking
agents:
Anesthetics, general: exaggeration of the hypotension induced by general anesthetics.
Antidiabetic drugs (oral agents and insulin): hypoglycemia or hyperglycemia; adjust dosage of
antidiabetic drug accordingly.
Catecholamine-depleting drugs (e.g., reserpine): additive effect; monitor closely for evidence of
hypotension and/or excessive bradycardia (e.g., vertigo, syncope, postural hypotension).
Response to Treatment for Anaphylactic Reaction: While taking beta-blockers, patients with a history
of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either
accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to
treat allergic reaction.
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