Chronopharmacology
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This document provides an overview of chronopharmacology, which studies the effects of drugs on biological rhythms. It discusses circadian rhythms and zeitgebers that modulate them. The molecular basis, modulators, and physiological variations related to circadian changes are examined. Disease patterns due to circadian disruptions and divisions of chronopharmacology involving pharmacokinetics, pharmacodynamics, therapeutics, and toxicity are summarized. Applied areas like asthma treatment and delivery systems are reviewed. The conclusions emphasize that circadian biology influences pharmacology and identifying rhythmic markers can improve drug effects and reduce side effects.
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Chronopharmacology
- 2. Flow of the seminar • Definition • Biorhythms • The Biological Clock • Circadian Rhythm • Zeitgebers • Molecular Basis • Modulators • Physiologic Variations • Disease pattern • Divisions of Chronopharmacology • ChronoPharmacokinetics • ChronoPharmacodynamics/ Chronesthesy • ChronoTherapeutics • ChronoToxicity • Chrono Drug Delivery Systems • Applied Chronopharmacology • Chronopharmacology in Ayurveda • Conclusion
- 4. Definition The investigative science concerned with the effects of drugs upon the timing of biological events and rhythms. It also links effects of drugs due to variations in the biological rhythms.
- 5. Ultra radian Cir cadian Infra radian Circa Septan Circa Di Septan Circa Vi gintan Circa Tri gintan Circa Annual Biorhythms T<20 h 20h<T<28 h T = 7 dT>28 h T = 1 yT = 30 dT = 21 dT = 14 d
- 6. The Biological Clock/ Circadian Rhythm
- 7. SCN Input Light SCN Output Sleep/Wakefulness Feeding and Energy Expenditure Glucose Homeostasis Hormonal Regulation Blood Pressure & Respiratory changes Peripheral Clocks Input Feeding/ Fasting Signals from SCN Peripheral Clocks Output Lipogenesis Insulin Secretion Glucose Clearance Food Absorption Fat Accumulation
- 8. Zeitgeber
- 9. Zeitgeber Light – Darkness Warmth – Cold Eating – Fasting Social Contact – Isolation Noise – Quiet Pharmacological Manipulation
- 10. Shift Work Jet Lag
- 11. Molecular Basis of Circadian Rhythm
- 13. E Box PER 1 PER 3 PER 2 CRY 1 CRY 2 REVERB WD40 NONO CK1 WDR5
- 15. Circadian rhythm modulators • REVERB agonists – SR9009 • CK1 inhibitor – Longdaysin, LH846 • GSK3b inhibitor – Indirubin
- 16. Physiologic variations in relation to Circadian changes
- 19. Disease pattern due to circadian changes
- 21. ChronoPharmacokinetics Subdivision of chronopharmacology which deals with the study of the temporal changes in the pharmacokinetics of the drugs with respective time.
- 23. Factors affecting pharmacokinetic variations Gastric acid secretions and pH Gastric motility g.i blood flow Drug protein binding Liver enzyme activity Hepatic blood flow Glomerular Filtration Rate Renal Blood Flow Urinary pH Tubular resorption
- 29. Clearance
- 30. ChronoPharmacodynamics Chronesthesy Biological rhythms at the cellular and subcellular level can give rise to significant dosing-time differences in the pharmacodynamics of medications that are unrelated to their pharmacokinetics.
- 32. ChronoTherapeutics Discipline of medical treatment which allows for the consideration of a patient’s biological rhythm, changes in the severity of a disease state during the day, and the synchronizing of dosing and delivery of a particular drug to allow for the optimal efficacy in the patient.
- 33. ChronoToxicity Predictable- in-time variation in patient vulnerability to the side effects of medications due to biological rhythm determinants. Eg. irinotecan hydrochloride.
- 34. Chrono Drug Delivery Systems (Chrono-DDS) OROS, CODAS, CEFORM, TIMERx, POLYMERS, MICROCHIPS
- 36. Asthma
- 44. Arthritis
- 45. Peptic Ulcer
- 49. Hypertension
- 50. Valsartan
- 52. Antidepressants
- 53. Anticancer Drugs
- 55. Chronopharmacology in Ayurveda Abhakta Drugs in morning absorption is maximum and more efficient Pragbhakta Just before food. For diseases of apana vayu – for strengthening and preventing the disease of lower half of body and treating obesity. Madhyabhakta In between foods. For diseases of samana vayu, disease of koshtas and for paittic diseases. Sanya Pscadbhakta In evenings after food. For diseases of udana vayu. Muhurmuhuh Drugs given repeatedly for treating swasa (dyspnoea), kasa (cough), hikka (hiccoughs), chardi (vomitting), visa (poisoning) and pipasa (Thirst). Samudga Before and after light food in hikka, akepsa(convulsions) and in diseases of head and neck. Sabhakta Drugs as appetizers with food, in children with weak constitution.
- 56. Conclusions • Circadian biology influences nearly every aspect of physiology and pharmacology. • Ongoing research has begun to unveil the molecular mechanisms by which circadian clock genes regulate pharmacokinetic and pharmacodynamic processes. • Many drugs are still given without regard to the time of day.
- 57. Conclusions • Identification of rhythmic markers for selecting dosing time and further research in the field of chronopharmaceuticals will lead to improved progress and diffusion of chronotherapeutics. • To monitor rhythmic markers such as clock genes it may be useful to choose the most appropriate time of day for administration of drugs that may increase their therapeutic effects and/or reduce their side effects.
- 58. Conclusions • To produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs appears to lead to a new concept of chronopharmacotherapy. • One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are most effective.
Notes de l'éditeur
- PR prolongation was significantly greater when verapamil is given in morning than evening.
- PR prolongation was significantly greater when verapamil is given in morning than evening.
- For valsartan a morning administration resulted in lower systolic blood pressure for the three time periods studied