Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

Anticholinergics are administered in two different dosing: one is used for 12 hours and second is used for 24 hours. These dosing where studied by Izquierdo and colleagues to find adherence in a large population of over sixteen thousand people. These people were not given anything different than their regular inhalers and were asked to keep their regimens similar to what they were on previously. This study monitored these people for a year and watched for adherence between people using 12 hours vs. 24 hours. Long-acting cholinergics (LAMA) were the main focus of the study, as the researchers believed that 24 hour dosing, which is one time dosing daily, will increase adherence in patients with COPD. As a result, adherence between both long-acting and regular were similar. LAMA was seen to have a very high adherence compared to twice daily dosing, but there was no evidence that showed that twice daily dose caused lower adherence.

This study was short but it’s an evidence towards something that pharmacists have been looking for in patients. Pharmacists role in the community is to help improve the adherence of patients medications with the right guidance and understand the community. This research studied proved that the difference between LAMA and twice daily dose was very similar, even though there was evidence that LAMA had higher adherence. This does not show particularly that patients should switch to one time dosing. Rather, this shows that the adherence comes from patients understanding as these patients in the research study were well explained about their use of anticholinergic for COPD. Would counseling every patient on how to use the medication and following up on the medication, help improve adherence for both LAMA and twice-daily dosing?

 

Izquierdo, J. L., Paredero, J. M., & Piedra, R. (2016). Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD. International Journal of Chronic Obstructive Pulmonary Disease, 11, 289–293. http://doi.org.pitt.idm.oclc.org/10.2147/COPD.S96948

Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug

I found out about this article through a P4 student who was preparing for a case presentation on rotations. I was pleased to realize that the topic relates to our current anatomy and physiology material and even more so that Dr. Coons authored it!

This article evaluates the use of disopyramide in patients with hypertrophic cardiomyopathy (HCM). Before jumping into how disopyramide works and whether it’s effective (topic of the article), I’ll give some basic background information on the disease state. Hypertrophic cardiomyopathy sounds like a mouthful, but it’s essentially an inherited disease of the heart muscle (myopathy) in which the muscle is enlarged/ thickened (hypertrophic) for no apparent reason. If you remember from the anatomy and physiology lectures, thickened heart muscle can lead to a lot of problems. It makes it more difficult for the heart to work efficiently as the thickening decreases elasticity. About 1 in 500 people have this condition, and about two thirds of those with HCM have obstruction of the left ventricular outflow tract (LVOT). This obstruction occurs when the ventricle contracts and drag force pushes the mitral valve leaflet toward the septum. HCM is typically treated with ß blockers or verapamil, and for those with particularly bad cases that don’t respond to medication therapy, surgery is an option. There is another therapy, however, that has been proven to be effective and safe in those with HCM and LVOT obstruction– disopyramide.

Disopyramide is a class 1A antiarrhythmic, but it can be used off-label as treatment in patients with HCM with LVOT obstruction who do not respond to ß blockers or verapamil. This drug works by slowing phase 0 of the cardiac muscle action potential (remember phase 0 is the opening of sodium channels and rapid influx of sodium). Thus it has strong negative inotropic activity (weakens the force of heart contraction) which slows the outflow from the left ventricle which delays or eliminates the mitral-septal contact responsible for obstruction. A review of 3 clinical studies shows that disopyramide improves heart failure symptoms and reduces the need for surgery in those with HCM and LVOT obstruction who don’t respond to ß blockers or verapamil. There are some concerns with this therapy, however. Its pharmacokinetics are interesting– it has nonlinear, saturable protein binding meaning that it’s hard to predict concentrations of free disopyramide given small increases in plasma concentrations. With this in mind, dosing and monitoring in a hospital setting is important when administering disopyramide. Anticholinergic effects and pro-arrhythmias can occur if therapy is not carefully managed.

While we haven’t covered this disease state nor antiarrhythmics in detail in class, I was glad that I could use my current knowledge to better understand disopyramide and HCM. It’s interesting to see how the conceptual groundwork laid in anatomy and physiology and principles of drug action paves the way toward understanding more complex issues. One thing unclear to me, however, is how a drug like disopyramide can have anticholinergic adverse effects. How does the slowing phase 0 of cardiac action potentials relate to the parasympathetic system?

Verlinden N. J., Coons J. C., Pharmacotherapy. Disopyramide for hypertrophic cardiomyopathy: a pragmatic reappraisal of an old drug. 2015; 35:1164-72