CHRONOPHARMACOLOGY
(RIGHT DRUG AT RIGHT TIME)
Presented by:
AVNESH KUMAR SINGH
Associate Professor
MM College of Pharmacy
History :
• Jean-Jaques d’Ortous de Mairan described
circadian rhythms of plants in the 18th century
Franz Halberg coined the term
‘Circadian’ in 20th century.
(circa – about or approximately;
dian-day, or about 24 hour).
Considered as one of the founders
of Modern Chronobiology.
Rhythm and Cycles
Rhythms are a series of bodily functions regulated by
your internal clock.
They control cycles like sleep and wakefulness, body
temperature, hormone secretion, and more.
Body maintains its biological rhythms through a
variety of chemicals at the molecular level in response
to environment.
Chronobiology-
Chronos (time),
Bios (life),
Logos (study).
The science dealing with the phenomenon of
rhythmicity in living organisms is called
CHRONOBIOLOGY.
What is Chronopharmacology ?
Chrono-pharmacology is the science dealing with the
optimization of drug effects and minimization of
adverse effects by timing the medication in relation to
the biological rhythms.
It is the science concerned with the variations in the
pharmacological actions of various drugs over a
biological timings & endogenous periodicities.
BIOLOGICAL RHYTHMS IN
HUMANS
Biological Rhythm
A determined rhythmic biological process
or
function.
A biological rhythm is a self-sustaining
oscillation with the duration of time
between successive repetitions (i.e; the
period) being rather non-varying under
normal conditions.
Example-
CIRCADIAN RHYTHM:
Circadian (circa - about; dies, day, or about 24
hour)
Oscillations in the biological, physiological &
behavioral functions of an organism with a
periodicity of 24 hrs.
Continue…
Circadian rhythms are particularly important in
medicine.
A circadian clock in the brain coordinates daily
physiological cycles.
– sleep/wake - digestion
– temperature - hormones
Physiological day is about 24 hours .
– Clock is reset daily by the environment .
• day/night
• social schedules
Types of Rhythm
Ultradian ( <20h): cycles shorter than
a day e.g. micro sec. for a neuron to fire.
Circadian (20< <28h):Lasting for
about 24 hrs. e.g. sleep and wake cycles.
Infradian (≥28 h): Cycles longer than
24 hrs e.g. menstrual cycle.
sleep-wake cycle
BIORHYTHMS
External cues which reset the circadian clock =
ZEITGEBERS = synchronizers
Definition-Endogenously generated, and can be
entrained by external factors, called zeitgebers.
LD- Light-Darkness
EF- Eating-Fasting
SI- Social Contact- Isolation
NQ- Noise-Quiet
Biological Clock
An internal biological clock, located, in mammals, in the
suprachiasmatic nucleus of the hypothalamus (SCN),
delivering its message of time throughout the body.
It is responsible for circadian rhythm.
The SCN uses its connections with the autonomic nervous
system for spreading its time-of-day message, either by
setting the sensitivity of endocrine glands (i.e., thyroid,
adrenal, ovary) or by directly controlling an endocrine
output of pineal gland (i.e., melatonin synthesis).
Significance leading to
chronotherapy
Chronotherapy found useful in:
Hypertension
Bronchial asthma
Peptic ulcer
Myocardial infarction
Arthritis
Cerebrovascular accidents
Hypercholesterolemia.
Hyper Tension:
It is the physiological condition described as morning
surge.
In hypertension the systolic bloods pressure rises up to
3mmHg/hour for 4-6 hours after getting up which is called
as post-awakening and the diastolic blood pressure also
rises up to 2mmHg/hours .
Blood pressure and heart rate will be high at the time of
walking in the morning and it will begin to decrease in the
afternoon and reaches minimum at mid night.
Myocardial Infarction:
Platelet aggregation and the vascular tone is high in the morning when the
release of the catecholamine and cortisol is high.
The main regions for the outburst of the myocardial infarction in the morning
with 34% events taking place from 6 a.m. till noon.
Cyclooxygenase inhibitor-2 will relieve the pain effectively when taken in the
morning .
Peptic Ulcer Disease:
Histamine antagonist given at night shows the better result unlike when
given at the regular intervals around the clock.
But more pain and more acid secretion thus formation of gastric and duodenal
ulcers are more subjective at night time then day time.
Hyper Cholesterolemia:
Cholesterol intake and its biosynthesis is more in the evening hour.
Therefore after the discovery of circadian rhythms the first HMG co-
A inhibitor was reevaluated and evening doses were recommended
inspite of the morning doses.
Bronchial Athma:
Asthma disease has more circadian variation then the other
diseases.
Intake of time released theophyllin at 3 P.M. achieves therapeutic
dose at night and toxic levels during the day are avoided .
Cerebrovascular Accidents:
In the morning hours between 10 A.M to 12 Noon, the cerebrovascular accidents
are more common.
It decreases considerably from noon to midnight.
Chonotherapy is done for this condition to deliver the drug in higher doses in the
morning and little doses at the noon and in midnight.
Atenolol, Nifedipine, Amlodipine and ACE inhibitors are more effective when
administered during the night.
Arthritis:
In accordance with the chronotherapeutic study, more desirable results have been
achieved for rheumatoid arthritis when the dose was given in the evening time.
Cyclooxygenase inhibitor-2 taken in the morning time relieves the pain effectively.
Diabetes:
The circadian rhythms of insulin and its action are of physiological interest.
Insulin can show cylic rhythms for 8-30 mins. to show its optimal action.
The modulators of insulin release and its action are secreted in a circardian pattern
and therefore insulin effects are altered .
Cancer:
The rhythmic circadian changes in cancer growth and tumour blood flow are
relevant when the tumours are small and growing rapidly.
The blood flow to tumours is threefold greater during each daily activity phase of
circadian cycle then during the daily rest phase.
More tumour cells are killed by treatment at mid night and with the same dose of
active cytotoxic therapy with little bone marrow damage.
Duodenal Ulcer:
In duodenal and peptic ulcer, gastric acid secretion is
highest during the night.
Therefore a daily dose at bedtime is recommended
for H2 antagonists.
At night time gastric motility, drug disintegration,
dissolution and absorption may be slower and thus the
relieve in peptic ulcer is efficient.
ThankX !!
