Chronobiology is the study of biological rhythms and how living organisms adapt to solar and lunar cycles, influencing their behaviors and biochemistry. It encompasses various types of rhythms including circadian, diurnal, ultradian, and infradian, each with distinct characteristics and implications for physiological processes. The document also explores the role of circadian rhythms in health, particularly in relation to diseases and the timing of drug administration to enhance therapeutic outcomes.

1. CHRONOBIOLOGYCHRONOBIOLOGY
AVILEEN KAUR
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
ISF COLLEGE OF PHARMACY
WEBSITE: - WWW.ISFCP.ORG
EMAIL: avileenkaurbrar@gmail.com
ISF College of Pharmacy, Moga
Ghal Kalan, nGT Road, Moga- 142001, Punjab, INDIA

2. DEFINATION
2
 Chronobiology is a field of biology that examines periodic phenomena in living
organisms and their adaptation to solar- and lunar-related rhythms.
These cycles are known as biological rhythms.
 Chronobiology comes from the ancient Greek word (chrónos, meaning "time"),
and biology, which pertains to the study, or science, of life.
 Chronobiology is the science of biological rhythms, more specifically the impact of
the 24- hour light- dark cycle on our biochemistry and therefore behaviors.

3. 3HISTORY OF CHRONOBIOLOGY
 In 18th century, Jean- Jacques d’ Ortous de Mairan (1678-1771)
described circadian rhythms of plants.
 In 20th century, Franz Halberg (1919-2013) created the term
circadian. Considered as one of founders of modern chronobiology.

4. 4
 It is defined as the periodic component of temporal series of biological data
whose waveform profile has been analytically validated.
 In other words, biological rhythm is a bio-signal whose period of oscillation has
been validated by analytical models of periodic regression using one or more
harmonic components.
Examples : Heart beat, breathing, hormone secretion, menstrual cycle, body
temperature and sleep/wake cycle.
BIOLOGICAL RHYTHM

5. 5Classification of biological rhythm
1. Circadian rhythms- it is cyclical variation in metabolic, physiological or
behavioral process with a period of about 24 hours when in constant
conditions.
2. Diurnal rhythms- a circadian rhythm that is synchronized with day/ night
cycle.
3. Ultradian rhythms- biological rhythm (e.G. Feeding cycles) with a period
much shorter (i.E. Frequency much higher) than that of a circadian rhythm.
4. Infradian rhythms- biological rhythms with a cycle of more than 24 hours
(e.g. The human menstrual cycle).

6. 6
 Circadian is derived from a latin phrase i.e. Circa = about and dia = day ( about
a day).
 Circadian rhythms are physiological and behavioral rhythms and include:
•Sleep/ wakefulness cycle
•Body temperature
•Patterns of hormone secretion
•Blood pressure
•Digestive secretions
•Levels of alertness
•Reaction times

7. 7Mechanism

8. 8
 In humans (and other mammals), a circadian clock is located in the
suprachiasmatic nuclei (SCN).
The SCN is in hypothalamus. It is a tiny cluster of about 10 thousand nerve cells.
This circadian clock is synchronized to external cycles of light and darkness and
social contact.
 The SCN clock ensures that melatonin is secreted only at night. Melatonin
secretion last longer on the longer winter nights.
 Disruption of the clock detrimentally affects our well- being and mental and
physical performance occurs during jet-lag, shift work and old-age.
 SCN is active during the day in both diurnal and nocturnal animals.
The SCN tells the animal whether it’s day or night, but not how to behave.

9. 9Shift work
The term shift work is defined as an arrangement of work hours that uses two or
more teams (shifts) of workers in order to extend the hours of operation of the
work environment, beyond that of the conventional office hours.
Problems with swift work
1. Phase advance: rising early or retiring to bed earlier than normal is an
example of phase advance.
2. Phase delay: going to bed late or getting up late is example of phase delay.
On average it takes approx 3 days to adjust to a 12 hour shift in time.

10. 10JET LAG
Jet lag does not
occur form
north-south and
vice versa!!
Jet Lag only
occurs when flying
from East-West or
from West to East.
In other words
when we change
time zones.
To lessen the effect of jet lag:
1. Use melatonin to reset the body clock.
2. Adopt local eating times etc to help reset the biological clock as
soon as possible.

11. 11

12. 12Diseases and their circadian rhythm
1. CARDIOVASCULAR SYSTEM
• A highly significant circadian variation was observed with many adverse
CV events in human body.
• 30 studies, >65,000 patients: 40%increased risk of myocardial infarction
between 6 AM and noon.
• Other studies, appox 20,000 patients: increase in sudden cardiac death by
29% during the early morning hours, and increase in stroke risk by 49%
between 6 am and noon.
• BP is not steady over 24 h period.
Disturbance in circadian BP patterns:
1. Dipper: normal nocturnal lowering of BP(10-20%)
2. Non-dipper: inadequate noctural lowering lowering of BP(less than 10%).
3. Extreme dipper: too high noctural decrease of BP (>20%)
4. Morning surge: excessive morning increase of BP(>50 mm Hg for systolic
and >20 mm Hg for diastolic BP).

13. 132. Chronotherapy for BP Disturbance
 Dipper: long lasting drugs, once per 24th
(in the morning).
 Non- dipper : once daily in the evening (drug given in morning has
lessen hypotensive effect in second half of day).
 Extreme dipper: long lasting drugs administered in the morning.
 Morning surge:
1. Non-dipper: bedtime dosing should prevent morning surge (doxazosin
is particularly effective).
2. Dipper: evening administration of slowing acting preparation
(telmisartan, amlodipine) is safer approach.

14. 14
1. Thiazide diuretics: Administered in morning can strongly lower the
pressure in night.
• Normalize non- dippers.
• Cannot normalize morning surge.
• Long lasting preparations are preferred (indapamide, hygroton).
2. Β- adrenolytics: Hypotensive effect mainly focused on day time.
• Have no effect on morning surge.
• Examples are betaxolol. Bisoprorol.: Better control of BP in the night
and morning than atenolol.
3. Chronotherapy of Hypertension

15. 15
3. Calcium Antagonists: Do not normalize BP profile of non- dipper.
Amlodipine, lacidipine: lasting for 24 h, morning administration for
dippers. Maybe effective for morning surge.
Nitrendipine : better effect if administered in the evening.
Isradipine: hypertensive patients with renal failure, effective only if
administered in the evening.
4. ACE-inhibitors:
Morning administration of 24h lasting drugs (perindopril) : can be
effective in morning surge.
Smaller doses of stronger acting drugs (ramipril, quinapril) administered
in the evening are considered safe.

16. 16
 The risk of asthmatic attack is almost 70 times higher at 04:00-05:00 AM,
compared with the afternoon.
 Exogenous factors: allergen exposure, temperature changes during the day, night
break in bronchodilator use, supine position during sleep, gastroesophageal reflux.
 Endogenous factors: small bronchi diameter significantly increases during the day
and decreases at night adrenergic blockade of s-receptors dominance of α-adrenergic
pathways cholinergic dominance lowest concentrations of cortisol, and ig e with
highest concentration of histamine around 04:00 am.
 Evening administration of these special dosage forms results in elevated
theophylline concentration during the nighttime when the likelihood of asthma is
greatest and reduced drug level during the day when the risk of disease is lowest.
4. Chronotherapy for Asthma

17. 175. Chronotherapy for Peptic ulcer
 Pathogenesis of stomach ulcers is associated with Helicobacter pylori and
H+ secretion by the stomach.
 Acidity (H+) reaches its peak in the evening in both the healthy and patients
affected by gastric ulcers.
 Evening administration of ranitidine is justified from the point of view of
chronopharmacology.

18. 18Chronotherapeutics
Chronotherapeutics refers to a treatment method in which drug availability is
timed to match rhythms of disease in order to optimize therapeutics
outcomes and minimize side effects.
One approach to increase the efficiency of pharmacotherapy is the
administration of drugs at times at which they are most effective and best
tolerated.
ADVANTAGES OF CHRONOPHARMACOTHERAPHY:
1. It prevents an overdosing of any class of drug.
2. It makes the utilization of the drug more appropriate and thus value of a
drug is increased.
3. It reduces the unnecessary side effects of a drug and helps in caring out
treatment for only a particular or limited period of time.

19. 19
1. To limit the duration of therapy especially in cases where patients are
already having compromised renal, cardiac and hepatic or nay other function
of the body.
2. Ant type of accumulation of drugs in these organs causes greater toxicity
which may led to diminished function of the organ.
Thus the chronopharmacotherapy becomes a very important part of treatment of
several diseases particularly those effecting targeted body parts.
Need for Chronopharmacotherapy