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Chronopharmacology
The document discusses circadian rhythms and chronotherapy. It explains that circadian clocks influence physiology and disease pathology in a time-of-day dependent manner. Drugs have circadian pharmacokinetics due to daily protein oscillations, and circadian pharmacodynamics due to oscillating physiological systems. Chronotherapy aims to optimize drug effects and minimize adverse effects by timing medication administration to biological rhythms.
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Chronopharmacology
- 2. :- • Most facetsof mammalian physiology and behavior vary according to time of- day, thanks to an endogenous “circadian” clock. • Daily oscillations of proteins is necessary for either drug absorption or metabolism results in circadian pharmacokinetics; and oscillations in the physiological systems targeted by these drugs result in circadian pharmacodynamics. • Circadian clocks influence all major organ systems, and this influence translates directly into disease pathology that also varies with time of day
- 3. • Circadian: Lastingfor about 24 hours. -Sleep wake cycles • Infradian: Cycles longer than 24 hours. -Menstrual cycle • Ultradian: Cycles shorter than a day. -Neuronal firing time • Seasonal: Seasonal affective disorders.
- 5. > Science dealingwith optimization of drug effects & minimization of adverse effects by timing medications in relation to biological rhythm. > It is concerned with the effects of drugs upon the timing of biological events and rhythms. • Subdivided into - Chronopharmacokinetics - Chronotoxicity - Chronesthesy - Chronotherapy
- 6. • It dealswith the study of the temporal changes in the pharmacokinetics of the drugs with respect to time. • Study of absorption, distribution, metabolism, and excretion of drugs according to the time of the day or year.
- 12. • Biological processes,including the sleep-wake cycle is controlled by pacemaker present in the suprachiasmatic nuclei (SCN) . • Due to alterations in biological activity many diseases like allergic rhinitis ,arthritis, asthma, cardiovascular diseases, peptic ulcer disease, etc. shows exacerbation of symptoms. • Circadian rhythms, physiology, and behavior of mammalian bodies are controlled by clock genes namely Per1, Per2 and Per3, which are rhythmically expressed in the SCN.
- 15. Because of Increasedbronchoconstriction at night due to… • ↑Parasympathetic tone • ↓ Adrenaline • ↓ Cortisol at midnight • ↑Sensitivity to irritants and allergens at night leads to exacerbations of allergic rhinitis & asthma • Rx - Theophylline and Beta 2 agonist are timed at evening .
- 18. • Heart rateand blood pressure are increased in the early morning hours (morning or A.M. surge). The blood pressure declines form mid afternoon and is minimum at midnight • In most hypertensive patients, there is marked rise in blood pressure upon awakening that is called the morning or "a.m." surge.
- 19. • • Aspirin– maximum antiplatelet effect in the morning. • • Thrombolytics and Heparin – ↓ benefit during early morning hours. • • Labetalol – more effective in early morning hours. • • Enalapril - Peak effect in the afternoon after morning dose.
- 22. Because of higherrates of cholesterol intake and hepatic Cholesterogenesis occur during the evening hours, even in the fasting state.
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- 28. • Controlled releaseformulations can be divided into rate-controlled release, delayed-release and pulsed-release formulations. • Time-controlled release and site-specific dosages forms. • When constant drug plasma levels need to be avoided, as in chronotherapy, time-controlled or pulsed-release formulations are preferable. By timing drug administration, plasma peak is obtained at an optimal time and the number of doses per day can be reduced.
- 29. Here a targeteddrug is deliverd at specific site due to induction of certain physiochemical stimuli at target site. > Release of certain enzymes, hormones, antibodies, pH of the site, temperature of the site, presence of certain cells, and concentration of biomolecules (glucose, neurotransmitters, inflammatory mediators) acts as stimuli to trigger the release of drug from these types of drug delivery systems.