SUBMITTED BY GUIDED BY

AMIT M.DURKAR Mrs. R S.SAHANE

M.PHARM (IInd SEM) (PHARMACOLOGY)

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 CHRONOPHARMACOLOGY

Investigative science concerned with the biological rhythm

dependencies of medications.

Chronopharmacology is focused on 2 areas:

 Biologic rhythm dependencies of medications and underlying

mechanisms.

 Effect of timing pharmacotherapy on biologic time structure and

relationships among rhythms.
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 Circadian rhythm (about 24 hr)

 Ultradian rhythm (Less than 24 hr)

 Infradian rhythm (more than 24 hr)

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CHRONOPHARMACOLOGY is subdivided into :

 Chronotherapy

Chronopharmacokinetics

Chronodynamics

Chronotoxicity.

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 Chronopharmacokinetics

Definition:
It deals with study of temporal changes in drug absorption, distribution,
metabolism and elimination.

Aim :
Control the time of administration.

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 Need:

Daily variations in pharmacokinetics

e.g. Some antimicrobial agents .

 when drugs have a narrow therapeutic range ,

 when symptoms of a disease are clearly circadian phase-

dependent.
e.g. nocturnal asthma, angina pectoris.

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Continue…..

 when drug plasma concentrations are well correlated

to the therapeutic effect.

 when the drug has some serious adverse effects that

can be avoided or minimized because they are related
to time of administration
e.g. amino glycosides nephrotoxicity.

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Drugs that under go chronokinetics

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Circadian rhythms implicated in drug absorption :

 Gastric acid secretion and pH ,motility, gastric

emptying time, gastrointestinal blood flow .

 Circadian changes of pH- modification of drug

ionization.

 Oral route of administration.

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Circadian rhythms implicated in drug distribution:

 Circadian changes in biological fluid and tissue.

 Diurnal increase and nocturnal decrease in blood flow .

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Circadian rhythms implicated in drug metabolism:

 Enzyme activity and blood flow.

 Enzyme activity is circadian time dependent.

 High hepatic extraction ratio, hepatic blood flow

induce change in drug metabolism.
 

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Circadian rhythms implicated in drug elimination:

 Glomerular filtration, renal blood flow, urinary pH,

tubular resorption - higher value in daytime

 Change in urinary pH modifies the drug ionization

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 Chronopharmacodynamics

 Chronesthesy
Biological rhythms - cellular and sub cellular level
give rise to significant dosing-time differences in the
pharmacodynamics of medications.

 E.g. The antitumor effect of IFN- and the

antiviral effect and lymphocyte stimulating effect of
IFN- in mice are more efficient during the early rest
phase than during the early active phase.
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 Chronotoxicity

 Chronotoxicity refers specifically to predictable- in-time

variation in patient to the side effects of medications .

 Lower toxicity of CPT-11 observed - DNA synthesis

and type I DNA topoisomerase activity in bone marrow
cells decrease and higher toxicity observed when these
activities begin to increase.

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 CHRONOPATHOLOGY & CHRONOTHERAPY

 Endogenous factors: Small bronchi diameter

significantly increases in the day and decreases at
night.

 Exogenous factors : Allergen exposure, temperature

changes during the day, night break in bronchodilator use,
gastro esophageal reflux.

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 CHRONOTHERAPEUTICS OF CARDIOVASCULAR
DISEASES

 Circadian rhythms of blood pressure -Nocturnal lowering

of BP, rapid elevation between 05:00-09:00o’clock in the
morning.

 Bed time dosing of long acting agents helps to restore

BP control in the morning .

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 CHRONOTHERAPEUTICS OF ASTHMA

 Risk of asthmatic attack 70 times higher in patients at

04:00-05:00 in the morning,compared with afternoon.

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 CHRONOTHERAPEUTICS OF ULCER

 Pathogenesis of stomach ulcers associated with

Helicobacter pylori and H+ secretion by stomach.

 Acidity(H+) reaches its peak in the evening in both

the healthy and persons affected by gastric ulcers

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 USE OF CHRONOPHARMACOLOGY
 Oncology
 Asthma therapy
 Hypertension
 CAD
 Strokes
 Sleep apnea
 GI tract disorders
 Allergies
 Immunologic disorders.

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