Chrono -PharmacologyChronology : The arrangement of events according to the time of occurrence .RhythmCHRONOBIOLOGYThe science dealing with the phenomenon ofrhythmicity in living organisms
In medicine, 3 disciplines take intoaccount the influence of time: CHRONOPHYSIOLOGY CHRONOPATHOLOGY CHRONOPHARMACOLOGY
Definition ????The study of rhythmic, predictable-in-time differences in the effects and/orpharmacokinetics of drugs both inexperimental animals and in men. Itinvestigates the effects/side effects ofdrugs upon temporal changes inbiological functions or symptoms of adisease as well as drug effects as afunction of biologic timing.
Chronopharmacology Investigative science concerned with the biological rhythm dependencies of medications.Subdivided into chronopharmacokinetics chronotoxicity chronesthesy chronotherapy
Biological rhythm ( biological clock)same events occurring in the body of aliving being over a particular time intervalFlowersFruitsHuman body
“Dhire dhire re mana dhere sab kuch hoi Mali siche sau ghada ritu aay phal hoi” --- KABIR
Applied Chronopharmacology Endocrine systemChronotherapy for Addison’s diseaseAsymmetrical morning high and late-afternoon low-dosecorticosteroid substitution best corrects fatigue andabnormal circadian time structure.
Dawn Phenomenon2010 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24Cause: Treatment:Less insulin in body Use enough dose.Spurt in GH, cortisol. Reduce bed time snack.Rise in blood sugar at night
Applied Chronopharmacology Endocrine systemBedtime ADH analogue dosing helps to alleviatenocturnal bedwetting in children and nocturia in adults.
Applied Chronopharmacology CVSMyocardial infarction, acute cardiacarrest , transient myocardial ischemiaOnset – early morning – 34% eventsReason – release of catecholamines , cortisol , increase in platelet aggregation , vascular tone , heart rate surge.
Applied Chronopharmacology CVSObjectiveDeliver drug in high conc. During greatneedACE inhibitorsNifedipine NightAmlodipine
Applied Chronopharmacology CVS• The first chronotherapeutic therapy for hypertension and angina pectoris• Matches drug delivery to the circadian patternof blood pressure and rhythm of myocardialischemia.• Verapamil has been employed
Applied Chronopharmacology CVSWhen the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors were firstintroduced,morning dosing was recommended.
Applied Chronopharmacology CVSThis strategy was re-evaluated after the discovery ofthe circadian rhythm of cholesterol biosynthesis inwhich higher rates of cholesterol intake and hepaticcholesterogenesis occur during the evening hours,even in the fasting state.Except Atorvastatin all (HMG-CoA) reductaseinhibitors are administered between the eveningmeals and sleep.
Applied Chronopharmacology CVSBedtime (but not morning) aspirindosing best for preventing pregnancy-inducedhypertension and preeclampsia.
Applied Chronopharmacology RSAsthma the most common disease with the largestcircadian variation.Because asthma has such a striking circadian variation,several types of chronotherapy have been tried.
Applied Chronopharmacology RS• A single daily dose of inhaled corticosteroids, when administered at 5:30 pm rather than 8 am, was nearly as effective as four doses a day.• Oral prednisone has been shown to be much more effective inimproving several features of nocturnal asthma[FEV1]and response to a standard dose ofinhaled beta2 agonist when administered at 3 pm ratherthan 8 am
Applied Chronopharmacology RSTheo-24Use of a timed-release formulation of theophylline achievedtherapeutic drug concentrations during the night and avoided toxiclevels during the day.
Applied Chronopharmacology Autoimmune diseasesArthritisThe new cyclooxygenase-2 inhibitors effectively relieveosteoarthritis symptoms when taken in the evening;better results are obtained in rheumatoid arthritis whenpart of the dose is taken in the morning.
Applied Chronopharmacology GITMaximal acid secretion, peptic ulcer disease pain, andperforation of gastric and duodenal ulcers are morecommon at night, administration of these drugs at bedtimeis more effective.Nocturnal administration not only reduces acid secretionmore effectively but also promotes ulcer healing andreduces ulcer recurrence
Applied Chronopharmacology CNSChlorpromazine would be most effective in producingsedative and antipsychotic effects when administered atmidnight and immediately after rising, respectively.For haloperidol, administration in the evening would bebest for obtaining either a sedative or antipsychotic effect.
Acknowledgements• Wikipedia• Google• Concepts of Chronopharmacology by N. Udupa• Lullman’s atlas of pharmacology
Presented on• 30-03-2011/national CME on personalized medicine / MGMC / Puducherry• 23-07-2011/zonal CME for post graduates/ DR NTR University/ mamata medical college/ Vijaywada