Yin and Yang: Do Beta-Blockers cause Harm in Patients Using Beta-Agonist Inhalers?
We’ve all seen it: the drug interaction report on a respiratory patient showing a possible problem between a patient’s beta-blocker and their inhaler containing a beta-agonist like albuterol. Often times both of these medications play important roles in the management of chronic conditions in our patients and can even be irreplaceable in their therapeutic space. Our knee jerk reaction is to call the doc and inform them of this interaction, but let’s take a step back and review the evidence before we reach for that phone.
First let’s review how each class of medication works and what they’re used for.
Beta-blockers include popular agents like metoprolol succinate, propranolol, carvedilol and bisoprolol. These medications work on the adrenergic beta receptors by blocking their receptor sites and competitively inhibiting binding of the catecholamines epinephrine and norepinephrine. They prevent the normal physiological actions of these two molecules on the nervous system. In short these agents generally decrease heart rate and blood pressure to varying degrees. These agents are used in treatment of disease states such as abnormal heart rhythms, high blood pressure, anxiety and hypothyroidism.
Beta-agonists work on the same system and receptors with the distinction being that instead of blocking the actions of epinephrine and norepinephrine they emulate their functions. These agents are used to induce smooth muscle relaxation (opening up the airways or bronchodilation) and are typically used in inhaler or nebulizer formulations in the treatment of respiratory diseases such as asthma and COPD.
Now let’s talk about selectivity. There are a number of different sub-types of beta-receptors in the body but for our purposes we’ll focus on two types: the beta-1 receptors and the beta-2 receptors. These two subtypes are mostly expressed in different places: with beta-1 expressed *mostly* in heart tissue and beta-2 expressed *mostly* in bronchial smooth muscle tissue.
Why is this important? Well it’s because certain medications tend to favor which type of receptor they bind to. This phenomenon is known as selectivity. For example beta-1 selective antagonists are agents known to prefer binding to beta-1 receptors and their effects are mostly localized to the cardiac system. Likewise non-selective agents do not prefer either beta-1 or beta-2 receptors and act more or less on both of them.
In general beta-agonist agents (albuterol, salmeterol, formoterol) are localized in their effect on lung tissue. Beta-blockers however vary in their sites of action. As seen in the graphic above cardioselective beta-blockers work mostly on cardiac tissue and non-cardioselective beta-blockers work on both heart and lung systems.
The interaction between the beta-agonists and beta-antagonists
Now that we can tell the difference between agents and their sites of activity, so what?
In order to understand what to do we need to cover the nature of the drug interaction first. The logic is that because the patient is taking both types of medicines they will “cancel” each other out or even exert unwanted effects outside of their desired organ system. For example an asthmatic requiring bronchodilation because of an asthma attack might be taking a beta-blocker for something else, and the beta-blocker may diminish the bronchodilatory effects of the inhaler. This could be a dangerous scenario.
So what does the evidence say? Let’s look at the two most common disease states: asthma and COPD.
Asthma
For patients with asthma the recommendation is to either avoid concomitant use of non-selective beta-blockers and beta-agonists for patients with mild to moderate asthma. In practice what this translates to is keeping patients on their rescue inhalers but possibly changing their non-selective beta-blocker to a cardioselective one.
This recommendation comes from a meta-analysis of 10 studies looking at co-administration of non-selective beta-blockers and beta-agonist inhalers in mild to moderate asthmatics. They found no decrease in respiratory measures such as FEV1, symptoms and rescue inhaler frequency.
Very little data exists on the use of non-selective beta-blockers in the severely asthmatic population and current recommendations are to avoid their use altogether if possible.
COPD
In patients with COPD the answer is also complicated. Patients with COPD generally tolerated co-administration of beta-blockers (selective and non-selective) and beta-agonists, with one retrospective study noting that patients on both even showed a statistically significant decrease in exacerbation rate (it should be noted however that in this study most patients were receiving a cardioselective beta-blocker).
Other studies have shown no change in FEV1 in patients on non-selective beta-blockers and beta-agonists vs selective beta-blockers and beta-agonists both at baseline and after a challenge using a bronchoconstricting agent. There was a delay detected in the rate of recovery after bronchonstriction challenge in the non-selective group however.
In Summary
Both asthmatics and COPD patients can potentially benefit from changing from non-selective to cardioselective beta-blocker agents if possible. There is more evidence in the COPD group that non-selective blockers may be better tolerated.
Thank you for reading,
Stephen Wang
2020 PharmD Candidate
