Inflammation from beta blockers is caused by a cellular process known as autophagy.
Beta blockers can interfere with the breakdown of defective cell components, causing cells to release messengers that trigger immune-mediated inflammatory reactions, according to a new study published in Autophagy.1
Beta blockers are a class of drugs that block beta-adrenergic substances, such as adrenaline (epinephrine), a key agent in the “sympathetic” portion of the autonomic, or involuntary, nervous system and activation of heart muscle. These drugs are used for the treatment of irregular heart rhythms, chest pain, heart attack, hypertension, migraine headaches, social phobias, tremors, and glaucoma. By blocking the action of the involuntary nervous system on the heart, beta blockers slow the heartbeat and relieve stress on the heart, according to the Texas Heart Institute.2
Previous research has shown that beta blockers can cause severe skin inflammation; however, researchers were not certain as to the reason for this adverse event. In order to determine the cause, the study authors examined an active substance called propranolol.
Regardless of blocking beta adrenergic receptors, the substances’ inflammatory adverse events are most likely due to a combination of 2 factors: it is both fat-soluble and slightly alkaline, according to the release.
The substances’ fat solubility enables it to cross biomembranes, which are thin, fat-like membranes that enclose cells and some of their components. The slightly alkaline nature means that propranolol becomes positively charged in an acidic environment. In this state, the substance can no longer return through the membrane.
This fat-soluble and slightly alkaline combination becomes problematic in autophagy, in which cells place defective proteins and other cell components into bubbles to fuse with the lysosome, which contains decomposing enzymes. These enzymes break down the contents of the bubble and release the building blocks back into the cell.
Because the liquid is slightly acidic, a propranolol molecule that randomly finds its way through the membrane into the bubble becomes positively charged and trapped. Over time, this effect causes more and more propranolol to accumulate in the lysosome. This process disrupts the autophagy and alters the number of processes in the cell.
As a result, the cell releases inflammatory messengers, such as interleukin-23, which is mainly secreted by immune cells, thereby producing adverse inflammatory events in the skin.
The researchers now hope to further investigate how exactly these processes are related at the molecular level. However, their results already indicated that the inflammatory events occur primarily with fat-soluble beta-blockers. There are, in fact, substances in this group that are less membrane-permeable. After testing them in their cell culture, the interleukin-23 release was significantly lower than after propranolol stimulation.
These results still have yet to be verified in living organisms. It has been known for a long time that dysfunctional autophagy can trigger serious diseases. These include dementia, inflammatory bowel disease, and diabetes.