Pharmacology of antihypertensive agents with multiple actions

Abstract

Compounds with two or more different pharmacodynamic activities in a single molecule are designated as hybrid drugs. If several stereoisomers with different pharmacodynamic activities exist in one molecule, the term pseudo-hybrid drug is applied. In the treatment of hypertension, the use of hybrid drugs enables a considerable reduction in the number of tablets to be taken per day. Conversely, the dose of each individual component cannot be tritrated. Most hybrid drugs used in antihypertensive treatment are beta-blockers with an additional vasodilator component, caused by different mechanisms such as alpha-adrenoceptor blockade, beta 2-adrenoceptor agonism, ACE inhibition or direct relaxation of vascular smooth muscle. Examples include labetalol (in fact, a mixture of four stereoisomers), carvedilol, celiprolol, dilevalol, tertatolol and BWA-575 C. A combination of beta-receptor blockade and vasodilation may be beneficial from a hemodynamic point of view. More recently it has been recognized that urapidil and ketanserin are hybrid drugs, each containing at least two pharmacodynamic activities in their molecules.

Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial

“…The discrepancy could be related to the use of urine samples for the assessment in most of the other studies, which could have led to detection long after drug administration. As half‐lives of antihypertensive agents and the amount excreted by the kidneys (unchanged or as metabolite) vary greatly, urine screening results are more difficult to relate to short‐term drug intake and concomitant BP . Of note, in one study reporting 50% nonadherence, patients were asked to give informed consent for adherence measurements beforehand, which could theoretically have led to an improvement in adherence .…”

“…In contrast, the results of objective adherence measurements using drug screening in urine and blood are unbiased. In general, the assessment based on screening in urine provides information on long‐term use, whilst detection in serum can be considered indicative of short‐term drug intake . From a pharmacological perspective, the latter is more related to BP measurements performed within the same time frame as sample collection .…”

Development of a Multiaction Beta Blocker

“…The development of several compounds has been focused on the principle of p-adrenergic blockade (table 1). One component of most of these drugs is vasodilatory activity, and it has been postulated that their different actions potentiate each other and at the same time negate the other's side effects, thus al lowing effective and well-tolerated treatment for a larger patient cohort [41 ]. One of the first multiaction beta blockers was sotalol, which not only acts as a nonselective beta blocker, but also has class III antiarrhythmic proper ties.…”

Vasorelaxant and Hypotensive Effects of Tilisolol Hydrochloride (N-696) in Isolated Rat Thoracic Aorta and Pithed Rats.

“…In addition to the 8 blocking activity, some of the recently devel oped 8-blockers have other pharmacological activities (2). Tilisolol hydrochloride (N-696) is a long acting /8-adrenoceptor blocking agent that also possesses vasodilator properties (3,4).…”