Chrono Pharmacology

8/11/2019 Chrono Pharmacology

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Basic Concepts

in

Chronopharmacology

DR.swanand s. pathakMBBS, MD ( Pharmacology),DACM,IDCR

[email protected]
mailto:[email protected]:[email protected]


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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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li d Ch h l


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Endocrine system

Congenital adrenal hyperplasia

Bedtime corticosteroid dosing controls excessive hormone

secretion in

A li d Ch h l


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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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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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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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CVS

Objective

Deliver drug in high conc. During great

need

ACE inhibitors

NifedipineAmlodipine

Night



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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



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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



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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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CVS

Bedtime (but not morning) aspirin

dosing best for preventing pregnancy-induced

hypertension and preeclampsia.



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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



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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



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RS

Theo-24

Use of a timed-release formulation of theophylline achievedtherapeutic drug concentrations during the night and avoided toxic

levels during the day.



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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



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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



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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



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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

Chrono Pharmacology

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