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8/11/2019 Chrono Pharmacology
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Basic Concepts
in
Chronopharmacology
DR.swanand s. pathakMBBS, MD ( Pharmacology),DACM,IDCR
mailto:[email protected]:[email protected]8/11/2019 Chrono Pharmacology
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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
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CHRONOPHYSIOLOGY
CHRONOPATHOLOGY
CHRONOPHARMACOLOGY
In medicine, 3 disciplines take into
account the influence of time:
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The study of rhythmic, predictable-in-time differences in the effects and/orpharmacokinetics of drugs both in
experimental animals and in men. It
investigates the effects/side effects ofdrugs upon temporal changes in
biological functions or symptoms of a
disease as well as drug effects as a
function of biologic timing.
Definition ????
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same events occurring in the body of a
living being over a particular time interval
FlowersFruits
Human body
Biological rhythm ( biological clock)
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Dhire dhire re manadhere sab kuch hoi
Mali siche
sau ghada
ritu aay phal hoi
--- KABIR
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Biological rhythm - types
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Blood Pressure Rhythm
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Peak time functions
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Disease rhythm
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Advantage
Time the administration
of the drugs
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Applied Chronopharmacology
Endocrine system
Corticosteroids
Once-daily morning dose dosing
minimizes risk of adrenal suppression
and other side effects.
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Peak time functions
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Applied Chronopharmacology
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Applied Chronopharmacology
li d Ch h l
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Applied Chronopharmacology
Endocrine system
Congenital adrenal hyperplasia
Bedtime corticosteroid dosing controls excessive hormone
secretion in
A li d Ch h l
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Applied Chronopharmacology
Endocrine system
Chronotherapy for Addisons disease
Asymmetrical morning high and late-afternoon low-dose
corticosteroid substitution best corrects fatigue and
abnormal circadian time structure.
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Peak time functions
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Dawn Phenomenon
0
10
20
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:
Less insulin in body
Spurt in GH, cortisol.
Rise in blood sugar at night
Treatment:
Use enough dose.
Reduce bed time snack.
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Somogyi henomenon
0
10
20
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:
too much insulin
Long acting
Blood sugar drop at night
Hormones to rise blood sugar levels
Treatment:Decrease pre-supper
intermediate insulin.Change or start pre-bed snack.
A li d Ch h l
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Applied Chronopharmacology
Endocrine system
Bedtime ADH analogue dosing helps to alleviate
nocturnal bedwetting in children and nocturia in adults.
A li d Ch h l
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Applied Chronopharmacology
CVS
Myocardial infarction, acute cardiac
arrest , transient myocardial ischemia
Onsetearly morning34% events
Reasonrelease of catecholamines ,cortisol , increase in platelet
aggregation , vascular tone ,
heart rate surge.
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A li d Ch h l
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Applied Chronopharmacology
CVS
Objective
Deliver drug in high conc. During great
need
ACE inhibitors
NifedipineAmlodipine
Night
Applied Chronopharmacology
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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
Applied Chronopharmacology
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Applied Chronopharmacology
CVS
When the 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors were firstintroduced,
morning dosing was recommended.
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Peak time functions
Applied Chronopharmacology
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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.
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Applied Chronopharmacology
CVS
Bedtime (but not morning) aspirin
dosing best for preventing pregnancy-induced
hypertension and preeclampsia.
Applied Chronopharmacology
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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.
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Peak time functions
Applied Chronopharmacology
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Applied Chronopharmacology
RS
A single daily doseof inhaled corticosteroids,
when administered at 5:30 pmrather than 8 am, wasnearly as effective as four doses a day.
Oral prednisone
has been shown to be much more effective inimproving 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
Applied Chronopharmacology
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Applied Chronopharmacology
RS
Theo-24
Use of a timed-release formulation of theophylline achievedtherapeutic drug concentrations during the night and avoided toxic
levels during the day.
Applied Chronopharmacology
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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 arthritiswhen
part of the dose is taken in the morning.
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Disease rhythm
Applied Chronopharmacology
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Applied Chronopharmacology
GIT
Histamine2 antagonists
In the past, were administered at regular intervals around
the clock, on the basis of pharmacokinetic properties.
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Peak time functions
Applied Chronopharmacology
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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 bedtimeis more effective.
Nocturnal administration not only reduces acid secretion
more effectively but also promotes ulcer healing and
reduces ulcer recurrence
Applied Chronopharmacology
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Applied Chronopharmacology
CNS
Chlorpromazine would be most effective in producing
sedative and antipsychotic effects when administered atmidnight and immediately after rising, respectively.
For haloperidol, administration in the evening would be
best for obtaining either a sedative or antipsychotic effect.
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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