Atenolol

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Continuing Education Activity

Atenolol is a second-generation beta-1-selective adrenergic antagonist that reduces heart rate and blood pressure and decreases myocardial contractility. It is FDA-approved and indicated in treating 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. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, monitoring, and toxicity of atenolol. It also highlights the role of the interprofessional team in managing patients using atenolol.

Objectives:

  • Outline the accepted indications for atenolol use.
  • Identify the mechanism of action of atenolol and other selective beta-blocking agents.
  • Summarize the adverse event profile of atenolol.
  • Review interprofessional team strategies for improving care coordination and communication to enhance patient outcomes and minimize adverse events with atenolol.

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][2] Atenolol may also be used as an alternative to propranolol in infantile hemangiomas; use requires additional research.[3]

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.[4] This activity results in a reduction in heart rate and 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.

It also exerts its effects in higher doses by competitively blocking beta-2-adrenoreceptors, primarily located in the bronchial and vascular musculature. It has no membrane stabilizing or intrinsic sympathomimetic activity. Atenolol has low lipid solubility, resulting in reduced brain penetrance, resulting in fewer CNS side effects.[5] 

Beta-adrenergic receptor antagonists also increase the AV node's refractory period. Therefore, it may also be used off-license to treat supraventricular tachycardia and prevent paroxysmal attacks of atrial fibrillation.[6] 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.[7]

Pharmacokinetics

Absorption: The bioavailability of orally administered atenolol is approximately 50%. Peak blood levels are attained between two and four hours after oral administration and within 5 minutes following intravenous administration.

Distribution: As discussed above, atenolol has low lipid solubility (hydrophilic beta blocker); hence there is low diffusion across the intestinal membrane and blood-brain barrier (BBB). Plasma protein binding is approximately 10%.[8]

Metabolism: The hepatic metabolism of atenolol is minimal, and the parent drug appears to be the major radiolabelled component in blood.[9]

Excretion: Atenolol is primarily excreted by the renal route by glomerular filtration and active secretion. The half-life elimination is approximately 6 to 7 hours.[10] Organic cation transporters play an important role in the elimination of atenolol.[11]

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 daily, 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.[12]

For renal-impaired or elderly patients, a lower dose of 25 mg daily may be used if they have a creatinine clearance of under 15 ml/min. Careful monitoring of their blood pressure before administering a new dose is necessary.[13]

Angina Pectoris 

For non-vasospastic angina, the initial adult dose is 50 mg once daily. 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.[14]

Acute Myocardial Infarction

Intravenous injection should occur as soon as possible after the patient arrives in the hospital within 12 hours of the myocardial infarction. For example, the FDA recommends the IV administration of 5 mg of atenolol for an adult 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.[15]

Migraine Prophylaxis

The initial adult daily dose is  25 mg once daily; titrated every 1-2 weeks to 100 mg once daily.[16]

Supraventricular Tachycardia

According to ACC and AHA guidelines, the initial adult dose of atenolol is 25- 50 mg per day which is titrated based on tolerability and response to 100 mg once daily.

Myocardial Infarction

beta-blocker should be started within the first 24 hours of myocardial infarction for most patients and continue for secondary prophylaxis titrating gradually up to 50 mg twice daily based on BP, heart rate, and adverse events.[15] 

Thyrotoxicosis

The initial daily dose is 25-50 mg once daily, titrated as needed to control tachycardia, palpitations, and tremulousness up to a maximum of 100mg twice-daily regimen.[17]

Use in the Specific Patient Populations

Patients with Hepatic Impairment: No dosage adjustments are provided in the manufacturer's labeling. In addition, atenolol undergoes minimal hepatic metabolism, as discussed above.[9]

Patients with Renal Impairment: Patients with impaired renal function should be monitored, and the dose needs to be adjusted based on creatinine clearance.[13]

  • Creatinine clearance >30 mL/minute:  no dose adjustment is needed.
  • Creatinine clearance 10-30 mL/minute: maximum dose up to 50 mg daily.
  • Creatinine clearance <10  mL/minute: maximum dose up to 25 mg daily.
  • Patients on hemodialysis: Atenolol is considerably cleared by hemodialysis; administer atenolol post-dialysis.[18]

Pregnancy Considerations: Atenolol is a former FDA pregnancy category D.[19] According to The American college of obstetricians and gynecologists (ACOG) guidelines, atenolol is not recommended in pregnancy due potential risk of growth restriction and low birth weight. The preferred beta blocker for chronic hypertension in pregnant women is labetalol.[20]

Breastfeeding Considerations: The excretion of beta blockers in breast milk predominantly depends on plasma protein binding (PPB). Drugs with low plasma protein binding, like atenolol(10% PPB), are extensively excreted into breast milk. The accumulation of drugs in the infant is also associated with the fraction of the drug excreted in the urine. With 85% renal excretion, atenolol has a high risk for accumulation in infants, especially neonates. Use caution in breastfeeding women. The use of other beta-blockers may be preferred while nursing newborn and preterm infants.[21]

Adverse Effects

According to product labeling following are the adverse effects of atenolol.

  • Boxed Warning: Atenolol should not be stopped abruptly - doing so may exacerbate angina, acute myocardial infarction, or ventricular arrhythmias. Gradual tapering of the dose is recommended.[22]  if there is a worsening of angina or development of acute coronary insufficiency, it is suggested that atenolol be rapidly restarted temporarily. 
  • Common side effects include bradycardia, diarrhea, dizziness, constipation, confusion, dyspnea, headache, heart failure, erectile dysfunction, nausea, fatigue, paraesthesia, peripheral coldness, rash, sleep disorders, syncope, visual impairment, and bronchospasm.[23]
  • Rare side effects include alopecia, dry mouth, postural hypotension, psychosis, psoriasis, thrombocytopenia, depression, mild transaminitis, and depression.[24][25]
  • The BRASH syndrome is characterized by severe bradycardia, renal failure, atrioventricular blockade, shock, and hyperkalemia. Discontinue atenolol if BRASH syndrome is suspected.[26]

Drug-Drug Interactions

  • Concomitant use of rivastigmine with beta blockers like atenolol requires caution, particularly when patients have sick sinus syndrome or cardiovascular comorbidities due to the risk of syncope and bradycardia.[27][28]
  • Administering atenolol concurrently with amiodarone, digoxin, or verapamil may cause heart block, bradycardia, and left ventricular dysfunction.
  • Antipsychotics and beta blockers have the potential for interactions. Case report of risperidone and atenolol-induced bradycardia has been reported.[29]
  • Amifostine can lead to a rapid drop in blood pressure; avoid using blood pressure-lowering agents such as atenolol with amifostine.[30]
  • Beta-blockers like atenolol should be tapered and stopped several days before clonidine discontinuation to decrease the risk of rebound hypertension, according to the AAFP guidelines.[31]

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 this case, it may be given alongside a bronchodilator.[32][33]
  • 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.[19]
  • American Academy of Pediatrics advises against using atenolol during breastfeeding due to the risk of neonatal hypoglycemia and bradycardia.[34]
  • Atenolol is contraindicated in patients with a history of hypersensitivity to atenolol or excipients. Cases of anaphylaxis have been reported with beta-blockers.[35]

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 24 hours. 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 treatment. In addition, 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.[13]

Blood pressure and heart rate should also undergo periodic monitoring.[12] Calculate the ASCVD risk for primary prevention; if the risk is >10%, a target blood pressure of  <130/80 mm hg is recommended by AHA/ACC guidelines.[36]

Patients with a history of obstructive airway disease should have regular lung function tests, and patients with diabetes should monitor blood glucose levels.[37]

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 (if administered orally) is removable by gastric lavage or activated charcoal (within 1 to 2 hours), while hemodialysis can remove atenolol from general systemic circulation.[38]

Inotropes and chronotropes, such as intravenous epinephrine and atropine, are recommended for treating 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. In addition, a transvenous cardiac pacemaker may be used in refractory cases or for treating second or third-degree heart block. 

A titrated glucagon bolus at a dose of 50 mcg/kg can improve myocardial contractility and 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 refractory to the usual treatment,high-dose insulin euglycaemic therapy at 1 unit/kg bolus followed by 1 unit/kg per hour drip may be used to treat overdose in consultation with a toxicologist.[39] Lignocaine can be used in arrhythmias due to beta-blocker toxicity.[40] Veno-arterial extracorporeal membrane oxygenation is also associated with reduced mortality.[40]

In cases of asymptomatic beta-1-blocker overdoses, the recommendation is to monitor the patient for at least 6 hours.[41] 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 to treat hypertension, angina, and myocardial infarction. According to AHA, beta-blockers as initial pharmacological therapy for hypertension are common in clinical practice even though beta blockers are not the first-line treatment in hypertensive patients without compelling indications.[42] 

An interprofessional team, including all clinicians(MD, DO, NP,  PA), and pharmacists, must be aware of atenolol's indications, adverse drug reactions, and contraindications. Nurses who administer atenolol need to monitor for adverse drug reactions and be mindful that the effects of the drug could mask the symptoms of hypoglycemia and thyrotoxicosis. Pharmacists should verify dosing based on individual patient parameters and check for potential interactions that could alter therapeutic results. Nursing staff can counsel on medicine administration, verify patient adherence, assess regimen effectiveness on follow-up visits, and report concerns to the clinician. All interprofessional team members must maintain accurate, updated records. If they note any problems, they must immediately communicate with the prescriber to share these concerns and open the way for possible therapy modification.

The interprofessional team involved in the patient's care must also ensure that they regularly monitor renal function, heart rate, and blood pressure. All healthcare providers should educate the patients on the importance of compliance with atenolol therapy, administration, and adverse drug reactions. This interprofessional team approach will lead to therapeutic success and ensure an optimal outcome for the patients using atenolol.[Level V] In a pragmatic randomized controlled trial, a team-based care (TBC) intervention between clinicians, pharmacists, and nurses was utilized for patients suffering from uncontrolled hypertension. The results indicated that the interprofessional approach could reduce long-term systolic BP among uncontrolled hypertensive patients related to antihypertensive therapy, including beta blockers.[43] [Level 2]


Article Details

Article Author

Baryiah Rehman

Article Author

Daniela P. Sanchez

Article Editor:

Saumya Shah

Updated:

10/12/2022 8:32:35 AM

PubMed Link:

Atenolol

References

[1]

Wadworth AN,Murdoch D,Brogden RN, Atenolol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs. 1991 Sep     [PubMed PMID: 1720383]

[2]

Ailani J,Burch RC,Robbins MS,Board of Directors of the American Headache Society., The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021 Jul     [PubMed PMID: 34160823]

[3]

Ji Y,Chen S,Yang K,Zhang X,Zhou J,Li L,Xiang B,Qiu T,Dai S,Jiang X,Lu G,Qiu L,Kong F,Zhang Y, Efficacy and Safety of Propranolol vs Atenolol in Infants With Problematic Infantile Hemangiomas: A Randomized Clinical Trial. JAMA otolaryngology-- head & neck surgery. 2021 Jul 1     [PubMed PMID: 33856430]

[4]

Helfand M,Peterson K,Christensen V,Dana T,Thakurta S, . 2009 Jul     [PubMed PMID: 21089245]

[5]

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 PMID: 38096]

[6]

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 PMID: 6111522]

[7]

Page RL,Joglar JA,Caldwell MA,Calkins H,Conti JB,Deal BJ,Estes NA 3rd,Field ME,Goldberger ZD,Hammill SC,Indik JH,Lindsay BD,Olshansky B,Russo AM,Shen WK,Tracy CM,Al-Khatib SM,Evidence Review Committee Chair‡., 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2016 Apr 5     [PubMed PMID: 26399663]

[8]

Chen X,Slättengren T,de Lange ECM,Smith DE,Hammarlund-Udenaes M, Revisiting atenolol as a low passive permeability marker. Fluids and barriers of the CNS. 2017 Oct 31     [PubMed PMID: 29089037]

[9]

Zisaki A,Miskovic L,Hatzimanikatis V, Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches. Current pharmaceutical design. 2015;     [PubMed PMID: 25341854]

[10]

Ripley TL,Saseen JJ, ?-blockers: a review of their pharmacological and physiological diversity in hypertension. The Annals of pharmacotherapy. 2014 Jun     [PubMed PMID: 24687542]

[11]

Yin J,Duan H,Shirasaka Y,Prasad B,Wang J, Atenolol Renal Secretion Is Mediated by Human Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Proteins. Drug metabolism and disposition: the biological fate of chemicals. 2015 Dec     [PubMed PMID: 26374172]

[12]

Whelton PK,Carey RM,Aronow WS,Casey DE Jr,Collins KJ,Dennison Himmelfarb C,DePalma SM,Gidding S,Jamerson KA,Jones DW,MacLaughlin EJ,Muntner P,Ovbiagele B,Smith SC Jr,Spencer CC,Stafford RS,Taler SJ,Thomas RJ,Williams KA Sr,Williamson JD,Wright JT Jr, 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension (Dallas, Tex. : 1979). 2018 Jun;     [PubMed PMID: 29133354]

[13]

Kirch W,Köhler H,Mutschler E,Schäfer M, Pharmacokinetics of atenolol in relation to renal function. European journal of clinical pharmacology. 1981 Jan;     [PubMed PMID: 7461026]

[14]

Fihn SD,Gardin JM,Abrams J,Berra K,Blankenship JC,Dallas AP,Douglas PS,Foody JM,Gerber TC,Hinderliter AL,King SB 3rd,Kligfield PD,Krumholz HM,Kwong RY,Lim MJ,Linderbaum JA,Mack MJ,Munger MA,Prager RL,Sabik JF,Shaw LJ,Sikkema JD,Smith CR Jr,Smith SC Jr,Spertus JA,Williams SV,Anderson JL,American College of Cardiology Foundation/American Heart Association Task Force., 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012 Dec 18;     [PubMed PMID: 23166211]

[15]

O'Gara PT,Kushner FG,Ascheim DD,Casey DE Jr,Chung MK,de Lemos JA,Ettinger SM,Fang JC,Fesmire FM,Franklin BA,Granger CB,Krumholz HM,Linderbaum JA,Morrow DA,Newby LK,Ornato JP,Ou N,Radford MJ,Tamis-Holland JE,Tommaso CL,Tracy CM,Woo YJ,Zhao DX,Anderson JL,Jacobs AK,Halperin JL,Albert NM,Brindis RG,Creager MA,DeMets D,Guyton RA,Hochman JS,Kovacs RJ,Kushner FG,Ohman EM,Stevenson WG,Yancy CW,American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines., 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Jan 29;     [PubMed PMID: 23247304]

[16]

Silberstein SD, Preventive Migraine Treatment. Continuum (Minneapolis, Minn.). 2015 Aug     [PubMed PMID: 26252585]

[17]

Ross DS,Burch HB,Cooper DS,Greenlee MC,Laurberg P,Maia AL,Rivkees SA,Samuels M,Sosa JA,Stan MN,Walter MA, 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid : official journal of the American Thyroid Association. 2016 Oct     [PubMed PMID: 27521067]

[18]

Tieu A,Velenosi TJ,Kucey AS,Weir MA,Urquhart BL, {i}β{/i}-Blocker Dialyzability in Maintenance Hemodialysis Patients: A Randomized Clinical Trial. Clinical journal of the American Society of Nephrology : CJASN. 2018 Apr 6     [PubMed PMID: 29519953]

[19]

Regitz-Zagrosek V,Roos-Hesselink JW,Bauersachs J,Blomström-Lundqvist C,Cífková R,De Bonis M,Iung B,Johnson MR,Kintscher U,Kranke P,Lang IM,Morais J,Pieper PG,Presbitero P,Price S,Rosano GMC,Seeland U,Simoncini T,Swan L,Warnes CA,ESC Scientific Document Group ., 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. European heart journal. 2018 Sep 7     [PubMed PMID: 30165544]

[20]

American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics, ACOG Practice Bulletin No. 203: Chronic Hypertension in Pregnancy. Obstetrics and gynecology. 2019 Jan     [PubMed PMID: 30575676]

[21]

Atenolol Drugs and Lactation Database (LactMed). 2006;     [PubMed PMID: 30000201]

[22]

Koracevic G,Micic S,Stojanovic M, By Discontinuing Beta-Blockers Before an Exercise Test, We may Precipitate a Rebound Phenomenon. Current vascular pharmacology. 2021;     [PubMed PMID: 33653252]

[23]

Beta Adrenergic Blocking Agents LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012     [PubMed PMID: 31643457]

[24]

Atenolol LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012     [PubMed PMID: 31643700]

[25]

Bu J,Ding R,Zhou L,Chen X,Shen E, Epidemiology of Psoriasis and Comorbid Diseases: A Narrative Review. Frontiers in immunology. 2022     [PubMed PMID: 35757712]

[26]

Bailuni Neto JJ,Siqueira BL,Machado FC,Boros GAB,Akamine MAV,Cordeiro de Paula LJ,Rodrigues de Assis AC,Soares PR,Scudeler TL, BRASH Syndrome: A Case Report. The American journal of case reports. 2022 Jan 21;     [PubMed PMID: 35058422]

[27]

Khoury R,Rajamanickam J,Grossberg GT, An update on the safety of current therapies for Alzheimer's disease: focus on rivastigmine. Therapeutic advances in drug safety. 2018 Mar;     [PubMed PMID: 29492246]

[28]

Paulison B,Léos CL, Potential cardiotoxic reaction involving rivastigmine and beta-blockers: a case report and review of the literature. Cardiovascular toxicology. 2010 Dec;     [PubMed PMID: 20865460]

[29]

Siwek M,Woroń J,Gorostowicz A,Wordliczek J, Adverse effects of interactions between antipsychotics and medications used in the treatment of cardiovascular disorders. Pharmacological reports : PR. 2020 Apr;     [PubMed PMID: 32124390]

[30]

Varghese JJ,Schmale IL,Mickelsen D,Hansen ME,Newlands SD,Benoit DSW,Korshunov VA,Ovitt CE, Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection. Journal of dental research. 2018 Oct;     [PubMed PMID: 29634396]

[31]

Carpenter M,Berry H,Pelletier AL, Clinically Relevant Drug-Drug Interactions in Primary Care. American family physician. 2019 May 1;     [PubMed PMID: 31038898]

[32]

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 PMID: 2878680]

[33]

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 PMID: 6125185]

[34]

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 PMID: 20145263]

[35]

White JL,Greger KC,Lee S,Kahoud RJ,Li JT,Lohse CM,Campbell RL, Patients Taking β-Blockers Do Not Require Increased Doses of Epinephrine for Anaphylaxis. The journal of allergy and clinical immunology. In practice. 2018 Sep - Oct     [PubMed PMID: 29449164]

[36]

Arnett DK,Blumenthal RS,Albert MA,Buroker AB,Goldberger ZD,Hahn EJ,Himmelfarb CD,Khera A,Lloyd-Jones D,McEvoy JW,Michos ED,Miedema MD,Muñoz D,Smith SC Jr,Virani SS,Williams KA Sr,Yeboah J,Ziaeian B, 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2019 Sep 10     [PubMed PMID: 30894318]

[37]

Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ (Clinical research ed.). 1998 Sep 12     [PubMed PMID: 9732338]

[38]

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 PMID: 26344579]

[39]

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 PMID: 20141425]

[40]

Rotella JA,Greene SL,Koutsogiannis Z,Graudins A,Hung Leang Y,Kuan K,Baxter H,Bourke E,Wong A, Treatment for beta-blocker poisoning: a systematic review. Clinical toxicology (Philadelphia, Pa.). 2020 Oct     [PubMed PMID: 32310006]

[41]

Tucker WD,Theetha Kariyanna P, Selective Beta-1-Blockers . 2019 Jan     [PubMed PMID: 29763157]

[42]

Chan You S,Krumholz HM,Suchard MA,Schuemie MJ,Hripcsak G,Chen R,Shea S,Duke J,Pratt N,Reich CG,Madigan D,Ryan PB,Woong Park R,Park S, Comprehensive Comparative Effectiveness and Safety of First-Line β-Blocker Monotherapy in Hypertensive Patients: A Large-Scale Multicenter Observational Study. Hypertension (Dallas, Tex. : 1979). 2021 May 5;     [PubMed PMID: 33775125]

[43]

Santschi V,Wuerzner G,Pais B,Chiolero A,Schaller P,Cloutier L,Paradis G,Burnier M, Team-Based Care for Improving Hypertension Management: A Pragmatic Randomized Controlled Trial. Frontiers in cardiovascular medicine. 2021     [PubMed PMID: 34760950]