Related Experiment Videos
Pharmacology of cardiovascular chronotherapeutic agents
1Memorial Research Medical Clinic, Long Beach, California, USA.
Insights
Blood pressure (BP) naturally rises in the morning, increasing cardiovascular risk. Chronotherapy hypertension treatments aim to optimize medication delivery during these peak BP times for better control.
Area of Science:
- Cardiology
- Pharmacology
- Chronobiology
Background:
- Cardiovascular events like heart attack and stroke show increased incidence in the morning.
- Blood pressure (BP) exhibits a distinct circadian rhythm, with a rapid rise after waking and a decline during sleep.
Purpose of the Study:
- To explore the rationale behind chronotherapy for hypertension.
- To highlight the importance of aligning antihypertensive medication delivery with the body's natural BP patterns.
Main Methods:
- Review of physiological mechanisms driving morning BP surges, including catecholamine and renin activity.
- Analysis of the limitations of traditional sustained-release medications in addressing circadian BP variations.
Main Results:
- Morning hours are characterized by increased BP, heart rate, vascular tone, and peripheral resistance.
- A significant BP drop occurs during nighttime sleep, reaching its lowest point typically between 8 PM and 2 AM.
Conclusions:
- Chronotherapy aims to deliver higher antihypertensive drug concentrations in the morning and lower concentrations during sleep.
- Novel delivery systems, such as those in Verelan PM and Covera HS, enable 24-hour BP control by adapting to circadian rhythms.
Abstract:
Although sudden cardiac death, myocardial infarction, or stroke can occur at any time of day, event rates increase during the waking hours, particularly in the morning. In most people-both normotensive and hypertensive-blood pressure (BP) rises rapidly in the early morning hours, the time when most individuals wake and begin their day. This rise in BP corresponds to increased secretion of catecholamines and increased plasma renin activity. Thus, vascular tone and total peripheral resistance increase in the morning hours, and BP rises as a result. At the same time, heart rate increases. In the late morning or early afternoon, BP reaches its peak. After that, BP declines, falling 15 to 20 mm Hg between about 8 PM and 2 AM, the time when BP is usually lowest. These findings have led to an interest in chronotherapy for hypertension. A major objective of chronotherapy for hypertension is to deliver the drug in higher concentrations during the early-morning post-awakening period, when BP is highest, and in lesser concentrations during the middle of a sleep cycle, when BP is low. Traditional sustained-release pharmacologic agents, which deliver a near-constant drug concentration, were not designed to complement the circadian pattern. There are currently two antihypertensive agents, Verelan PM (verapamil HCl) and Covera HS (verapamil HCl), that provide chronotherapy for hypertension. These drugs use novel delivery systems that provide 24-h BP control while maximizing drug concentrations in the morning and minimizing drug concentrations during sleep.