Introduction
Atenolol is a selective β1-adrenergic receptor blocking agent belonging to the class of cardioselective beta-blockers. First introduced in 1976, it has become a cornerstone in the management of various cardiovascular conditions. As a water-soluble beta-blocker, atenolol exhibits distinct pharmacokinetic properties that differentiate it from lipid-soluble alternatives like propranolol.
Mechanism of Action
Atenolol competitively blocks β1-adrenergic receptors in the heart and vascular smooth muscle, with minimal effect on β2-adrenergic receptors. This selective blockade results in:
- Decreased heart rate (negative chronotropy)
- Reduced myocardial contractility (negative inotropy)
- Slowed atrioventricular conduction
- Decreased cardiac output
- Reduced blood pressure through multiple mechanisms including decreased renin release from the kidneys
The cardioselectivity of atenolol is dose-dependent and diminishes at higher doses (>100 mg daily).
Indications
FDA-approved indications:- Hypertension (monotherapy or in combination)
- Angina pectoris management
- Acute myocardial infarction (early treatment)
- Supraventricular tachycardia
- Migraine prophylaxis
- Essential tremor
- Symptomatic relief in hyperthyroidism
- Performance anxiety
Dosage and Administration
Hypertension:- Initial dose: 25-50 mg once daily
- Maintenance: 50-100 mg once daily
- Maximum dose: 100 mg daily (some guidelines recommend up to 200 mg)
- Initial: 50 mg once daily
- Maintenance: 100 mg once daily
- Maximum: 200 mg daily
- 5 mg IV over 5 minutes, followed by 50 mg orally after 10 minutes
- Then 50 mg every 12 hours or 100 mg once daily for 6-9 days
- Renal impairment: Adjust based on creatinine clearance
- CrCl 15-35 mL/min: Maximum 50 mg daily - CrCl <15 mL/min: Maximum 25 mg daily
- Hepatic impairment: No specific adjustment needed
- Elderly: Start with lower doses (25 mg daily)
- Pediatrics: Not routinely recommended
Pharmacokinetics
Absorption: Approximately 50% oral bioavailability with peak plasma concentrations in 2-4 hours Distribution: Low lipid solubility, limited CNS penetration; volume of distribution 50-75 L Protein binding: <5% protein bound Metabolism: Minimal hepatic metabolism (<10%) Elimination: Primarily renal excretion unchanged (85-100%); half-life 6-7 hours (prolonged in renal impairment) Dialyzability: Yes (hemodialysis)Contraindications
- Cardiogenic shock
- Sinus bradycardia or heart block greater than first degree
- Overt cardiac failure
- Hypersensitivity to atenolol or beta-blockers
- Severe peripheral arterial disease
- Sick sinus syndrome (unless pacemaker present)
- Uncontrolled heart failure
Warnings and Precautions
Black Box Warning: Do not abruptly discontinue therapy (can exacerbate angina, cause MI, or ventricular arrhythmias)- May mask signs of hypoglycemia in diabetics
- Can precipitate heart failure in susceptible patients
- May cause bronchospasm in patients with reactive airway disease
- Reduced exercise tolerance
- Depression and sleep disturbances
- Cold extremities and Raynaud's phenomenon
- May enhance sensitivity to allergens
Drug Interactions
Major interactions:- Calcium channel blockers (verapamil, diltiazem): Additive bradycardia and AV block
- Antiarrhythmics (disopyramide): Increased negative inotropic effects
- Clonidine: Rebound hypertension if discontinued concurrently
- Insulin and oral hypoglycemics: Masked hypoglycemia symptoms
- NSAIDs: Reduced antihypertensive effect
- Digoxin: Additive bradycardia
- Epinephrine: Unopposed alpha-adrenergic effects
- MAO inhibitors: Enhanced hypotensive effects
- Theophylline: Antagonistic effects
Adverse Effects
Common (>10%):- Fatigue
- Dizziness
- Cold extremities
- Bradycardia
- Hypotension
- Depression
- Sleep disturbances
- Impotence
- Gastrointestinal disturbances
- Bronchospasm
- Heart failure exacerbation
- AV block
- Hallucinations
- Rash
- Blood dyscrasias
Monitoring Parameters
- Blood pressure (standing and supine)
- Heart rate and rhythm
- ECG (periodically)
- Renal function (serum creatinine)
- Signs of heart failure
- Blood glucose in diabetics
- Mental status changes
- Exercise tolerance
Patient Education
- Take at the same time each day, with or without food
- Do not abruptly stop taking medication
- Rise slowly from sitting/lying position to prevent dizziness
- Monitor pulse rate regularly
- Report unusual weight gain, shortness of breath, or edema
- Inform all healthcare providers about atenolol use
- Use caution with alcohol consumption
- Be aware of potential masking of hypoglycemia symptoms
- Notify provider before surgery or dental procedures
- Store at room temperature away from moisture
References
1. Frishman WH. Atenolol and timolol, two new systemic β-adrenoreceptor antagonists. N Engl J Med. 1982;306(24):1456-1462. 2. Cruickshank JM. The clinical importance of cardioselectivity and lipophilicity in beta blockers. Am Heart J. 1980;100(2):160-178. 3. Package Insert: Tenormin (atenolol). AstraZeneca Pharmaceuticals LP. 4. Wiysonge CS, Bradley HA, Volmink J, et al. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2017;1:CD002003. 5. American College of Cardiology/American Heart Association Hypertension Guidelines. J Am Coll Cardiol. 2018;71(19):e127-e248. 6. McDevitt DG. Comparison of pharmacokinetic properties of beta-adrenergic blocking drugs. Eur Heart J. 1987;8 Suppl M:9-14.