Atenolol

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
CAS Number: 29122-68-7
Brands: Tenoretic, Tenormin

Introduction

β₁-Selective adrenergic blocking agent.^{111 118 120 274 c}

Uses for Atenolol

Hypertension

Management of hypertension; used alone or in combination with other classes of antihypertensive agents.^{100 108 109 110 111 128 152 153 154 155 156 157 158 159 170 171 172 173}

One of several preferred initial therapies in hypertensive patients with ischemic heart disease,^{170 223} heart failure,^{220 231 246 252} or diabetes mellitus.²¹⁴

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.²³¹

Angina

Management of chronic stable angina pectoris.^{111 112}

A component of the standard therapeutic measures in the management of unstable angina or non-ST-segment elevation/non-Q-wave MI†.^{223 224 274}

AMI

Secondary prevention following AMI to reduce the risk of cardiovascular mortality.^{111 113 120 122 123 124 132 169 274}

Supraventricular Tachyarrhythmias

β-Adrenergic blocking agents, including atenolol, are one of several preferred antiarrhythmic agents for the treatment of stable, narrow-complex supraventricular tachycardias (e.g., paroxysmal supraventricular tachycardia† [reentry supraventricular tachycardia], ectopic† or multifocal atrial tachycardia†, junctional tachycardia†) if the rhythm is not controlled by vagal maneuvers or adenosine in patients with preserved left ventricular function and for rate control in atrial fibrillation or flutter† in patients with preserved left ventricular function.²⁷⁴

Ventricular Tachyarrhythmias

Reducing the incidence of ventricular fibrillation† associated with myocardial ischemia or infarction.^{169 211 274}

Treatment of sustained polymorphic ventricular tachycardia† following AMI.^{169 211}

CHF

Bisoprolol, carvedilol, and extended-release metoprolol have been shown to be effective in reducing the risk of death in patients with chronic heart failure; however, these positive findings should not be considered indicative of β-adrenergic blocking agent class effect.²⁶¹

Vascular Headache

Prophylaxis of migraine headache†.²²⁸

Atenolol is not recommended for the treatment of a migraine attack that has already started.²²⁸

Alcohol Withdrawal

Management of acute alcohol withdrawal† in conjunction with a benzodiazepine.^{101 229}

Atenolol should not be used as monotherapy for acute alcohol withdrawal†.^{229 230}

Atenolol Dosage and Administration

General

• 
  

  Individualize dosage according to patient response.¹¹¹

  
  


• 
  

  β₁-Adrenergic blocking selectivity diminishes as dosage is increased.^{111 120}

  
  


• 
  

  If long-term therapy is discontinued, reduce dosage gradually over a period of about 2 weeks.^{111 120}

  
  

Administration

Administer orally or by slow IV injection.^c

Oral Administration

Once-daily dosing usually is sufficient in the management of hypertension.^c

IV Administration

Monitor heart rate, BP, and ECG during IV therapy.¹²⁰

Dilution

May be administered undiluted by slow IV injection or diluted in dextrose injection, sodium chloride injection, or dextrose and sodium chloride injection prior to administration.¹²⁰

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

Administer at a rate of 1 mg/minute.¹²⁰

Dosage

Pediatric Patients

Hypertension†

Oral

Some experts recommend an initial dosage of 0.5–1 mg/kg daily given as a single dose or in 2 divided doses.²⁵⁸ Increase dosage as necessary up to a maximum dosage of 2 mg/kg (up to 100 mg) daily given as a single dose or in 2 divided doses.²⁵⁸

Adults

Hypertension

Monotherapy

Oral

Initially, 25–50 mg once daily.^{214 215} Full hypotensive response may require 2 weeks.^c

If necessary, increase to 100 mg once daily.²¹⁴ Some patients may have improved BP control with twice-daily dosing.¹⁷⁰

Combination Therapy.

Oral

Atenolol in fixed combination with chlorthalidone: initially, 50 mg of atenolol and 25 mg of chlorthalidone once daily.¹¹⁸ If response is not optimal, 100 mg of atenolol and 25 mg of chlorthalidone once daily.¹¹⁸

Initial use of fixed-combination preparations is not recommended; adjust by administering each drug separately, then use the fixed combination if the optimum maintenance dosage corresponds to the ratio of drugs in the combination preparation.^{118 c} Administer separately for subsequent dosage adjustment.^c

May add another antihypertensive agent when necessary (gradually using half of the usual initial dosage to avoid an excessive decrease in BP).¹¹⁸

Angina

Oral

Initially, 50 mg once daily.¹¹¹

If optimum response is not achieved within 1 week, increase to 100 mg once daily.¹¹¹

Some patients may require 200 mg once daily for optimum effect.¹¹¹

AMI

Early Treatment

IV

Initially, 2.5–5 mg over 2–5 minutes.^{113 120 169}

If initial dose is tolerated, ¹¹³ then 2.5–5 mg every 2–10 minutes to a total of 10 mg over 10–15 minutes.^{113 120 169}

Oral (following IV dosage)

If the total IV dose is tolerated, administer 50 mg orally 10 minutes later, then 50 mg orally 12 hours later.^{111 113 120 169}

Continue 100 mg daily (as a single daily dose or in 2 equally divided doses) for 6–9 days (or until a contraindication [e.g., bradycardia or hypotension requiring treatment] develops or the patient is discharged).^{111 113 120 124 169}

If necessary, may reduce to 50 mg daily.^{111 113}

Oral alternative dosage

May eliminate IV doses and administer orally when safety of IV use is questionable and oral therapy is not contraindicated.^{111 120}

Administer 100 mg once daily or in 2 equally divided doses for at least 7 days^{111 120}

Late Treatment

Oral

If not initiated acutely (see AMI: Early Treatment, under Dosage and Administration), initiate long-term therapy within a few days of an AMI.¹⁶⁹

Optimum duration remains to be clearly established,^{111 120} but studies suggest optimum benefit with at least 1–3 years of therapy after infarction (if not contraindicated).^{111 113 120 122 132 134}

Indefinite continuation of therapy (unless contraindicated) has been recommended.^{169 173}

Supraventricular Tachyarrhythmias†

Paroxysmal Supraventricular Tachycardia†, Junctional Tachycardia†, Ectopic Tachycardia†, Multifocal Atrial Tachycardia†)

IV

5 mg by slow IV infusion over 5 minutes has been used.²⁷⁴ If arrhythmia persists 10 minutes after first dose and the first dose was well tolerated, give a second 5-mg dose over 5 minutes.²⁷⁴

Atrial Fibrillation†

IV

Slow IV infusion: 2.5–5 mg over 2–5 minutes as necessary to control rate, up to 10 mg over a 10- to 15-minute period.^{169 211}

Alternatively, 5 mg by slow IV infusion over 5 minutes has been used.²⁷⁴ If arrhythmia persists 10 minutes after first dose and the first dose was well tolerated, give a second 5-mg dose over 5 minutes.²⁷⁴

Monitor heart rate, BP, and ECG; discontinue when efficacy is achieved, SBP declines to <100 mm Hg, or heart rate slows to <50 bpm.¹⁶⁹

Vascular Headache†

Prevention of Common Migraine†

Oral

Dosage has not been established; in clinical studies 100 mg daily was usual effective dosage.²²⁸

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Maximum 2 mg/kg (up to 100 mg) daily.²⁵⁸

Adults

Hypertension

Monotherapy

Oral

Increasing beyond 100 mg daily usually does not result in further improvement in blood pressure control.^{111 c}

AMI

Early Treatment

IV

Maximum 10 mg over 10–15 minutes.^{113 120 169}

Supraventricular Tachyarrhythmias†

Atrial Fibrillation†

IV

Maximum 10 mg over a 10- to 15-minute period.^{169 211}

Special Populations

Hepatic Impairment

Minimal hepatic metabolism; no dosage adjustment recommended.^{111 120}

Renal Impairment

Hypertension

Oral

Modify doses and/or frequency of administration in response to the degree of renal impairment.^c

Initial dose of 25 mg daily may be necessary.¹¹¹

Measure BP just prior to the dose to ensure persistence of adequate BP reduction.¹¹¹

Cl_cr 15–35 mL/minute per 1.73 m²

Maximum 50 daily.¹¹¹

Cl_cr<15 mL/minute per 1.73 m²

Maximum 25 mg daily or 50 mg every other day.^{111 120}

Hemodialysis

May administer 25 or 50 mg after each dialysis.¹¹¹

Marked reductions in BP may occur; give under careful supervision.¹¹¹

Geriatric Patients

Hypertension

Oral

Modification of dosage may be necessary because of age-related decreases in renal function.¹¹¹

Initially, 25 mg daily may be necessary.¹¹¹

Measure BP just prior to a dose to ensure persistence of adequate BP reduction.¹¹¹

Bronchospastic Disease

Oral

Initially, 50 mg daily and use lowest possible dosage.¹¹¹ If dosage must be increased, consider administering in 2 divided doses daily to decrease peak blood levels.¹¹¹ A β₂-adrenergic agonist bronchodilator should be available.¹¹¹ (See Bronchospastic Disease under Cautions.)

Cautions for Atenolol

Contraindications

• 
  

  Patients with sinus bradycardia,^{111 118 120 220} AV block greater than first degree,^{111 118 120 220 274} cardiogenic shock,^{111 118 120 220} overt or decompensated cardiac failure. Patients with AMI not promptly and effectively controlled by 80 mg IV furosemide or equivalent therapy.^{111 118 120 220}

  
  


• 
  

  Do not use in patients with untreated pheochromocytoma.^{111 118 120}

  
  


• 
  

  Hypersensitivity to atenolol or any ingredient in the formulation.^{111 118 120 220}

  
  

Warnings/Precautions

Warnings

Cardiac Failure

Possible precipitation of CHF; possible decreased exercise tolerance in patients with left ventricular dysfunction.

Initiate therapy and subsequent dosage adjustments in patients with CHF under close medical supervision. Prior to initiation of the drug, stabilize patient on other therapy (e.g., ACE inhibitor, diuretic, and/or cardiac glycoside). Symptomatic improvement may not be evident for 2–3 months after initiating therapy.

Avoid use in patients with decompensated CHF; use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with ACE inhibitors, cardiac glycosides, and/or diuretics); use with extreme caution in patients with substantial cardiomegaly.

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.

History of Anaphylactic Reactions

Possible increased reactivity to a variety of allergens; patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.^{111 118 120}

Calcium-channel Blocking Agents

Concomitant use may cause bradycardia, heart block, increased left ventricular and diastolic blood pressure, particularly in patients with preexisting conduction abnormalities or left ventricular dysfunction.^{111 120} (See Specific Drugs under Interactions.)

Bronchospastic Disease

Possible bronchoconstriction, especially at dosages >100 mg daily.^c Cautious use recommended in patients with bronchospastic disease (patients who do not respond to or cannot tolerate other hypotensive agents).^{111 120}

Initiate therapy with 50 mg daily and use lowest possible dosage; β₁-selectivity is not absolute.^{111 120} Twice-daily dosing and concomitant use of a β₂-adrenergic agonist bronchodilator may minimize risk of bronchospasm.^{111 120 c}

If bronchospasm occurs, reduce dosage or discontinue atenolol (gradually if possible) and administer supportive treatment.^{111 120 c}

Anesthesia and Major Surgery

Possible increased risks associated with general anesthesia.¹¹¹ (See Anesthetics, General [Myocardial Depressant] under Interactions.)

Withdrawal of β-adrenergic blocking agent prior to surgery is not recommended in most patients.¹¹¹

Correct vagal dominance (if any) with atropine (1–2 mg IV).¹¹¹

Atenolol effects can be reversed by cautious administration of β-agonists (e.g., dobutamine, isoproterenol).^{111 120}

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia, particularly tachycardia.^{111 120}

β₁-Selective atenolol does not potentiate insulin-induced hypoglycemia or delay recovery of blood glucose to normal levels.^{111 120}

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.^{111 120}

Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.^{111 120}

General Precautions

Peripheral Arterial Circulatory Disorders

May be aggravated.^{111 118 120}

Other Precautions

Atenolol shares the toxic potentials of β-adrenergic blocking agents; observe usual precautions of these agents.^c

When used in fixed combination with chlorthalidone, consider the cautions, precautions, and contraindications associated with thiazide diuretics.^{115 116 117 118}

Specific Populations

Pregnancy

Category D.^{111 118 120}

Lactation

Distributed into milk;^{103 107 111 118 120 125 129} caution if used in nursing women.^{111 118 120 151}

Pediatric Use

Safety and efficacy remain to be fully established in children;^{111 118 120} however, some experts have recommended dosages for hypertension based on current limited clinical experience.²⁵⁸

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults; however, use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.^{111 118 120}

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary.¹¹¹ Evaluation of geriatric patients with hypertension or MI should always include assessment of renal function.^{111 120} (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Decreased clearance; use with caution and adjust dosage based on degree of renal impairment.^{111 120} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Tiredness,^{111 120} hypotension,^{111 120} heart failure,^{111 120} bradycardia,^{111 113 120 124} ventricular tachycardia,^{111 120} dizziness,^{111 120} cold extremities,^{111 120} depression,^{111 120} supraventricular tachycardia (atrial fibrillation or flutter),^{111 120} bundle branch block and major axis deviation,^{111 120} fatigue,^{111 120} dyspnea.^{111 120}

Interactions for Atenolol

Specific Drugs

Drug	Interaction	Comments
β-Adrenergic blocking agents	Potential additive effect111 120	Adjust initial and subsequent atenolol dosage downward based on clinical findings (e.g., blood pressure, heart rate)111 120
Anesthetics, general (myocardial depressant)	Increased risk of hypotension and heart failurec	Use with caution111 (see Anesthesia and Major Surgery under Cautions)
Calcium-channel blockers (e.g., verapamil, diltiazem)	Additive hypotensive effect; may be used to therapeutic advantagec Potential for bradycardia and heart block, increase in left ventricular end diastolic pressure111 120	Adjust dosage carefullyc Patients with preexisting conduction abnormalities or left ventricular dysfunction particularly susceptible111 120
Catecholamine-depleting drugs (e.g., reserpine)	Potential for additive effects (increased hypotension and marked bradycardia)111 120	Monitor closely for symptoms (e.g., vertigo, syncope, postural hypotension)111 120
Clonidine	May exacerbate rebound hypertension following discontinuance of clonidine111 120	Discontinue atenolol therapy several days before clonidine discontinuance.111 120 If replacing clonidine, delay initiation of atenolol for several days after stopping clonidine111 120
Hydralazine	Additive hypotensive effect; may be used to therapeutic advantagec	Adjust dosage carefullyc
Methyldopa	Additive or potentiated hypotensive effect; may be used to therapeutic advantagec	Adjust dosage carefully when used concurrentlyc
NSAIAs (e.g., indomethacin, aspirin)	Potential for decreased atenolol antihypertensive effect111 118 120	Studies indicate no clinically important interaction; concomitant administration appears safe and effective111 118 120

Atenolol Pharmacokinetics

Absorption

Bioavailability

50–60% following oral administration.^c

Onset

1 hour following oral administration.^{111 120} Within 5 minutes following IV administration.^{111 120}

Duration

At least 24 hours following oral administration (antihypertensive and β-adrenergic blocking effects).^{111 120} About 12 hours following IV administration (effect on heart rate).¹²⁰

Special Populations

In geriatric patients, plasma concentrations are increased.^{111 118 120}

Distribution

Extent

Well distributed into most tissues and fluids except brain and CSF.^c

Readily crosses the placenta, has been detected in cord blood.^{102 111 118 120}

Distributed into milk in concentrations higher than those in serum.^{103 107 111 118 120 125 129 131}

Plasma Protein Binding

Approximately 6–16%.^{111 118 120}

Elimination

Metabolism

Little or no hepatic metabolism.^c

Elimination Route

40–50% excreted unchanged in urine following oral administration;^c remainder in feces, principally as unabsorbed drug.^c

Half-life

6–7 hours.^c

Special Populations

In patients with Cl_cr 15–35 mL/minute per 1.73 m², plasma half-life is increased to 16–27 hours; in progressive renal impairment plasma half-life is >27 hours.^c

In geriatric patients, total clearance is decreased by about 50%, plasma half-life is prolonged.^{111 118 120}

Hemodialysis: 1–12% removed.^c

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 20–25°.¹¹¹

Tablets (Atenolol and Chlorthalidone)

Tight, light-resistant containers at 20–25°.¹¹¹

Parenteral

Injection

20–25°.¹²⁰

Protect from light.¹²⁰

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Manufacturer states that dilutions in dextrose injection, sodium chloride injection, or sodium chloride and dextrose injection are stable for 48 hours if not used immediately.¹²⁰

Drug Compatibility

Y-Site CompatibilityHID

Compatible
Meperidine HCl
Meropenem
Morphine sulfate
Incompatible
Amphotericin B cholesteryl sulfate complex

ActionsActions

• 
  

  Inhibits response to adrenergic stimuli by competitively blocking β₁-adrenergic receptors within the myocardium.^c Blocks β₂-adrenergic receptors within bronchial and vascular smooth muscle only in high doses (e.g., >100 mg daily).^c

  
  


• 
  

  Decreases resting and exercise-stimulated heart rate and reflex orthostatic tachycardia by about 25–35%.^c Slows AV nodal conduction.^c

  
  


• 
  

  No intrinsic sympathomimetic activity and little or no membrane-stabilizing effect on the heart.^c

  
  


• 
  

  Reduces BP by decreasing cardiac output, suppressing renin release, and/or decreasing sympathetic outflow from the CNS.^c

  
  


• 
  

  In patients with angina pectoris, blocks catecholamine-induced increases in heart rate, myocardial contractility, and BP, resulting in decreased myocardial oxygen consumption.^{111 120 c}

  
  


• 
  

  Possibly increases oxygen requirements in patients with heart failure due to increased left ventricular fiber length and end diastolic pressure.¹¹¹

  
  


• 
  

  Increases airway resistance (at doses >100 mg) in patients with asthma and/or COPD.^c

  
  


• 
  

  Produces little or no changes in serum insulin concentrations, time to recovery from insulin-induced hypoglycemia, or free fatty acid response to hypoglycemia.^c

  
  

Advice to Patients

• 
  

  Importance of taking medication exactly as prescribed.^c

  
  


• 
  

  Importance of not interrupting or discontinuing therapy without consulting clinician.^c

  
  


• 
  

  If a dose is missed, importance of patient taking only the next scheduled dose (i.e., the next dose should not be doubled).^c

  
  


• 
  

  Importance of advising patients with coronary artery disease to temporarily limit their physical activity when discontinuing therapy.^{111 118 120}

  
  


• 
  

  Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure (e.g., weight gain, increased shortness of breath) or if any difficulty in breathing occurs.^c

  
  


• 
  

  Importance of patients undergoing major surgery informing anesthesiologist or dentist they are receiving the drug.^c

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.^c

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{111 118 120}

  
  


• 
  

  Importance of clinician informing women who are or plan to become pregnant of risk to fetus.^{111 118 120}

  
  


• 
  

  Importance of informing patient of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atenolol

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	25 mg*	Atenolol Tablets
			Tenormin	AstraZeneca
		50 mg*	Atenolol Tablets
			Tenormin (scored)	AstraZeneca
		100 mg*	Atenolol Tablets
			Tenormin	AstraZeneca
Parenteral	Injection, for IV use	0.5 mg/mL	Tenormin I.V.	AstraZeneca

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atenolol Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	50 mg with Chlorthalidone 25 mg*	Atenolol and Chlorthalidone Tablets
			Tenoretic (scored)	AstraZeneca
		100 mg with Chlorthalidone 25 mg*	Atenolol and Chlorthalidone Tablets
			Tenoretic	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atenolol 100MG Tablets (SANDOZ): 90/$19.99 or 180/$39.98

Atenolol 25MG Tablets (SANDOZ): 90/$14.99 or 180/$23.98

Atenolol 50MG Tablets (SANDOZ): 90/$17.99 or 180/$27.97

Atenolol-Chlorthalidone 100-25MG Tablets (MYLAN): 90/$30.99 or 180/$59.97

Atenolol-Chlorthalidone 50-25MG Tablets (MYLAN): 30/$13.99 or 90/$32.97

Tenoretic 100 100-25MG Tablets (ASTRAZENECA): 30/$86.99 or 90/$240.98

Tenoretic 50 50-25MG Tablets (ASTRAZENECA): 30/$61.99 or 90/$170.96

Tenormin 100MG Tablets (ASTRAZENECA): 30/$82.98 or 90/$227.13

Tenormin 25MG Tablets (ASTRAZENECA): 30/$61.15 or 90/$159.4

Tenormin 50MG Tablets (ASTRAZENECA): 30/$61.14 or 90/$163.78

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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122. Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. JAMA. 1988; 260:2088-93. [IDIS 246179] [PubMed 2901501]

123. ISIS-1 (First International Study of Infarct Survival) Collaborative Group. Mechanisms for the early mortality reduction produced by beta-blockade started early in acute myocardial infarction: ISIS-1. Lancet. 1988; 1:921-3. [PubMed 2895838]

124. Yusuf S, Sleight P, Rossi P et al. Reduction in infarct size, arrhythmias and chest pain by early intravenous beta blockade in suspected acute myocardial infarction. Circulation. 1983; 67(6 Part 2):I-32-41. [IDIS 171441] [PubMed 6851037]

125. Schimmel MS, Eidelman AJ, Wilschanski MA et al. Toxic effects of atenolol consumed during breast feeding. J Pediatr. 1989; 114:476-8. [IDIS 251776] [PubMed 2921694]

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127. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988; 2:349-60. [PubMed 2899772]

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