Hypnotics : Based on New Concepts (orexin/hypocretin antagonism, melatonin agonism, GABA-agonism) in the back-drop of old drugs. Dr. Ashok Kumar Batham.
This slide share is all about the sleeping-pills available to the practitioners of modern medicine. Hypnotics, the drugs used to treat insomnia (difficulty in falling asleep, staying asleep, frequent awakenings in the night, morning awakening without feeling fresh) are described with special reference to drugs based on New Concepts (orexin/hypocretin antagonism, melatonin agonism, GABA-agonism) in the back-drop of old drugs. This way all the hypnotic drugs, including the new as well old, and drugs having sedating effects, such as, some anti-histaminics, used in insomnia, are included in this presentation, with the hope that medical students and those studying pharmacology in pharmacy and ayurvedic colleges will find it useful.
MANAGEMENT OF SUBSTANCE RELATED PSYCHIATRIC DISORDERSEDATIVE, HYPNOTIC AND A...Dr Slayer
SEDATIVE, HYPNOTIC AND ANXIOLYTIC - 3 groups of drugs associated with this class of substance-related disorders
Associated with physical and psychological dependence also withdrawal symptoms
MANAGEMENT OF SUBSTANCE RELATED PSYCHIATRIC DISORDERSEDATIVE, HYPNOTIC AND A...Dr Slayer
SEDATIVE, HYPNOTIC AND ANXIOLYTIC - 3 groups of drugs associated with this class of substance-related disorders
Associated with physical and psychological dependence also withdrawal symptoms
Narcotic and Nonnarcotic analgesic(Medicinal Chemistry)Yogesh Tiwari
Analgesics are agents that relieve pain by acting centrally to elevate pain threshold without disturbing consciousness or altering other sensory modalities.
opioid analgesics with detailed description of introduction, mechanism of action, adverse effect, uses and contraindication along with examples for under graduates.
Narcotic and Nonnarcotic analgesic(Medicinal Chemistry)Yogesh Tiwari
Analgesics are agents that relieve pain by acting centrally to elevate pain threshold without disturbing consciousness or altering other sensory modalities.
opioid analgesics with detailed description of introduction, mechanism of action, adverse effect, uses and contraindication along with examples for under graduates.
Similar to Hypnotics : Based on New Concepts (orexin/hypocretin antagonism, melatonin agonism, GABA-agonism) in the back-drop of old drugs. Dr. Ashok Kumar Batham.
Sentra PM is a patented medical food designed specifically for the dietary management of the altered metabolic processes of sleep disorders.
The safety and efficacy of Sentra PM is supported by multiple clinical trials and over a decade of clinical use. Sentra PM is recommended by physicians as an alternative to addictive and dangerous prescription sleep aids.
For more information please visit www.medicalfoods.com or call (844)474-3111
Intravenous Anaesthetics are a group of fast-acting
compounds that are used to induce a state of impaired
awareness of complete sedation.
These are drugs that, when given intravenously in an
appropriate dose, cause a rapid loss of consciousness.
Now days due to various lifestyle people cannot able to sleep and having good sleep
There is difficulty in initiation, maintaining, & awakening during sleep.
I will try to help for understanding normal sleep, neurophysiology, sleep disorder & its Pharmacotherapy by this seminar session.
slides collected from many eminent teachers nd few from sildeshare in view of ug/pg studnets not to miss any topic.
Similar to Hypnotics : Based on New Concepts (orexin/hypocretin antagonism, melatonin agonism, GABA-agonism) in the back-drop of old drugs. Dr. Ashok Kumar Batham. (20)
Antidepressants: Mechanisms based classification & challenges in therapeutic ...DrAshok Batham
Mechanisms based classification & challenges in therapeutic applications. Hopefully it would be useful to medical students and also students of pharmacy, Ayurveda, homeopathy studying pharmacology.
Anti epileptic drugs used for non-epileptic disorders : Dr. Ashok Kumar BathamDrAshok Batham
This presentation highlights the uses of anti-epileptic drugs in non-epileptic disorders, such as painful neuropathies like diabetic polyneuropathy, post-herpetic neuralgia, sciatic pain with spinal cord disease, trigeminal neuralgia; bipolar disorder; generalised anxiety disorder; cardiac arrhythmias, migraine prophylaxis; obesity etc. It would be useful to students of pharmacology studying in medical, pharmacy, Ayurvedic and homeopathic colleges, and those working in pharmaceutical industry.
Anti-epileptic Drugs : Applications Outside Epilepsy
(Reverse Engineering)
Anti-epileptic Drugs are Approved and Used Outside Epilepsy. Phenytoin, Carbamazepine, and Oxcarbazepine have proven efficacies in Trigeminal Neuralgia.
Gabapentin and Pregabalin are established in the treatment of postherpetic neuralgia (PHN) and painful diabetic neuropathy (PDN).Divalproex sodium is approved for use in the treatment of bipolar disorder and prevention of migraine.
Overlapping pathophysiology of some disorders and mechanisms of action of many Anti-epileptic Drugs : Applications Outside Epilepsy
(Reverse Engineering)antiepileptic drugs are evidently responsible for the applications of anti-epileptic drugs (AEDs) in clinical conditions outside epilepsy.
New drug candidates will, therefore, be developed for both the sets of therapeutic applications (epilepsy and outside epilepsy).
Depressive Disorders: An Overview of Full Spectrum. Dr. Ashok Kumar Batham.DrAshok Batham
Medical specialists outside the area of psychiatry and those who practice family medicine generally get fragmented information about mental depression. Therefore, an endeavour has been made to provide a complete overview of various depressive disorders, such as, Major Depressive Disorder (MDD), Persistent Depressive Disorder (PDD) or Dysthymia, Disruptive Mood Dysregulation Disorder (DMDD), Premenstrual Dysphoric Disorder (PMDD), Substance/Medication Induced Depressive Disorder, Depressive Disorder Due to Another Medical Condition, and other depressive disorders. DSM-5 diagnostic criteria of each of these disorders are given along with vignettes of diagnosis and treatment of the same are presented. Hopefully, this slide share will help non-psychiatrists to understand the complete spectrum of depressive disorders.
Anti-anxiety Drugs:Benzodiazepine Receptor Agonists. Dr. Ashok Kumar Batham, ...DrAshok Batham
This presentation titled “Anti-anxiety Drugs: Benzodiazepine Receptor Agonists” includes the pharmacological actions, mechanism of actions, pharmacokinetics, and clinically relevant classifications of Benzodiazepines. Non-Benzodiazepine drugs acting through Gaba-ergic benzodiazepine receptors are also described comprehensively.
Benzodiazepine receptor antagonist, flumazenil, used as an anti-dote in poisoning is also described.
Hopefully, students of pharmacology and medicine in medical and pharmacy colleges will find it useful. Marketing and sales teams of pharmaceutical companies may also find this presentation useful from the point-of-view of understanding their products in proper perspective.
Anti-migraine drugs. Dr. Ashok Kumar Batham,MB,BS,MD,DCR, DrAshok Batham
This presentation on Migraine and Anti-Migraine Drugs provides a comprehensive description of migraine including its symptomatology and pathophysiology. On the basis of these aspects drugs used in the treatment of migraine are described with special emphasis on ergotamines and tryptans.
Hopefully, students of pharmacology and medicine in medical and pharmacy colleges will find it useful. Marketing and sales teams of pharmaceutical companies may also find this presentation useful from the point-of-view of understanding their products in proper perspective.
This presentation is made for students of Pharmacology and Medicine to apprise them of the basic features of Parkinson's Disease and evolution of its drug treatment strategies. Important drugs used in Parkinso's Disease are described. Marketing and Sales teams of pharmaceutical companies may also find it useful.
Bioequivalence study Exemptions- and Waivers:Ashok Kumar Batham.ashokpharmaco...DrAshok Batham
BIOEQUIVALENCE STUDY: EXEMPTIONS AND WAIVERS
This presentation is based on:
1. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry
U.S. Department of Health and Human Services Food and Drug Administration
Center for Drug Evaluation and Research (CDER).December 2017. Biopharmaceutics.
2. ICH guideline Q3D M9 on biopharmaceutics classification system based biowaivers
EMA/CHMP/ICH/493213/2018
3. Guidelines For Bioavailability & Bioequivalence Studies
Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, New Delhi.
(March 2005)
Objectives of this presentation:
Understand the drug regulatory requirements for:
Conducting Bioequivalence Study or
Not Conducting Bioequivalence Study for obtaining regulatory marketing authorization for pharmaceutical formulations,
Bioequivalence studies are required or mandatory for certain formulations,
Exemptions are available for Bioequivalence Studies on certain formulations,
Waivers are granted by drugs regulatory authorities in certain cases, like Biopharmaceutical Classification System (BCS) Class-I and Class-III, Pharmaceutical Drugs, and some drug products with high safety margin,
Propose a clinical classification system-Biotherapeutics Classification System (BTCS) based upon:
Bioavailability of pharmaceutical drug, and
Clinical Safety Margin of pharmaceutical drug
Based on this Biotherapeutics Classification System (BTCS) Waivers may be requested for some pharmaceutical drug formulations, such as those with High Bioavailability and High safety Margin.
New Drugs For Multiple Sclerosis approved by The US FDA in 10 Years.DrAshok Batham
There is no specific curative drug available for the treatment of multiple sclerosis.
Fortunately, a large number of disease modifying drugs have been developed.
New drug development for the treatment of multiple sclerosis is a hot-area, a large number of disease modifying drugs have been developed in the last 2 decades.
Nearly 70 different drugs are now available to deal with this debilitating and disabling disease.
The list presented here includes 10 disease modifying drugs approved by the US FDA in the last 10 years, from January 2010 to October 2019.
In addition to these, a drug, Ampyra (Dalfampridine) 10 mg tablet has been approved by the US FDA in January 2010 for improvement of walking capacity in multiple sclerosis.
Drugs function by altering the existing bodily functions in disease and health; they do not produce any new thing in the body. Essentially, drugs either stimulate or inhibit existing physiological activities, kill disease causing germs, destroy cancer cells, replenish endogenous hormones and correct their deficiencies, and correct deficiencies of vitamins, minerals, essential amino acids, essential fatty acids and anti-oxidants.
This slide presentation gives an overview of all the basic disease processes or mechanisms through which diseases occur and would help the common man have a good understanding of diseases.
Anti-depressant drugs. Dr. Ashok Kumar Batham,M.D.,DrAshok Batham
This presentation gives a broad and comprehensive overview of anti-depressants. Mono-aminergic theory of depression which forms the basis of development of anti-depressant drugs is given along with the history of development of these drugs. Subsequently, mechanism-based classification, uses, efficacy and general adverse effects of anti-depressants are systematically described. Hopefully, this slide-share would be useful to medical students and also to those studying clinical pharmacy, and undergoing basic training in pharmaceutical marketing.
This comprehensive presentation is aimed at opening the window to the knowledge of Anti-epileptic Drugs (AEDs). It provides a very useful mechanism-based classification explaining the mechanisms of action and therapeutic applications of AEDs. Common problems associated with AEDs and important pharmacokinetic features of these drugs are described. Salient features of the available AEDs are described.
This presentation is aimed at putting to-day's antihistamine drugs in a broad and proper perspective. Anti-histamines are classified based on their chemistry and more importantly on the chronology of their introduction. Their general actions, uses, pharmacokinetic features, and adverse effects are described making it easy for medical and pharmacy students to understand this class of widely used drugs.
Epilepsy and antiepileptics. Dr.Ashok Kumar Batham,M.D.,DrAshok Batham
This presentation provides relevant description and classification of epilepsy with easy-to-remember mechanism-based and chemistry-based classifications of Anti-epileptic Drugs (AEDs). General features and salient details of all the Anti-epileptic Drugs (AEDs) are provided that can be used as short-notes. Hopefully, this presentation would be useful to students of medicine, pharmacology, pharmacy, clinical pharmacy, and representatives of pharmaceutical companies.
This presentation provides all the relevant information about mental depression and anti-depressants. It will be useful to students of medicine, pharmacology, pharmacy, and pharmaceutical industry.
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
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.
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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!
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.
Hypnotics : Based on New Concepts (orexin/hypocretin antagonism, melatonin agonism, GABA-agonism) in the back-drop of old drugs. Dr. Ashok Kumar Batham.
1. HYPNOTICS : BASED ON NEW CONCEPTS
(orexin/hypocretin antagonism, melatonin agonism, GABA-
agonism) in the back-drop of old drugs
Dr. Ashok Kumar Batham, MB,BS,MD,DCR,
Chief Consultant, Dr Batham Pharma Consultants,
EMAIL: ASHOKPHARMACOL@GMAIL.COM
TELEPHONE:0919328018777
2. INSOMNIA
Insomnia is defined as repeated difficulty with sleep initiation,
maintenance, consolidation, or quality that occurs despite adequate time
and opportunity for sleep and that results in some form of daytime
impairment.
Specific criteria vary, but common ones include taking longer than 30
minutes to fall asleep, staying asleep for less than 6 hours, waking more
than 3 times a night, or experiencing sleep that is chronically
nonrestorative or poor in quality.
Dr.Ashok Kumar Batham 2
3. INSOMNIA (DSM-5)
DSM-5 defines insomnia as dissatisfaction with sleep quantity
or quality, associated with one (or more) of the following
symptoms:
• Difficulty initiating sleep
• Difficulty maintaining sleep, characterized by frequent
awakenings or problems returning to sleep after awakenings
• Early-morning awakening with inability to return to sleep
Dr.Ashok Kumar Batham 3
4. INSOMNIA (DSM-5)
• Other criteria include the following:
• The sleep disturbance causes clinically significant distress or impairments in social, occupational,
educational, academic, behavioral, or other important areas of functioning
• The sleep difficulty occurs at least 3 nights per week
• The sleep difficulty is present for at least 3 months
• The sleep difficulty occurs despite adequate opportunity for sleep
• The insomnia cannot be explained by and does not occur exclusively during the course of another
sleep-wake disorder
• The insomnia is not attributable to the physiological effects of a drug of abuse or medication.
• Coexisting mental disorders and medical conditions do not adequately explain the predominant
complaint of insomnia
Dr.Ashok Kumar Batham 4
5. INSOMNIA(DSM-5)
The Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5) makes no distinction between primary
and comorbid insomnia.
Insomnia is Insomnia whether it is Primary or Secondary or
associated with other diseases.
Dr.Ashok Kumar Batham 5
6. HYPNOTICS APPROVED FOR USE IN INSOMNIA
• Benzodiazepines: flurazepam, temazepam, quazepam, estazolam, and
triazolam.
• Non-Benzodiazepines acting on GABAergic Benzodiazepine receptors:
zaleplon, zopiclone, eszopiclone, zolpidem
• Melatonin receptor agonists: ramelteon, tasimelteon
• Orexin or Hypocretin receptor antagonists: Suvorexant, Lemborexant
• Barbiturates: Secobarbital , Butabarbital (almost obsolete)
7. DRUGS WITH SEDATIVE EFFECTS USED IN INSOMNIA
• Benzodiazepines: diazepam, chlordiazepoxide, alprazolam,
lorazepam etc.
• Antidepressants: amitriptyline, nortriptyline, trimipramine,
imipramine, doxepine
• Atypical antipsychotics: quetiapine
• OTC anti-histaminics: doxylamine, diphenhydramine
8. MELATONIN
• Natural hormone produced by pineal gland, the levels of which rise
and fall in a circadian fashion in the suprachiasmatic nucleus.
• Melatonin levels start increasing in the evening as the individual
prepares for sleep, peaking between 11 pm and 3 am, reaching the
plateau and start falling sharply before daylight (daytime levels are
about 10 times lower than nighttime).
• Responsible for maintaining wake-sleep cycle (biological-clock).
Dr.Ashok Kumar Batham 8
9. MELATONIN (CONTD.)
• Light at night blocks production of melatonin and can lead to sleep disturbances.
• Advancing age is associated with declining levels of melatonin, which may
contribute to insomnia in elderly people.
• Melatonin acts on:
• MT1 receptors to promote onset of sleep
• MT2 receptors to shift the timing of circadian system, and
• MT3 receptor (quinone reductase 2)
• Melatonin is reported to possesses anti-oxidative, immuno-modulating and anti-
tumor activities.
Dr.Ashok Kumar Batham 9
10. MELATONIN (CONTD.)
• Synthetic melatonin available as an over-the-counter (OTC) dietary supplement in
the US.
• Melatonin supplementation has been suggested for sleep disorders, Jet-Leg, and
sleep cycle adjustment in shift-workers, and blind people.
• Effective starting doses for jet lag range from 0.3 to 0.5 mg.
• Lower doses may work for some people, while others may need a higher dose, up to
3 to 5 mg.
• Doses over 5 mg appear to be no more effective than lower doses.
Dr.Ashok Kumar Batham 10
11. RAMELTEON
• Synthetic tricyclic analog of Melatonin. Binds to M1 and M2 receptors.
• MT1 and MT2 are thought to promote sleep and to be involved in maintenance of the
circadian rhythm and normal sleep-wake cycle.
• Stimulation of the MT1 receptor in the suprachiasmatic nucleus (SCN) inhibits neuronal
firing (reduces alerting effect of the SCN), and stimulation of the MT2 receptor in the SCN
affects the circadian rhythm, causing a phase advance (earlier sleep time).
• Does not bind to M3 receptors and receptors of other neurotransmitters, such as nicotinic
acetylcholine, neuropeptide, dopamine, opiate, benzodiazepine-binding sites on GABAA
receptors.
• Appears to act by producing a phase advance of the endogenous circadian rhythm.Dr.Ashok Kumar Batham 11
12. RAMELTEON (CONTD.)
• Appears to act by producing a phase advance of the endogenous circadian rhythm.
• Rapidly absorbed on oral administration reaching peak concentration within 1-hour.
• Undergoes significant first-pass metabolism, therefore its bioavailability is less than
2%.
• Half-life ~2 hours.
• Plasma protein biding of the drug is 80%.
• Metabolized by CYPs 1A2, 2c, and 3A4. Of the 4-metabolites, one M-II is active.
Dr.Ashok Kumar Batham 12
13. RAMELTEON (CONTD.)
• Approved for the treatment of insomnia, specifically sleep onset
difficulties.
• Shortens sleep latency, and increases sleep time.
• Does not produce impairment of cognitive functions on next-day.
• Beneficial effects found to be sustained up to 6-months in clinical trials.
• No development of Tolerance and Dependence.
• No reports of withdrawal reactions and rebound insomnia on
discontinuation.
• Administered in doses of 8, 16 mg up to 64 mg.Dr.Ashok Kumar Batham 13
14. TASIMELTEON (HETLIOZ)
• Tasimelteon is a selective agonist for the melatonin receptors MT1 and MT2, similar to
ramelteon (2005).
• Approved by the US FDA in January 2014 for the treatment of non-24-hour sleep–wake
disorder (Non-24, N24 and N24HSWD).
• Approved in Europe by EME in July 2015 for the treatment of non-24-hour sleep-wake
rhythm disorder in totally blind adults, but not in the rarer cases of non-24 in people with
normal eyesight.
• Treatment of N24HSWD with Tasimelteon leads to improved sleep timing while taking the
drug. Reversion to baseline sleep performance occurs within a month of discontinuation.
15. HYPOCRETIN (OREXIN): HYPOTHALAMIC NEUROPEPTIDE
Hypocretin/Orexin was independently discovered by two groups using different
techniques.
• de Lecea et al.(1998) identified the pro-hormone pre-prohypocretin, and its peptide products- Hypocretin-1 (Hcrt-1)
and Hypocretin-2 (Hcrt-2), and
• Sakurai et al (1998) reported discovery of the orexins, orexin-A (Orx-A) and orexin-B (Orx-B).
Hypocretin/Orexin systems have roles in:
• sleep–wake cycle,
• arousal state,
• regulating feeding and drinking behavior,
• metabolism, and
• endocrine system.
16. HYPOCRETIN (OREXIN) RECEPTORS
• Receptors for these neuropeptides Hcrtr1 [Orxr1] and Hcrtr2 [Orxr2]) have been
identified as G-protein coupled receptors (GPCR).
• Hcrtr1 receptor has a much higher (100 to 1000-fold) affinity for Hcrt-1 than for
Hcrt-2.
• Hcrtr2 receptor seems to have equal affinities for both neuropeptides.
• Hcrtr1 is hypothesized to have a sleep-specific role.
• Hcrtr2 receptor is hypothesized to have more general role.
• The receptors have been mapped on human chromosome 1p33 and 6cen,
respectively.
17. HYPOCRETIN (OREXIN) IN SLEEP AND OTHER DISORDERS
• Strong evidence indicates that narcolepsy is associated with abnormalities of the hypocretin
neurotransmitter system.
• Low or undetectable levels of hypocretin are found in most patients of Narcolepsy.
• Some patients of Narcolepsy may have ‘hypocretin resistance’ which may lead to overproduction of
hypocretin.
• Hypocretin/orexin system may be involved in other sleep disorders, such as primary
hypersomnolence, insomnia, Kleine-Levin syndrome, and sleep disorders affecting the ageing
population.
• The hypocretin system may be important in affective disorders such as major depression and
bipolar affective disorder.
18. SUVOREXANT (BELSOMRA)
• Suvorexant is an orexin receptor antagonist. The orexin neuropeptide
signaling system is a central promoter of wakefulness. Blocking the binding of
wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and
OX2R by Suvorexant is thought to suppress wake drive.
• Approved by the US FDA in 2014, as the first orexin-antagonist.
• It is indicated for the treatment of insomnia characterized by difficulties with
sleep onset and/or sleep maintenance.
• Available as film coated tablets containing 5 mg, 10 mg, 15 mg, and 20 mg.
• Recommended dose is 10 mg, taken no more than once per night and within
30 minutes of going to bed, with at least 7 hours remaining before the
planned time of awakening. The dose can be increased upto 20 mg once per
night daily.
19. LEMBOREXANT (DAYVIGO)
• Dual orexin antagonist (DORA), blocks OX1R and OX2R. Lemborexant has been reported to inhibit the
orexin signaling pathway and promote both REM and non-REM sleep.
• 5 and 10 mg Tablets.
• Indicated for insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
• Effective in primary insomnia and in insomnia associated with other diseases, such as depression.
• Most common adverse events reported in clinical trials was somnolence (10 mg, 10%; 5 mg, 7%;
placebo, 1.0%).
• The most common adverse events leading to discontinuation of lemborexant were somnolence (10
mg, 1.0%; 5 mg, 0.7%; placebo, 0.4%) and nightmares (10 mg, 0.3%; 5 mg, 0.3%; and placebo, 0%).
20. BENZODIAZEPINES USED AS HYPNOTICS
• Benzodiazepine receptor agonists approved by the US FDA for use as hypnotics include:
• Flurazepam (Dalmane),
• Temazepam (Restoril),
• Quazepam (Doral),
• Estazolam (ProSom), and
• Triazolam (Halcion).
• All have variable half-lives and different metabolites that affect their onset and duration of action.
• These drugs bind to a specific benzodiazepine site on the gamma-aminobutyric acid (GABA)
receptor complex, resulting in increased neuronal permeability to chloride ions. The shift in
chloride ions results in hyperpolarization and stabilization of the neuronal membrane leading to
inhibitory effects of this neurotransmitter.
• This class of drugs suppresses rapid eye movement (REM) sleep and reduces stages 3 and 4 sleep
while increasing stage 2 sleep.
21. BENZODIAZEPINES USED AS HYPNOTICS
Estazolam (ProSom) - Intermediate-acting drug for the short-term treatment of sleep disorders. Effective
in increasing the time spent asleep as well as reducing awakenings during the night. Half-life 10-24 Hrs.
Administered orally in a dose of 1-2 mg.
Temazepam (Restoril) – Intermediate-acting drug. Half-life 11 + 6 Hrs. Administered orally in a dose of 7.5-
30 mg.
Indicated for severe insomnia and other severe or disabling sleep disorders.
Acts in 1-hour and its effect lasts for 8-hours.
The United States Air Force uses temazepam as one of the hypnotics approved as a "no-go pill" to help
aviators and special-duty personnel sleep in support of mission readiness. "Ground tests" are necessary
prior to required authorization being issued to use the medication in an operational situation, and a 12-
hour restriction is imposed on subsequent flight operation.
22. BENZODIAZEPINES USED AS HYPNOTICS (CONTD.)
Triazolam (Halcion) - Half-life 2.9 + 1 Hrs. Administered orally in a dose of 0.125-0.250 mg. Triazolam was
the first short-acting benzodiazepine for promoting sleep but fell out of favour after reports of amnesia
with its use.
Flurazepam (Dalmane) – Long-acting; half-life 74-24 Hrs. Administered orally in a dose of 15-30 mg.
Officially indicated for mild to moderate insomnia with difficulty falling asleep, frequent awakening,
early awakenings or a combination of each.
Quazepam (Doral) – Long-acting agent with a half-life 39 Hrs. Administered orally in a dose of 7.5-15 mg.
Effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.
Has less overdose potential than other benzodiazepines (due to its novel receptor-subtype selectively).
23. SHORTCOMINGS OF BENZODIAZEPINES AS
HYPNOTICS
• Tolerance
• Dependence
• Psychomotor retardation
• Memory impairment
• Paradoxical inhibition (e.g., increased excitement, irritability, and impulsivity)
• depression,
• Teratogenic effects in pregnant women.
• Cognitive impairment, delirium, falls, and fractures in elderly.
24. NOVEL BENZODIAZEPINE RECEPTOR AGONISTS
• These drugs are collectively called “Z-Compounds” and include:
• Zaleplon
• Zolpidem
• S-Zopiclone
• Specifically act as agonists of GABAA receptors subunit ⍺1 and therefore
produce selective hypnotic effect without muscle relaxant, anticonvulsant
and other effects of other benzodiazepines which produce varying effects on
⍺2, ⍺3 and ⍺5 subunits.
• Produce a predominant hypnotic effect
• Exhibit weak anticonvulsant and skeletal muscle relaxant effects.
• Like benzodiazepines, intoxication caused by these drugs can be reversed by
Flumazenil (benzodiazepine receptor antagonist).Dr.Ashok Kumar Batham 24
25. ZOLPIDEM (AMBIEN)
• Shortens sleep latency and prolongs sleep duration.
• No effects on sleep stages.
• Beneficial effects found to be sustained upto 6-months in clinical trials.
• No development of Tolerance and Dependence.
• Beneficial effects on sleep persist upto 1-week after discontinuation.
• Has a short half-life ~ 2 hour.
• Does produce hang-over on waking up with sedation, delayed reaction time and anterograde amnesia.
• Approved for short-term treatment of insomnia.
• Available as immediate-release tablets of 5 and 10 mg; modified-release tablets of 6.25 and 12.5 mg
(Ambien and Ambien CR, respectively ); as sublingual tablets (Edluar and Intermezzo); and as an oral spray
(ZolpiMist, NovaDel Pharma).
• Immediate release and Modified-release tablets administered in doses of 5 or 10, and 6.25 or 12.5 mg,
respectively.
Dr.Ashok Kumar Batham 25
26. ZALEPLON (SONATA)
• A pyrazolopyrimidine derivative.
• Produces quick induction of sleep and has an an ultra-short duration of action.
• Absorption delayed by approximately two hours and is reduced by 35% if taken with high-fat or heavy
meals.
• Has a short half-life ~ 1 hour.
• Does not affect the duration of sleep and number of awakenings during sleep.
• Used for administration at bedtime for induction of sleep in patients having difficulty in falling asleep.
• Can be administered even in the later part of night (within 4-hours of anticipated waking time).
• Does not produce hang-over on waking up because of short half-life.
• Administered in doses of 5, 10 or 20 mg.
Dr.Ashok Kumar Batham 26
27. ESZOPICLONE (LUNESTA)
• S(+) enantiomer of Zopiclone which is used in many countries.
• Shortens sleep latency, prolongs sleep duration, improves sleep efficiency, and reduces sleep awakenings.
• Beneficial effects found to be sustained upto 12-months in clinical trials.
• No development of Tolerance and Dependence.
• Severe withdrawal reactions (rebound insomnia or seizures) not reported.
• Very mild withdrawal reaction in less than 2% patients in the form of abnormal dreams, anxiety, upset
stomach
• Has a short half-life ~ 6 hour.
• No observed psychomotor effects on the next day.
• Approved for long-term treatment of insomnia.
• Administered in doses of 1, 2 or 3 mg.
Dr.Ashok Kumar Batham 27
28. ANTIDEPRESSANTS USED FOR INSOMNIA
• Doxepin is approved by the US FDA or the treatment of insomnia with difficulty with sleep maintenance.
• Other tricyclic antidepressants (TCAs), such as amitriptyline, nortriptyline, trimipramine, and imipramine have
been used off-label to treat insomnia.
• Trazodone and Mirtazapine are also used ‘off-label’ for insomnia because of their sedative effects attributed to
5HT2 and H1-receptor blockades, respectively. Trazodone is administered at an initial dose of 25 to 50 mg at
bedtime, which is escalated up to 100 mg per night. Mirtazapine is used in a dose of 30 mg at bedtime for
insomnia.
• Nefazodone inhibits serotonin reuptake and is a potent antagonist at the 5-HT2 receptor. The US FDA has added a
Black Box warning regarding rare cases of liver failure associated with this drug.
• These drugs, cause an increased risk of atropine-like side effects, cardiac conduction abnormalities, orthostatic
hypotension, which, in turn, may increase the risk of falls and resulting injury. and slowed cardiac conduction.
• TCAs have been listed as potentially inappropriate for use in older adults.
• Safer treatment options have diminished the usefulness of these drugs.
29. ATYPICAL ANTIPSYCHOTICS
• Effects of antipsychotics on sleep have been studied in patients with comorbid conditions, such as depression and
psychosis.
• Not evaluated in subjects with primary insomnia.
• Not approved by FDA for the treatment of insomnia.
• Atypical antipsychotics, such as quetiapine, olanzapine, and risperidone, are commonly prescribed for sleep
disorders.
• The sedation associated with these drugs results from their antagonistic effects on multiple neurotransmitter
systems, particularly serotonin (5-HT2) and histamine (H1) receptors.
• Quetiapine is the most commonly prescribed antipsychotic for insomnia.
• Serious adverse events, such as metabolic syndrome and extrapyramidal effects, make these drugs less attractive
than agents approved by the FDA for this indication.
30. OTC ANTI-HISTAMINES
• Diphenhydramine and doxylamine are commonly used in over-the-counter insomnia
medications. They exert their effect by disrupting wake-promoting histaminergic
neurotransmission from the tuberomammillary nucleus by antagonism of the H1 receptor.
• These drugs are minimally effective in inducing sleep, may reduce sleep quality, and may
cause residual drowsiness. Therefore, the use of these drugs in insomnia patients is not
recommended.
• Moreover, antihistamines are associated with potent anticholinergic effects, such as dry
mouth, constipation, and confusion. Older individuals are particularly susceptible to these
effects.