Chronopharmacologu

1. CHRONOPHARMACOLOGY Prepared By Ms. Prexita Patel Dept. of Pharmacology Anand Pharmacy College, Anand

2. Chronopharmacology It is the study of how the effects of drugs vary with biological timing and endogenous periodicities. The goal is to improve our understanding of periodic and thus predictable (e.g. circadian) changes in both desired effects (Chrono effectiveness) and tolerance (Chrono tolerance) of medications.

3. There are four biological rhythms: • circadian rhythms: the 24-hour cycle that includes physiological and behavioral rhythms like sleeping. (about once a day) • diurnal rhythms: the circadian rhythm synced with day and night. (about once a year) • ultradian rhythms: biological rhythms with a shorter period and higher frequency than circadian rhythms. (shorter than once a day) • infradian rhythms: biological rhythms that last more than 24 hours, such as a menstrual cycle. (about once a month)

4. What is rhythm in biology? Biological rhythms are the repeating cycles of activity which occur in living organisms. Or Biological rhythms are the natural cycle of change in our body’s chemicals or functions. It’s like an internal master “clock” that coordinates the other clocks in your body. The “clock” is located in the brain, right above the nerves where the eyes cross. It’s made up of thousands of nerve cells that help sync your body’s functions and activities.

5. BIOLOGICAL RHYTHMS Biological rhythms are innately determined rhythmic biological process or function and self-sustaining oscillation with the duration of time between successive repetitions (i.e., the period) being rather non varying under normal conditions. Circadian (circa about dies, day, or about 24 hour) Physiological day is about 25 hours Clock is reset daily by the environment night day social schedules. A circadian clock in the brain coordinates daily physiological cycles like sleep/wake, digestion, temperature, hormones. Biologic rhythms are endogenous nature of circadian. Lack of external synchronizers leads to free running rhythms. The period of free-running rhythms is longer or shorter than 24 hours and is characteristic for each species. Our internal clocks are genetically determined.

6. An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body. It is responsible for circadian rhythms and annual/seasonal rhythms. The SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands or by directly controlling an endocrine output of pineal gland (i.e., melatonin synthesis). CIRCADIAN RHYTHMS Circadian rhythmsare physical, mental, and behavioral changes that follow a daily cycle. They respond primarily to light and darkness in an organism's environment. Sleeping at night and being awake during the day is an example of a light-related circadian rhythm.

8. REGULATION OF CIRCADIAN RYTHM

10. CIRCADIAN RHYTHM OF DISEASES

12. APPLICATION OF CHRONOPHARMACOLOGY

16. CHRONOTHERAPY It studies the drugs effecting the biological clock of the disease and biological clock affecting the drugs and applies the same for better dosing and dosing time of drugs. This is the design and evaluation of drug delivery systems that release bioactive drug in specific time intervals and rhythm that matches with the biological rhythm of the disease. Branches of CHRONOTHERAPY 1. Chronopharmacokinetics :- This is the study of temporal changes that occurs to the Absorption , Distribution , Metabolism and Excretion of the drug due to the time of administration in a specific biological cycle. 2. Chronopharmacodymnamics :- This is the study of differences of the activity of the drug administered at the specific time of biological clock of body and also the effect of any particular drug that changes the biological clock of the body.

17. CHRONOPHARMACOKINETICS AIM OF CHRONOPHARMACOKINETICS It is to control the time of administration, which among others, can be responsible for variations of drug kinetics but also may explain Chrono pharmacological effects observed with certain drugs. NEED FOR CHRONOPHARMACOKINETICS *  When possible daily variations in pharmacokinetics may be responsible for time dependent variations in drug effects (Ex: some antimicrobial agents are more effective at a specific time)*When drugs have a narrow therapeutic range.*  When symptoms of a disease are clearly circadian phase-dependent (Ex: Nocturnal asthma, angina pectoris, myocardial infarction, ulcer disease)*  When drug plasma concentrations are well correlated to the therapeutic effect in case the latter is circadian phase-dependent*  when the drug has some serious adverse effects that can be avoided or minimized because they are related to time of administration (Ex: Aminoglycosides nephrotoxicity)

18. CHRONOPHARMACODYNAMICS NEED FOR CHRONOPHARMACODYNAMICS 1. Cardiovascular drugs :- e.g. The peak concentration of propranololwas achieved in the application between 8 A.M. and 2 P.M.. However, when applied on 2 A.M., the heart rate can be slightly changed in the following 6 hours. CCB and in general their blood pressure lowering effect was found to be higher in daytime than night time 2. Anticancer drugs :- 5‑fluorouracilinduced toxicity (e.g., bone marrow, skin, and oral and rectal mucosa) is lowest during the night and highest during daytime. 3. NSAID :- A peak of morphine in pain relief occurred late in the afternoon (5.30 P.M.) and a trough in the early morning hours (5.30 A.M.).