Abstract
This paper explores the applications of chronotherapy in aligning medical treatments with the body’s circadian rhythms, which are regulated by the suprachiasmatic nucleus (SCN) in the brain. The primary aim is to illustrate how circadian rhythms influence physiological
processes and the potential for enhanced drug efficacy when treatments are timed
accordingly. Key case studies include asthma and cardiovascular disease, highlighting
findings from trials that demonstrate improved therapeutic outcomes through
circadian-aligned medication timing. These results underscore the potential of chronotherapy to reduce symptom severity and improve disease management.
Introduction
Chronotherapeutics is a field where an individual's circadian rhythm can be utilized to maximize the efficiency of the medication. Circadian rhythms are biological, 24-hour cycles that are found in most organs of the body. They are governed by ‘clocks’. The main biological clock is a group of nerve cells located in the brain, known as the suprachiasmatic nucleus (SCN). All other clocks are known as peripheral clocks,located all around the body. However, these are all governed by the master clock, the SCN. Circadian rhythms can be found in the liver, the intestine, and other organs around the body (Paudel et al., 2021). Circadian rhythms have significant applications in pharmacology, providing insights into optimal medication timing to maximize drug efficacy and improve overall public health outcomes.
Figure 1 illustrates how circadian rhythms can influence the timing of various health conditions, highlighting the connection between biological cycles and disease progression. For example, asthma symptoms tend to peak in the early morning hours, while cardiovascular incidents like heart attacks are more likely to occur in the morning. This emphasizes the importance of synchronizing medical treatments with the body’s natural rhythms to enhance drug effectiveness.
Abstract
The application of circadian rhythms is found in many conditions. In this case, asthma. Asthma is a lung condition involving inflammation of the airways and has symptoms such as coughing, and wheezing that can cause an asthma attack in severe cases. Triggers may include allergies (to dust, or pollen), pollution, and more (NHS, 2021). This condition's characteristics include the varying severity of symptoms at different points in a 24-hour period. Symptoms of asthma tend to be worse at night ( known as nocturnal asthma) and tend to peak at 4 am (Paudel et al., 2021). Medication consumption at 4 am would be inconvenient for most since people tend to be sleeping, and awakening can disrupt the sleep cycle. Qureshi et al. found a solution to this.
Methods
The method conducted involved an independent group's experimental design, with 6 rabbits, divided equally into 2 groups. Both groups were treated with salbutamol, a common drug used to treat asthma.The first group of rabbits were administered salbutamol in its regular capsule, while the second group were given a form of salbutamol that had been encapsulated into a pulsatile drug. Pulsatile drug delivery is a system in which the time taken for the release of the drug into the bloodstream can be controlled. This time is controlled by the researchers, and is also known as the lag time (Jain, Raturi, Jain, Bansal, & Singh, 2011). The researchers then monitored the release of the drugs in both groups to investigate how long the lag time of salbutamol was in its regular form compared to its pulsatile form (Qureshi et al., 2014).
Results
The results were that in the pulsatile capsule, salbutamol release had a lag time of 4.25 hours, while the regular capsule immediately released salbutamol into the blood once administered. The AUC0-inf is a measurement of the total drug exposure to the body from when it is released into the bloodstream up until clearance of the drug (Abrams et al., 2013). This was measured in both the rabbits who had received salbutamol in its regular form and in its encapsulated form , and it was found that there was no significant difference between the AUC values in both groups using the ANOVA test (analysis of variance) at a significant difference of p < 0.05 (CI 95%), suggesting that the pulsatile system still released a similar concentration of salbutamol into the bloodstream as the regular form of the drug. (Qureshi et al., 2014).
Conclusions
These findings suggest that the pulsatile system of drug release does not affect the bioavailability of salbutamol in the body and can be used to help combat the severe symptoms of asthma by administering the drug before sleep, so symptoms at night and during the early hours of the morning can be reduced, an innovative application of chronotherapy (Qureshi et al., 2014).
Cardiovascular diseases
Beyond respiratory conditions, the principles of chronotherapy also extend to cardiovascular diseases (CVD). CVD is a general term underpinning all conditions that can affect the functioning of the heart or blood vessels. (National Health Service, 2022) The Hygia chronotherapy trial was a controlled clinical trial that aimed to investigate any differences in hypertension (when one’s blood pressure is excessively high) when medication for hypertension was taken at different times of the day, eventually discovering whether there was reduced CVD in those who treated their hypertension at different times of the day. (Smolensky, Hermida, & Geng, 2021)
Method
19,084 hypertensive patients who were diagnosed by an ABPM (ambulance blood pressure monitor) and were approximately 60.5 years of age were divided into 2 independent groups. One group was instructed to take their entire daily dose of at least 1 hypertension medication before sleeping (n = 9552), whereas the other group was instructed to take all of their hypertension medication in the morning upon awakening (n = 9532). The participants were checked on at minimum, annually, and their ABP was taken for 48 hours to see the effects of the medication timings. (Smolensky, Hermida, & Geng, 2021)
Results
After the 6.3-year patient median follow-up, 1752 patients had heart-related issues. These included death, heart failure, heart attack, coronary revascularisation, or stroke. Hazard ratios were adjusted for many influential characteristics that could have impacted the results of the study, which include but aren’t limited to: age, sex, type 2 diabetes, cholesterol, and more. It was found that the hypertensive patients prescribed at least 1 blood pressure medication before sleeping were 45% less likely [0.55 (95% CI 0.50-0.61), P < 0.001] to develop heart-related issues described above than those who took all of their medications after waking up, and also had a significantly lower blood pressure while sleeping, and finally, an overall decrease in CVD events such as heart attacks, strokes or death. (Smolensky, Hermida, & Geng, 2021)
Conclusions
These results illustrate the significance of ingesting medication in accordance with the circadian rhythms of the affected organs, in this case, the heart. The findings highlight the potential for further research into pulsatile formulations for hypertension, mirroring advances seen in asthma treatment. Implementing chronotherapy could significantly reduce global mortality from CVD-related health issues.
Summary
To conclude, this report summarised two different applications of chronotherapy in modern medicine. This truly fascinating field of pharmacology which draws on our innate rhythms to reduce symptoms of ill health is constantly advancing to produce a healthy and flourishing population.
Written By: Sania Bhatti
Works Cited
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Jain, D., Raturi, R., Jain, V., Bansal, P., & Singh, R. (2011). Recent technologies in pulsatile drug delivery systems. Biomatter, 1(1), 57–65.
National Health Service. (2022, April 22). Cardiovascular disease. Retrieved October 24, 2024, from NHS website: https://www.nhs.uk/conditions/cardiovascular-disease/
NHS. (2021, April 19). Asthma. Retrieved October 23, 2024, from NHS website: https://www.nhs.uk/conditions/asthma/
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Qureshi, M. J., Ali, J., Baboota, S., Ahuja, A., & Mallikarjun, C. (2014). Pharmacokinetic Study of a Capsule-based Chronomodulated Drug Delivery System of Salbutamol Sulphate in Rabbits. Tropical Journal of Pharmaceutical Research, 13(1), 17.
Smolensky, M. H., Hermida, R. C., & Geng, Y.-J. (2021). Chronotherapy of cardiac and vascular disease: timing medications to circadian rhythms to optimise treatment effects and outcomes. Current Opinion in Pharmacology, 57, 41–48.
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