November 4th, 2014

Cardiovascular Drugs May Up Anaphylaxis Risk Via Mast Cells

Cardiovascular Drugs May Up Anaphylaxis Risk Via Mast Cells

November 4, 20140 Comments

By David Douglas

NEW YORK - Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, particularly in combination, may increase the risk of anaphylaxis by decreasing the threshold of mast cell activation, according to German researchers.

In a report online October 16 in the Journal of Allergy and Clinical Immunology, Dr. Margitta Worm of Charite-Universitatsmedizin Berlin and colleagues note that drugs can interact with the anaphylactic response at several levels and through different mechanisms. However, little is known about drug-drug interactions in this context.

To investigate, the team analyzed data from nearly 4,800 patients in an anaphylaxis registry. They found that both beta-blocker and ACE inhibitor monotherapy increased the risk of severe anaphylaxis. This was more pronounced when both drugs were combined.

To further study of the effect of the combination of a beta-blocker (metoprolol) and an ACE inhibitor (ramipril) the researchers treated mice with either drug or both combined for 14 days. They found monotherapy "augmented the severity of anaphylaxis but that the degree of this potentiation was rather weak." However, as in humans, the effect was much stronger with the combination.

Further in vitro studies showed that although the agents slightly enhanced mast cell activation in single treatments, when combined they "elicited a clearly stronger mast cell activation."

Thus, the team says, "even though individual drugs might contribute to anaphylactic responses only marginally, the combination of several suboptimal events could be sufficient to eventually trigger anaphylaxis."

Their model, the researchers conclude, "might not only help to identify additional cofactors of anaphylaxis and their mechanisms, through which they operate, but also uncover drug combinations with more favorable safety profiles."

Dr. Elina Jerschow of Albert Einstein College of Medicine in New York, who was not involved in the work, called it "a very important study that sheds light on the mechanism of ACE inhibitors and beta-blockers acting as co-factors to anaphylaxis."

Dr. Jerschow, who is director of the Drug Allergy Center at Montefiore Medical Center, concluded that the study "offers an explanation for a frequently observed and reported association of anaphylaxis with these medications."

Dr. Worms did not respond to requests for comments.

SOURCE: http://bit.ly/10q0S5b

Ann Allergy Asthma Immunol 2014.