Atenolol


Article Author:
Baryiah Rehman


Article Editor:
Saumya Shah


Editors In Chief:
Casey Ciresi


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Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
10/19/2019 2:37:49 PM

Indications

Atenolol is a second-generation beta-1-selective adrenergic antagonist indicated in the treatment of hypertension, angina pectoris, and acute myocardial infarction. Non-FDA approved indications include treatment of arrhythmias, migraine prophylaxis, paroxysmal supraventricular tachycardia, alcohol withdrawal, thyrotoxicosis, and prophylaxis against secondary myocardial infarction.[1]

Mechanism of Action

Cardioselective beta-1-adrenergic antagonists such as atenolol work by selectively binding to the beta-1 adrenergic receptors found in vascular smooth muscle and the heart, blocking the positive inotropic and chronotropic actions of endogenous catecholamines such as isoproterenol, norepinephrine, and epinephrine, thereby inhibiting sympathetic stimulation.[2] This activity results in a reduction in heart rate, blood pressure, and decreases myocardial contractility. However, in heart failure patients, Atenolol can increase the end-diastolic pressure and left ventricular fiber lengths - conversely resulting in increased oxygen demand. In higher doses, it also exerts its effects by competitively blocking beta-2-adrenoreceptors primarily located in the bronchial and vascular musculature. Due to lack of membrane stabilizing or intrinsic sympathomimetic activity, atenolol has low lipid solubility, and reduced brain penetrance is thereby resulting in fewer CNS side effects.[3] Beta-adrenergic receptor antagonists are also known to increase the AV node's refractory period. Therefore it may also be used off-license for the treatment of supraventricular tachycardia and the prevention of paroxysmal attacks of atrial fibrillation.[4] The duration of action is dose-related - following administration of a dose, the effects are apparent within an hour and are maximal at 2 to 4 hours, persisting for at least 24 hours.

Administration

Atenolol is available in 25 mg, 50 mg and 100 mg tablets for oral administration or 0.5 mg/mL for intravenous injection. The dosage and route of administration vary depending on the indication:

Hypertension: 

The initial adult dose of atenolol is 50 mg per day, given either as a single table or in conjunction with diuretic therapy. In the absence of an adequate therapeutic response after a few weeks, the dosage may be increased to a single 100 mg tablet once a day. Daily doses higher than this are unlikely to produce further benefits. For renal-impaired or elderly patients, a lower dose of 25 mg once a day may be used if they have a creatinine clearance of under 15 ml/min or a maximum dose of 50 mg a day if the creatinine clearance is 15 to 35 ml/min. Careful monitoring of their blood pressure before administering a new dose is necessary.

Angina Pectoris: 

The initial adult dose is 50 mg tablet once a day. If, after a week, the patient has not reached the optimal response, the dose should be increased to one 100 mg tablet daily. Some patients may need 200 mg daily for an optimal therapeutic response. However, withdrawal should be achieved gradually with the patient monitored and advised to limit physical activity during this time.

 Acute Myocardial Infarction: 

Intravenous injection should be initiated as soon as possible after the patient's arrival in the hospital within 12 hours of the myocardial infarction. The FDA recommends for an adult, the IV administration of 5mg of atenolol over 5 minutes followed by another 5 mg IV injection after 10 minutes. A 50 mg oral dose should follow 12 hours later. After that, oral dosing can be either 50 mg twice a day or 100 mg once a day for 6 to 9 days or until discharged from the hospital. 

Adverse Effects

Common side effects include bronchospasm; bradycardia; diarrhea; dizziness; constipation; confusion; dyspnoea; headache; heart failure; erectile dysfunction; nausea; fatigue; paraesthesia; peripheral coldness; rash; sleep disorders; syncope; visual impairment and vomiting.

Rare side effects include alopecia, dry mouth, hepatic disorders, depression, postural hypotension, psychosis, skin reactions, and thrombocytopenia. 

Atenolol should not be stopped abruptly - doing so may result in exacerbation of angina, acute myocardial infarction, or ventricular arrhythmias. Administering atenolol concurrently with amiodarone, digoxin, or verapamil may cause heart block, bradycardia, and left ventricular dysfunction.

Contraindications

Contraindications to atenolol include sinus bradycardia, second or third-degree heart block, cardiogenic shock, heart failure, severe peripheral arterial disease, metabolic acidosis, and pheochromocytoma. It should also be avoided in patients with a history of asthma, bronchospasm, or other obstructive airway diseases unless there is no alternative, in which case it may be given alongside a bronchodilator.[5][6]

Caution is necessary when prescribing to diabetic or thyroid patients as its effects may mask the symptoms of hypoglycemia and thyrotoxicosis - rapid withdrawal may also precipitate a thyroid storm. Prescribers should exercise caution during pregnancy - Atenolol has been shown to cross the placental barrier and is associated with intrauterine growth restriction. Use during breastfeeding is recommended against by the American Academy of Pediatrics due to a risk of neonatal hypoglycemia and bradycardia.[7]

Monitoring

The elimination half-life of atenolol is approximately 6 to 7 hours. The beta-blocking effects manifest within an hour of ingesting a single oral dose and last for 24 hours, whereas, with an intravenous dose, effects are evident within 5 minutes but dissipate after 12 hours. Unlike its other beta-1-blocking counterparts, there is little hepatic metabolism of atenolol - it is primarily renally excreted. Therefore, while no hepatic dosage adjustment is needed, it is imperative to assess renal function before starting treatment, with regular monitoring throughout the duration of treatment. Impaired glomerular function results in a significant accumulation of the drug in the body; therefore, patients with creatinine clearance under 35 mL/min should receive much lower doses. Blood pressure and heart rate should also undergo periodic monitoring, while patients with a history of obstructive airway disease should have regular lung function tests. 

Toxicity

Symptoms of atenolol toxicity may include bradycardia, lethargy, hypotension, respiratory drive disorders, hypothermia, hypoglycemia, and/or seizures. Treatment of beta-blocker toxicity is primarily supportive.  Any unabsorbed drug is removable by gastric lavage, induced emesis, or activated charcoal (if within 1 to 2 hours), while hemodialysis may be used to remove atenolol from general systemic circulation.[8]

The use of inotropes and chronotropes such as intravenous epinephrine and atropine is a recommended measure for the treatment of severe bradycardia. Usually, atropine is administered as a 0.5 mg IV or IO bolus and repeated every 3 to 5 minutes to a total dose of 3 mg. A transvenous cardiac pacemaker may be used in refractory cases or for the treatment of second or third-degree heart block. A titred bolus of glucagon at a dose of 50 mcg/kg can improve myocardial contractility, atrioventricular conduction, and increase heart rate in patients. Blood pressure must undergo continuous monitoring, and in cases of hypotension, vasopressors such as levarterenol are an option. For patients with bronchospasm, a beta-2 agonist such as aminophylline or isoproterenol may be used to alleviate symptoms. In cases that are refractory to the usual treatment, high dose insulin at 1 unit/kg bolus followed by 1 unit/kg per hour drip may be used to treat overdose in consultation with a toxicologist.[9]

In cases of asymptomatic, beta-1-blocker overdoses, the recommendation is to monitor the patient for at least 6 hours.[10] The use of atenolol is not recommended in children, as even small amounts can result in an overdose.

Enhancing Healthcare Team Outcomes

Beta-1-selective adrenergic antagonists such as atenolol are widely used worldwide for the treatment of hypertension, angina, and myocardial infarction. Therefore, an interprofessional team approach, including all physicians, pharmacists, and PAs/nurse practitioners who prescribe the drug, must be aware of the side effects and contraindications, as well as nurses who will perform administration. They need to actively monitor for signs of accidental overdose and be mindful that the effects of the drug could be masking the signs of hypoglycemia and thyrotoxicosis. Pharmacists should verify dosing based on the individual patient parameters and check for potential interactions that could alter therapeutic results. Nursing can counsel on administration, verify patient compliance, and assess the effectiveness of the regimen on followup visits. The healthcare team involved in the patient's care must also ensure that they are regularly monitoring renal function, heart rate, and blood pressure to ensure an optimal outcome for the patient. This interprofessional team approach will lead to optimal patient outcomes. [Level V]


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Atenolol - Questions

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A 66-year-old patient walks in with anxiety, dizziness, and distress. He says that he feels a fast heart rate and heaviness across the chest. On further questioning, he mentions that the pain also radiates to the left jaw and other areas of the upper body. He is short of breath and in visible respiratory distress. He is diagnosed with an acute myocardial infarction. Atenolol 5 mg is given intravenously stat. This medication improves the symptoms by which of the following mechanism of action?



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Which is a selective beta-adrenergic antagonist?



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Tenormin is the brand name for which of the following beta-blockers?



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A 27-year-old man presents to his family provider following an eight-month history of migraines. He is unhappy with the side effects of his current medication. He says his mother suffered similar headaches and was prescribed atenolol, which worked well in preventing further episodes. Which of the following is a common side effect of atenolol?



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A 77-year-old lady presents to the clinic for a follow-up appointment six months after acute myocardial infarction. She has a history of migraines, asthma, and type 2 diabetes. She was prescribed a beta-blocker by her cardiologist after her myocardial infarction and had since been researching the medication online. However, she found conflicting information. Which of the following statements about atenolol is correct?



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Atenolol - References

References

Kanno M,Nakaya H,Hattori Y,Izumi T,Nishimura T,Sakai K,Abiko Y, [Atenolol, its cardioselective property for adrenergic beta-receptor blocking action and effect on the cardiac function (author's transl)]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 1980 Oct;     [PubMed]
Stellpflug SJ,Harris CR,Engebretsen KM,Cole JB,Holger JS, Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. Clinical toxicology (Philadelphia, Pa.). 2010 Mar;     [PubMed]
Wadworth AN,Murdoch D,Brogden RN, Atenolol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs. 1991 Sep     [PubMed]
Helfand M,Peterson K,Christensen V,Dana T,Thakurta S, . 2009 Jul     [PubMed]
Heel RC,Brogden RN,Speight TM,Avery GS, Atenolol: a review of its pharmacological properties and therapeutic efficacy in angina pectoris and hypertension. Drugs. 1979 Jun     [PubMed]
Lammers JW,Müller ME,Folgering HT,van Herwaarden CL, A comparative study on the ventilatory and haemodynamic effects of xamoterol and atenolol in asthmatic patients. British journal of clinical pharmacology. 1986 Nov     [PubMed]
Ruffin RE,McIntyre EL,Latimer KM,Ward HE,Crockett AJ,Alpers JH, Assessment of beta-adrenoceptor antagonists in asthmatic patients. British journal of clinical pharmacology. 1982     [PubMed]
Eyal S,Kim JD,Anderson GD,Buchanan ML,Brateng DA,Carr D,Woodrum DE,Easterling TR,Hebert MF, Atenolol pharmacokinetics and excretion in breast milk during the first 6 to 8 months postpartum. Journal of clinical pharmacology. 2010 Nov     [PubMed]
Graudins A,Lee HM,Druda D, Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. British journal of clinical pharmacology. 2016 Mar     [PubMed]
Tucker WD,Theetha Kariyanna P, Selective Beta-1-Blockers . 2019 Jan     [PubMed]

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