Chronopharmacology basic concepts
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Basic Concepts in
Chronopharmacology
DR.swanand s. pathak
MBBS, MD ( Pharmacology),DACM,IDCR
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Chrono -Pharmacology
Chronology : The arrangement of events according to the time of occurrence .
Rhythm
CHRONOBIOLOGY
The science dealing with the phenomenon of
rhythmicity in living organisms
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CHRONOPHYSIOLOGY
CHRONOPATHOLOGY
CHRONOPHARMACOLOGY
In medicine, 3 disciplines take into account the influence of time:
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The study of rhythmic, predictable-in-time differences in the effects and/or pharmacokinetics of drugs both in experimental animals and in men. It investigates the effects/side effects of drugs upon temporal changes in biological functions or symptoms of a disease as well as drug effects as a function of biologic timing.
Definition ????
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Investigative science concerned with the biological rhythm dependencies of medications.
Chronopharmacology
Subdivided into
chronopharmacokinetics chronotoxicitychronesthesy
chronotherapy
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same events occurring in the body of a living being over a particular time interval
Flowers
Fruits
Human body
Biological rhythm ( biological clock)
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“Dhire dhire re mana dhere sab kuch hoi
Mali siche sau ghada
ritu aay phal hoi”
--- KABIR
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Biological rhythm - types
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Blood Pressure Rhythm
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Peak time functions
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Disease rhythm
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Advantage Time the administrationof the drugs
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Applied Chronopharmacology
Endocrine system
Corticosteroids
Once-daily morning dose dosing minimizes risk of adrenal suppression and other side effects.
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Peak time functions
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Applied Chronopharmacology
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Applied Chronopharmacology
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Applied Chronopharmacology
Endocrine system
Congenital adrenal hyperplasia
Bedtime corticosteroid dosing controls excessive hormone secretion in
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Applied Chronopharmacology
Endocrine system
Chronotherapy for Addison’s disease
Asymmetrical morning high and late-afternoon low-dose corticosteroid substitution best corrects fatigue and abnormal circadian time structure.
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Peak time functions
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Dawn Phenomenon
0
10
20
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Cause: Less insulin in body
Spurt in GH, cortisol.
Rise in blood sugar at night
Treatment: Use enough dose.
Reduce bed time snack.
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Somogyi PhenomenonSomogyi Phenomenon
0
10
20
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Cause: too much insulin
Long acting
Blood sugar drop at night
Hormones to rise blood sugar levels
Treatment: Decrease pre-supper intermediate insulin.
Change or start pre-bed snack.
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Applied Chronopharmacology
Endocrine system
Bedtime ADH analogue dosing helps to alleviate nocturnal bedwetting in children and nocturia in adults.
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Applied Chronopharmacology
CVS
Myocardial infarction, acute cardiac arrest , transient myocardial ischemia
Onset – early morning – 34% events
Reason – release of catecholamines , cortisol , increase in platelet aggregation , vascular tone , heart rate surge.
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Applied Chronopharmacology
CVS
Objective
Deliver drug in high conc. During great need
ACE inhibitors
Nifedipine
Amlodipine
Night
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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
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Applied Chronopharmacology
CVS
When the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors were first introduced,
morning dosing was recommended.
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Peak time functions
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Applied Chronopharmacology
CVS
This strategy was re-evaluated after the discovery of the circadian rhythm of cholesterol biosynthesis in which higher rates of cholesterol intake and hepatic cholesterogenesis occur during the evening hours, even in the fasting state.
Except Atorvastatin all (HMG-CoA) reductase inhibitors are administered between the evening meals and sleep.
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Applied Chronopharmacology
CVS
Bedtime (but not morning) aspirin
dosing best for preventing pregnancy-induced hypertension and preeclampsia.
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Applied Chronopharmacology
RS
Asthma the most common disease with the largest circadian variation.
Because asthma has such a striking circadian variation, several types of chronotherapy have been tried.
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Peak time functions
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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 in
improving several features of nocturnal asthma [FEV1]and response to a standard dose of inhaled beta2 agonist when administered at 3 pm rather than 8 am
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Applied Chronopharmacology
RS
Theo-24
Use of a timed-release formulation of theophylline achieved therapeutic drug concentrations during the night and avoided toxic levels during the day.
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Applied Chronopharmacology
Autoimmune diseases
Arthritis
The new cyclooxygenase-2 inhibitors effectively relieve osteoarthritis symptoms when taken in the evening; better results are obtained in rheumatoid arthritis when part of the dose is taken in the morning.
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Disease rhythm
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Applied Chronopharmacology
GIT
Histamine2 antagonists
In the past, were administered at regular intervals around the clock, on the basis of pharmacokinetic properties.
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Peak time functions
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Applied Chronopharmacology
GIT
Maximal acid secretion, peptic ulcer disease pain, and perforation of gastric and duodenal ulcers are more common at night, administration of these drugs at bedtime is more effective.
Nocturnal administration not only reduces acid secretion more effectively but also promotes ulcer healing and reduces ulcer recurrence
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Applied Chronopharmacology
CNS
Chlorpromazine would be most effective in producing sedative and antipsychotic effects when administered at midnight and immediately after rising, respectively.
For haloperidol, administration in the evening would be best for obtaining either a sedative or antipsychotic effect.
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Acknowledgements
• Wikipedia • Google • Concepts of Chronopharmacology by N. Udupa • Lullman’s atlas of pharmacology
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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