Unappreciated Side Effects of Antihypertensive Therapy

Abstract

To the Editor: The excellent study and report by Hajjar and colleagues regarding cerebral hemodynamics in individuals receiving antihypertensive therapy1 merits additional clinical commentary. The clinical side-effect profiles of all antihypertensive drugs are generally well known and accepted. Several decades of personal observation and experience has led me to believe that there is no antihypertensive drug without perceptible or demonstrable side effects or complications. Patients and physicians uniformly agree on those that are most common, but there are significantly important effects that have received little or no attention in the medical literature or lay press. These effects are extracted only through careful in-depth discussion. The most frequently used classes of drugs in formulating the following commentary are beta-blockers (BB), calcium channel blockers (CCB), ace inhibitors (ACEI), and thiazide diuretics (TZD). Dryness of the eyes and mucus membranes occurs frequently but becomes more of a problem when individuals have difficulty wearing contact lenses because of diminished tear flow and alteration in composition. The latter probably involves lipid and protein components, producing qualitative and quantitative decrements in tear production. The consequences necessitate frequent removal, recleaning, and relubricating of the lenses. Interference with the normal sleep pattern consists of awakening from a sound sleep at a particular hour of the early morning, the same time each night, described as being awakened as though there was an alarm in their head and leaving them with a completely awakened feeling and the inability to go back to sleep. Greater frequency of dreams may also be noted. This may be more common with BBs. Diminished exercise capacity may be evidenced by fatigue, shortness of breath, and difficulty achieving a particular state of physical conditioning. Muscle weakness appears to be at least partially involved. It appears to be associated with all classes of drugs, but most notably with BBs and CCBs, and can be aggravated by simultaneous use of statin drugs for control of dyslipidemia and influenced by age and physical status in the absence of comorbid conditions. The most disconcerting and possibly serious side effects are those that involve the central nervous system (brain). The most frequently encountered side effect in this category is diminished rapid recall, involving recent and past memory. Individuals complain of having to take minutes to hours to recall something that has been or is usually quickly remembered, such as a name, place, or event. These deficits improve after a brief drug-free period. A major concern is the possibility of permanency and greater severity. It appears to be associated to some degree with all drug categories listed and is more common with BBs and CCBs. Decreased mental acuity as indicated by slower thought-pattern formulation may also be present in individuals with the most notable need and capability (e.g., physicians, school teachers, lawyers, accountants), who most frequently noted these memory deficits. Individuals with less need of “brain power” are less likely to notice or complain of these adverse effects. Diminished ability to gauge depth perception (distance) while driving a motor vehicle may be a less-common complaint of individuals taking BBs. Depression is a variable symptom that is presumably more common in individuals taking BBs. It can be difficult to determine the difference between causation or exacerbation without a drug-free interval. Heckbert and colleagues have reported significant cerebral white matter changes on magnetic resonance imaging in individuals taking CCBs or loop diuretics.2 Solomon and colleagues3 reported verbal memory impairment, often not recognized by the individual, many years ago at a time when antihypertensive therapy was less complex. The present study by Hajjar and colleagues offers another clue in the probable pathophysiology associated with antihypertensive therapy.1 Considerably more long-term observation and study is needed to resolve this problem. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this paper. Author Contributions: Dr. RuDusky is the sole author and is responsible for the entire content of this paper. Sponsor's Role: N/A.