Circadian Effects of Drug Responses

Abstract

Circadian rhythms describe physiological systems that repeat themselves with a cycle of approximately 24 h. Our understanding of the cellular and molecular origins of these oscillations has improved dramatically, allowing us to appreciate the significant role these oscillations play in maintaining physiological homeostasis. Circadian rhythms allow living organisms to predict and efficiently respond to a dynamically changing environment, set by repetitive day/night cycles. Since circadian rhythms underlie almost every aspect of human physiology, it is unsurprising that they also influence the response of a living organism to disease, stress, and therapeutics. Therefore, not only do the mechanisms that maintain health and disrupt homeostasis depend on our internal circadian clock, but also the way drugs are perceived and function depends on these physiological rhythms. We present a holistic view of the therapeutic process, discussing components such as disease state, pharmacokinetics, and pharmacodynamics, as well as adverse reactions that are critically affected by circadian rhythms. We outline challenges and opportunities in moving toward personalized medicine approaches that explore and capitalize on circadian rhythms for the benefit of the patient. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Radical pairs can explain magnetic field and lithium effects on the circadian clock

“…It has been suggested that environmental perturbations in the circadian period could increase the risk of selected cancers and hence the circadian clock could be a therapeutic target for cancer risks [101]. It also appears that the way drugs function depends on the circadian clock [102, 103]. Notably, it has been shown that the circadian clock is vital for maintaining the anti-oxidative defense [104].…”

Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines

“…Drug efficacy and toxicology are also under circadian control; it has been long known that timing matters in terms of drug dosing, with clinically relevant, time of day effects being observed across myriad drug classes, including psychotropic medications ( Nagayama, 1993 ; Kawai et al, 2019 ; Ruben et al, 2019 ; Nahmias and Androulakis, 2021 ; Walton et al, 2021 ). Mechanistically, these effects are due to circadian regulation of gene expression for enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion, with ultimate effects on circadian pharmacokinetics and medication chrono efficacy and chrono toxicity ( Bicker et al, 2020 ; Lu et al, 2020 ; Nahmias and Androulakis, 2021 ). Given the high rate of consumption of psychiatric medications world-wide, and the medication associated effects on energy metabolism and prevalence of metabolic diseases including NAFLD, the further impact of circadian regulation of psychiatric drug effects deserves further investigation.…”

Precision caffeine therapy for apnea of prematurity and circadian rhythms: New possibilities open up

“…Interestingly, the onsets and symptoms of many diseases, such as stroke, asthma, and depression, also display clear circadian characteristics ( Jagannath et al, 2013 ; Hsieh et al, 2018 ; Cederroth et al, 2019 ; Dobrek, 2021 ; Ruan et al, 2021 ), which are called as the circadian pathology signs ( Cederroth et al, 2019 ). Speaking of pharmacology, circadian rhythms affect the absorption, distribution, metabolism, and excretion (ADME) or called the pharmacokinetic processes as well as the efficacy and adverse effects of many drugs, which is well known as the chronopharmacology or chronotherapy ( Dallmann et al, 2016 ; Ohdo et al, 2019 ; Dong et al, 2020 ; Dobrek, 2021 ; Nahmias and Androulakis, 2021 ). Given the importance of circadian rhythms, three researchers who discovered the basic of biological clock in studies of Drosophila were awarded the Nobel Prize in 2017 ( Dobrek, 2021 ; Ruan et al, 2021 ).…”

“…The concept of chronopharmacology holds that the ADME processes and the sensitivity of a biological target to a drug are determined by the endogenous biological circadian oscillations ( Ohdo et al, 2019 ; Bicker et al, 2020 ; Dong et al, 2020 ; Dobrek, 2021 ). Variable efficacy and safety profiles would be exhibited for many drugs if they are administered at different times of the day ( Dallmann et al, 2016 ; Cederroth et al, 2019 ; Nahmias and Androulakis, 2021 ). For preterm infants, interestingly, several circadian-related gene polymorphisms were found to be significantly associated with the response to caffeine therapy for AOP ( Guo et al, 2022 ).…”