Beta Blockers

Mechanism of Action

The catecholamines, epinephrine, and norepinephrine bind to B1 receptors and increase cardiac automaticity as well as conduction velocity. B1 receptors also induce renin release, and this leads to an increase in blood pressure. In contrast, binding to B2 receptors causes relaxation of the smooth muscles along with increased metabolic effects such as glycogenolysis.

Beta-blockers vary in their specificity towards different receptors, and accordingly, the effects produced depend on the type of receptor(s) blocked as well as the organ system involved. Some beta-blockers also bind to alpha receptors to some degree, allowing them to induce a different clinical outcome when used in specific settings.

Once beta-blockers bind to the B1 and B2 receptors, they inhibit these effects. Therefore, the chronotropic and inotropic effects on the heart undergo inhibition, and the heart rate slows down as a result. Beta-blockers also decrease blood pressure via several mechanisms, including decreased renin and reduced cardiac output. The negative chronotropic and inotropic effects lead to a decreased oxygen demand; that is how angina improves after beta-blocker usage. These medications also prolong the atrial refractory periods and have a potent antiarrhythmic effect.

Beta-blockers classify as either non-selective or beta-1 selective. There are also beta-blocking drugs that affect both beta-2 and/or beta-3 selectively; neither has a known clinical purpose to date. Non-selective agents bind to both beta-1 and beta-2 receptors and induce antagonizing effects via both receptors. Examples include propranolol, carvedilol, sotalol, and labetalol. Beta-1 receptor-selective blockers like atenolol, bisoprolol, metoprolol, and esmolol only bind to the beta-1 receptors; therefore, they are cardio-selective.[3][4][5]

Beta-blockers lower the secretion of melatonin and hence may cause insomnia and sleep changes in some patients.[6]

Alpha-1 receptors induce vasoconstriction and increased cardiac chronotropy; this means agonism at the alpha-1 receptors leads to higher blood pressure and an increased heart rate. In contrast, antagonism at the alpha-1 receptor leads to vasodilation and negative chronotropic, which leads to lower blood pressure and decreased heart rate. Some beta-blockers, such as carvedilol, labetalol, and bucindolol, have additional alpha-1 receptor blockage activity in addition to their non-selective beta receptor blockage. This property is clinically useful because beta-blockers that block the alpha-1 receptor have a more pronounced clinical effect on treating hypertension.[7]

Sotalol is a beta blocker and also blocks potassium channels. It is a class III antiarrhythmic. 

Administration

Beta-blockers are available in oral, intravenous, or ophthalmic forms and are also injectable intramuscularly.

Dosages are available in various ranges, depending on the specific medication. Outpatient prescriptions may include once-a-day dosing for longer-acting beta-blockers, such as metoprolol succinate. However, most beta blockers are often dosed at least twice per day. Certain beta-blockers, such as propranolol, with a half-life of approximately 4 hours, are dosed up to 3 or 4 times a day, depending on the indication and dose.

Adverse Effects

Beta receptors are found all over the body and induce a broad range of physiologic effects. The blockade of these receptors with beta-blocker medications can lead to many adverse effects. Bradycardia and hypotension are two adverse effects that may commonly occur. Fatigue, dizziness, nausea, and constipation are also widely reported. Some patients report sexual dysfunction and erectile dysfunction.

Less commonly, bronchospasm presents in patients on beta-blockers. Asthmatic patients are at a higher risk.[8] Patients with Raynaud syndrome are also at risk of exacerbation. Beta-blockers can induce hyperglycemia and mask the hemodynamic signs usually seen in a hypoglycemic patient, such as tachycardia.

Some patients report insomnia, sleep changes, and nightmares while using beta-blockers. This effect is more pronounced with beta-blockers that cross the blood-brain barrier. Some patients can experience fatigue or weight gain while on beta blockers. Managing these adverse events involves discontinuing the medication. Certain beta blockers are more likely to induce weight gain or fatigue. 

Carvedilol may increase edema in some patients.[9]

Sotalol blocks the potassium channels in the heart and thereby induces QT prolongation. It increases the risk of torsades de pointes.[10]

All beta-blockers, especially in patients with cardiac risk factors, carry a risk of heart block.

Contraindications

Traditionally, beta-blockers have been contraindicated in asthmatic patients. However, recommendations have aligned for allowing cardio-selective beta-blockers, also known as beta-1 selective, in asthmatics but not non-selective beta-blockers. Non-selective beta-blockers should not be used in patients with asthma.

Patients who have either acute or chronic bradycardia and/or hypotension have relative contraindications to beta-blocker usage. 

Specific beta-blockers are contraindicated depending on the patient's past medical history. Patients diagnosed with long QT syndrome or who have had torsades de pointes in the past should not use the drug sotalol. Patients with the Raynaud phenomenon should avoid beta-blockers due to the risk of exacerbation.[11][10]

Monitoring

The patient's heart rate and blood pressure require monitoring while using beta-blockers. When using sotalol, the clinician must monitor the QTc interval as sotalol has QT-prolonging effects.[12] Other side effects, such as fatigue and weight gain, can also occur with outpatient beta-blocker use. 

Toxicity

The antidote for beta-blocker overdose is glucagon. It is especially useful in beta-blocker-induced cardiotoxicity. The second line of treatment is cardiac pacing if glucagon fails, and this may include transcutaneous pacing or transvenous pacing. 

Potential acute toxicity can be mitigated by using extended-release formulations as a preventative strategy, which will delay peak toxicity.[13]

Enhancing Healthcare Team Outcomes

Beta-blockers are a broad class of medications that are used for various clinical benefits but also carry the potential for adverse effects. They are prescribed by clinicians (MDs, DOs, NPs, or PAs) in both outpatient and inpatient settings, largely for the treatment of cardiovascular-related illnesses. When a patient is admitted to an inpatient ward, monitoring the clinical effects and potential adverse effects is an interprofessional task. This is crucial because excessively high serum levels can have serious or even fatal consequences.

Nurses will generally be the first caregivers to take note of any unwanted effects, such as a change in vital signs. In contrast, outpatient settings differ in that the pharmacist may be the closest line of healthcare contact for a patient. The pharmacist will dispense the medication, perform medication reconciliation, verify dosing, and also advise other interprofessional team members and the patient of any potential adverse effects. It is also imperative to take note of any patients who are currently on beta-blockers, as it provides a clinical context for potential symptoms. Many clinical trials have been conducted on beta-blockers and shown to prolong life in patients with cardiovascular disease.[14][15][16] [Level 2]

The interprofessional healthcare team needs to prescribe, manage, and monitor the use of beta-blockers safely and effectively. [Level 5]