CHRONOLOPHARMACOLOGY

This slide contain about description of CHRONOLOPHARMACOLOGY with their types and biological cycles of life .

1. CHRONOPHARMACOLOGY

PREPARED BY :-
PRANJAL SAXENA
B.PHARMACY 6
TH
SEM.
ORIENTAL UNIVERSITY

2. •
•
•
•
•
•
INTRODUCTION
BIOLOGICAL RHYTHM AND IT’S TYPES
DISORDERS OF BIOLOGICAL RHYTHM
FACTORS INFLUENCING BIOLOGICAL RHYTHM
CIRCADIAN RHYTHM AND IT’S MECHANISM
BIOLOGICAL CLOCK

3. CHRONOPHARMACOLOGY
•
•
•
•
CHRONOPHARMACOLOGY IS THE STUDY OF HOW THE EFFECTS OF DRUGS
VARY WITH BIOLOGICAL TIMING AND ENDOGENOUS PERIODICITIES.
THE GOAL IS TO IMPROVE OUR UNDERSTANDING OF PERIODIC AND THUS
PERDICTABLE (E.G. CIRCADIAN) CHANGES IN BOTH DESIRED EFFECTS
(CHRONOEFFECTIVENESS) AND TOLERANCE (CHRONOTOLERANCE) OF
MEDICATIONS.
DOSING TIME-DEPENDENT CHANGES ALSO INCLUDE QUANTIFICATION OF
PARAMETERS CHARACTERIZING ENDOGENOUS CIRCADIAN RHYTHMS (CR), IN
TERMS OF PHARMACOLOGIC EFFECTS, E.G. THE 24-H ADJUSTED MEAN (M),
THE PERIOD , THE AMPLITUDE (A, THE PEAK-TO TROUGH DIFFERENCE), AND
THE ACROPHASE( F, THE PEAK TIME LOCATION IN THE 24-H SCALE).
CHRONOPHARMACOLOGY BECAME RECOGNIZED AS A SCIENTIFIC DOMAIN
OFINVESTIGATIONONLYINTHEEARLY1970S

4. BIOLOGICAL RHYTHM
•BIOLOGICAL RHYTHMS ARE THE NATURAL CYCLE OF CHANGE IN OUR
BODY'S CHEMICALS OR FUNCTIONS. IT'S LIKE AN INTERNAL MASTER "
CLOCK" THAT COORDINATES THE OTHER CLOCKS IN YOUR BODY. THE "
CLOCK" IS LOCATED IN THE BRAIN, RIGHT ABOVE THE NERVES WHERE
THE EYES CROSS. IT'S MADE UP OF THOUSANDS OF NERVE CELLS
THAT HELP SYNC YOUR BODY'S FUNCTIONS AND ACTIVITIES.

5. TYPES OF BIOLOGICAL RHYTHM:-
•
•
•
•
•
THERE ARE FOUR TYPES OF BIOLOGICAL RHYTHMS:-
CIRCADIAN RHYTHMS
DIURNAL RHYTHMS
ULTRADIAN RHYTHMS
INFRADIAN RHYTHMS

6. CIRCADIAN RHYTHMS
•
•
CIRCADIAN RHYTHMS ARE DEFINED AS AN ENDOGENOUS RHYTHM
PATTERN THAT CYCLES ON A DAILY (APPROXIMATELY 24 HOUR) BASIS
UNDER NORMAL CIRCUMSTANCES, THE NAME CIRCADIAN COMES FROM
THE LATIN CIRCA DIA, MEANING ABOUT A DAY.
THE CIRCADIAN CYCLE REGULATES CHANGES IN PERFORMANCE,
ENDOCRINE RHYTHMS, BEHAVIOR AND SLEEP TIMING. MORE
SPECIFICALLY THESE PHYSIOLOGICAL AND BEHAVIORAL RHYTHMS
CONTROL THE WAKING/SLEEP CYCLE, BODY TEMPERATURE, BLOOD
PRESSURE, REACTION TIME, LEVELS OF ALERTNESS, PATTERNS OF
HORMONE SECRETION, AND DIGESTIVE FUNCTIONS. DUE TO THE LARGE
AMOUNT OF CONTROL OF THE CIRCADIAN RHYTHM CYCLE IT IS OFTEN
REFERRED TO AS THE PACEMAKER.

7. CIRCADIAN RHYTHMS:-
•
•
•
•
TWO SPECIFIC FORMS OF CIRCADIAN RHYTHMS COMMONLY DISCUSSED IN
RESEARCH ARE MORNING AND EVENING TYPES.
THERE IS A DIRECT CORRELATION BETWEEN THE CIRCADIAN PACEMAKER AND
THE BEHAVIORAL TRAIT OF MORNINGNESS-EVENINGNESS.
PEOPLE CONSIDERED MORNING PEOPLE RISE BETWEEN 5 A.M. AND 7 A.M. GO TO
BED BETWEEN 9 P.M. AND 11 P.M., WHEREAS EVENING PEOPLE TEND TO WAKE UP
BETWEEN 9 A.M. AND 11 A.M. AND RETIRE BETWEEN 11 P.M. AND 3 A.M. THE
MAJORITY OF PEOPLE FALL SOMEWHERE BETWEEN THE TWO TYPES.
EVIDENCE HAS SHOWN THAT MORNING TYPES HAVE MORE RIGID CIRCADIAN
CYCLES EVENING TYPES, WHO DISPLAY MORE FLEXIBILITY IN ADJUSTING TO NEW
SCHEDULES ONE THEORY IS THAT EVENING TYPES DEPEND LESS ON LIGHT CUES
FROM THE ENVIRONMENT TO SHAPE THEIR SLEEP/WAKE CYCLE, AND
THEREFORE EXHIBIT MORE INTERNAL CONTROL OVER THEIR CIRCADIAN
RHYTHMS.

8. MECHANISM OF CIRCADIAN RHYTHMS:-
•
1.
2.
3.
CIRCADIAN CLOCK PRESENT IN BRAIN COORDINATES DAILY PHYSIOLOGICAL CYCLE LIKE :-
SLEEP WAKE CYCLE
DIGESTION AND TEMPERATURE
HORMONES ETC..
INTERNAL BIOLOGICAL CLOCK SYNCHRONISES WITH ENVIRONMENTAL CONDITIONS. IN MAMMALS, THE
CIRCADIAN CLOCK RESIDES IN TWO CLUSTERS OF NERVE CELLS CALLED THE SUPRACHIASMATIC NUCLEI
(SCN). WHICH ARE LOCATED IN A REGION AT THE BASE OF THE BRAIN CALLED THE ANTERIOR
HYPOTHALAMUS. INFORMATION ON DAY LIGHT OR ITS LIMITATION BY ARTIFICIAL ILLUMINATION IS
RECEIVED BY RETINA CELLS AND PROJECT VIA THE RETINOHYPOTHALAMIC TRACT INTO THE SCN IN
THE HYPOTHALAMUS. SPECIAL LIGHT SENSITIVE GANGLION CELLS ACT IN THE RETINA AS BRIGHTNESS
RECEPTORS AND SEND APPROPRIATE INFORMATION USEFUL FOR THE REGULATION OF CIRCADIAN
RHYTHMS.
SCN USES ITS CONNECTION WITH THE AUTONOMIC NERVOUS SYSTEM FOR ITS TIME OF DAY MESSAGE
BY SETTING THE SENSITIVITY OF ENDOCRINE GLANDS (THYROID, ADRENAL, AND OVARY) OR BY
DIRECTLYCONTROLLING ON ER LOCRINE OUTPUT OF PINEAL GLAND (I.E. ACLATONIN SYNTHESIS).

9. DIURNAL RHYTHMS:-
•DIURNAL RHYTHMS ARE AN EXTENSION OF CIRCADIAN RHYTHMS SIMPLY PUT THE
DIURNAL CYCLE IS IDENTICAL TO THE CIRCADIAN CYCLE WITH THE ONE ADDITIONAL
COROLLARY THAT IT MUST BE IN SYNE WITH THE DAY AND NIGHT CYCLE. IN OTHER
WORDS, FOR AN INDIVIDUALS CIRCADIAN RHYTHMS TO BECOME DIURNAL THAT
SUBJECT MUST BE AWAKE AND FUNCTIONING NORMALLY DURING DAYLIGHT HOURS
AND SLEEPING DURING NIGHT HOURS ON A FAIRLY CONSISTENT BASIS. NOTE THAT IT
IS POSSIBLE TO HAVE A CIRCADIAN CYCLE WITHOUT BEING DIUMAL BUT NOT VISA
VERSA.

10. ULTRADIAN RHYTHMS(BASIC REST- ACTIVITY
CYCLE)
•ULTRADIAN RHYTHMS ARE DEFINED AS AN ENDOGENOUS RHYTHM
PATTERN THAT OCCURS ON A SHORTER TIME SCALE THAN CIRCADIAN
RHYTHMS. AS A RESULT OF THE BRIEF CYCLE TIME THE FREQUENCY OF
OCCURRENCE IS MUCH HIGHER. A PRIME EXAMPLE OF AN ULTRADIAN
RHYTHM IS FEEDING PATTERNS. FOR THE AVERAGE PERSON THIS CYCLE
REPEATS ABOUT 3 TIMES A DAY. UNLIKE DIURNAL RHYTHMS ULTRADIAN
RHYTHMS ARE SHARE NO OVERLAPPING RELATIONSHIP WITH CIRCADIAN
RHYTHMS.

11. INFRADIAN RHYTHMS
•
•
•
•
INFRADIAN RHYTHMS ARE DEFINED AS AN ENDOGENOUS RHYTHM PATTERN THAT HAS A CYCLE
DURATION LONGER THAN CIRCADIAN RHYTHMS. THAT IS MORE THAN 24 HOURS PER CYCLE.
DUE TO THE LONGER TIME FRAME FOR EACH CYCLE THE FREQUENCY OF OCCURRENCE IN THESE
CYCLES IS LOWER THAN THAT OF THE CIRCADIAN RHYTHMS.
THE FEMALE MENSTRUAL CYCLE IS AN EXAMPLE OF AN INFRADIAN RHYTHRM. IT IS A CYCLICAL
BIOLOGICAL EVENT THAT OCCURS IN A FAIRLY REGULAR PATTERN ON A MONTHLY BASIS.
SIMILAR TO THE ULTRADIAN CYCLE THE INFRADIAN RHYTHMS ARE NOT DIRECTLY LINKED TO
CIRCADIAN AND DIURNAL RHYTHMS. ADDITIONALLY THESE RIHYTHMS ARE NOT BELIEVED TO BE
INFLUENCED BY THE DAYTIME/NIGHTTIME SCHEDULE OR CHANGES IN AVAILABLE NATURAL LIGHT
DUE TO THE FACT THAT INFRADIAN RHYTHMS OCCUR IN AN UNRELATED TIME PATTERN.

12. DISORDERS OF BIOLOGICAL RHYTHMS:-
•
•
•
•
•
DISORDERS MAY DEVELOP WHEN NATURAL BIOLOGICAL RHYTHMS ARE
DISTURBED. THESE DISORDERS INCLUDE:
1. SLEEP DISORDERS: THE BODY IS "WIRED" TO SLEEP AT NIGHT.
DISRUPTIONS IN THE BODY'S NATURAL RHYTHMS CAN LEAD TO AFFECTED
SLEEP, INCLUDING INSOMNIA.
2. JET LAG: A DISRUPTION IN CIRCADIAN RHYTHMS WHEN TRAVELING
ACROSS TIME ZONES OR OVERNIGHT.
3. MOOD DISORDERS: LACK OF EXPOSURE TO SUNTIGHT CAN LEAD TO
CONDITIONS LIKE DEPRESSION, BIPOLAR DISORDER, AND SEASONAL
AFFECTIVE DISORDER (SAD).
4. SHIFT WORK DISORDERS: WHEN A PERSON WORKS OUTSIDE THE
TYPICAL WORK DAY IT CAUSES CHANGES IN TYPICAL CIRCADIAN RHYTHMS.

13. FACTORS INFLUENCING BIOLOGICAL RHYTHMS:-
•
1.
2.
3.
4.
THERE ARE SOME FACTORS INFLUENCING THE BIOLOGICAL RHYTHMS:-
THE CIRCADIAN CLOCK:- IN THE PHYSICAL SENSE CIRCADIAN CYCLES ARE CONTROLLED BY
THE CIRCADIAN CLOCK, A CLUSTER OF APPROXIMATELY TEN THOUSAND NERVE CELLS
LOCATED ON THE SUPRACHIASMATIC NUCLEI (SCN) FOUND ON THE HYPOTHALAMUS IN THE
BRAIN.
INFLUENCE OF LIGHT:- LIGHT LIGHT IS AN IMPORTANT FACTOR FOR MAINTAINING BIOLOGICAL
RHYTHMS. THE CIRCADIAN CLOCK RELIES HEAVILY ON CHANGES IN LIGHT TO DETERMINE
TRANSHTIONS FROM NIGHT TO DAY.
DISRUPTION IN FEEDING CYCLE
CAFFEINE INFLUENCE ON THE CIRCADIAN CLOCK

14. BIOLOGICAL CLOCK
•
•
•
A. AN INTERNAL BIOLOGICAL CLOCK, LOCATED IN MAMMALS, IN THE
SUPRACHIASMATIC NUCLEUS OF THE HYPOTHALAMUS (SCN),
DELIVERING ITS MESSAGE OF TIME THROUGHOUT THE BODY.
B. IT IS RESPONSIBLE FOR CIRCADIAN RHYTHMUS AND ANNUAL/
SEASONAL RHYTHMS.
C. THE SCN USES ITS CONNECTIONS WITH THE AUTONOMIC
NERVOUS SYSTEM FOR SPREADING ITS TIME-OF-DAY MESSAGE,
EITHER BY SETTING THE SENSITIVITY OF ENDOCRINE GLANDS (I.E.,
THYROID, ADRENAL, OVARY) OR BY DIRECTLY CONTROLLING AN
ENDOCRINE OUTPUT OF PINEAL GLAND (I.E., MELATONIN SYNTHESIS).

16. •
•
•
•
•
•
•
•
•
IN MEDICINE 3 DISCIPLINES TAKEN ACCOUNT ACC. TO TIME:
1. CHRONOPHYSIOLOGY
2. CHRONOPATHOLOGY
3. CHRONOPHARMACOLOGY
A. CHRONOTHERAPEUTICS
B. CHRONOKINETIC
C. CHRONESTHESY
D. CHRONERGY
E. CHRONOTOXICITY

17. •
•
•
•
•
•
•
1.
2.
A. CHRONOTHEREPEUTICS
I. NEW TECHNOLOGY M AKES POSSIBLE CHRONOTHERAPY.
II. (-CHRONOTHERAPEUTICS), THAT IS, INCREASE OF THE EFFICIENCY AND SAFETY OF
MEDICATIONS BY PROPORTIONING THEIR CONCENTRATIONS DURING THE 24 HOURS IN
SYNCHRONY WITH BIOLOGICAL RHYTHM DETERMINANTS OF DISEASE.
B.CHRONOKINETIC:- TIME DEPENDENT AND PREDICTABLE CHANGES IN PK PARAMETER.
C.CHRONESTHESY:- CIRCADIAN OR OTHER SYSTEMIC CHANGES IN THE SUSCEPTIBILITY AND
SENSITIVITY OFTHE TARGET SYSTEM TO A DRUG.
D.CHRONERGY:- RHYTHMIC DIFFERENCE IN EFFECTS OF DRUG ON THE ORGANISM AS A WHOLE
WHICH INCLUDES BOTH DESIRED AND UNDERSIRED EFFECTS.
E.CHRONOTOXICITY:-
THE TOXIC EFFECT OF DRUG ON THE ORGANISM, WHICH IS UNDESIRALBE AND EFFECTS THE
RHYTHMIC SYSTEM.
IRINOTECAN INDUCED LEUCOPENIA IS MORE PRONOUNCED.

18. APPLICATIONS AND USES:-
•
1.
2.
3.
4.
5.
6.
7.
8.
APPLICATIONS & USES:
CHRONOTHERAPY FOUND USEFUL IN:
ONCOLOGY,
ASTHMA THERAPY
HYPERTENSION
STROKES
SLEEP APNEA
GL TRACT DISORDERS
ALLERGIES.

19. THANK YOU