Understanding what Schizophrenia is along with the Hypothesis of Dopamine, glutamate, and Serotonin.
Conventional antipsychotics along with novel drugs and targets in the treatment of Schizophrenia.
Recent advances in the treatment of psychosesKarun Kumar
This presentation deals with atypical antipsychotics & new drugs in the pipeline (Clozapine, Risperidone, Olanzapine, Quetiapine, Ziprasidone, Aripiprazole, Second generation antipsychotics, atypical antipsychotics, Aspirin, Minocycline, Raloxifene, Estrogen, N-acetylcysteine). Introduction
Major psychiatric disorders Psychoses & affective disorders
Psychoses Disorders in which patients exhibit gross disturbances in their comprehension of reality as evidenced by false perception (hallucinations), false beliefs (delusions) and loss of contact with reality; schizophrenia most common form of psychosis (+ve n –ve symptoms)
Mostly concerned Abt –ve because poor prognosis , more difficult to treat, persist after positive symptoms have resolved
Mesolimbic Dopamine travels from the midbrain tegmental area to the nucleus accumbens. Increased activity in this pathway may cause delusions, hallucinations, and other so-called positive symptoms of schizophrenia.
Mesocortical pathways Decreased activity in the pathway that goes from the midbrain to the prefrontal lobe cortex can cause apathy, withdrawal, lack of motivation and pleasure, and other so-called negative symptoms of schizophrenia. Mesocortical dysfunction also disinhibits the mesolimbic pathway.
Nigrostriatal pathway from the substantia nigra to the striatum is involved in the coordination of body movements. Inhibition of this pathway causes the extrapyramidal side effects of antipsychotic drugs.
Tuberoinfundibular pathway from the hypothalamus to the pituitary inhibits the release of prolactin. Inhibition of this pathway leads to elevated serum prolactin levels.
2nd generation antipsychotics Clozapine, Risperidone, Olanazapine, Quetiapine, Ziprasidone, Aripiprazole (MOA, Dose, Brand name & A/E and receptor affinities)
Why do 1st gen. antipsychotics cause EPS & 2nd gen. do not? “Hit and run” hypothesis
Inflammation & schizophrenia
New drugs in pipeline Aspirin, Minocycline, Raloxifene, Estrogen, N-acetylcysteine (MOA and rationale of use)
Potential future targets of schizophrenia
Recent advances in the treatment of psychosesKarun Kumar
This presentation deals with atypical antipsychotics & new drugs in the pipeline (Clozapine, Risperidone, Olanzapine, Quetiapine, Ziprasidone, Aripiprazole, Second generation antipsychotics, atypical antipsychotics, Aspirin, Minocycline, Raloxifene, Estrogen, N-acetylcysteine). Introduction
Major psychiatric disorders Psychoses & affective disorders
Psychoses Disorders in which patients exhibit gross disturbances in their comprehension of reality as evidenced by false perception (hallucinations), false beliefs (delusions) and loss of contact with reality; schizophrenia most common form of psychosis (+ve n –ve symptoms)
Mostly concerned Abt –ve because poor prognosis , more difficult to treat, persist after positive symptoms have resolved
Mesolimbic Dopamine travels from the midbrain tegmental area to the nucleus accumbens. Increased activity in this pathway may cause delusions, hallucinations, and other so-called positive symptoms of schizophrenia.
Mesocortical pathways Decreased activity in the pathway that goes from the midbrain to the prefrontal lobe cortex can cause apathy, withdrawal, lack of motivation and pleasure, and other so-called negative symptoms of schizophrenia. Mesocortical dysfunction also disinhibits the mesolimbic pathway.
Nigrostriatal pathway from the substantia nigra to the striatum is involved in the coordination of body movements. Inhibition of this pathway causes the extrapyramidal side effects of antipsychotic drugs.
Tuberoinfundibular pathway from the hypothalamus to the pituitary inhibits the release of prolactin. Inhibition of this pathway leads to elevated serum prolactin levels.
2nd generation antipsychotics Clozapine, Risperidone, Olanazapine, Quetiapine, Ziprasidone, Aripiprazole (MOA, Dose, Brand name & A/E and receptor affinities)
Why do 1st gen. antipsychotics cause EPS & 2nd gen. do not? “Hit and run” hypothesis
Inflammation & schizophrenia
New drugs in pipeline Aspirin, Minocycline, Raloxifene, Estrogen, N-acetylcysteine (MOA and rationale of use)
Potential future targets of schizophrenia
Second and third generation antipsychoticsDr Wasim
SECOND & THIRD GENERATION ANTIPSYCHOTIC mechanism of actionmechanism of side effectmanagment of side effect BY DR WASIM UNDERGUIDANCE OF DR SANJAY JAIN
First generation=typical antipsychoticaka conventionalprimary pharmacological property of D2 antagonistSecond generation=atypical antipsychoticlow EPS and good for negative symptomsThird generation=aripiprazole metabolic friendly
MECHANISM OF ACTION
1) serotonin dopamine antagonists
4)serotonin partial agonist
MECHANISM OF SIDE EFFECT
Serotonin-2C, muscarinic-3, and histamine-1 receptors as well as receptors X
identified are all hypothetically linked to cardiometabolic risk.
antagonism of serotonin-2C and histamine-1 receptors is associated with weight gain, while antagonism atmuscarinic-3 receptors can impair insulin regulation.
An unknown receptor X may be involved in the rapid production of insulin resistance and may also rapidly cause elevated fasting plasma triglyceride levels in some patients who experience increased cardiometabolic risk on certain atypical antipsychotics
Atypical antipsychotic and risk for weight gain.FDA and experts agree on three tiers of risk
Atypical antipsychotic and cardiometabolic risk.FDA and experts disagree on one versus three teirs of risk
Metabolic friendly antipsychotic.Low- risk agents for weight gain and cardiacmetabolic illness.
Monitoring and Managment
Baseline investigations :
Family h/o diabetes
BMI
Fasting TG levels (also monitored throughout treatment)
If raised : consider switching to another agent +/- lifestyle changes
For obese/ prediabetic/ diabetic pts :
Monitor BP
Fasting glucose
Waist circumference (before and after Rx)
Be vigilant for DKA/HHS
Sedation
ARIPIPRAZOLE KNOWN AS THIRD GENERATION ANTIPSYCHOTIC
THANK YOU
Major depressive disorder and its treatmentAmruta Vaidya
A concise presentation on major depressive disorder, the drug treatment options available i.e. conventional and emerging therapies which are available.
Presentation is about different types of dopaminergic receptors, dopamiergic pathway, its different functions, agonists, antagonists and various disorders associated with it along with its treatment.
Second and third generation antipsychoticsDr Wasim
SECOND & THIRD GENERATION ANTIPSYCHOTIC mechanism of actionmechanism of side effectmanagment of side effect BY DR WASIM UNDERGUIDANCE OF DR SANJAY JAIN
First generation=typical antipsychoticaka conventionalprimary pharmacological property of D2 antagonistSecond generation=atypical antipsychoticlow EPS and good for negative symptomsThird generation=aripiprazole metabolic friendly
MECHANISM OF ACTION
1) serotonin dopamine antagonists
4)serotonin partial agonist
MECHANISM OF SIDE EFFECT
Serotonin-2C, muscarinic-3, and histamine-1 receptors as well as receptors X
identified are all hypothetically linked to cardiometabolic risk.
antagonism of serotonin-2C and histamine-1 receptors is associated with weight gain, while antagonism atmuscarinic-3 receptors can impair insulin regulation.
An unknown receptor X may be involved in the rapid production of insulin resistance and may also rapidly cause elevated fasting plasma triglyceride levels in some patients who experience increased cardiometabolic risk on certain atypical antipsychotics
Atypical antipsychotic and risk for weight gain.FDA and experts agree on three tiers of risk
Atypical antipsychotic and cardiometabolic risk.FDA and experts disagree on one versus three teirs of risk
Metabolic friendly antipsychotic.Low- risk agents for weight gain and cardiacmetabolic illness.
Monitoring and Managment
Baseline investigations :
Family h/o diabetes
BMI
Fasting TG levels (also monitored throughout treatment)
If raised : consider switching to another agent +/- lifestyle changes
For obese/ prediabetic/ diabetic pts :
Monitor BP
Fasting glucose
Waist circumference (before and after Rx)
Be vigilant for DKA/HHS
Sedation
ARIPIPRAZOLE KNOWN AS THIRD GENERATION ANTIPSYCHOTIC
THANK YOU
Major depressive disorder and its treatmentAmruta Vaidya
A concise presentation on major depressive disorder, the drug treatment options available i.e. conventional and emerging therapies which are available.
Presentation is about different types of dopaminergic receptors, dopamiergic pathway, its different functions, agonists, antagonists and various disorders associated with it along with its treatment.
Schizophrenia A chronic mental disorder involving a breakdown in the relation between thought, emotion, and behaviour, leading to faulty perception, inappropriate actions and feelings, withdrawal from reality and personal relationships into fantasy and delusion, and a sense of mental fragmentation.
Antipsychotic Agents Antipsychotic drugs are able to reduce psychotic symptoms in a wide variety of conditions, including schizophrenia, bipolar disorder, psychotic depression and drug induced psychosis. They have also been termed neuroleptics, because they suppress motor activity and emotionalityClinical Efficacy of Antipsychotic Drugs
Antipsychotic drugs are effective in controlling symptoms of acute schizophrenia, when large doses may be needed.
Long-term antipsychotic treatment is often effective in preventing recurrence of schizophrenic attacks, and is a major factor in allowing schizophrenic patients to lead normal lives.
Classification of Antipsychotic Drugs Typical antipsychotics Phenothiazines (Chlorpromazine, Perphenazine, Fluphenazine, Thioridazine) Thioxanthenes (Flupenthixol, Clopenthixol) Butyrophenones (Haloperidol, Droperidol)
Atypical antipsychotics (Clozapine, Risperidone, Sulpiride, Olanzapine, Aripiprazole)
Depot preparations are often used for maintenance therapy.
Approximately 40% of chronic schizophrenic patients are poorly controlled by antipsychotic drugs; clozapine may be effective in some of these ‘antipsychotic-resistant’ cases.
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
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
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.
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.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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.
Follow us on: Pinterest
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
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!
2. What is Schizophrenia ?
Psychotic condition characterized by
Disturbances in thinking,
Emotion and perception of clear
consciousness
Leading to Social withdrawal (1)
lot of symptoms
different patients ~ different symptoms
of Control
of reference
absence of sensation
word salad
DISORGANISED SPEECH
DISORGANISED BEHAVIOUR
bizarre, no purpose
CATATONIC BEHAVIOUR
Movements & responses
POSITIVE
*psychotic symptoms*
DELUSIONS
HALLUCINATIONS
* S Y M P T O M S *
NEGATIVE
*removal of normal process
* emotions
*Loss of interests
FLAT EFFECT
Inappropriate response
ALOGIA
poverty of speech
AVOLITION
motivation
COGNITIVE
*affects
memory
learning
understanding
*Subtle; difficult to notice
Category of Risk factors Specific Risk Factor
Genetic Factors
Child/Sibling of Schizophrenic patient (46%)
Twin of Schizophrenic patient (14-46%)
Environmental Factors
High levels of stress production of hormone cortisol.
Prenatal exposure to Viral Infection & low O2 levels during birth.
Physical or Sexual abuse in childhood.
Physiological Factors
Enlarged Brain ventricles – Deficit in the volume of brain tissue.
Abnormally low activity in the frontal lobe
Abnormalities in the Temporal lobes, hippocampus & Amygdala.
(2)
3. Affects 1% of the Global population (3)
*Pathophysiology*
• Enlargement of lateral ventricles
• Smaller than normal brain volume
• Cortical atrophy
• Widening of third ventricle
• Smaller hippocampus
• Abnormal neurotransmission
*Hypotheses of Schizophrenia*
Dopamine Hypotheses
Dopamine hyperactivity in mesolimbic pathway
Hypofunction in mesocortical pathway
Glutamate Hypotheses
NMDA Hypofunction
Serotonin Hypotheses
5-HT2A receptor hyperfunction in the cortex
*Diagnosis* (DSM-V)
a) Two of the following:
Hallucinations
Delusions
Disorganized speech
Negative symptoms
Disorganized/
Catatonic behavior
(At least one
of these)
b) Ongoing for
6 months
Prodromal
[ Active ] ~ 1 month
Residual
c) Not another
condition
eg. Drug abuse
(4)
4. *Current approaches in the treatment of Schizophrenia*
Pharmacological
treatment
Non-
Pharmacological
treatment
Antipsychotic
agents
First generation
Antipsychotics
(Typical)
Chlorpromazine
Fluphenazine
Haloperidol
Perphenazine
Thioridazine
Trifluoperazine
Second generation
Antipsychotics
(Atypical)
Clozapine
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Ziprasidone
Antipsychotic
polypharmacy
Psychotherapy
Cognitive Behavior
Therapy (CBT)
Family intervention
Art therapy
Social skill therapy
Electroconvulsive therapy
& other treatments
(5)
5. First-Generation Antipsychotics
Effective against positive symptoms
Working of FGA’s :
a) inhibits D2 Dopamine receptors
b) blocking activity on noradrenergic, cholinergic, and
histaminergic receptors.
Mesocortical pathway
Nigrostriatal pathway
Mesolimbic pathway
Tuber infundibular
pathway
Cognitive impairments & Negative symptoms
High dose ~ block pathway ~ cause Side effects
D2 receptor antagonism ~ Increase in EPS
Inhibit D2 receptors throughout the pathway
D2 blockade raises prolactin levels ~ weight
gain & neuropsychological disturbances
Effective in positive and negative symptoms
Advantage ~ (clozapine, risperidone, olanzapine) but not
all atypicals when compared with typicals.
Working of SGA’s:
a) D2 dopamine receptor activity (weak) &
b) 5-HT2A subtype of serotonin receptor activity
Second-Generation Antipsychotics
SGA
Presynaptic
neuron
SGA
Presynaptic
neuron
Presynaptic
neuron
(6)
6. Electroconvulsive therapy
(ECT)
• Effective ~ symptoms of
Catatonia present or drug
resistance
• Seizures ~ electrically
induced grand mal seizure
• In conjunction ~ clozapine
Psychotherapy
• Scheduled talks b/w ~
Patient & mental health
professional
• Supportive, reality
oriented, individual
therapy ~ beneficial for
outpatients with
schizophrenia
Family intervention
• Reduced feelings ~
isolation, burden & stress
of family members
• Various coping strategies
& problem solving skills ~
improved outcome of the
patient
Social skill therapy
• Along with
pharmacological therapy
• Focuses on improving
communications & social
interactions.
• Not effective for reducing
symptoms/preventing
relapse
Cognitive behavior therapy
• Learning & strengthening
skills ~ coping & reducing
symptoms & stress
• Problem solving strategies
~ reduce relapse
• Critical analysis ~ beliefs
about auditory
hallucinations
Art therapy
• complementary treatment
~ antipsychotics
• Aim ~ enhance creativity,
emotional expression,
communication, insight &
ability to relate
• Improvement in the
positive symptoms.
(7) (8)
7. *Need for Novel approach in the treatment of Schizophrenia*
• Improving negative & cognitive symptoms
• Better side effect profiles
• Safety/tolerability of current treatments
Cost of nonadherence
• Identifying novel treatments based on better understanding of pathophysiology
Refining approach to current targets
Novel Treatment Targets
Hypothesis Target Strategy
Dopamine Dopaminergic stabilizers Improve medication adherence
Glutamate NMDAR, AMPA receptor, or
metabotropic receptors
Improve negative symptoms and
cognitive impairments
Serotonin 5-HT1A agonists, 5-HT reuptake
inhibitors, 5-HT2C antagonists and
agonists, 5-HT3 antagonists, 5-HT6
antagonists, and 5HT7 antagonists
Reduce the extrapyramidal effects
Improve negative symptoms and
cognitive impairments
Potential treatment for different
phases of the illness
Acetylcholine α-7 nicotinic and M1
muscarinic agonists and
positive allosteric modulators
Nicotinic agonists for cognitive symptoms
Muscarinic agonists for positive symptoms
Gamma-aminobutyric acid Selective GABA-A agonists, GABA-B
antagonists, and allosteric modulators
at GABA-A receptor subtypes
Augmentation of psychosis treatment
(9)
8. Dopaminergic Antagonists and Stabilizers
• Antipsychotic therapies developed ~ antagonism of dopaminergic receptors/stabilizers including D2/D3 partial agonists
aripiprazole
• Armodafinil ~ improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions such as weight gain.
• Cariprazine ~ dopamine D3/D2 receptor partial agonist ~ higher affinity for the D3 receptor ~ alleviated symptoms of schizophrenia
~ minimal effect on metabolic parameters, prolactin level, & cardiac conduction.
• Molindone ~ blocking the effects of dopamine ~ diminished symptoms of psychosis.
• Aplindore fumarate, nemonapride, thiothixene (causes EPS)
(9) (10)
9. Glutamatergic Agents
• NMDAR agonists are neurotoxic ~ NMDARs indirectly
stimulated by using glycinergic agents (serine and
cycloserine) and glycine transport (GlyT1) inhibitors
(bitopertin)
• Moderate benefits ~ negative a during clinical trials
• D-serine ~ effective in reducing cognitive dysfunction
Animal studies ~ memory deficits in S-D rats treated
with the NMDA receptor antagonist PCP at different
developmental stages ~ reversed with D-serine
administration
Rare side effects even at high doses
MODULATORY
SITES
RECEPTOR
SITE
glycine
polyamines
Glycine
antagonists
Polyamine
antagonists
glutamate
-Mg 2+
NMDA
antagonists
Channel blocking
drugs
-
(9) (10)
10. Serotonin Agents
• Alternative 5-HT approaches ~ 5-HT1A agonists, 5-HT
reuptake inhibitors, 5-HT2C antagonists & agonists, 5-HT3
antagonists, 5-HT6 antagonists, & 5HT7 antagonists
individually/combination with D2 antagonism / 5-HT2A
antagonism or both
• 5-HT3 antagonists ~ ondansetron, tropisetron and
granisetron ~ adjunctive agents for negative and cognitive
symptom
• tropisetron ~ improve cognitive and perceptual disturbances
with risperidone.
• Lurasidone ~ potent 5-HT7 antagonism ~ reduce the risk of
relapse ~ minimal side effects
GABAAllosteric Modulators
• Allosteric modulators at GABA-A receptor ~ evaluated in
schizophrenia treatment
• Quercetin ~ blocking GABA-A receptors push synaptic
activity levels above the threshold ~ trigger homeostatic
mechanisms ~ restore inhibition and functional E/I balance
• several GABA-A receptor inverse agonists ~ potential for
treating cognitive symptoms
Cholinergic Agonists
• α-7 nicotinic and M1 muscarinic agonists and positive
allosteric modulators are of greatest interest
• Encenicline ~ potent and selective partial agonist at α7
nAChR ~ improve overall cognition & reduce negative
symptoms (phase II trial)
(5) (10)
(15)
(16)
11. Neuropeptides
NK3 receptor antagonists ~
• Activation of NK3 receptors lead to activation & release of DA, 5HT & NA
• Osanetant, Talnetant ~ NK3 receptor antagonists suggest clinical efficacy
• Evaluated in double blind, placebo controlled Clinical trials in Schizophrenia
• Osanetant & Talnetant show distinct chemical class & properties
• common traits of NK3 receptor antagonism & similar efficacy
(9,11)
Ligand Affinity at receptor
Osanetant 1.2
Talnetant 1.0
Cannabinoid receptor antagonist
• THC may be psychotogenic through involvement in dopaminergic, GABA,
and glutamatergic neurotransmission
• Cannabidiol ~ prevent psychotic-like symptoms induced by high doses of
THC by acting as an indirect antagonist of cannabinoid (CB) receptors
• CBD decreases Mesolimbic DA activity
(12, 13)
12. Treatment Company Receptor/mechanism of action Adverse effects
F17464 (Phase-II) Pierre Fabre Medicament D3 antagonist, 5-HT1A partial agonist Insomnia, agitation, and increased
triglycerides
Lumateperone (Phase-III,
under FDA review)
Intracellular therapies (ITI) 5-HT2A antagonist, 5-HT transport
inhibitor, presynaptic D2 partial agonist and
postsynaptic D2 antagonist, D1-regulated
NMDA and AMPA agonist
Somnolence, dry mouth, headache
RO5263397 & SEP-363856
(Phase-III)
N/A TAAR1 agonist Somnolence, nausea, diarrhoea,
dyspepsia
BI-425809 (Phase-II) Boehringer Ingelheim Glycine-transporter-1 (GLYT-1) inhibitor N/A
Paliperidone Palmitate (Phase-II) Janssen 5-HT2A antagonist D2 antagonist N/A
Samidorphan + Olanzapine
(ALKS3831)
(Phase-III, under FDA review)
Alkermes μ-opioid antagonist + olanzapine Weight gain, somnolence, dry mouth,
anxiety, headache, and schizophrenia
Aripiprazole Lauroxil
NanoCrystal ® Dispersion (FDA
approved)
Alkermes Partial D2 agonist Injection pain, headache, weight gain,
insomnia, dyspepsia, and anxiety1
Novel and emerging pharmacological treatments for schizophrenia
(13)
13. Sodium nitroprusside (nitric oxide donor)
• Nitric oxide ~ pathophysiology of Schizophrenia ~ gas that mediates the release of neurotransmitters, and seems to be involved in
learning, memory, and neurodevelopment
• Administration of sodium nitroprusside ~ improvement of positive, negative, anxiety, and depressive symptoms taking
antipsychotics.
• Efficacy of sodium nitroprusside ~ consideration future trials
Novel FDA approved antipsychotics
Fazaclo (Sept, 14, 2005)
Paliperidone (December 19, 2006)
Illoperidone (May 7, 2009)
Asenapine (August 15, 2009)
Lurasidone (October 29, 2010)
New drugs in the pipeline
Aspirin
Minocycline
Raloxifene
Estrogen
N-acetylcysteine
(13)
14. Lurasidone
• Maximum recommended dose was originally 80 mg/day
• In May 2012 FDA approved an extended dose range of 40-
160 mg/day for schizophrenia
• minimal changes in body weight, no significant changes in
total cholesterol, triglycerides, LDLs, HDLs or fasting glucose
• Risk of akathisia at higher doses
• No QTc prolongation
• Small increase in prolactin
Cariprazine
• D2 partial agonist
• higher doses for schizophrenia and mania (antagonist actions)
• lower doses for depression (agonist action)
• Stronger affinity for D3 than D2 receptors
• Few metabolic side effects and low risk for EPS
Brexpiprazole
• • D2 partial agonist
• Very low risk for EPS and rare akathisia so far despite
strong affinity for D2 receptors
• Possibly due to potent 5HT2A antagonism, 5HT1A
antagonism and alpha 1 antagonism
• Potential treatment for agitation and psychosis in
dementia
(14)
(17)
(18)
15. Aspirin
• Aspirin as adjuvant therapy ~ ↓ symptoms of schizophrenia
spectrum disorders
• Future studies ~ Patients with recent onset of disease & more
disturbed immune functions
Minocycline
• Addition of minocycline to atypical antipsychotic drugs in
early schizophrenia ~ Significant efficacy on negative
symptoms
• Normalized microglial cytokine production in the
hippocampus
(19)
(20)
16. Raloxifene
• Exhibit agonistic and protective action ~ modulating the
monoaminergic neurotransmission of dopamine, serotonin and
GABA
• In women addition to regular antipsychotic treatment ↓
negative, positive & general psychopathological symptoms
Estrogen
• Alters serotonergic system & modifies synthesis in dopamine
receptors
• Promotes neuronal regeneration & blocks mechanisms of
neuronal death
* Agmatine (NMDA receptor blockade) could be a new target in the treatment of schizophrenia.
N -acetyl cysteine
• Glutathione is a major antioxidant that protects cells against oxidative stress
• Improvements in insight, self-care, social interaction, motivation, volition, psychomotor stability and stabilization of mood
(21) (21)
(22)
(23)
17. Advances in somatic therapies
Repetitive transcranial magnetic stimulation
• Modifying cortical excitability, with high frequency or fast rTMS(>1Hz) ~ activating effect on neuronal circuits and slow rTMS(<1Hz)
an inhibitory effect
• rTMS efficiently reduces resistant auditory hallucinations in patients
• beneficial effects on measures of negative symptoms with improvement
• Not been approved for use in patients with schizophrenia and there is insufficient data to recommend its use in clinical practice.
Advances in psychosocial interventions
Yoga therapy
• As add on treatment along with antipsychotic ~ beneficial in psychopathology, social and occupational functions, and quality of life
Group music therapy
• Significant effects of music therapy ~ on self-evaluation of the psychosocial orientation and negative symptoms.
(24)
(25)
18. Current treatment modalities have certain
limitations: about
30% of patients with schizophrenia are refractory
There are no effective remedies for primary negative
symptoms.
patients have relapsing and remitting course
even while on medication.
Development of effective treatment ~ clinical
importance ~ poor functional outcome
lack of efficacy for these domains ~ search for
alternate pathophysiological hypothesis
Conclusion
Dated 9th October 2019
(www.nytimes.com/2019/10/08/health/johnson-
and-johnson-risperdal-verdict)
19. References:
1. Owen MJ, Sawa A MP. Substance misuse. Psychiatry by Ten Teach Second Ed. 2017;388(10039):114-128. doi:10.1201/9781315380612
2. Klaus F, Kaiser S, Kirschner M. Negative symptoms in schizophrenia — An overview. Ther Umschau. 2018. doi:10.1024/0040-
5930/a000966
3. Sommer IE, Murray RM, Meyer-lindenberg A, et al. Schizophrenia, PRIMER. 2015;(November). doi:10.1038/nrdp.2015.67
4. Stępnicki P, Kondej M, Kaczor AA. Current concepts and treatments of schizophrenia. Molecules. 2018;23(8).
doi:10.3390/molecules23082087
5. Chien WT, Yip ALK. Current approaches to treatments for schizophrenia spectrum disorders, part I: An overview and medical
treatments. Neuropsychiatr Dis Treat. 2013;9:1311-1332. doi:10.2147/NDT.S37485
6. Gründer G, Heinze M, Cordes J, et al. Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of
life in schizophrenia: a double-blind, randomised study. The Lancet Psychiatry. 2016. doi:10.1016/S2215-0366(16)00085-7
Sanghani SN, Petrides G, Kellner CH. Electroconvulsive therapy (ECT) in schizophrenia: A review of recent literature. Curr Opin
Psychiatry. 2018;31(3):213-222. doi:10.1097/YCO.0000000000000418
8. Veerman SRT, Schulte PFJ, de Haan L. Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review. Drugs. 2017.
doi:10.1007/s40265-017-0789-y
9. Yang AC, Tsai SJ. New targets for schizophrenia treatment beyond the dopamine hypothesis. Int J Mol Sci. 2017;18(8).
doi:10.3390/ijms18081689
20. 10. Kumar A, Yadav M, Parle M, Dhingra S, Dhull DK. Potential drug targets and treatment of schizophrenia. Inflammopharmacology.
2017;25(3):277-292. doi:10.1007/s10787-017-0340-5
11. Chan V. Schizophrenia and Psychosis: Diagnosis, Current Research Trends, and Model Treatment Approaches with Implications for
Transitional Age Youth. Child Adolesc Psychiatr Clin N Am. 2017;26(2):341-366. doi:10.1016/j.chc.2016.12.014
12. Lally J, MacCabe JH. Antipsychotic medication in schizophrenia: A review. Br Med Bull. 2015. doi:10.1093/bmb/ldv017
13. Perspectives NEW, The IN, Insomnia MOF. Cns Spectrums Pectrums. CNS Spectr. 2018;12.
14. Loebel A, Citrome L. Lurasidone: A novel antipsychotic agent for the treatment of schizophrenia and bipolar depression. Psychiatrist.
2015. doi:10.1192/pb.bp.114.048793
15. Page CE, Coutellier L. Reducing inhibition: A promising new strategy for the treatment of schizophrenia. EBioMedicine. 2018.
doi:10.1016/j.ebiom.2018.07.043
16. Hashimoto K. Targeting of α7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia and the Use of Auditory Sensory
Gating as a Translational Biomarker. Curr Pharm Des. 2015. doi:10.2174/1381612821666150605111345
17. Neill JC, Grayson B, Kiss B, Gyertyán I, Ferguson P, Adham N. Effects of cariprazine, a novel antipsychotic, on cognitive deficit and
negative symptoms in a rodent model of schizophrenia symptomatology. Eur Neuropsychopharmacol. 2016.
doi:10.1016/j.euroneuro.2015.11.016
21. 18. Fleischhacker WW, Hobart M, Ouyang J, et al. Efficacy and safety of brexpiprazole (OPC-34712) as maintenance treatment in adults
with schizophrenia: A randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2017. doi:10.1093/ijnp/pyw076
19. Andrade C. Anti-inflammatory strategies in the treatment of schizophrenia. Expert Rev Clin Pharmacol. 2016.
doi:10.1586/17512433.2016.1095086
20. Zhang L, Zheng H, Wu R, et al. Minocycline adjunctive treatment to risperidone for negative symptoms in schizophrenia: Association
with pro-inflammatory cytokine levels. Prog Neuro-Psychopharmacology Biol Psychiatry. 2018. doi:10.1016/j.pnpbp.2018.04.004
21. Kindler J, Weickert CS, Schofield PR, Lenroot R, Weickert TW. Raloxifene increases prefrontal activity during emotional inhibition in
schizophrenia based on estrogen receptor genotype. Eur Neuropsychopharmacol. 2016. doi:10.1016/j.euroneuro.2016.10.009
22. Rapado-Castro M, Dodd S, Bush AI, et al. Cognitive effects of adjunctive N-acetyl cysteine in psychosis. Psychol Med. 2017.
doi:10.1017/S0033291716002932
23. Cunha AS, Matheus FC, Moretti M, et al. Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric
oxide and glutamate NMDA receptors. Behav Brain Res. 2016. doi:10.1016/j.bbr.2016.06.014
24. Iimori T, Nakajima S, Miyazaki T, et al. Effectiveness of the prefrontal repetitive transcranial magnetic stimulation on cognitive profiles
in depression, schizophrenia, and Alzheimer’s disease: A systematic review. Prog Neuro-Psychopharmacology Biol Psychiatry. 2019;88(April
2018):31-40. doi:10.1016/j.pnpbp.2018.06.014
25. Govindaraj R, Naik S, Manjunath N, Mehta U, Gangadhar B, Varambally S. Add-on yoga therapy for social cognition in schizophrenia: A
pilot study. Int J Yoga. 2018. doi:10.4103/ijoy.ijoy_45_17
26. https://www.youtube.com/watch?v=Pr8IyNGAqlw&t=4s
22. THANK YOU
“If you talk to God, you’re praying,
If God talks to you, you may have Schizophrenia”