There’s a lot that goes into selecting beta blocking agents. In pharmacy school we’ve learned that beta blockers fall into two major categories with respect to their pharmacotherapeutic properties: Selective (B1) and nonselective (B1,B2) beta antagonists. B1-receptors are known to be found in high concentration in cardiac tissues; while the majority B2 receptors are found in the lungs. Since the stimulation of B1 receptors increases heart rate by inducing cardiac contractility, blocking the receptor will have the opposite effect: slows contractility and lowers the heart rate. On the other hand, the stimulation of B2 receptors results in bronchodilation. Thus, blocking B2-receptors will lead into constriction of bronchi.

There are also some beta blockers that possess alpha blocking properties. These include labetalol and Carvedilol.

Understanding such differences has significant clinical importance and aid healthcare professionals in prescribing an appropriate medication on the basis of the drugs’ pharmacokinetic properties and a patient’s known comorbidities.

For example, use of nonselective B-blockers in patients with respiratory disorders such as Asthma and COPD carries a high risk in exacerbating these conditions.  In addition, some beta blockers may alter glucose metabolism by interfering with the release of insulin from pancreatic cells, hence may not be ideal agents to use in people with diabetes.

While most beta blockers can and have been used interchangeably in the management of hypertension +/- heart failure for the majority patients with great success there are some subtle differences between them that pharmacists should pay close attention to when making recommendations.

Pharmacokinetics/dynamic properties

Pharmacokinetics/dynamic properties of beta blockers are also important factors to consider when selecting one of these agents for patients with cardiovascular disorder.

For instances drugs such as Atenolol have a longer duration of action and are much preferred for outpatient use. Atenolol use in cardiac conditions such as CHF or ventricular tachycardia have not been well studied and are not recommended. It’s primarily used as an adjunct therapy in the management of hypertension.

Metoprolol on the other hand is widely used in the management of high blood pressure, acute coronary syndrome and tachycardia. The succinate formation has long duration of action, thus administered once daily. Metoprolol tartrate is an agent with intermediate action and is given 2-3 times per day.

Bisoprolol is a selective inhibitor of beta1-adrenergic receptors; competitively blocks beta1-receptors, with little or no effect on beta2-receptors at doses ≤20 mg.

Carvedilol, as a racemic mixture, has nonselective beta-adrenoceptor and alpha-adrenergic blocking activity.

Labetalol is highly selective for postsynaptic alpha1- adrenergic, and non-selective for beta-adrenergic receptors. It is about equipotent in blocking both beta1- and beta2- receptors. The ratios of alpha- to beta-blockade differ depending on the route of administration: 1:3 (oral) and 1:7 (IV).

One of the main advantages with agents that possess an alpha blocking property pertains to their added effect in lowering blood pressure by relaxing the smooth muscles of the blood vessels.

Other beta blockers such as Propranolol have little use in managing hypertension because of their minimal effect in lowering blood pressure. Propranolol and Atenolol are two beta blockers that are also commonly used in the management of other conditions such as migraine headache and thyrotoxicosis.

COPD/Bronchospasm

Because of its nonselective beta blocking property, Carvedilol may exacerbate respiratory conditions such as COPD by causing bronchospasm.

In general, patients with bronchospastic disease should not receive beta-blockers; however, metoprolol, with B1 selectivity, has been used cautiously with close monitoring.

Bisoprolol is generally safe in patients with respiratory disorders so long as the daily dose does not exceed 20mg, the threshold below which it possesses selective b1- blocking activity.

Glucose Metabolism

β-blockers are thought to contribute to the development of hyperglycemia by impairing the release of insulin from the pancreatic β-cell.

In people with diabetes, β-blockers such as propranolol, metoprolol, and atenolol can result in consistently elevated fasting blood glucose levels. In a recent study, atenolol was also shown to contribute to new-onset diabetes and to worsen hyperglycemia in people with abdominal obesity. In this study, adverse metabolic effects, including the development of hyperglycemia manifesting as impaired fasting glucose, were apparent within 9 weeks of therapy initiation.

Some beta blockers may potentiate hypoglycemia and/or mask signs and symptoms (eg, sweating, anxiety, and tachycardia). In patients with heart failure and diabetes, use of carvedilol may worsen hyperglycemia; may require adjustment of antidiabetic agents.

Potential Barriers

Of note, despite the well-known differences among the beta blockers pharmacologic properties the prescribing habit of practitioners may not always be in line with what the literatures recommend. The reasons could be of three folds. Some practitioners are well accustomed and feel comfortable to using a particular agent to manage their patients’ blood pressure and heart conditions they’d rather treat the side effects as they come than switching the drug entirely. Drug costs could also influence physician’s prescribing habit since some beta blockers can be less affordable to low-income patients without insurance. The other reason pertains to lack of proper training. When teaching pharmacotherapy schools may need to put greater emphasis on the clinical significance when one beta blocker is used over the other; comorbidities that are negatively impacted when inappropriate agent is used routinely.

Submitted By: Amanuel Tseggai, Pharm.D., BCPS

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Note: The intention of this article is solely to highlight the major differences between beta blockers in terms of their pharmacologic properties and to help guide practicing pharmacists select an agent appropriate for a given patient with hypertension and/or heart disease who also have other comorbidities such as diabetes and/or chronic obstructive pulmonary disorder (COPD). A.T.

 

 References:

1. Lexicomp; Official website for Drug information for healthcare professionals, 2016
2. Rehman, Abdur etal, Diabetes Spectrum,  Drug-Induced Hyperglycemia 2011 Nov; 24(4): 234-238
3. Disease and Conditions -High Blood Pressure, Alpha Blockers, Mayo Clinic Staff, June 15, 2016