Selective Beta-1-Blockers

Article Author:
William Tucker
Article Editor:
Pramod Theetha Kariyanna
Updated:
4/2/2019 6:33:04 PM
PubMed Link:
Selective Beta-1-Blockers

Indications

The cardio-selective beta blockers include atenolol, betaxolol, bisoprolol, esmolol, acebutolol, metoprolol, and nebivolol[1]. FDA approved uses of beta-1-selective blockers include hypertension, chronic stable angina, heart failure, post-myocardial infarction, and decreased left ventricular function after a recent myocardial infarction. Non-FDA approved uses include migraine prophylaxis, treatment of arrhythmias, tremor reduction, and the symptomatic treatment of anxiety disorders. Their use is associated with decreased morbidity and mortality post-myocardial infarction. Treatment with beta-1 blockers decreases the risk of stroke, coronary artery disease, and congestive heart failure.

Mechanism of Action

Beta-1 receptors primarily are found in cardiac nodal tissue, cardiac myocytes, other heart conduction pathway tissues, and in the kidneys. Beta-1 blockers exert their effect by binding to the beta-1 receptor sites selectively and inhibiting the action of epinephrine and norepinephrine on these sites. Beta-1 receptors are G-protein-coupled receptors whose action is exerted through the cyclic AMP (cAMP) and cAMP-dependent protein kinase action with resultant calcium ion concentration increases [2][3]. Ordinarily, this adrenergic response results in increased inotropy, chronotropy, and dromotropy. The blockade of this pathway with beta-1 blockers results in decreased contractility (inotropy), decreased heart rate (chronotropy), increased relaxation (lusitropy), and decreased cardiac conduction times (dromotropy).

Administration

Cardio-selective beta blockers can be administered either intravenously or by mouth depending on the desired medication. The circumstances of acuity and the severity of the disease symptoms affect this decision. Intravenous administration allows for the immediate onset of action and complete bioavailability, while oral administration with most beta-1 blockers allows for maximal absorption between 1 to 4 hours post-ingestion. Extended-release formulations are available for oral use as well, allowing for less frequent dosing. Esmolol is a beta-1 blocker that is strictly administered intravenously due to its short half-life of approximately 9 minutes.

Adverse Effects

Common adverse effects of cardio-selective beta blockers include bradycardia, decreased exercise capacity, hypotension, atrioventricular nodal block, and heart failure. Some other common adverse effects include nausea, vomiting, abdominal discomfort, dizziness, weakness, headache, fatigue, and dry mouth and eyes. Less common adverse effects are sexual dysfunction, memory loss, and confusion. An additional risk of beta-1 blockers is the masking of hypoglycemia induced tachycardia in the diabetic patient, which serves as a warning sign of the patient blood glucose levels being too low. Some medications when paired with the use of beta-1 blockers that may cause adverse effects include nitrates, phosphodiesterase inhibitors, ACE inhibitors, calcium channel blockers, and other blood pressure lowering or anti-arrhythmic medications. Adverse effects also occur in overdose. In excessive doses, cardio-selective beta blockers lose their selective binding and begin to interact with beta-2 and beta-3 adrenergic receptors.

Contraindications

According to the American College of Cardiology, beta-1 blockers should not be prescribed to patients with a recent or current history of fluid retention without concurrent diuretic use. Beta-1 blockers are contraindicated in patients with complete heart block and should be used with great caution in patients with second-degree heart block. Beta-1 blockers generally are contraindicated in patients with moderate to severe asthma and patients with chronic obstructive pulmonary disease[4]. Controversy exists over the safety of beta-1 blocker use in persons with mild to moderate asthma. Studies examining the efficacy of beta-1 blocker use in patients with concurrent mild to moderate asthma showed little to no adverse outcomes compared to those who did not have underlying asthma, but they generally are not used due to the potential risks[5].

Monitoring

Beta-1 blockers are monitored via the patient's vital signs. Heart rate and blood pressure checks along with regular physical examination are sufficient for basic patient monitoring. Regular blood level monitoring of beta-1-blocker levels is not indicated in most circumstances. If there are reasons to be concerned about therapeutic levels being reached or toxicity, then blood levels of specific beta-1 blockers can be ordered and reviewed. During situations of refractory treatment for an overdose, more intensive measures can be taken including continuous monitoring of heart rate, cardiac electrical activity, and blood pressure.

Toxicity

Intravenous fluid administration for treatment of hypotension and intravenous glucagon to antagonize beta-1-blocker effects are the initial reversal agents of choice for beta-1-blocker toxicity.

Beta-1 blockade toxicity typically presents with signs and symptoms of bradycardia and hypotension. These signs are sometimes accompanied by a state of hypoglycemia and hyperkalemia, though not always. It is critical to remember that in overdose beta-1 blockers can lose their selectivity; this means bronchopulmonary symptoms may be present. Additionally, neurologic functioning can be impaired, resulting in altered mental status in toxicity with highly lipophilic beta-1 blockers like propranolol, acebutolol, and oxprenolol. Suspected cardio-selective beta-1-blocker toxicity needs to be verified with a meticulous history, and physical examination focused on identifying specific medications ingested and any co-ingestions that could affect patient treatment[6].

Immediate monitoring of blood pressure with a blood pressure cuff and cardiac electrical activity with EKG are required. Acquiring blood glucose levels, a basic metabolic panel, and acetaminophen and salicylate levels are helpful in identifying sequalae of beta-1-blocker overdose and toxicity as well as identifying any medications that may have been co-ingested. In severely hypotensive patients, one should consider obtaining a lactate level due to the possibility of mesenteric ischemia. Patients being treated within 1 to 2 hours of ingestion may benefit from activated charcoal.

Propranolol overdoses are especially life-threatening. Sotalol overdoses require prolonged monitoring due to the possibility of the corrected QT interval prolongation and potential for torsades de pointes. Patients suspected of overdosing with either of these cardio-selective beta blockers should be treated more aggressively.

Treatment of beta-1-blocker toxicity or overdose involves the administration of intravenous glucagon and intravenous fluid resuscitation. Following administration of glucagon and crystalloid fluids, the patient may require calcium and sodium bicarbonate. It is important to be aware of the potential for initial treatment failure and take steps to prepare for invasive measures. More invasive measures include the use of hyperinsulinemia-euglycemia therapy, lipid emulsion therapy, vasopressors, intubation, or intra-aortic balloon pump if hemodynamic instability is present[7]

Patient monitoring is recommended for at least 6 hours in cases of asymptomatic, unintentional beta-1-blocker overdose. In cases of overdose with propranolol, monitoring is advised for at least 12 hours. In circumstances of sotalol overdose, monitoring for 24 hours is preferred due to the potential late-onset cardiac effects.

Some cardio-selective beta blockers have intrinsic agonist activity and are used in patients at an increased risk of overdose.

Enhancing Healthcare Team Outcomes

While Beta-1 blockers provide numerous benefits to patients there is always a potential for toxicity. The interprofessional team of clinicians, pharmacists, and nurses caring for a patient on these drugs should beware of and report any signs or symptoms of toxicity. A team approach to monitoring for side effects will enhance patient outcomes. [Level V]


References

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[2] The structure and function of G-protein-coupled receptors., Rosenbaum DM,Rasmussen SG,Kobilka BK,, Nature, 2009 May 21     [PubMed PMID: 19458711]
[3] Structure of a beta1-adrenergic G-protein-coupled receptor., Warne T,Serrano-Vega MJ,Baker JG,Moukhametzianov R,Edwards PC,Henderson R,Leslie AG,Tate CG,Schertler GF,, Nature, 2008 Jul 24     [PubMed PMID: 18594507]
[4] Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis., Salpeter SR,Ormiston TM,Salpeter EE,, Annals of internal medicine, 2002 Nov 5     [PubMed PMID: 12416945]
[5] [True and presumed contraindications of beta blockers. Peripheral vascular disease, diabetes mellitus, chronic bronchopneumopathy]., Pozzi R,, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology, 2000 Aug     [PubMed PMID: 10993010]
[6] Toxicity, Beta-Blocker, Khalid MM,Hamilton RJ,,, 2018 Jan     [PubMed PMID: 28846217]
[7] Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers., Shepherd G,, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2006 Oct 1     [PubMed PMID: 16990629]