Chronopharmacology is the study of variations in drug effects over biological times and circadian rhythms. It considers how drugs interact with living systems depending on the time of day they are administered. Biological rhythms like circadian (24-hour), ultradian (<20 hours), and infradian (>28 hours) rhythms influence physiological functions and drug pharmacokinetics and pharmacodynamics. Chronotherapy aims to increase drug efficacy and safety by timing drug administration according to biological rhythms. It has applications in treating cancers, asthma, hypertension, strokes, and other conditions. Recent advances include circadian-aligned drug delivery systems and future approaches may integrate chronopharmacology with systems biology and nanomedicine.
In this presentation Pharmacology III Unit V covered
Following points are included;
Various Definitions:
Acute toxicity
Subacute toxicity
Chronic toxicity
Genotoxicity,
Carcinogenicity,
Teratogenicity
Mutagenicity
General principles of treatment of poisoning
Clinical symptoms and management of various poisoning conditions.
like Barbiturate poisoning, Morphinpoisoning, Organophosphoruspoisoning, Lead poisoning, mercury poisoning, Arsenin poisoning, And its specific antidote
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
In this presentation Pharmacology III Unit V covered
Following points are included;
Various Definitions:
Acute toxicity
Subacute toxicity
Chronic toxicity
Genotoxicity,
Carcinogenicity,
Teratogenicity
Mutagenicity
General principles of treatment of poisoning
Clinical symptoms and management of various poisoning conditions.
like Barbiturate poisoning, Morphinpoisoning, Organophosphoruspoisoning, Lead poisoning, mercury poisoning, Arsenin poisoning, And its specific antidote
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
Expt. 6 Bioassay of histamine using guinea pig ileum by matching methodVISHALJADHAV100
Objective
Principle
Requirements
Experimental specifications (conditions)
Preparation of histamine standard solution
Preparation of Tyrode solution (PSS)
Procedure
Kymograph recording of contractions
Observation table
Calculation
Result and interpretation
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
Expt. 7 Bioassay of acetylcholine using rat ileum by four point bioassayVISHALJADHAV100
Objective
Principle
Requirements
Experimental specifications (conditions)
Preparation of ACh stock and standard solutions
Preparation of frog ringer solution (PSS)
Procedure
Kymograph recording of contractions
Observation table
Calculation
Result and interpretation
Introduction to chronology, chronotherapy, and chronopharmacology.
How chronopharmacology involved in asthma and helps to manage asthma?.
Biological rhythms in bronchial asthma.
Factors associated with nocturnal exacerbation of bronchial asthma.
Introduction to asthma and their symptoms.
Introduction to Antiasthmatic drugs like beta-blockers, leukotriene antagonists, steroids, etc.
Chronopharmacology division & their examples.
Advantages and disadvantages of chronopharmacology.
Marketed preparation and their images along with the price in India.
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
Expt. 6 Bioassay of histamine using guinea pig ileum by matching methodVISHALJADHAV100
Objective
Principle
Requirements
Experimental specifications (conditions)
Preparation of histamine standard solution
Preparation of Tyrode solution (PSS)
Procedure
Kymograph recording of contractions
Observation table
Calculation
Result and interpretation
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
Expt. 7 Bioassay of acetylcholine using rat ileum by four point bioassayVISHALJADHAV100
Objective
Principle
Requirements
Experimental specifications (conditions)
Preparation of ACh stock and standard solutions
Preparation of frog ringer solution (PSS)
Procedure
Kymograph recording of contractions
Observation table
Calculation
Result and interpretation
Introduction to chronology, chronotherapy, and chronopharmacology.
How chronopharmacology involved in asthma and helps to manage asthma?.
Biological rhythms in bronchial asthma.
Factors associated with nocturnal exacerbation of bronchial asthma.
Introduction to asthma and their symptoms.
Introduction to Antiasthmatic drugs like beta-blockers, leukotriene antagonists, steroids, etc.
Chronopharmacology division & their examples.
Advantages and disadvantages of chronopharmacology.
Marketed preparation and their images along with the price in India.
The role of chronopharmacology in therapeutics drinjetiInjeti Prabhakar
Many drugs are still given without regard to the time of day
Identification of rhythmic marker for selecting dosing time will lead to progress of chronopharmacotherapy.
To monitor rhythmic markers such as clock genes it may be useful to choose the most appropriate time of day for administration of drugs that may increase their therapeutic effects and reduce their side effects .
To produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules for several drugs appears to lead to a new concept of chronopharmacotherapy
All behavior patterns are co-ordinated sequences of neuromuscular activity. A rhythm is a periodically recurring event.
chronobiology is the study of science of life in relation with time.
The majority of organisms show daily and annual cycles of activity and development.
Proceedings of the National Conference on "Chronobiology and Health" organised at by Deptt of Physiology, MGMCRI, Sri Balaji Vidyapeeth at Pondicherry, India on 18-19 March 2016.
Chronobiology is a field of biology that examines periodic phenomena in living organisms and their adaptation to solar- and lunar-related rhythms.
These cycles are known as biological rhythms.
Chronobiology comes from the ancient Greek word (chrónos, meaning "time"), and biology, which pertains to the study, or science, of life.
Chronobiology is the science of biological rhythms, more specifically the impact of the 24- hour light- dark cycle on our biochemistry and therefore behaviors.
It is defined as the periodic component of temporal series of biological data whose waveform profile has been analytically validated.
In other words, biological rhythm is a bio-signal whose period of oscillation has been validated by analytical models of periodic regression using one or more harmonic components.
Examples : Heart beat, breathing, hormone secretion, menstrual cycle, body temperature and sleep/wake cycle.
Chronopharmacology is the science dealing with the optimization of drug effect and the minimization of adverse effects by timing medication in relation to biological rhythm.
The molecular mechanisms that underlie the function of the biological clocks are universally present in all cells and consists of gene-protein-gene feedback loops in which proteins can downregulate their own transcription and stimulate the transcription of other clock proteins.
Chronobiology –
It is the branch of sciences dealing with the “Biological rhythm” and their mechanism in the living organism.
Biological Rhythm –
It is the determined rhythmic biological process or function within a defined time period.
Chronotherapeutics –
i.e. increase in efficacy and safety of medications by proportioning their concentrations during the 24 hrs in synchrony with biological rhythm determinants of disease.
Chronokinetics –
Time dependent and predictable changes in PK parameter.
Eg; Cmax, tmax, AUC, T1/2
Chronesthesy –
Circadian or other systemic changes in the susceptibility and sensitivity of the target system of the target system to a drug.
Chronergy –
Rhythmic differences in effects of drugs on the organisms as a whole includes both desired and undesired effects.
Chronotoxicity –
The toxic effect of drug on the organism, which is undesirable and affects the rhythmic system. Specifically with anti-tumor agents.
The basic unit of circadian timekeeping is the cell. Even in very complex organisms, most cells contain autonomous circulatory for circadian oscillations.
Generally speaking, this mechanism is comprised of negative feedback loops of transcription and translation: activation of a repressor gene results in its later repression by its own protein products, and the instability of this repressor ensures this repression is short lived, so that a new cycle can begin.
In mammals, the principle activators within this system are the CLOCK and BMAL-1 proteins and their homolog, which dimerize and bind to certain elements to activate transcription of a large number of circadian genes.
CHRONOTHERAPEUTICS: A NEW VISTA IN NOVEL DRUG DELIVERY SYSTEMSSarvan Mani
Chronotherapeutics is the delivery of medications in the
right concentration to the right targeted tissues at the
right time to meet biological rhythm-determined needs,
e.g., rhythms in the mechanisms of disease, symptom
intensity, and/ or patient tolerance, to optimize desired
and minimize and avert adverse effects.
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.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
1. Presented by:
ASHUTOSH MISHRA
M. Pharm. [Pharmacology] 1st Yr.
KIET School Of Pharmacy
2.
3. What is Chronopharmacology ?
It is the science concerned
with the variations in the
pharmacological actions of
various drugs over a
biological timings &
endogenous periodicities.
4. Pharmacology-
It is the science of drugs.
Phamacon - (Drug),
Logos – (study)
It deals with the interaction of administered
Chem. molecule (Drug) with living
systems.
But most importantly those that are
relevant to effective and safe use for
medicinal purposes.
5. Chronobiology-
Chronos (time),
Bios (life),
Logos (study).
The science dealing with the phenomenon of
rhythmicity in living organisms is called
CHRONOBIOLOGY.
6.
7. Biological Rhythm
A determined rhythmic biological process or
function.
A biological rhythm is a self-sustaining
oscillation with the duration of time
between successive repetitions (i.e; the
period) being rather non-varying under
normal conditions.
8. Example-
CIRCADIAN RHYTHM:
Circadian (circa - about; dies, day, or about 24
hour)
Oscillations in the biological, physiological &
behavioral functions of an organism with a
periodicity of 24 hrs.
9. Continue…
Circadian rhythms are particularly important in
medicine.
A circadian clock in the brain coordinates daily
physiological cycles.
– sleep/wake - digestion
– temperature - hormones
Physiological day is about 24 hours .
– Clock is reset daily by the environment .
• day/night
• social schedules
10. Types of Rhythm
Ultradian ( <20h): cycles shorter than
a day e.g. micro sec. for a neuron to fire.
Circadian (20< <28h):Lasting for
about 24 hrs. e.g. sleep and wake cycles.
Infradian (≥28 h): Cycles longer than
24 hrs e.g. menstrual cycle.
sleep-wake cycle
11. BIORHYTHMS
External cues which reset the circadian clock =
ZEITGEBERS = synchronizers
Defination-Endogenously generated, and can be
entrained by external factors, called zeitgebers.
LD- Light-Darkness
EF- Eating-Fasting
SI- Social Contact- Isolation
NQ- Noise-Quiet
12. 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 rhythms.
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).
14. In medicine 3 disciplines taken
account acc. To time-
- CHRONOPHYSIOLOGY
- CHRONOPATHOLOGY
- CHRONOPHARMACOLOGY
•Chronotherapeutics
•Chronokinetic
•Chronesthesy
•Chronergy
•Chronotoxicity
15. Chronotherepeutics-
New technology makes possible
CHRONOTHERAPY
(=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.
16. Chronokinetic-
Time dependent and predictable changes in PK
parameter .
Chronesthesy-
Circadian or other systemic changes in the
susceptibility and sensitivity of the target system to a
drug.
17. Chronergy-
Rhythmic difference in effects of drug on the
organism as a whole which includes both desired
and undesired effects.
Chronotoxicity- The toxic effect of drug on
the organism, which is undesirable and affects the
rhythmic system. Specifically with antitumor agents
Irinotecan induced leucopenia is more pronounced.
19. Cancers-
Different biological rhythms for normal and tumor
cells
Appropriate timing.
Cancer Cells
1.Duration of the phase of cell cycle
2.Cell proliferation rate
TATO (theoretical analysis of treatment outcome)
Tumor: fast growing-2 am, slow growing-10 pm
Later half of the menstrual cycle have more clearance
rate then early half of the cycle.
20. Progesterone in the later half inhibit the enzymes
responsible for spread of cancer cells.
Cancer drug administered more in night
time, because cancer cells divide more in night time.
But not all, Treatment with 6-mercaptopurine and
methotrexate , evening dose is given to patient.
Colorectal cancer- Oxaliplatin is given in during
daytime & flurouracil at night.
21. Asthma- The risk of asthmatic attack is almost 70
times higher in patients at 04:00-05:00 in the
morning, compared with the afternoon.
Causes :
•Exogenous factors-
Allergen exposure,
Dust and pollution,
temperature changes during the day,
position during sleep.
22. Endogenous factors- Small bronchi diameter
significantly increases during the day and decreases at
night b’coz-
Adrenergic blockade of ß-receptors,
Dominance of alpha-adrenergic pathways,
Cholinergic dominance,
Smallest conc. of Ig E and
Highest concentration of histamine around 04:00.
23. Treatment-
SR formulation of theophyline once daily
Increase efficacy
Avoid multiple dosing
Nocturnal vagus nerve hyperactivity
Relieved by cholinergic antagonist
eg. Ipratropium bromide
oxitropium bromide
24. Stroke-
B.P rises about 20% immediately after awakening & least
during sleep.
1st two hours after arising are the peak hrs. for
MI, hemorrhagic stroke & thrombotic infarcts.
Reasons - ↑ physical activity (sudden)
- ↑ catecholamine levels
- ↑ platelet aggregation
- ↑ vascular tone
26. Treatment-
A new COER verapamil use in HT
It is formulated as a pill with a shell that dissolves
slowly. Taken at bed-time, this exerts peak effects
btw 5 am and noon & no mid-night dip in B.P is
seen.
Diltiazam- once in a morning strong influence in
evening.
27. Peptic Ulcer-
Pathogenesis- Helicobacter pylori and H+ ions
secretion by the stomach.
Acidity(H+) peak-evening.
Treatment-
Once daily given conventional H2blockers
(Ranitidine, Cemitidine, famotidine) are given at
evening time.
28. Allergic Rhinitis-
Rhinitis- worst in the morning and evening.
It is a Type-I (Anaphylactic) reaction, in which
antibodies (Ig E) are produced which get fixed to
the mast cells. On exposure to antigen, AG:AB
reaction takes place on mast cell surface releasing
Histamine, -HT, LTs, PGs etc.
Resulting in
urticaria, itching, bronchiospasm, rhinitis like
conditions.
Immediate Hypersensitivity.
29. 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.
30. Drug delivery systems-
1. Enteric-coated systems
2. Pulsatile drug dilivary systems
3. Membrane diffusion controlled
systems
4. Osmotic systems
5. Compression coated system
6. Layered system
31. Recent Advances-
Due to advances in
chronobiology, chronopharmacology, and global market
constraints, the traditional goal of pharmaceutics (e.g.
design drug delivery systems with a constant drug release
rate) is becoming obsolete.
However, the major bottleneck in the development of drug
delivery systems that match the circadian rhythm
(chronopharmaceutical drug delivery systems: ChrDDS)
may be the availability of appropriate technology.
32. Continue…
The last decade has witnessed the emergence of
ChrDDS against several diseases. The increasing
research interest surrounding ChrDDS may lead to the
creation of a new sub-discipline in pharmaceutics
known as chronopharmaceutics.
33. Futuristic Approach-
Future development in chronopharmaceutics may be
made at the interface of other emerging disciplines
such as-
System biology and
Nanomedicine
Such novel and more biological approaches to drug
delivery may lead to safer and more efficient disease
therapy in the future.