Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on Verapamil

The binding of verapamil to the protein human serum albumin (HSA) was examined by using highperformance affinity chromatography. Many previous reports have investigated the binding of verapamil with HSA, but the exact strength and nature of this interaction (e.g., the number and location of binding sites) is still unclear. In this study, frontal analysis indicated that at least one major binding site was present for R-and S-verapamil on HSA, with estimated association equilibrium constants on the order of 10 4 M −1 and a 1.4-fold difference in these values for the verapamil enantiomers at pH 7.4 and 37°C. The presence of a second, weaker group of binding sites on HSA was also suggested by these results. Competitive binding studies using zonal elution were carried out between verapamil and various probe compounds that have known interactions with several major and minor sites on HSA. R/S-Verapamil was found to have direct competition with S-warfarin, indicating that verapamil was binding to Sudlow site I (i.e., the warfarin-azapropazone site of HSA). The average association equilibrium constant for R-and S-verapamil at this site was 1.4 (±0.1) × 10 4 M −1 . Verapamil did not have any notable binding to Sudlow site II of HSA but did appear to have some weak allosteric interactions with L-tryptophan, a probe for this site. An allosteric interaction between verapamil and tamoxifen (a probe for the tamoxifen site) was also noted, which was consistent with the binding of verapamil at Sudlow site I. No interaction was seen between verapamil and digitoxin, a probe for the digitoxin site of HSA. These results gave good agreement with previous observations made in the literature and help provide a more detailed description of how verapamil is transported in blood and of how it may interact with other drugs in the body.

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“…One drug that binds to HSA is verapamil (see Figure 1) [12–14]. Verapamil is used to treat hypertension, angina and arrhythmia.…”

Section: Introductionmentioning

confidence: 99%

Studies of verapamil binding to human serum albumin by high-performance affinity chromatography

Mallik

Yoo

Chen

et al. 2008

Journal of Chromatography B

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“…Similar experimental procedures are applied to the study of antagonists. Verapamil (VP), classified as a Ca 2+ channel blocker, 28 falling under the category of phenylalkylamines, 29 functions by inhibiting channels in the membranes of cardiomyocytes, resulting in a diminished influx of Ca 2+ . This mechanism extends the overstimulation period of the atrioventricular node, counteracting arrhythmias triggered by rapid atrial beats.…”

Section: Evaluation Of the Toxic Effects Of Typical Antagonists On Ca...mentioning

confidence: 99%

Multifunctional cardiac microphysiological system based on transparent ITO electrodes for simultaneous optical measurement and electrical signal monitoring

Li,

Niu,

Zhou

et al. 2024

Lab Chip

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“…All subclasses of CCBs exhibit some degree of vasodilatory effect on peripheral vessels and therefore can exhibit similar side effects if their serum concentration exceeds therapeutic dosing ranges, although DHPs are more commonly associated with vasodilatory side effects [30]. The vasodilatory effects of CCBs can precipitate headaches, flushing, and hypotension, although peripheral edema is the most common side effect that impacts continued usage of these drugs [31,32]. As disproportionate changes in arteriolar resistance occur, there is an increase in precapillary hydrostatic pressure, which promotes fluid shifting into the interstitial compartment [30].…”

Section: Side Effects and Contraindicationsmentioning

confidence: 99%

The Evolving Role of Calcium Channel Blockers in Hypertension Management: Pharmacological and Clinical Considerations

Jones,

Hayden,

Meyer

et al. 2024

CIMB

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Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

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Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on Verapamil

Cited by 12 publications

References 176 publications

Studies of verapamil binding to human serum albumin by high-performance affinity chromatography

Studies of verapamil binding to human serum albumin by high-performance affinity chromatography

Multifunctional cardiac microphysiological system based on transparent ITO electrodes for simultaneous optical measurement and electrical signal monitoring

The Evolving Role of Calcium Channel Blockers in Hypertension Management: Pharmacological and Clinical Considerations

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