chronopharmacology basic concepts

Basic Concepts in

Chronopharmacology

DR.swanand s. pathak

MBBS, MD ( Pharmacology),DACM,IDCR

[email protected]

mailto:[email protected]

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

CHRONOPHYSIOLOGY

CHRONOPATHOLOGY

CHRONOPHARMACOLOGY

In medicine, 3 disciplines take into account the influence of time:

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.

Definition ????

Investigative science concerned with the biological rhythm dependencies of medications.

Chronopharmacology

Subdivided into

chronopharmacokinetics chronotoxicitychronesthesy

chronotherapy

same events occurring in the body of a living being over a particular time interval

Flowers

Fruits

Human body

Biological rhythm ( biological clock)

“Dhire dhire re mana dhere sab kuch hoi

Mali siche sau ghada

ritu aay phal hoi”

--- KABIR

Biological rhythm - types

Blood Pressure Rhythm

Peak time functions

Disease rhythm

Advantage Time the administrationof the drugs

Applied Chronopharmacology

Endocrine system

Corticosteroids

Once-daily morning dose dosing minimizes risk of adrenal suppression and other side effects.

Peak time functions


Endocrine system

Congenital adrenal hyperplasia

Bedtime corticosteroid dosing controls excessive hormone secretion in


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.

Peak time functions

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.

Somogyi PhenomenonSomogyi 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: 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.


Endocrine system

Bedtime ADH analogue dosing helps to alleviate nocturnal bedwetting in children and nocturia in adults.


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.


CVS

Objective

Deliver drug in high conc. During great need

ACE inhibitors

Nifedipine

Amlodipine

Night


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


CVS

When the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors were first introduced,

morning dosing was recommended.

Peak time functions


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.


CVS

Bedtime (but not morning) aspirin

dosing best for preventing pregnancy-induced hypertension and preeclampsia.


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.

Peak time functions


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


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.


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.

Disease rhythm


GIT

Histamine2 antagonists

In the past, were administered at regular intervals around the clock, on the basis of pharmacokinetic properties.

Peak time functions


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


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.

Acknowledgements

• Wikipedia • Google • Concepts of Chronopharmacology by N. Udupa • Lullman’s atlas of pharmacology

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

chronopharmacology basic concepts

Education

applied chronopharmacologycvs

peak time functions

time differences

influence of time

disease rhythm

bed time snack

blood pressure rhythm

morning dosing