Chronopharmacology is the study of how biological rhythms affect medication. It considers how the effects and pharmacokinetics of drugs vary based on the time of day they are administered. Proper timing of medication can maximize benefits and minimize side effects by matching drug delivery to circadian rhythms in conditions like cardiovascular disease, respiratory disease, and endocrine disorders. For example, inhaled corticosteroids administered in the evening are nearly as effective as multiple daily doses for asthma, and beta blockers taken at night better prevent morning heart attacks. Chronopharmacology aims to deliver medications when the body's need or the disease's symptoms are greatest.

1. Basic Concepts
in
Chronopharmacology
DR.swanand s. pathak
MBBS, MD ( Pharmacology),DACM,IDCR
drswanandp@yahoo.co.in

2. 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

3. CHRONOPHYSIOLOGY
CHRONOPATHOLOGY
CHRONOPHARMACOLOGY
In medicine, 3 disciplines take into
account the influence of time:

4. 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 ????

5. Investigative science concerned with the
biological rhythm dependencies of
medications.
Chronopharmacology
Subdivided into
chronopharmacokinetics
chronotoxicity
chronesthesy
chronotherapy

6. same events occurring in the body of a
living being over a particular time interval
Flowers
Fruits
Human body
Biological rhythm ( biological clock)

7. “Dhire dhire re mana
dhere sab kuch hoi
Mali siche
sau ghada
ritu aay phal hoi”
--- KABIR

9. Biological rhythm - types

10. Blood Pressure Rhythm

11. Peak time functions

12. Disease rhythm

13. Advantage
Time the administration
of the drugs

14. Applied Chronopharmacology
Endocrine system
Corticosteroids
Once-daily morning dose dosing
minimizes risk of adrenal suppression
and other side effects.

15. Peak time functions

16. Applied Chronopharmacology

17. Applied Chronopharmacology

18. Applied Chronopharmacology
Endocrine system
Congenital adrenal hyperplasia
Bedtime corticosteroid dosing controls excessive hormone
secretion in

19. 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.

20. Peak time functions

21. 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.

22. 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.

23. Applied Chronopharmacology
Endocrine system
Bedtime ADH analogue dosing helps to alleviate
nocturnal bedwetting in children and nocturia in adults.

24. 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.

26. Applied Chronopharmacology
CVS
Objective
Deliver drug in high conc. During great
need
ACE inhibitors
Nifedipine
Amlodipine
Night

27. 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

28. Applied Chronopharmacology
CVS
When the 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors were first
introduced,
morning dosing was recommended.

29. Peak time functions

30. 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.

31. Applied Chronopharmacology
CVS
Bedtime (but not morning) aspirin
dosing best for preventing pregnancy-induced
hypertension and preeclampsia.

32. 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.

35. Peak time functions

36. 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

37. 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.

38. 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.

39. Disease rhythm

40. Applied Chronopharmacology
GIT
Histamine2 antagonists
In the past, were administered at regular intervals around
the clock, on the basis of pharmacokinetic properties.

41. Peak time functions

42. 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

43. 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.

46. Acknowledgements
• Wikipedia
• Google
• Concepts of Chronopharmacology by N. Udupa
• Lullman’s atlas of pharmacology

48. 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