Chronopharmacology- Biological/Circadian Rhythm, applications with diseases

biological rhythm, chronotherapy, applications, chrono drug delivery system.

1. CHRONOPHARMACOLOGY 1

2. Contents Introduction Biological rhythm Clock genes Factors affects circadian rhythm Chronotherapy Human sleep cycle Applications Chronomodulated drug delivery systems Reference 2

3. INTRODUCTION Chronopharmacology   is the study of how the effects of drugs vary with biological timing. Subdivided into - Chronopharmacokinetics - Chronotoxicity - Chronesthesy - Chronotherapy 3

4. Biological rhythms 4 Circadian Last for about 24 hours. -Sleep wake cycle Infradian Cycles longer than 24 hours. -Menstrual cycle, bird migration Ultradian Cycles shorter than a day. -Neuronal firing time Seasonal Seasonal affective disorders.

5. The suprachiasmatic nucleus controls circadian rhythms in response to hormonal variation in the body 5

6. 6

7. Clock genes Circadian Locomotor Output Cycles Kaput Circadian rhythms driven by a group of genes clock genes . 7

8. Jet Lag - Sleep disorder that affect those who travel quickly across multiple time zones. All Nighter - marathon study session 8

9. Chronopharmacotherapy Investigation of drug effects as a function of biologic timing and investigation of drug effects upon rhythm characteristics. Advantages – prevents an overdosing of any class of drug. utilization of the drug more appropriate. particular or limited period of time. 9

10. Chrono pharmacokinetics Study of the temporal changes in the pharmacokinetics of the drugs with respective time. Lipophilic drugs fast absorption @ morning than evening. Ex: valproic acid 10

11. Drugs undergoing CHRONOKINETICS 11

12. Chronesthesy - The rhythmic changes in susceptibility or sensitivity of a target system to a drug. Chronergy - Rhythmic changes of both the desired [effectiveness] and undesired [toxicity, tolerance] effects on the organism as a whole. 12

13. Human Sleep Cycle 13

14. Applications of Chronopharmacology 14

15. Applications of Chronopharmacology 15

16. 16 Disease Common onset time Atrial fibrillation Morning/ night Ventricular tachycardia/fibrillation Morning Acute coronary syndrome Early morning Cerebral infraction Morning Pulmonary embolism Early morning

17. Applications of Chronopharmacology 17

18. Peptic ulcer Pathogenesis- Helicobacter pylori Acid secretion Acidity(HCl) peak-evening H 2 blockers:-  @ evening time Eg: Ranitidine, Cimetidine 18

19. Applications of Chronopharmacology 19

20. Chronomodulated drug delivery systems The pulsatile drug delivery system Drug released suddenly after a well-defined lag time or time gap according to the circadian rhythm of disease states. No drug is released from the device within this lag time. 20

21. Chrono Drug Delivery Systems (Chrono-DDS) Technology Mechanism Proprietary name and Dosage form API Disease OROS Osmotic mechanism Covera -HS XL tablet Verapamil HCL Hypertention CODAS Multi particulate pH dependent system Verelan XL release capsule Verapamil HCL Hypertention DIFFUCAPS Multiparticulate system Innopran XL tablet Verapamil HCL Propranolol HCL Hypertention 21

22. Conclusion Effectiveness and toxicity of a drug are not constant over 24 hr period. Understanding the biological rhythms can optimize and individualize drug therapy to a great extent. Thus it can help to decrease the drug related toxicity and enhance effectiveness. 22

23. References Ko CH, Takahashi JS. Molecular components of the mammalian circadian clock. Hum Mol Genet 2006; 15(Spec No 2): R271–7. Maurya K.K et al. Chronopharmacology: A tool for therapy of diseases.IRJP 2012,3(5):128-132 V S Chopra et al. Chronotherapy: A Novel Concept In Drug Delivery Der Pharmacia Lettre , 2010, 2(3): 136-153 23