CHRONOPHARMACOLOGY.pptx

Chronopharmacology is the branch of science which deals with the pharmacological action of a drug in relation to biological rhythm.
(Chronos: time; Pharmacon: drug; Logos: study)
It is concerned with the effects of drugs upon the timing of biological events and rhythms.
It is important to enhance the therapeutic efficacy, optimization of drug effects, minimization of adverse effects by using timing medications in relation to biological rhythm.

History:
Jean-Jaques d’Ortous de Mairan: Described circardian rhythm in plants in the 18th century.
Franz Halberg : coined the term ‘Circardian’ in 20th century (about 24 hr or about a day)
Franz Halberg : Founder of Chronobiology.

Biological Rhythm:
Biological rhythm: It is the determined rhythmic biological process or function within a defined time period.
TYPES OF RHYTHM
Circadian (last for 24 hr) – Sleep wake cycle
Infradian (> 24 hr) – Menstrual cycle
Ultradian (< 24 hr) – Neuronal firing time

Biological Clock:
An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body.
It is responsible for circadian rhythms and annual/seasonal rhythm.
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 (thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal gland (i.e. melatonin synthesis)
Application:
Chronotherapy found useful in
Asthma therapy, Strokes, Sleep disorders, GI tract disorders, Allergies, Oncology etc

Recent Advances:
Casein Kinase 1 (CK-1) inhibitor: Potential new drug
Reset the circadian clock enzymes.
Uses: Jet lag, sleep disorder, bipolar disorder
Animal trials completed.
Clinical trials are awaited.

1. CHRONOPHARMACOLOGY Ms. Pranali A. Chandurkar Assistant Professor Department of Pharmacology Dr. Rajendra Gode Institute of Pharmacy, Amravati

2. history Jean- Jaques d’Ortous de Mairan : Described circardian rhythm in plants in the 18 th century. Franz Halberg : coined the term ‘ Circardian ’ in 20 th century (about 24 hr or about a day) Franz Halberg : Founder of Chronobiology .

3. Chronobiology Chronos : time Bio: life Logos: study It is the branch of science which deals with the study of biological rhythm & their mechanism in the living organism. It is concerned with the effects of drugs upon the timing of biological events and rhythms.

4. Chronopharmacology Chronos : time Pharmacon : drug Logos: study It is the branch of science which deals with the pharmacological action of a drug in relation to biological rhythm . It is concerned with the effects of drugs upon the timing of biological events and rhythms. It is important to enhance the therapeutic efficacy, optimization of drug effects, minimization of adverse effects by using timing medications in relation to biological rhythm.

5. Biological rhythm Biological rhythm: It is the determined rhythmic biological process or function within a defined time period. TYPES OF RHYTHM Circadian (last for 24 hr) – Sleep wake cycle Infradian (> 24 hr) – Menstrual cycle Ultradian (< 24 hr) – Neuronal firing time

6. CIRCADIAN RHYTHM CYCLE

7. Biological clock An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body. It is responsible for circadian rhythms and annual/seasonal rhythm. 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 (thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal gland (i.e. melatonin synthesis)

8. chronopharmacology Chronotherapeutics Chronokinetics Chronesthesy Chronergy Chronotoxicity

9. Chronotherapeutics : - Effective therapy relation to biological rhythm of a disease. It refers to treatment method in which drug availability is timed to match rhythm of disease in order to optimize the therapeutic outcomes and minimize side effects. Chronokinetics : It deals with the study of the temporal changes in the pharmacokinetics (ADME) of the drug with respective time. Chronesthesy : - The rhythmic changes in susceptibility or sensitivity of a target system to a drug

10. Chronergy : - Rhythmic changes of both the desired (effectiveness) and undesired (toxicity, tolerance) effects on the organism as a whole. Chronotoxicity : - It may be defined as the changes in an organisms sensitivity to toxicants in relation to time.

11. Application of chronopharmacology Chronotherapy found useful in Asthma therapy Strokes Sleep disorders GI tract disorders Allergies Oncology

12. ASTHMA Acute attack of asthma: more common between midnight and 6.00 am. Increase bronchoconstriction at night due to: Increase parasympathetic tone Decrease adrenaline Decrease cortisol at midnight Increase sensitivity to irritant and allergens at night E.g. Chronopharmacotherapy for asthma is aim to getting max. beneficial effect from bronchodilators during early morning. Sustained release long acting theophylline taken once a day in the evening causes theophylline blood levels to reach their peak and improve lung function.

13. STROKE BP rises about 20% immediately after awakening & leaser during sleep. 1 st two hours after arising are the peak hours for Myocardial infraction, hemorrhagic stroke and thrombiotic infarcts. Reasons: Physical activity catecholamine levels platelet aggregation vascular tone

14. Treatment: A new COER Verapamil use in Hypertension. It is formulated as a pill with a shell that dissolves slowly. Taken at bed-time , exerts peak effects between 5 am and noon & no mid-night dip in BP is seen. Diltiazam : once in a morning strong influence in evening.

15. PEPTIC ULCER Pathogenesis: Helicobacter pylori and H+ ions secretion by the stomach. Acidity (H+) peak-evening. Treatment: - Once daily given conventional H 2 blockers (Ranitidine, Cemitidine , Famotidine ) are given at evening time.

16. ALLERGIC RHINITIS Rhinitis worst in the morning and evening. It is a Type-I (Anaphylactic) reaction, in which antibodies ( IgE ) are produced which get fixed to the mast cells. On exposure to antigens, AG:AB reaction takes place on mast cell surface releasing Histamine, LTs, PGs etc. Resulting in urticaria , itching, brochospasm , rhinitis like conditions. Immediate Hypersensitivity.

17. Treatment: Once daily, non-sedating antihistamine (like chlorpheniramine 10-20 mg) by giving it before bedtime to control overnight exacerbations and during sleep. Morning oral corticosteroid therapy for severe allergic rhinitis.

18. CANCERS Different biological rhythms for normal and tumor cells. Appropriate timing Cancer cells Duration of the phase of cell cycle Cell proliferation rate Tumor: fast growing- 2 am , slow growing- 10 pm Later half of the menstrual cycle have more clearance rate than early half of the cycle

19. Treatment: Progesterone in the later half inhibit the enzymes responsible for spread of cancer cells. Cancer drug administered more in night time (Not all drugs), because cancer cells divide more in night time. Treatment with 6-mercaptopurine and methotrexate – evening dose given to patients. Oxaliplatin : given during daytime Flurouracil : at night

20. Recent advances Casein Kinase 1 (CK-1) inhibitor: Potential new drug Reset the circadian clock enzymes. Uses: Jet lag, sleep disorder, bipolar disorder Animal trials completed. Clinical trials are awaited.

21. Thank you….