This document provides an overview of chronopharmacology, which is defined as the study of how biological rhythms influence drug effects. It discusses how circadian rhythms can impact drug absorption, distribution, metabolism, and excretion. Administering drugs at times aligned with biological rhythms can optimize efficacy and reduce side effects. Examples are given of disease processes and medications known to exhibit circadian rhythms. Future areas of research may explore integrating chronopharmacology with fields like systems biology and nanomedicine to further tailor drug delivery to an individual's biological clock. In summary, chronopharmacology studies how biological timing impacts drug action and aims to maximize therapeutic effects by synchronizing administration with a body's natural rhythms.

1. Chronopharmacology
Prepared by:
Dr. Vijita Shah
2nd Year Resident in Pharmacology,
Department of Pharmacology,
Government Medical College, Surat.
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2. Introduction
• The biological function of all living organisms including humans are
influenced with change of time in a rhythmic pattern that results in
biological rhythm.
• In Medicine, 3 disciplines are taken into account under the influence
of time:
1. Chronophysiology
2. Chronopathology
3. Chronopharmacology
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3.  Chronopharmacology is defined as a branch of chronobiology
concerned with the effects of drugs upon the timing of biological
events and rhythms and the relation of biological timing to the
effects of drugs.
 Chronobiology
Chronos : Time, Bios : Life, Logos : Study of
Chronobiology is the scientific study of the effect of time on living
systems and biological rhythms. 3

4. Biological rhythm
Self sustaining oscillation with duration of time between successive
repetition being rather non varying under normal conditions. e.g,
 Ultradian
 Circadian
 Infradian
Disruption : Shift work
• Phase advance
• Phase delay
: Jet lag 4

5. Circadian Rhythms
Circa means ‘about’; Dian means ‘day’
Circadian rhythm is defined as
oscillations in the biological,
physiological, and behavioral
function of an organism with a
periodicity of 24 hrs.
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6. • When a drug is administered, the pharmacological action of the drug can be
predicted based on the body’s circadian rhythm.
 Sleep – Awake
 Feed – Hunger regulated by living clocks
 Joy – Depression
• Maximum efficacy and toxicity achieved if administered at appropriate time
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7. Circardian rhythms are
particularly important in
medicine as a circadian clock
in brain coordinates with daily
physiological activity such as
maintaining body temperature,
heart rate, blood pressure,
organ blood flow, pulmonary
and kidney functions.
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8. 8

9. History
• In 18th Century, Jean- Jacques d’Ortous
de Mairan described circardian
rhythms in plants
• Franz Halberg coined the word
circadian in 1960 and is considered as
one of the founders of chronobiology.
Franz Halberg 9

10. Subdivisions
Chronopharmacology is the investigative science concerned
with the biological rhythm dependencies of medications and
subdivided into :
 Chronotherapeutics
 Chronopharmacokinetics
 Chronopharmacodynamics
 Chronesthesy
 Chronergy
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11. Chronotherapeutics
• Drug administration synchronized with biological rhythms
• Involves both :
- function of biologic timing
- rhythm characteristics
• In time variation of disease with evidence of circadian rhythms
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12. Advantage
• Prevents an overdosing
• Utilization - more appropriate
• Value - increased
• Side effect - reduces
• Treatment - limited period
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13. Chronopharmacokinetics
Temporal changes in absorption(gastrointestinal tract,plasma protein binding),
distribution(fat, muscle etc),
metabolism(enzyme activity & hepatic ), and
elimination(renal drug excretion)
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14. Chronopharmacodynamics
• Biological rhythms at the cellular and subcellular level
• Chronotoxicology
predictable in time variation in patient vulnerability to
side effects of medications
• Circadian rhythm experiments
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15. Chronesthesy
Circadian or other systemic changes in the susceptibility and
sensitivity of the target system towards drug.
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16. Chronergy
Rhythmic difference in effects of drug on the organism as a
whole, which includes both desired and undesired effects.
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17. Aim of
Chronopharmacology
• Control the time of administration
• Investigates the effect / side effects of drugs
• Optimize the therapeutic effect and control the adverse effect
• Monitor therapy so as to limit the duration
• Individualization of pharmacotherapy
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18. Biological rhythms
observed
Hormones and their circadian rhythm
Circadian rhythmicity Hormone/Biological functions affected
Late at night or early during sleep • Gastric acid secretion
• WBC count
• Calcitonin gene related peptide
• Atrial natriuretic peptide
Peaks during sleep • Growth hormone
• Thyroid stimulating hormone
• Melatonin , Prolactin
• ACTH
• FSH
Peaks during the morning • Cortisol
• Angiotensin
• Renin
• Vascular resistance
• Platelet aggregation
• Blood viscocity
Peaks at noon • Hemoglobin
• Insulin release
Peaks during evening • Triglyceride
• Cholesterol
• Diuresis
Biological rhythms observed in various
biological systems
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19. 19

20. Diseases following
biological rhythm
• Migraine
• Allergic rhinitis
• Rheumatoid arthritis
• Osteoarthritis
• Stroke
• Ischemic events
• Peptic ulcer
• Epilepsy
• Congestive heart failure
Disease or
Syndrome
Circadian rhythm
Allergic rhinitis Worse in early morning / upon rising
Bronchial asthma Exacerbation more during sleep
Rheumatoid
arthritis
Symptoms are more intense while awakening
Osteoarthritis Symptoms are more pronounced in the middle or latter
portion of the day
Angina pectoris Chest symptoms and ECG changes are more prominent
during early morning
Myocardial
infarction
more common during morning time
Sudden cardiac
death
more common during morning while awakening
Peptic ulcer Symptoms worse at early morning while sleeping
Stroke Incidence more in early morning 20

21. Influence of biological
rhythm on pharmacokinetics
Why to study Chronopharmacokinetics ?
• Absorption : Lipophilic drugs
• Distribution : Sympathetic and parasympathetic systems
• Metabolism : Drug metabolizing enzymes
: Solute carrier transporter
: Ion transporter genes
• Excretion : Renal physiological function
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22. Influence of biological rhythm
on pharmacodynamics
• Rhythms in receptor number or conformation, second messangers,
metabolic pathways, and / or free to bound fraction of medications
help to explain this phenomenon
• Examples : Antitumor effect of IFN beta
: Methionine aminopeptidase 2
: Chronotoxicity
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23. Steps involved in evaluation
of Chronopharmacology
• Identification of its occurrence
• Determination of parameter affected
• Mechanism of non linearity
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24. • Antiasthmatic drugs i.e, theophylline
• Antibiotics i.e, amikacin
• Anticancer drugs i.e, dehydropyrimidine dehydrogenase
• Antiulcer drugs i.e, H2 blockers
• Antihypertensive drugs i.e, nifedipine, nitrates etc.
• Anti inflammatory drugs i.e, NSAIDS
• Opioid analgesics i.e, tramadol
• Antiepileptic drug i.e, carbamazepine
Chronopharmacokinetics
of drugs
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25. • Local anesthetics i.e, lidocaine, ropivacaine etc.
• Antimigraine drugs i.e, sumatriptan
• Antihyperlipidemic agents i.e, HMG CoA reductase
• Heparin
• Topical steroids
• Antipsychotics i.e, chlorpromazine
• General anesthetics i.e, barbiturates,
benzodiazepine,
ketamine, etomidate etc. 25

26. • Methyl prednisolone
• Theophylline
• Zileuton
• HMG CoA reductase antagonists
• H2 receptor antagonist
• Hypnotics
• Testosterone
• Antitumor medications
Chronopharmacology
in medical practice
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27. • Tocolytics
• Antihistaminic drugs
• Corticosteroids
• Calcium antagonists
• Verapamil
• Aspirin
• Thiazide
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28. Futuristic Approach
Future development in chronopharmaceutics may be made at the
interface of other emerging disciplines such as -
• System biology and
• Nanomedicine
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29. Conclusion
• Identification of rhythmic marker for selecting dosing time will lead
to improve progress and discussion of chronopharmacotherapy.
• Chronopharmacology principle is used for treatment of various
diseases like diabetes, hypertension, angina pectoris, pulmonary
embolism etc.
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30. Bibliography
• Smolensky MH, Portaluppi F. Chronopharmacology and chronotherapy of cardiovascular
medications : Relevance to prevention and treatment of coronary heart disease. American
Heart Journal 1999; 137: S14-S24
• Prasanthi N, Swathi G and Manikiran SS. Chrotherapeutics : A new vista in novel drug
delivery systems. International Journal of Pharmaceutical Sciences Review and Research
2011; 6(2):66-75.
• Koppisetti VS and Hema Shree S. Chronopharmacology and Chronopharmacotherapy - A
guide to better health. Research Journal of Pharmaceutical, Biological and Chemical Sciences
2011;2(1):266-272.
• Labrecque G and Belanger PM. Biological rhythms in the absorption, distribution, metabolism
and excretion of drugs. Pharmacology & Therapeutics i1991;52:95-107.
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31. Thank you
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