Atenolol
Tenormin
Approved Indications & Off-Label Uses
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Hypertension | Adults | Monotherapy or combination | FDA Approved |
| Angina pectoris (chronic stable) | Adults | Monotherapy or combination | FDA Approved |
| Acute myocardial infarction (hemodynamically stable) | Adults | IV then oral (early intervention) | FDA Approved |
Atenolol is a hydrophilic, cardioselective beta-1 blocker with no intrinsic sympathomimetic activity and no membrane-stabilizing properties. It was one of the most widely prescribed antihypertensives for decades; however, since the 2002 LIFE trial demonstrated inferior stroke prevention compared with losartan, and subsequent meta-analyses raised concerns about cardiovascular outcomes, current guidelines (2017 ACC/AHA) no longer recommend atenolol as first-line monotherapy for uncomplicated hypertension. It retains important roles in angina, rate control, and secondary prevention post-MI. Notably, atenolol is not one of the three evidence-based beta-blockers recommended for heart failure with reduced ejection fraction.
Rate control in atrial fibrillation/flutter — Once-daily dosing and 24-hour beta-blocking effect support sustained rate control; recommended by AHA/ACC/HRS guidelines as a class option. Evidence quality: High.
Supraventricular tachycardia (SVT) — Used for acute management and prophylaxis of recurrent SVT. Evidence quality: Moderate.
Migraine prophylaxis — Supported by some evidence but less studied than propranolol or metoprolol for this indication. Evidence quality: Low–Moderate.
Thyrotoxicosis symptom control — Controls adrenergic symptoms (tachycardia, tremor); hydrophilic nature means less CNS penetration. Evidence quality: Moderate.
Dosing by Clinical Scenario
Adult Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Essential hypertension | 50 mg once daily | 50–100 mg once daily | 100 mg/day | Full effect within 1–2 weeks; doses >100 mg/day unlikely to provide additional benefit Measure trough BP to confirm 24-hour coverage; may use with thiazide diuretics for additive effect |
| Chronic stable angina | 50 mg once daily | 100 mg once daily | 200 mg/day | Increase after 1 week if response is inadequate; taper gradually over 1–2 weeks if discontinuing Doses of 50–100 mg provide maximum exercise tolerance effect; 200 mg may be needed in some patients |
| Acute MI — early intervention (hemodynamically stable) | 5 mg IV over 5 min x 2 doses | 50 mg PO 10 min after last IV dose, then 50 mg 12 h later, then 100 mg QD | 100 mg/day (oral maintenance) | Give second IV dose 10 min after first; monitor HR, BP, ECG during IV dosing Continue oral therapy for at least 7 days; data suggest benefit may extend to 1–3 years |
| Rate control — atrial fibrillation (off-label) | 25–50 mg once daily | 50–100 mg once daily | 200 mg/day | Hydrophilic nature means fewer CNS side effects; target resting ventricular rate per guidelines |
Special Populations
| Population | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Renal impairment (CrCl 15–35 mL/min) | 25 mg once daily | 25–50 mg once daily | 50 mg/day | No significant accumulation until CrCl <35; half-life markedly prolonged in severe renal impairment |
| Hemodialysis patients | 25–50 mg after each session | 25–50 mg post-dialysis | 50 mg post-dialysis | Atenolol IS dialyzable (unlike most beta-blockers); give dose after each dialysis session under hospital supervision; marked BP drops can occur |
| Hepatic impairment | No dose adjustment required. Atenolol undergoes little or no hepatic metabolism; the absorbed portion is eliminated primarily by renal excretion. | |||
| Elderly (≥65 years) | 25 mg once daily | Titrate cautiously | Standard max | Plasma levels ~50% higher and clearance ~50% lower than younger patients; assess renal function before starting |
Atenolol’s hydrophilic nature is a double-edged sword. On the positive side, it crosses the blood-brain barrier minimally, leading to fewer CNS side effects (depression, nightmares, insomnia) compared with lipophilic agents like metoprolol or propranolol. This makes it particularly suitable for patients troubled by central side effects on other beta-blockers. On the negative side, its renal-dependent elimination means dose adjustments are critical in patients with impaired kidney function, and the drug is removed by hemodialysis, requiring post-dialysis dosing.
Pharmacology
Mechanism of Action
Atenolol is a second-generation, cardioselective beta-1 adrenergic receptor antagonist. It competitively blocks beta-1 receptors in the heart, reducing heart rate, contractility, and AV conduction velocity. These effects lower cardiac output and myocardial oxygen demand. Like other cardioselective agents, atenolol’s beta-1 selectivity is relative, and at higher doses it may also block beta-2 receptors in bronchial and vascular smooth muscle. Atenolol lacks intrinsic sympathomimetic activity, meaning it does not partially activate the receptors it blocks. It is also devoid of membrane-stabilizing activity, and increasing the dose beyond that required for beta-blockade does not further depress myocardial contractility. Notably, atenolol produces a moderate (~10%) increase in stroke volume at rest and during exercise, distinguishing it from some other beta-blockers.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Rapid but incomplete; ~50% absorbed from GI tract; Tmax 2–4 h; remainder excreted unchanged in feces; food does not significantly affect absorption | 50% oral bioavailability is lower than bisoprolol (80%) but higher than carvedilol (25–35%); once-daily dosing effective despite moderate bioavailability |
| Distribution | Hydrophilic (log P = 0.23); protein binding 6–16%; minimal CNS penetration | Very low protein binding virtually eliminates displacement interactions; hydrophilicity limits blood-brain barrier crossing, reducing CNS side effects (nightmares, depression) |
| Metabolism | Little or no hepatic metabolism; NOT metabolized by CYP enzymes; no active metabolites | No hepatic dose adjustment needed; no CYP-mediated drug interactions; pharmacokinetically simpler than metoprolol or carvedilol |
| Elimination | t½ 6–7 h; absorbed portion excreted primarily unchanged by kidneys; renal excretion closely tracks GFR; half-life markedly prolonged in CrCl <35; atenolol IS dialyzable | Renal-dependent elimination makes dose adjustment essential in kidney disease; dialyzability (unlike most beta-blockers) requires post-dialysis dosing; 24-hour beta-blocking effect despite 6–7 h half-life |
Atenolol Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Tiredness | 26% vs 13% placebo | Most commonly elicited complaint; true drug-attributable rate is approximately half the reported figure when placebo rate is subtracted; may improve over weeks |
| Cold extremities | 12% vs 5% placebo | Peripheral vasoconstriction from beta-2 blockade at higher plasma levels; more troublesome in patients with Raynaud phenomenon or peripheral vascular disease |
| Dizziness | 13% vs 6% placebo | Multifactorial: blood pressure reduction and heart rate slowing; counsel patients to change positions slowly |
| Depression | 12% vs 9% placebo | When elicited by checklist, rates appear high, but placebo-subtracted difference is modest (~3%); recent meta-analyses suggest beta-blockers may contribute more to sleep disturbances than overt depression |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Dizziness (volunteered) | 4% vs 1% placebo | When voluntarily reported (US data), rate is substantially lower than when elicited by checklist; more clinically representative |
| Fatigue (volunteered) | 3% vs 1% placebo | Distinct from “tiredness”; both volunteered at lower rates than elicited; dose-related in longer trials |
| Bradycardia | 3% vs 0% placebo | Expected pharmacologic effect; clinically significant if HR <50 bpm with symptoms; reduce dose or hold |
| Nausea | 3% vs 1% placebo | Usually mild; taking with food may reduce symptoms; persistent nausea warrants evaluation |
| Postural hypotension | 2% vs 1% placebo | Less pronounced than with alpha-blocking agents (carvedilol); counsel slow position changes |
| Vertigo | 2% vs 0.5% placebo | Distinguish from lightheadedness; evaluate for other causes if persistent |
| Diarrhea | 2% vs 0% placebo | Usually self-limiting; maintain hydration |
| Leg pain | 3% vs 1% placebo (elicited) | May reflect peripheral vasoconstriction or underlying vascular disease; assess for claudication |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Severe bradycardia | 1–3% | Days to weeks | Reduce dose or hold; atropine 1–2 mg IV; isoproterenol cautiously; transvenous pacing for refractory cases |
| Worsening heart failure | Uncommon | Days to weeks | Increase diuretics; consider dose reduction or discontinuation; atenolol is NOT recommended for HFrEF treatment |
| AV block (2nd/3rd degree) | Rare | Days to weeks | Discontinue atenolol; atropine or isoproterenol; evaluate need for pacing |
| Bronchospasm | Rare at therapeutic doses | Any time | Administer beta-2 agonist; selectivity is dose-dependent; atenolol produces less FEV1 decline than non-selective agents |
| Rebound angina/MI on abrupt withdrawal | Rare (if tapered properly) | 1–14 days post-discontinuation | Taper gradually; reinstate promptly if rebound symptoms occur; limit physical activity during taper |
| IUGR in pregnancy | Documented risk | Chronic gestational exposure | Atenolol crosses the placenta; associated with intrauterine growth restriction; consider labetalol as preferred alternative per ACOG |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Bradycardia | Most common in acute MI setting | Usually responded to atropine or dose reduction; less frequent in hypertension trials |
| Hypotension | More common in acute MI | Resolved with dose withholding in most cases |
| Cardiac failure | Infrequent | Incidence of heart failure was not increased by atenolol in MI trials overall |
The Tenormin PI presents adverse event rates from two distinct methodologies. US studies used volunteered reporting (patients spontaneously mentioned symptoms), while foreign studies used a symptom checklist (elicited). Elicited rates are consistently higher for both atenolol and placebo groups. For clinical decision-making, the volunteered US data is more representative of what patients will spontaneously report in practice, while the elicited data captures subclinical effects that may affect quality of life if specifically asked about.
Drug Interactions
Atenolol undergoes minimal hepatic metabolism and is not a CYP enzyme substrate, which eliminates most pharmacokinetic drug interactions that affect lipophilic beta-blockers. Its interaction profile is primarily pharmacodynamic, involving other negative chronotropes, agents with additive hypotensive effects, and drugs that mask hypoglycemia. No clinically relevant pharmacokinetic interactions have been documented with warfarin or common antihypertensives.
Because atenolol undergoes minimal hepatic metabolism and is not a CYP substrate, it has no pharmacokinetic interactions with CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) or CYP3A4 inhibitors/inducers. This is a meaningful clinical advantage over metoprolol and carvedilol in patients requiring complex medication regimens. Similarly, no clinically relevant interaction exists with warfarin or thiazide diuretics.
Monitoring Parameters
- Heart RateEvery visit
RoutineBeta-blocking effect is apparent within 1 hour and persists for 24 hours. Hold or reduce dose if HR <50 bpm with symptoms. During IV dosing for acute MI, monitor continuously. - Blood PressureEvery visit; trough measurement
RoutineMeasure trough BP (just before next dose) to confirm 24-hour coverage, especially at lower doses where end-of-dose BP control may attenuate. - Renal FunctionBaseline; periodically
RoutineAtenolol is renally excreted; no significant accumulation until CrCl <35. Assess CrCl before starting and regularly in patients with known or suspected renal impairment. Age-related renal decline must be factored in. - ECGBaseline; if symptomatic
Trigger-basedAssess for pre-existing conduction abnormalities. Repeat if syncope, presyncope, or palpitations develop. Continuous monitoring required during IV dosing. - Blood GlucosePeriodically in diabetics
RoutineBeta-1 selectivity makes atenolol less likely than non-selective agents to mask hypoglycemia or impair glucose recovery, but caution is still warranted. - Signs of Heart FailureEach visit
Trigger-basedWatch for dyspnea, edema, weight gain. Atenolol can precipitate heart failure in susceptible patients. It is NOT one of the three evidence-based beta-blockers for HFrEF.
Contraindications & Cautions
Absolute Contraindications
- Sinus bradycardia
- Heart block greater than first degree (without a functioning pacemaker)
- Cardiogenic shock
- Overt cardiac failure
- Untreated pheochromocytoma
- Known hypersensitivity to atenolol or its excipients
Relative Contraindications (Specialist Input Recommended)
- Bronchospastic disease (asthma, COPD) — atenolol produces significantly less FEV1 decline than non-selective agents, but should be avoided in asthma unless no alternative exists; if used, start at the lowest dose with a beta-2 agonist available
- Severe peripheral arterial disease — beta-blockade may aggravate claudication; metabolic acidosis is a contraindication
- Pregnancy — associated with intrauterine growth restriction; ACOG recommends labetalol as the preferred beta-blocker for gestational hypertension
Use with Caution
- Diabetes mellitus — may mask tachycardia of hypoglycemia; beta-1 selectivity reduces but does not eliminate this risk
- Thyrotoxicosis — may mask tachycardia; abrupt withdrawal can precipitate thyroid storm
- Renal impairment — dose reduction critical when CrCl <35; atenolol accumulates
- Elderly — clearance ~50% lower; start at lower doses and assess renal function
- Breastfeeding — excreted in breast milk at ratio 1.5–6.8 to plasma; clinically significant bradycardia reported in breastfed infants; AAP advises against
- Major surgery — do not routinely withdraw chronic beta-blocker therapy preoperatively
- History of anaphylaxis — patients on beta-blockers may have more severe reactions and be less responsive to epinephrine
Patients should not abruptly discontinue atenolol. Severe exacerbation of angina pectoris, myocardial infarction, and ventricular arrhythmias have been reported following sudden withdrawal. Taper the dose gradually and advise patients to limit physical activity during the withdrawal period. If angina worsens or acute coronary insufficiency develops, reinstate atenolol promptly.
Patient Counselling
Purpose of Therapy
Atenolol slows your heart rate and lowers your blood pressure, reducing the workload on your heart. Depending on your condition, it may be used to manage high blood pressure, prevent chest pain (angina), or protect your heart after a heart attack.
How to Take
Take atenolol once daily at the same time each day. It can be taken with or without food. Do not stop taking this medication suddenly without consulting your doctor, as this can cause serious heart problems. Your doctor will gradually reduce your dose if the medication needs to be stopped.
Sources
- Tenormin (atenolol) tablets — FDA-approved prescribing information (revised 2023). accessdata.fda.govPrimary regulatory source for all three approved indications, dosing, adverse reaction table (volunteered vs. elicited), PK parameters, and renal adjustment guidance.
- Tenormin (atenolol) tablets — FDA prescribing information (2011 revision). accessdata.fda.govCross-reference for the full adverse event table, ISIS-1 trial data, and contraindications including pregnancy warnings.
- ISIS-1 (First International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction. Lancet. 1986;2(8498):57–66. doi:10.1016/S0140-6736(86)90468-6Landmark trial demonstrating 15% relative reduction in mortality with early atenolol in acute MI (n=16,027); basis for the acute MI indication.
- Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). Lancet. 2002;359(9311):995–1003. doi:10.1016/S0140-6736(02)08089-3LIFE trial showing losartan superiority over atenolol for stroke prevention in hypertensive patients with LVH; contributed to atenolol’s decline as first-line antihypertensive.
- Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet. 2004;364(9446):1684–1689. doi:10.1016/S0140-6736(04)17355-8Influential meta-analysis questioning atenolol’s effectiveness as first-line antihypertensive; found no outcome benefit over placebo and inferior results vs. other agents for stroke and mortality.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA Guideline for the Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127–e248. doi:10.1016/j.jacc.2017.11.006Current US hypertension guideline; beta-blockers are no longer first-line for uncomplicated hypertension, partly based on atenolol outcome data (LIFE, Carlberg meta-analysis).
- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2022;79(17):e263–e421. doi:10.1016/j.jacc.2021.12.012Current US HF guideline specifying carvedilol, bisoprolol, and metoprolol succinate as the 3 evidence-based beta-blockers for HFrEF; atenolol is NOT included in this list.
- January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update on Atrial Fibrillation. J Am Coll Cardiol. 2019;74(1):104–132. doi:10.1016/j.jacc.2019.01.011Supports beta-blockers including atenolol as an option for ventricular rate control in atrial fibrillation.
- Barrett AM, Cullum VA. The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias. Br J Pharmacol. 1968;34(1):43–55. doi:10.1111/j.1476-5381.1968.tb07949.xEarly pharmacology establishing the beta-adrenergic receptor blocking properties relevant to atenolol’s class; foundational work for cardioselective beta-blocker development.
- Mason WD, Winer N, Kochak G, et al. Kinetics and absolute bioavailability of atenolol. Clin Pharmacol Ther. 1979;25(4):408–415. doi:10.1002/cpt1979254408Established the ~50% oral bioavailability, renal-dependent elimination, and 6–7 hour half-life of atenolol in healthy subjects.
- Kirch W, Görg KG. Clinical pharmacokinetics of atenolol — a review. Eur J Drug Metab Pharmacokinet. 1982;7(2):81–91. doi:10.1007/BF03188723Comprehensive PK review confirming minimal hepatic metabolism, renal excretion, hydrophilicity, and impact of renal impairment and aging on atenolol disposition.
- McAinsh J, Holmes BF, Smith S, Hood D, Warren D. Atenolol kinetics in renal failure. Clin Pharmacol Ther. 1980;28(3):302–309. PubMed: 7408390Quantified the relationship between GFR and atenolol clearance, establishing the CrCl <35 threshold for dose reduction and confirming dialyzability of atenolol.