Chronopharmacologic Issues in Space

Abstract

Times of heightened susceptibility are expressed by nonrandom patterns in the incidence of various diseases, not only along the scale of a day but also of a week and a year. Whereas these rhythms can be synchronized by the environment, their endogenicity is revealed by their persistence in the absence of time cues with a period slightly but statistically significantly different from the environmental match. In the case of some circadians, the gene involved has been identified and heritabiliy in humans determined by studies on twins. Vital signs are now amenable to automatic monitoring around the clock. When analyzed by chronobiologic software, the data provide information regarding the given individual's time structure (chronome). Such physiologic monitoring serves the multiple purposes of deriving time-specified reference norms on the basis of which rhythm alteration can detect an elevated risk early, thus prompting timely preventive action and timed treatment whenever warranted. For long journeys in space, the design of a multi-disease prophylactic pill poses a chronopharmacologic challenge. Drugs such as aspirin and carnitine, used for the prevention of strokes, myocardial infarctions and depression, all show striking chronome-dependent effects which can determine not only the presence or the absence of a desired effect, but even yield effects in opposite directions.

Chronobiologically Explored Effects of Telmisartan

“…Another compared the usual three-times-a-day administration schedule with the timing of propranolol. Clonidine, and α-methyl-dopa in a single dose given about 2 hr before the daily peak in SBP and/or DBP (14). Results from the latter study showed that the single dosing schedule was associated with an enhanced hypotensive effect, obtained with a lesser dose, and was accompanied by fewer side effects.…”