This document discusses the concepts of chronopharmacology. It begins by defining chronology, rhythm, and chronobiology. It then defines chronopharmacology as the study of rhythmic differences in drug effects and pharmacokinetics based on biological timing. The document outlines that chronopharmacology is subdivided into chronopharmacokinetics, chronotoxicity, chronesthesy, and chronotherapy. It provides examples of applying chronopharmacology concepts to treat conditions like hypertension, asthma, peptic ulcers, and psychiatric disorders by timing drug administration to biological rhythms. The document concludes by acknowledging references used.
Its a about chrono-pharmacology of diabetes
The accurate and detail information about chrono- pharmacology its not available but this information is sufficient or useful.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Assignment on Toxicokinetics- Toxicokinetic evaluation in preclinical studies, saturation kinetics Importance and applications of toxicokinetic studies. Alternative methods to animal toxicity testing.
Introduction to chronology, chronotherapy, and chronopharmacology.
How chronopharmacology involved in asthma and helps to manage asthma?.
Biological rhythms in bronchial asthma.
Factors associated with nocturnal exacerbation of bronchial asthma.
Introduction to asthma and their symptoms.
Introduction to Antiasthmatic drugs like beta-blockers, leukotriene antagonists, steroids, etc.
Chronopharmacology division & their examples.
Advantages and disadvantages of chronopharmacology.
Marketed preparation and their images along with the price in India.
Its a about chrono-pharmacology of diabetes
The accurate and detail information about chrono- pharmacology its not available but this information is sufficient or useful.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Assignment on Toxicokinetics- Toxicokinetic evaluation in preclinical studies, saturation kinetics Importance and applications of toxicokinetic studies. Alternative methods to animal toxicity testing.
Introduction to chronology, chronotherapy, and chronopharmacology.
How chronopharmacology involved in asthma and helps to manage asthma?.
Biological rhythms in bronchial asthma.
Factors associated with nocturnal exacerbation of bronchial asthma.
Introduction to asthma and their symptoms.
Introduction to Antiasthmatic drugs like beta-blockers, leukotriene antagonists, steroids, etc.
Chronopharmacology division & their examples.
Advantages and disadvantages of chronopharmacology.
Marketed preparation and their images along with the price in India.
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.
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.
Chronopharmacology is the science dealing with the optimization of drug effect and the minimization of adverse effects by timing medication in relation to biological rhythm.
The molecular mechanisms that underlie the function of the biological clocks are universally present in all cells and consists of gene-protein-gene feedback loops in which proteins can downregulate their own transcription and stimulate the transcription of other clock proteins.
Chronobiology –
It is the branch of sciences dealing with the “Biological rhythm” and their mechanism in the living organism.
Biological Rhythm –
It is the determined rhythmic biological process or function within a defined time period.
Chronotherapeutics –
i.e. increase in efficacy and safety of medications by proportioning their concentrations during the 24 hrs in synchrony with biological rhythm determinants of disease.
Chronokinetics –
Time dependent and predictable changes in PK parameter.
Eg; Cmax, tmax, AUC, T1/2
Chronesthesy –
Circadian or other systemic changes in the susceptibility and sensitivity of the target system of the target system to a drug.
Chronergy –
Rhythmic differences in effects of drugs on the organisms as a whole includes both desired and undesired effects.
Chronotoxicity –
The toxic effect of drug on the organism, which is undesirable and affects the rhythmic system. Specifically with anti-tumor agents.
The basic unit of circadian timekeeping is the cell. Even in very complex organisms, most cells contain autonomous circulatory for circadian oscillations.
Generally speaking, this mechanism is comprised of negative feedback loops of transcription and translation: activation of a repressor gene results in its later repression by its own protein products, and the instability of this repressor ensures this repression is short lived, so that a new cycle can begin.
In mammals, the principle activators within this system are the CLOCK and BMAL-1 proteins and their homolog, which dimerize and bind to certain elements to activate transcription of a large number of circadian genes.
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
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1. Basic Concepts
in
Chronopharmacology
DR.swanand s. pathak
MBBS, MD ( Pharmacology),DACM,IDCR
drswanandp@yahoo.co.in
2. Chrono -Pharmacology
Chronology : The arrangement of events according to
the time of occurrence .
Rhythm
CHRONOBIOLOGY
The science dealing with the phenomenon of
rhythmicity in living organisms
3. In medicine, 3 disciplines take into
account the influence of time:
CHRONOPHYSIOLOGY
CHRONOPATHOLOGY
CHRONOPHARMACOLOGY
4. Definition ????
The study of rhythmic, predictable-in-
time differences in the effects and/or
pharmacokinetics of drugs both in
experimental animals and in men. It
investigates the effects/side effects of
drugs upon temporal changes in
biological functions or symptoms of a
disease as well as drug effects as a
function of biologic timing.
5. Chronopharmacology
Investigative science concerned with the
biological rhythm dependencies of
medications.
Subdivided into
chronopharmacokinetics
chronotoxicity
chronesthesy
chronotherapy
6. Biological rhythm ( biological clock)
same events occurring in the body of a
living being over a particular time interval
Flowers
Fruits
Human body
7. “Dhire dhire re mana
dhere sab kuch hoi
Mali siche
sau ghada
ritu aay phal hoi”
--- KABIR
14. Applied Chronopharmacology
Endocrine system
Corticosteroids
Once-daily morning dose dosing
minimizes risk of adrenal suppression
and other side effects.
18. Applied Chronopharmacology
Endocrine system
Congenital adrenal hyperplasia
Bedtime corticosteroid dosing controls excessive hormone
secretion in
19. Applied Chronopharmacology
Endocrine system
Chronotherapy for Addison’s disease
Asymmetrical morning high and late-afternoon low-dose
corticosteroid substitution best corrects fatigue and
abnormal circadian time structure.
21. Dawn Phenomenon
20
10
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Cause: Treatment:
Less insulin in body Use enough dose.
Spurt in GH, cortisol. Reduce bed time snack.
Rise in blood sugar at night
22. Somogyi Phenomenon
20
10
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Cause: Treatment:
too much insulin Decrease pre-supper
intermediate insulin.
Long acting Change or start pre-bed snack.
Blood sugar drop at night
Hormones to rise blood sugar
levels
23. Applied Chronopharmacology
Endocrine system
Bedtime ADH analogue dosing helps to alleviate
nocturnal bedwetting in children and nocturia in adults.
24. Applied Chronopharmacology
CVS
Myocardial infarction, acute cardiac
arrest , transient myocardial ischemia
Onset – early morning – 34% events
Reason – release of catecholamines ,
cortisol , increase in platelet
aggregation , vascular tone ,
heart rate surge.
25.
26. Applied Chronopharmacology
CVS
Objective
Deliver drug in high conc. During great
need
ACE inhibitors
Nifedipine Night
Amlodipine
27. Applied Chronopharmacology
CVS
• The first chronotherapeutic therapy for
hypertension and angina pectoris
• Matches drug delivery to the circadian
patternof blood pressure and rhythm of
myocardialischemia.
• Verapamil has been employed
28. Applied Chronopharmacology
CVS
When the 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors were first
introduced,
morning dosing was recommended.
30. Applied Chronopharmacology
CVS
This strategy was re-evaluated after the discovery of
the circadian rhythm of cholesterol biosynthesis in
which higher rates of cholesterol intake and hepatic
cholesterogenesis occur during the evening hours,
even in the fasting state.
Except Atorvastatin all (HMG-CoA) reductase
inhibitors are administered between the evening
meals and sleep.
31. Applied Chronopharmacology
CVS
Bedtime (but not morning) aspirin
dosing best for preventing pregnancy-induced
hypertension and preeclampsia.
32. Applied Chronopharmacology
RS
Asthma the most common disease with the largest
circadian variation.
Because asthma has such a striking circadian variation,
several types of chronotherapy have been tried.
36. Applied Chronopharmacology
RS
• A single daily dose of inhaled corticosteroids,
when administered at 5:30 pm rather than 8 am, was
nearly as effective as four doses a day.
• Oral prednisone
has been shown to be much more effective in
improving several features of nocturnal asthma
[FEV1]and response to a standard dose of
inhaled beta2 agonist when administered at 3 pm rather
than 8 am
37. Applied Chronopharmacology
RS
Theo-24
Use of a timed-release formulation of theophylline achieved
therapeutic drug concentrations during the night and avoided toxic
levels during the day.
38. Applied Chronopharmacology
Autoimmune diseases
Arthritis
The new cyclooxygenase-2 inhibitors effectively relieve
osteoarthritis symptoms when taken in the evening;
better results are obtained in rheumatoid arthritis when
part of the dose is taken in the morning.
40. Applied Chronopharmacology
GIT
Histamine2 antagonists
In the past, were administered at regular intervals around
the clock, on the basis of pharmacokinetic properties.
42. Applied Chronopharmacology
GIT
Maximal acid secretion, peptic ulcer disease pain, and
perforation of gastric and duodenal ulcers are more
common at night, administration of these drugs at bedtime
is more effective.
Nocturnal administration not only reduces acid secretion
more effectively but also promotes ulcer healing and
reduces ulcer recurrence
43. Applied Chronopharmacology
CNS
Chlorpromazine would be most effective in producing
sedative and antipsychotic effects when administered at
midnight and immediately after rising, respectively.
For haloperidol, administration in the evening would be
best for obtaining either a sedative or antipsychotic effect.
44.
45.
46. Acknowledgements
• Wikipedia
• Google
• Concepts of Chronopharmacology by N. Udupa
• Lullman’s atlas of pharmacology
47.
48. Presented on
• 30-03-2011/national CME on personalized medicine / MGMC / Puducherry
• 23-07-2011/zonal CME for post graduates/ DR NTR University/ mamata medical college/
Vijaywada