Chronopharmacology is the science concerned with the variations in pharmacological actions of drugs over biological timings and endogenous periodicities. It influences physiological functions and diseases. Therapeutic administration of drugs can be optimized based on circadian rhythms. For example, antihypertensive drugs are best taken at bedtime to prevent mid-night blood pressure dips. New drug delivery systems and circadian clock enzyme inhibitors are being researched to better synchronize drug effects with the body's natural biorhythms. Understanding chronopharmacology allows tailoring therapy to endogenous rhythms for improved outcomes and reduced side effects.

1. CHRONOPHARMACOLOGY
ANKIT KUMAR MALIK
21161012
PH.D. 1ST SEM
2021-22
DEPARTMENT OF PHARMACEUTICAL
ENGINEERING & TECHNOLOGY,
INDIAN INSTITUTE OF TECHNOLOGY (BHU)
DATED: 15-10-2021

2. What is chrono-pharmacology?
It is the science concerned with the
variations in the pharmacological
actions of various drugs over a
biological timings & endogenous
periodicities.
CHRONOBIOLOGY
Chrono (time)
Bios (life)
Logos (study)
International Journal of Pharmacy and Pharmaceutical Sciences 2017, Vol. 9 (2): 87-99.

3. BIOLOGICAL CLOCK
• Also termed as circadian rhythm
• An internal biological clock, located, in mammals, in
the suprachiasmatic nucleus (SCN) of the hypothalamus,
delivering its message of time throughout the body.
• It is responsible for circadian rhythms and annual/
seasonal rhythms.
• The SCN uses its connections with the autonomic nervous
system for spreading its time-of-day message, either by setting
the sensitivity of the endocrine glands (i.e., thyroid, adrenal, ovary)
or by directly controlling an endocrine output of pineal gland
(melatonin synthesis)
International Journal of Pharmacy and Pharmaceutical Sciences 2017, Vol. 9 (2): 87-99.

4. BIORHYTHMS
• External cues which reset the circadian
clock=ZEITGEBERS = synchronizers
• LD, light-darkness
• EF, eating-fasting
• SI, social contact-isolation
• NQ, noise-quiet
Drug Metab. Pharmacokinet.2007; 22 (1): 3–14.

5. INFLUENCE OF BIOLOGICAL RHYTHMS ON PHYSIOLOGICAL FUNCTIONS
Drug Metab. Pharmacokinet.2007; 22 (1): 3–14.

6. INFLUENCE OF BIOLOGICAL RHYTHMS ON DISEASES
Drug Metab. Pharmacokinet.2007; 22 (1): 3–14.

7. THERAPEUTIC AREA DISEASE OR CONDITION CHRONO – PHARMACOLOGY RATIONALE
Cardiovascular Hypertension B.P rises about 20% immediately after awakening & least during sleep. Verapamil, Doxazosin
Taken at bed-time, this exerts peak effects btw 5am and noon & no mid-night dip in B.P is seen.
Angina Angina (variant) attacks occur 30 times more often between 2:00 a.m. and 4:00 a.m. -> Larger
doses of Nitorglycerin early in the morning.
Hypercholesterolemia More cholesterol systhesis takes place in the evening than in the morning. Hence, short acting
statins should be administered at evening rather than at morning for increased efficacy.
Heart Attacks and Strokes Heart attacks and stroke are most likely between 6:00 a.m and Noon-> Cardiovascular active
drugs after waking.
CNS
Degenerative
Disorder
Alzheimer’s
Disease
Automated dosing for patient compliance ->Rivastigimine, Mematine
Parkinson’s
Disease
Automated dosing for patient compliance ->Selegiline, Benztropine, Apomorphine
Epilepsy Epileptic seizure Epileptic seizures are most likely between 6:00 a.m. and 7:00 a.m. ->Gabapentan or other Epileptic
drugs after waking up.
Inflammation Rheumatoid
Arthritis, Osteoarthritis
Worst upon awakening. Cortisol and anti-inflammatory hormones are very low at night -
>Indomethacin or Valdecoxib after waking up.
Diabetes Diabetes (TypeII) Oral medication is poorly absorbed. ->.Miglitol before meals. Sulfonylureas 20-30 min before food,
alpha glucosidase inhibitors: with food
Mental Health Depression Selegiline at night can create sleeping disorders(nightmares), but depression symptoms are high
immediately upon waking up->Selegiline
after waking up
EXAMPLE OF DISEASE STATES WITH CHRONOPHARMACOLOGICAL APPLICATION
Journal of International Medicine and Dentistry 2015; 2 (1): 03-16

8. THERAPEUTIC AREA DISEASE OR CONDITION CHRONO – PHARMACOLOGY RATIONALE
Women’s Health Tocolytic Therapy Programmed – in – time administration of tocolytic medication relative to the circadian rhythm in uterine
contractility to avert preterm labor and birth. ->Nifedipine, Terbutaline or Ritodrine synchronized with uterine
contractions.
Pain Acute Pain Neurological pain is worst between 3:00 a.m. and 8:00 a.m. -> Fentanyl in the middle of
night.
Migraine
Headaches and /
or cluster
headaches
Migraine headaches usually begin and occur between 8:00 a.m. and 10:00 a.m. Cluster headaches start earlier,
around 4:00 a.m. - >Zolmitriptan or dihydroergotamine in the middle of night.
Oral contracetives Prescribed as per menstrual cycle
GI tract Peptic ulcer
disease
Acidity(H+) peak-evening
H2blockers(Ranitidine, Cemitidine, famotidine) are given at evening time
Pulmonary Asthma Asthma attacks midnight to early morning 2am to 6am. A long acting theophylline taken at evening.
Corticosteroids 8 am and 3 pm is more effective
Colds and Flu Heaviest symptoms overnight and in the morning. -> Cold/ Flu medicine during the night. Triprolidine, Doxylamine.
Journal of International Medicine and Dentistry 2015; 2 (1): 03-16

9. CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEMS
Spheroidal oral drug absorption system (SODAS)
Chronotherapeutics oral drug absorption system (CODAS)
Chronomodulating infusion pumps
Timerx
Diffucaps
International research journal of pharmacy 2012; 3 (5): 128-132
RECENT ADVANCES
 CASEIN KINASE 1 (CK-1) inhibitor- potential new drug
 Reset the circadian clock enzymes
 Use: jet lag, sleep disorder, bipolar disorder
 Animals trials completed, human trial awaited
 NEW DISCOVERY MAY ALLOW PEOPLE TO HIT “SNOOZE” BUTTON ON INTERNAL CLOCK

10. CONCLUSION
It prevents an overdosing of any class of drug
It makes the utilization of the drug more appropriate
and thus the value of a drug is increased
It reduces the unnecessary side effects of a drug and
help in caring out the treatment for only a particular or
limited period of time

11. REFERENCES
Lemmer, B., 2005. Chronopharmacology and controlled drug release. Expert Opin.
Drug Deliv. 2, 667–681.
Ohdo, S., 2007. Chronopharmacology Focused on Biological Clock. Drug Metab.
Pharmacokinet. 22, 3–14.
Dallmann, R., Brown, S.A., Gachon, F., 2014. Chronopharmacology: New Insights and
Therapeutic Implications. Annu. Rev. Pharmacol. Toxicol. 54, 339–361.
 Maurya, K.K., 2012. Chronopharmacology: A Tool For Therapy of Diseases. Intern. Res.
Journal. 3, 128-132.
Satyanarayan, V., 2015. Chronopharmacology: Tailoring Therapy to Endogeneous
Rhythms. Journal of Intern. Medi. And Dentistry. 2, 3-16.
Sajan, J., 2009. Chronotherapeutics and Chronotherapeutic Drug Delivery Systems.
Trop J Pharm Res. 8, 467-475.