Application Of Chronotherapy In Various Disease Like Cardiovascular Disease,Peptic Ulcer, Diabetes and Asthma

1. Application Of Chronotherapy In
Various Disease
Present By-
Mr. Dnyaneshwar Balu Gutale
M. Pharmacy (Pharmacology)
Roll No- 14203
Semester - II
Vidyabharti College of Pharmacy Amravati

2. Content
1. Introduction
2. Biological Cycle
3. Cardiovascular System
4. Diabetes Mellitus
5. Peptic Ulcer
6. Asthma
7. Reference

3. Introduction
• Chronotherapy –
Chronotherapy is the concept of optimizing the timing of drug
administration according to target receptor/gene expression
to maximize therapeutic efficacy and minimize the side effects

5. Cardiovascular diseases
• Myocardial infarction
• Sudden cardiac death
• Angina pectoris
• Transient ischemic attacks / Stroke
Capillary resistance and vascular reactivity are higher in the morning
and decrease later in the day.
Platelet aggregability is increased and fibrinolytic activity is decreased
in the morning, leading to a state of relative hypercoagulability of the
blood.

6. • Blood Pressure rises about 20% after immediately awakening & least
during sleep
• 1st two hours after arising are the peak hrs. for MI, hemorrhagic
stroke .
Reason
• ↑ physical activity (sudden)
• ↑ catecholamine levels
• ↑ platelet aggregation
• ↑ vascular tone
• Intrinsic thrombolytic activity

7. • Aspirin- Maximum antiplatelet effect in the morning
• Thrombolytics and Heparin- ↓ benefit during early morning hours
• Atenolol - More effective during day time.Labetalol - more effective in
early morning hours.
• Enalapril- Peak effect in the afternoon after morning dose, Early
morning after evening dose.

8. Diabetes Mellitus
• Morning hyperglycemia may be observed in patients with diabetes
mellitus
• In the middle of the night, there is a surge in the amount of growth
hormone the body releases, followed by a surge in cortisol, which
increases blood glucose production by the liver- Down Phenomenon
• Normally, these processes are offset by increased insulin secretion by
the pancreas, so blood glucose levels remain relatively stable.
• However, Diabetes Mellitus patients whose livers may not respond to
insulin well enough to achieve euglycemia, the blood glucose levels
rises during sleep and can have a powerful effect on morning blood
glucose levels.

9. Peptic Ulcer
• In peptic ulcer patients, gastric acid secretion is highest during the
night. Suppression of nocturnal acid is an important factor in peptic
ulcer healing.
• Therefore, for active duodenal ulcer, once daily at bedtime is the
recommended dosage regimen for H2 antagonists.
• At nighttime, when gastric motility are slower, drug disintegration,
dissolution, and absorption may be slower.
• H2-blockers (ranitidine, cimetidine, famotidine, roxatidine, nizatidine)
should be taken once a day in the late afternoon or early night when
acid secretion is increasing.

10. Asthma
The risk of asthmatic attack is almost 70times higher in patients at 04:00-
05:00 in the morning, compared with the afternoon.
Causes-
• Small bronchi diameter significantly increases during the day and
decreases at night because of:
• Adrenergic blockade of B-receptors,
• Dominance of alpha-adrenergic pathways,Cholinergic dominance,
• Lowest concentrations of cortisol Ig E with highest concentration of
histamine around 04:00 AM

11. Treatment
• Formulation of theophyline at night Increase efficacy
• Avoid multiple dosing
Corticosteroids
• 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.
• Single dose oral prednisolone at 3pm is most effective

12. Reference
• Essentials Of Medical Pharmacology by KD Tripathi 8th edition, Jaypee
Brothers Medical Publishers(P).Ltd. Page No. 242- 243
• Johnson, C. (2004). Chronobiology: Biological Timekeeping.
Sunderland, Massachusetts, USA: Sinauer Associates, Inc. pp. 67-105