nadolol (Corgard)

Introduction

Trademark: Corgard.

Indications

• hypertension
• tachyarrhythmias
  • thyrotoxicosis
• cardiac angina
• post myocardial infarction
  • secondary prevention in patients with cardiovascular disease
• mitral valve prolapse
• long QT syndrome
• migraine prophylaxis
• tremor

Contraindications

• bronchial asthma or COPD
• heart failure or cardiogenic shock
• 2nd or 3rd degree AV block
• severe sinus bradycardia

pregnancy category = c

safety in lactation = ?

Dosage

• start: 40 mg PO QD
• usual effective dose: 40-80 mg PO QD
• maximum: 320 mg/day
• taper over 1-2 weeks when discontinuing therapy

Tabs: 20, 40, 80, 120, 160 mg.

Dosage adjustment in renal failure

Table

creatinine clearance	dosage
31-50 mL/min	every 24-36 hours
10-30 mL/min	every 24-48 hours
< 10 mL/min	every 40-60 hours

Pharmacokinetics

• oral absorption averages 20-40%, no effect of food
• protein-binding 30%
• therapeutic levels:
  • peak steady state concentration 55-62 ng/mL 2-4 hours after oral administration
  • trough level: 32 ng/mL
• tissue distribution:
  • aqueous humor concentration 1/2 of serum concentration
• elimination 1/2life is 20-24 hours
• NOT appreciably metabolized
• eliminated unchanged in the urine & feces
• antihypertensive effect may take a few days to several weeks

elimination via kidney

1/2life = 14-18 hours

1/2life = 20-24 hours

protein binding = 16-24 %

protein binding = 30 %

elimination by hemodialysis = +

Adverse effects

• nausea
• diarrhea
• constipation
• bradycardia
• hypotension
• paresthesias
• dizziness
• sedation
• bronchospasm (0.1%)
• carpal tunnel syndrome (rare)
• hypoglycemia in type I diabetics:
  • may mask symptoms
  • may prolong hypoglycemia
• dry eyes (0.1-0.5%)
• papilledema (rare)
• cough & nasal congestion (0.1-0.5%)
• alopecia, rash, pruritus (0.1-0.5%)

• drug adverse effects of beta-adrenergic receptor antagonists
• drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
• drug adverse effects of antihypertensive agents

Drug interactions

• alpha-1 adrenergic antagonists: orthostatic hypotension
• amiodarone: symptomatic bradycardia & sinus arrest
• sympathomimetics
• lidocaine serum levels may increase by 20-30%
• methacholine
• methyldopa (paradoxical hypertensive response to stress)
• NSAIDs may interfere with antihypertensive effect
• phenothiazines may decrease metabolism of nadolol

• drug interaction(s) of beta-2 adrenergic receptor agonists with beta adrenergic receptor antagonists
• drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
• drug interaction(s) of beta-adrenergic receptor antagonists with thyroid hormone
• drug interaction(s) of beta-adrenergic receptor antagonists with sulfinpyrazone
• drug interaction(s) of beta-adrenergic receptor antagonists with salicylate
• drug interaction(s) of beta-adrenergic receptor antagonists with rifampin
• drug interaction(s) of beta-adrenergic receptor antagonists with ampicillin
• drug interaction(s) of beta-adrenergic receptor antagonists with colestipol
• drug interaction(s) of beta-adrenergic receptor antagonists with cholestyramine
• drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates
• drug interaction(s) of beta-adrenergic receptor antagonists with calcium salts
• drug interaction(s) of beta-adrenergic receptor antagonists with aluminum carbonate
• drug interaction(s) of beta-adrenergic receptor antagonists with aluminum hydroxide
• drug interaction(s) of beta-adrenergic receptor antagonists with prazosin
• drug interaction(s) of beta-adrenergic receptor antagonists with lidocaine
• drug interaction(s) of beta-adrenergic receptor antagonists with ergot alkaloids
• drug interaction(s) of beta-adrenergic receptor antagonists with clonidine
• drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists (except atenolol) with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with quinolones
• drug interaction(s) of beta-adrenergic receptor antagonists with quinidine
• drug interaction(s) of beta-adrenergic receptor antagonists with propafenone
• drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines
• drug interaction(s) of beta-adrenergic receptor antagonists with MAO inhibitors
• drug interaction(s) of beta-adrenergic receptor antagonists with loop diuretics
• drug interaction(s) of beta-adrenergic receptor antagonists with hydralazine
• drug interaction(s) of beta-adrenergic receptor antagonists with histamine H2 receptor antagonists
• drug interaction(s) of beta-adrenergic receptor antagonists with haloperidol
• drug interaction(s) of beta-adrenergic receptor antagonists with flecainide
• drug interaction(s) of beta-adrenergic receptor antagonists with oral contraceptives
• drug interaction(s) of beta-adrenergic receptor antagonists with calcium channel blockers
• drug interaction(s) of beta-adrenergic receptor antagonists with sulfonylureas
• drug interaction(s) of beta blockers with ACE inhibitors
• drug interaction(s) of spironolactone with beta blockers
• drug interaction(s) of NSAIDs with beta blockers
• drug interaction(s) of NSAIDs & antihypertensives

Laboratory

• specimen: serum, plasma (EDTA, heparin)
• methods: fluorometry, GC-MS, HPLC

Mechanism of action

• lipid insoluble non-selective beta-adrenergic antagonist

More general terms

• propanolamine
• non-specific beta-adrenergic receptor antagonist

Component of

• bendroflumethiazide/nadolol (Corzide)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=39147
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4411