SlideShare a Scribd company logo
Writing prescription is easy, understanding people is hard
Franz Kafka, (1883-1924)
 History
 Introduction
 Different hypothesis for schizophrenia
 Classification
 Mechanism of action
 Uses
 Adverse effects
 Recent advances
 1931 Sen and Bose – publish therapeutic effect of
reserpine in Hypertension and Insanity
 Hans Laborit – note the antipsychotic effect of
chlorpromazine, which was being tried as
preanesthetic medication
 1950 - Jean Delay and Piere Deniker conducted
trial
 1960-1970: identification of D2 blockade as the
key mechanism, development of these first-
generation of antipsychotic agents
 Janssen introduced Haloperidol & Pimozide
 Neuroleptics/ Major tranquillisers/ Dopamine
antagonist
 Psychoses and Neuroses
 Psychotic disorders – Schizophrenia, severe forms of
depression and mania
Positive symptoms: the presence of inappropriate
behaviors
Delusions
Hallucinations
Disorganized talking
Movements
Negative symptoms: the absence of appropriate behaviors
Flat affect
Anhedonia
Catatonia
 Excessive dopaminergic activity:
• Drugs which increase dopamine activity
• Postmortem – receptor density high in nucleus
accumbens, caudate, putamen
• Imaging studies – amphetamine – high
dopamine in striated areas
 Diminished dopaminergic activity
• Cortical/hippocampal – cognitive and negative
• Postmortem – cortical, limbic, nigral, striatal
 5HT2A and 5HT2C – hallucination
 5HT2A- depolarization of glutamate receptors
stabilization of NMDA
 5HT 2C- inhibition of cortical dopamine release
 5HT1C- anxiolytic effect, exert procognitive effects in
schizophrenia
 Hypofunctioning of NMDA receptors located on
GABAergic interneurons, leading to diminished
inhibitory influence on neuron function
 GABA ergic activity  induce disinhibiton of
downstream glutamate activity
hyperstimulation of cortical neuron through non
NMDA receptor
 NMDA requires glycine
 In schizophrenia, glycine site is not fully occupied
Antipsychotic
drugs
Classical
neuroleptics
Phenothiaz
ines
Thioxanthenes Butyrophenones
Miscellane
ous
Novel or
atypical
neuroleptics
Phenothiazines
With aliphatic
tertiary amine side
chain
Chlorpromazine
With piperadine
moiety in side chain
Thioridazine
With piperazine
moiety in side chain
Trifluperazine,
fluphenazine
Thioxathenes
Flupenthixol
Thiothixene
Butyrophenones
Haloperidol
Benperidol
Droperidol
Domperidone
Miscellaneous
Pimozide
Penfluridol
Molindone
Loxapine
Sulpiride
Remoxipride
Typical or first generation
antipsychotics (FGA)
Atypical antipsychotics or
second generation
antipsychotics (SGA)
D2 receptor blockade 5HT and Dopamine receptor
block
Less effective against negative
symptoms
More effective against
negative symptoms
Not effective in refractory
cases
Effective in refractory cases
More side effects (EPS) Less side effects profile
Clozapine
Olanzapine
Quetiapine
Zotepine
Risperidone
Ziprasidone
Paliperidone
Aripiprazole
Sertindole
Increased
dopamine
Rise in Number
of brain D2
receptors
Receptor
supersensitivity
Excess
availability of
dopamine due
to over
production
Reduced
destruction
through
enzyme
deficiency
SCHIZOPHRENIA
 Typical/ FGA – D2 antagonist
 Initially – increased synthesis of DA – later
decreases
 HVA and DOPAC level in blood & urine
 Molindone, loxapine, sulpiride and amisulpiride
 In between typical and atypical antipsychotics
 Most of the antipsychotics are given orally but
incompletely absorbed.
 Significant first-pass metabolism.
 Bioavailability is 25-65%.
 Most are highly lipid soluble.
 Most are highly protein bound (92-98%).
 High volumes of distribution (>20 L/Kg).
 Plasma half life
• Quetiapine – 7h
• Clozapine – 12h
• Fluphenazine- 20h (depot – 14.3days)
• Haloperidol – 24-48h (depot – 21days)
• Olanzapine – 33h
 Depot preparation – 2-4 weeks
 Measurable plasma concentration with I.M route
is seen within 15-30min
Most antipsychotics are almost completely
metabolized- phase 1 and subsequent phase 2
Exceptions are asenapine(phase 2),
ziprasidone(aldehyde oxidase system) and
paliperidone(oxidized metabolite)
Most metabolites- inactive.
Chlorpromazine – 160 metabolites, 70 have been
identified.
 Psychiatric indication:
• Schizophrenia – advantage V/s disadvantage
• First psychotic episode – start with atypical
• Olanzapine (10mg), risperidone (4mg), quetiapine (25mg)
• 2 weeks later increase the dose
• Previously treated with typical – continue
• Long acting depot preparations – haloperidol,
fluphenazine
• Rapid tranquillizers – lorazepam – 1-2mg i.v
• Haloperidol – 2-10mg i.m
Drug Dose Maximum
Chlorpromazine 25-100mg TDS 1g/day
Thioridazine 50-100mg TDS 800mg/day
Fluphenazine 1-3mg TDS 20mg/day
Trifluoperazine 2-5mg BD 40mg/day
Flupenthixol 3-9mg TDS 18mg/day
Zuclopenthixol 20-50 mg daily 200mg I.M depot
Haloperidol 0.5-5mg TDS 60mg /day
Penfluridol 20-60mg once a
week
250mg once a week
Pimozide 2-4mg /day 12mg/day
Loxapine 10-25mg BD 75mg/day
Drug Dose Maximum dose
Sulpiride 400-800mg
Amisulpride 200-400mg/day 1g/day
Levosulpride 200-300mg/day
Aripiprazole 10-15mg/day 30mg/day
Clozapine 12.5mg OD/BD 300mg/day
Olanzapine 5-10mg/day 20mg/day
Risperidone 1mg BD 3mg BD
Paliperidone 6mg/day 12mg/day
Ziprasidone 20mg BD 80mg BD
Quetiapine 25mg BD 300mg BD
• Drug induced psychoses –LSD , amphetamine
• Schizo-affective disorder – schizo part – antipsychotic,
affective part – anti depressant or lithium
 Neuro psychiatric indication
• Tourette’s syndrome – haloperidol or pimozide
• Huntington’s disease – haloperidol or chlorpromazine
 Non psychiatric indication:
• Antiemetic – D2 block at CTZ,GIT – prochlorperazine,
domperidone
• Preanaesthetic medication - promethazine
• Intractable hiccups – parenteral haloperidol, CPZ
 CNS side effects:
• Behavioral effects – sedation more with
phenothiazines, thioxanthenes, olanzapine
Less with butyrophenones, pimozide
• Tolerance and dependence – tolerance
develops to sedation and autonomic side
effects
Treatment: Promethazine,
Diphenhydramine
Treatment: non selective b-blocker like
Propranolol
Treatment: Trihexyphenidyl, Procyclidine
Treatment: withdraw neuroleptic drug
and add diazepam
*Parkinsonism
• Due to disturbance in
DA-Ach imbalance
• Treatment with
anticholinergic-
antiparkinsonian drugs
•Trihexyphenyidyl,
procyclidine
•DO NOT START WITH
LEVODOPA
*Neurolept malignant
syndrome
•Hyperpyrexia, muscle
rigidity, fluctuating BP,
increase CK, myoglobin
•Central mechanism
•Peripheral mechanism
•Stop neuroleptic
•Supportive care
•Dantrolene
•Diazepam, bromocriptine
 Autonomic (ANS) side effects:
• Alpha adrenergic blockade- Postural hypotension
• Antimuscarinic effects- dryness of mouth, constipation
etc. (except clozapine)
 Endocrinal side effects: chlorpromazine, thioxanthene
 Agranulocytosis - clozapine
 Photosensitivity – UV rays oxidizes phenothiazines –
accumulates in melanin containing tissues
 Retinal pigmentation, , corneal opacities- thioridazine
 Epileptogenic effects- clozapine, chlorpromazine
 Poikilothermic effects- impair the ability of hypothalamic
thermoregulation
Mechanism Therapeutic
effects
Adverse effects
α1 block -- Dizziness, orthostatic
hypotension, reflex
tachycardia.
D2 block +ve symptom ↓ EPS & ↑ Prolactin
D1 & D4
block
-ve symptom &
EPS ↓
--
H1 block Sedation Drowsiness & ↑ appetite
& weight
M block -- Dry mouth, etc.
5-HT2
block
-ve symptom &
EPS ↓
Anxiety & insomnia
 Thioridazine: ventricular arrythmias, cardiac
conduction block, sudden death
 Pimozide, ziprasidone: prolong QT, hypokalemia
 Quetiapine: cataract formation, priapism,
peripheral edema, hyperventilation
Drug Effects
Antacids Decrease absorption of antipsychotics
Anticholinergics Increased anticholinergic effect
Alcohol More sedation
Antithyroid drugs Agranulocytosis
Barbiturates Decreased effect but more sedation
Carbamazepines and phenytoin Decreased effect but lower threshold
Chloroquine May precipitate EPS
Lithium Enhancement of neurotoxicities
Levodopa Decrease efficacy
Oral contraceptives Hyperprolactinemia
Cigarette smoking Increased metabolism
 Aspirin
 Minocycline
 Raloxifene
 Estrogen
 N-acetyl cysteine
Raloxifene  Exhibit agonistic and protective
action on the brain by modulating the
monoaminergic neurotransmission of dopamine,
serotonin and GABA
Addition of Raloxifene (60 mg/day) to regular
antipsychotic treatment ↓ negative, positive &
general psychopathological symptoms in
comparison with women receiving antipsychotic
medication alone (Usall et al., 2011)
*Short term  Rapid membrane effects by altering
functional activity in the dopaminergic synapse (Di
Paolo, 1994)
*Long term  Modifies synthesis in dopamine receptors
(Di Paolo, 1994)
*Estrogen alters serotonergic system (Moses et al., 2000)
*Estrogen promotes neuronal regeneration & blocks
mechanisms of neuronal death (DonCarlos et al., 2009)
Glutathione is a major antioxidant that protects
cells against oxidative stress (Meister and
Anderson, 1983)
Glutathione potentiates NMDA receptors (Choi
and Lipton, 2000)
* Targeted gene therapy  Dysbindin, Neurogelin 1,
COMT, DISC1
* Enhancement of BDNF
* Targets  GSK 3, PKC , GABAA receptor
* PDE inhibitors (particularly at PDE1B)
*Cannabinoid receptor antagonist
*Currently glycine transport inhibitors are in trials
*Preliminary study with LY2140023 (agonist at
glutamate receptor) is also been tried
Thank you

More Related Content

What's hot

Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease
Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's DiseaseAnti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease
Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease
Kameshwaran Sugavanam
 
Antipsychotics agents
Antipsychotics agents Antipsychotics agents
Antipsychotics agents
Koppala RVS Chaitanya
 
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASEANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
Kameshwaran Sugavanam
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
Naser Tadvi
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
Dr. Pooja
 
Antiparkinsonian drugs - drdhriti
Antiparkinsonian drugs - drdhritiAntiparkinsonian drugs - drdhriti
Antiparkinsonian drugs - drdhriti
http://neigrihms.gov.in/
 
CNS stimulants - Parmacology
CNS stimulants - ParmacologyCNS stimulants - Parmacology
CNS stimulants - Parmacology
Areej Abu Hanieh
 
Sedatives & hypnotics
Sedatives & hypnoticsSedatives & hypnotics
Sedatives & hypnotics
Dr Resu Neha Reddy
 
Dopamine Receptors by Manisha
Dopamine Receptors by ManishaDopamine Receptors by Manisha
Dopamine Receptors by Manisha
Sachin kumar
 
CNS stimulants and cognition enhancers
CNS stimulants and cognition enhancersCNS stimulants and cognition enhancers
CNS stimulants and cognition enhancers
http://neigrihms.gov.in/
 
Anti depressant and its classifications
Anti depressant and its classificationsAnti depressant and its classifications
Anti depressant and its classifications
Natasha Puri
 
Antipsychotic agents
Antipsychotic agentsAntipsychotic agents
Antipsychotic agents
Steve Wilkins
 
Antipsychotics - Pharmacology
Antipsychotics - PharmacologyAntipsychotics - Pharmacology
Antipsychotics - Pharmacology
Areej Abu Hanieh
 
Antipsychotics - drdhriti
Antipsychotics - drdhritiAntipsychotics - drdhriti
Antipsychotics - drdhriti
http://neigrihms.gov.in/
 
Ssri n snri
Ssri n snriSsri n snri
Ssri n snri
Syed Shams
 
Antiepileptics (New) - drdhriti
Antiepileptics (New) - drdhritiAntiepileptics (New) - drdhriti
Antiepileptics (New) - drdhriti
http://neigrihms.gov.in/
 
Antiepileptics
AntiepilepticsAntiepileptics
Antiepileptics
http://neigrihms.gov.in/
 
Antidepressant drugs
Antidepressant drugsAntidepressant drugs
Antidepressant drugs
Amira Badr
 
Selective serotonin reuptake inhibitors 2016
Selective serotonin reuptake inhibitors 2016Selective serotonin reuptake inhibitors 2016
Selective serotonin reuptake inhibitors 2016
Mohamed Sedky
 
Antidepressants -pharmacology
Antidepressants -pharmacologyAntidepressants -pharmacology
Antidepressants -pharmacology
pavithra vinayak
 

What's hot (20)

Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease
Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's DiseaseAnti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease
Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease
 
Antipsychotics agents
Antipsychotics agents Antipsychotics agents
Antipsychotics agents
 
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASEANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
ANTI ALZHEIMER'S AGENTS / DRUGS USED IN THE TREATMENT OF ALZHEIMER'S DISEASE
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 
Antiparkinsonian drugs - drdhriti
Antiparkinsonian drugs - drdhritiAntiparkinsonian drugs - drdhriti
Antiparkinsonian drugs - drdhriti
 
CNS stimulants - Parmacology
CNS stimulants - ParmacologyCNS stimulants - Parmacology
CNS stimulants - Parmacology
 
Sedatives & hypnotics
Sedatives & hypnoticsSedatives & hypnotics
Sedatives & hypnotics
 
Dopamine Receptors by Manisha
Dopamine Receptors by ManishaDopamine Receptors by Manisha
Dopamine Receptors by Manisha
 
CNS stimulants and cognition enhancers
CNS stimulants and cognition enhancersCNS stimulants and cognition enhancers
CNS stimulants and cognition enhancers
 
Anti depressant and its classifications
Anti depressant and its classificationsAnti depressant and its classifications
Anti depressant and its classifications
 
Antipsychotic agents
Antipsychotic agentsAntipsychotic agents
Antipsychotic agents
 
Antipsychotics - Pharmacology
Antipsychotics - PharmacologyAntipsychotics - Pharmacology
Antipsychotics - Pharmacology
 
Antipsychotics - drdhriti
Antipsychotics - drdhritiAntipsychotics - drdhriti
Antipsychotics - drdhriti
 
Ssri n snri
Ssri n snriSsri n snri
Ssri n snri
 
Antiepileptics (New) - drdhriti
Antiepileptics (New) - drdhritiAntiepileptics (New) - drdhriti
Antiepileptics (New) - drdhriti
 
Antiepileptics
AntiepilepticsAntiepileptics
Antiepileptics
 
Antidepressant drugs
Antidepressant drugsAntidepressant drugs
Antidepressant drugs
 
Selective serotonin reuptake inhibitors 2016
Selective serotonin reuptake inhibitors 2016Selective serotonin reuptake inhibitors 2016
Selective serotonin reuptake inhibitors 2016
 
Antidepressants -pharmacology
Antidepressants -pharmacologyAntidepressants -pharmacology
Antidepressants -pharmacology
 

Viewers also liked

Antisychotic Drugs
Antisychotic DrugsAntisychotic Drugs
Antisychotic Drugs
Bhudev Global
 
Non neurological side effects of antipsychotic medications
Non neurological side effects of antipsychotic medicationsNon neurological side effects of antipsychotic medications
Non neurological side effects of antipsychotic medications
Kshamaa Girips
 
N:\ceutical2[1]
N:\ceutical2[1]N:\ceutical2[1]
N:\ceutical2[1]
guestd429cd9
 
Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...
Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...
Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...
Kevin Nasky
 
Haloperidol
HaloperidolHaloperidol
Haloperidol
Soldado Jhonn Peña
 
Conventional
ConventionalConventional
Conventional
Flavio Guzmán
 
Psychotropic Medications & Their Side Effects
Psychotropic Medications & Their Side EffectsPsychotropic Medications & Their Side Effects
Psychotropic Medications & Their Side Effects
Laura Kho Sui San, RPh, BCPP
 
Polypharmacy+in+Schizophrenia
Polypharmacy+in+SchizophreniaPolypharmacy+in+Schizophrenia
Polypharmacy+in+Schizophrenia
dhavalshah4424
 
chlorpromazine(Antipsychotic Drug)
chlorpromazine(Antipsychotic Drug)chlorpromazine(Antipsychotic Drug)
chlorpromazine(Antipsychotic Drug)
Syed Sunny
 
Antipsychotics, antipsychotic drugs, major tranquilizers, tranquilizers
Antipsychotics, antipsychotic drugs, major tranquilizers, tranquilizersAntipsychotics, antipsychotic drugs, major tranquilizers, tranquilizers
Antipsychotics, antipsychotic drugs, major tranquilizers, tranquilizers
Muthu Venkatachalam
 
Typical antipsychotics
Typical   antipsychoticsTypical   antipsychotics
Typical antipsychotics
Anant Rathi
 
Psychotherapeutics
PsychotherapeuticsPsychotherapeutics
Psychotherapeutics
Richard Asare
 
Test
TestTest
Pharmacological guidelines in the treatment of schizophrenia
Pharmacological guidelines in the treatment of schizophreniaPharmacological guidelines in the treatment of schizophrenia
Pharmacological guidelines in the treatment of schizophrenia
ehab elbaz
 
Antipsychotics long acting injections
Antipsychotics long acting injectionsAntipsychotics long acting injections
Antipsychotics long acting injections
vinodksahu
 
Quick Clinical Review of Antipsychotics
Quick Clinical Review of AntipsychoticsQuick Clinical Review of Antipsychotics
Quick Clinical Review of Antipsychotics
Shah Parind
 
Clozapine
ClozapineClozapine
Clozapine
Rami James
 
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparationsAntipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Rahul Kunkulol
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
raj kumar
 

Viewers also liked (19)

Antisychotic Drugs
Antisychotic DrugsAntisychotic Drugs
Antisychotic Drugs
 
Non neurological side effects of antipsychotic medications
Non neurological side effects of antipsychotic medicationsNon neurological side effects of antipsychotic medications
Non neurological side effects of antipsychotic medications
 
N:\ceutical2[1]
N:\ceutical2[1]N:\ceutical2[1]
N:\ceutical2[1]
 
Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...
Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...
Psychopharmacologic Advances of the 1950s, Part 2: Imipramine, iproniazid and...
 
Haloperidol
HaloperidolHaloperidol
Haloperidol
 
Conventional
ConventionalConventional
Conventional
 
Psychotropic Medications & Their Side Effects
Psychotropic Medications & Their Side EffectsPsychotropic Medications & Their Side Effects
Psychotropic Medications & Their Side Effects
 
Polypharmacy+in+Schizophrenia
Polypharmacy+in+SchizophreniaPolypharmacy+in+Schizophrenia
Polypharmacy+in+Schizophrenia
 
chlorpromazine(Antipsychotic Drug)
chlorpromazine(Antipsychotic Drug)chlorpromazine(Antipsychotic Drug)
chlorpromazine(Antipsychotic Drug)
 
Antipsychotics, antipsychotic drugs, major tranquilizers, tranquilizers
Antipsychotics, antipsychotic drugs, major tranquilizers, tranquilizersAntipsychotics, antipsychotic drugs, major tranquilizers, tranquilizers
Antipsychotics, antipsychotic drugs, major tranquilizers, tranquilizers
 
Typical antipsychotics
Typical   antipsychoticsTypical   antipsychotics
Typical antipsychotics
 
Psychotherapeutics
PsychotherapeuticsPsychotherapeutics
Psychotherapeutics
 
Test
TestTest
Test
 
Pharmacological guidelines in the treatment of schizophrenia
Pharmacological guidelines in the treatment of schizophreniaPharmacological guidelines in the treatment of schizophrenia
Pharmacological guidelines in the treatment of schizophrenia
 
Antipsychotics long acting injections
Antipsychotics long acting injectionsAntipsychotics long acting injections
Antipsychotics long acting injections
 
Quick Clinical Review of Antipsychotics
Quick Clinical Review of AntipsychoticsQuick Clinical Review of Antipsychotics
Quick Clinical Review of Antipsychotics
 
Clozapine
ClozapineClozapine
Clozapine
 
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparationsAntipsychotic : Dr Rahul Kunkulol's Power point preparations
Antipsychotic : Dr Rahul Kunkulol's Power point preparations
 
Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 

Similar to Antipsychotic drug

Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
Chetan Rastogi
 
Antiparkinsons
AntiparkinsonsAntiparkinsons
Antiparkinsons
MD Specialclass
 
Antiparkinsons
AntiparkinsonsAntiparkinsons
Antiparkinsons
MD Specialclass
 
Typical antipsychotic
Typical antipsychoticTypical antipsychotic
Typical antipsychotic
HAMAD DHUHAYR
 
Case study of schizophrenia
Case study of schizophreniaCase study of schizophrenia
Case study of schizophrenia
Dhanadharani Venkatesh
 
Parkisonism and anti parkinson's drugs
Parkisonism and anti parkinson's drugs Parkisonism and anti parkinson's drugs
Parkisonism and anti parkinson's drugs
Hajra Matloob (RPH)
 
Parkinson's Disease
Parkinson's DiseaseParkinson's Disease
Parkinson's Disease
Sandra saju
 
Obat psikosis
Obat psikosisObat psikosis
Obat psikosis
Fadhol Romdhoni
 
antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...
antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...
antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...
Vijay Salvekar
 
MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...
MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...
MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...
Govt Medical College & Hospital, Sector-32
 
Schizophrenia
SchizophreniaSchizophrenia
Schizophrenia
Dr. Irfan Ahmad Khan
 
An update on psychopharmacology
An update on psychopharmacology An update on psychopharmacology
An update on psychopharmacology
Pk Doctors
 
An update on psychopharmacology part i 22 june 2007 fountain house
An update on psychopharmacology part i 22 june 2007 fountain houseAn update on psychopharmacology part i 22 june 2007 fountain house
An update on psychopharmacology part i 22 june 2007 fountain house
Pk Doctors
 
Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...
Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...
Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...
Dr. Siddhartha Dutta
 
Anti parkinsons drugs
Anti parkinsons drugsAnti parkinsons drugs
Anti parkinsons drugs
Subhankar Debnath
 
Antipsychotic agents final PHARMACOLOGY.pdf
Antipsychotic agents final PHARMACOLOGY.pdfAntipsychotic agents final PHARMACOLOGY.pdf
Antipsychotic agents final PHARMACOLOGY.pdf
fafyfskhan251kmf
 
7) DRUG THERAPY FOR PARKINSONISM.ppt
7) DRUG THERAPY FOR PARKINSONISM.ppt7) DRUG THERAPY FOR PARKINSONISM.ppt
7) DRUG THERAPY FOR PARKINSONISM.ppt
VarshaPatel72
 
Classical versus atypical antipsychotics
Classical  versus  atypical antipsychoticsClassical  versus  atypical antipsychotics
Classical versus atypical antipsychotics
Akhil Joseph
 
Pharmacotherapy of antipsychotics
Pharmacotherapy of antipsychoticsPharmacotherapy of antipsychotics
Pharmacotherapy of antipsychotics
Novo Nordisk India
 
Treatment of psychosis
Treatment of psychosisTreatment of psychosis
Treatment of psychosis
Vijay Prasad Sangisetti
 

Similar to Antipsychotic drug (20)

Antipsychotics
AntipsychoticsAntipsychotics
Antipsychotics
 
Antiparkinsons
AntiparkinsonsAntiparkinsons
Antiparkinsons
 
Antiparkinsons
AntiparkinsonsAntiparkinsons
Antiparkinsons
 
Typical antipsychotic
Typical antipsychoticTypical antipsychotic
Typical antipsychotic
 
Case study of schizophrenia
Case study of schizophreniaCase study of schizophrenia
Case study of schizophrenia
 
Parkisonism and anti parkinson's drugs
Parkisonism and anti parkinson's drugs Parkisonism and anti parkinson's drugs
Parkisonism and anti parkinson's drugs
 
Parkinson's Disease
Parkinson's DiseaseParkinson's Disease
Parkinson's Disease
 
Obat psikosis
Obat psikosisObat psikosis
Obat psikosis
 
antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...
antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...
antiparkinson drug-Dopamine precursors,levodopa,cabidopa,bromocriptyne,rponir...
 
MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...
MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...
MANAGEMENT OF PARKINSONISM BY Dr.HARMANJIT SINGH, DEPARTMENT OF PHARMACOLOGY,...
 
Schizophrenia
SchizophreniaSchizophrenia
Schizophrenia
 
An update on psychopharmacology
An update on psychopharmacology An update on psychopharmacology
An update on psychopharmacology
 
An update on psychopharmacology part i 22 june 2007 fountain house
An update on psychopharmacology part i 22 june 2007 fountain houseAn update on psychopharmacology part i 22 june 2007 fountain house
An update on psychopharmacology part i 22 june 2007 fountain house
 
Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...
Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...
Dopamine, dopaminergic system, parkinson's disease, pharmacotherapy and modul...
 
Anti parkinsons drugs
Anti parkinsons drugsAnti parkinsons drugs
Anti parkinsons drugs
 
Antipsychotic agents final PHARMACOLOGY.pdf
Antipsychotic agents final PHARMACOLOGY.pdfAntipsychotic agents final PHARMACOLOGY.pdf
Antipsychotic agents final PHARMACOLOGY.pdf
 
7) DRUG THERAPY FOR PARKINSONISM.ppt
7) DRUG THERAPY FOR PARKINSONISM.ppt7) DRUG THERAPY FOR PARKINSONISM.ppt
7) DRUG THERAPY FOR PARKINSONISM.ppt
 
Classical versus atypical antipsychotics
Classical  versus  atypical antipsychoticsClassical  versus  atypical antipsychotics
Classical versus atypical antipsychotics
 
Pharmacotherapy of antipsychotics
Pharmacotherapy of antipsychoticsPharmacotherapy of antipsychotics
Pharmacotherapy of antipsychotics
 
Treatment of psychosis
Treatment of psychosisTreatment of psychosis
Treatment of psychosis
 

Recently uploaded

Hemodialysis: Chapter 5, Dialyzers Overview - Dr.Gawad
Hemodialysis: Chapter 5, Dialyzers Overview - Dr.GawadHemodialysis: Chapter 5, Dialyzers Overview - Dr.Gawad
Hemodialysis: Chapter 5, Dialyzers Overview - Dr.Gawad
NephroTube - Dr.Gawad
 
Ear and its clinical correlations By Dr. Rabia Inam Gandapore.pptx
Ear and its clinical correlations By Dr. Rabia Inam Gandapore.pptxEar and its clinical correlations By Dr. Rabia Inam Gandapore.pptx
Ear and its clinical correlations By Dr. Rabia Inam Gandapore.pptx
Dr. Rabia Inam Gandapore
 
Pharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and AntagonistPharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and Antagonist
Dr. Nikhilkumar Sakle
 
Abortion PG Seminar Power point presentation
Abortion PG Seminar Power point presentationAbortion PG Seminar Power point presentation
Abortion PG Seminar Power point presentation
AksshayaRajanbabu
 
K CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấu
K CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấuK CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấu
K CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấu
HongBiThi1
 
Top Travel Vaccinations in Manchester
Top Travel Vaccinations in ManchesterTop Travel Vaccinations in Manchester
Top Travel Vaccinations in Manchester
NX Healthcare
 
vonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentationvonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentation
Dr.pavithra Anandan
 
Travel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International TravelersTravel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International Travelers
NX Healthcare
 
DECLARATION OF HELSINKI - History and principles
DECLARATION OF HELSINKI - History and principlesDECLARATION OF HELSINKI - History and principles
DECLARATION OF HELSINKI - History and principles
anaghabharat01
 
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptx
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptxMuscles of Mastication by Dr. Rabia Inam Gandapore.pptx
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptx
Dr. Rabia Inam Gandapore
 
CHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdf
CHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdfCHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdf
CHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdf
rishi2789
 
Cervical Disc Arthroplasty ORSI 2024.pptx
Cervical Disc Arthroplasty ORSI 2024.pptxCervical Disc Arthroplasty ORSI 2024.pptx
Cervical Disc Arthroplasty ORSI 2024.pptx
LEFLOT Jean-Louis
 
Tests for analysis of different pharmaceutical.pptx
Tests for analysis of different pharmaceutical.pptxTests for analysis of different pharmaceutical.pptx
Tests for analysis of different pharmaceutical.pptx
taiba qazi
 
The Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of RespirationThe Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of Respiration
MedicoseAcademics
 
June 2024 Oncology Cartoons By Dr Kanhu Charan Patro
June 2024 Oncology Cartoons By Dr Kanhu Charan PatroJune 2024 Oncology Cartoons By Dr Kanhu Charan Patro
June 2024 Oncology Cartoons By Dr Kanhu Charan Patro
Kanhu Charan
 
Complementary feeding in infant IAP PROTOCOLS
Complementary feeding in infant IAP PROTOCOLSComplementary feeding in infant IAP PROTOCOLS
Complementary feeding in infant IAP PROTOCOLS
chiranthgowda16
 
CLEAR ALIGNER THERAPY IN ORTHODONTICS .pptx
CLEAR ALIGNER THERAPY IN ORTHODONTICS .pptxCLEAR ALIGNER THERAPY IN ORTHODONTICS .pptx
CLEAR ALIGNER THERAPY IN ORTHODONTICS .pptx
Government Dental College & Hospital Srinagar
 
10 Benefits an EPCR Software should Bring to EMS Organizations
10 Benefits an EPCR Software should Bring to EMS Organizations   10 Benefits an EPCR Software should Bring to EMS Organizations
10 Benefits an EPCR Software should Bring to EMS Organizations
Traumasoft LLC
 
CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1
CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1
CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1
rishi2789
 
Chapter 11 Nutrition and Chronic Diseases.pptx
Chapter 11 Nutrition and Chronic Diseases.pptxChapter 11 Nutrition and Chronic Diseases.pptx
Chapter 11 Nutrition and Chronic Diseases.pptx
Earlene McNair
 

Recently uploaded (20)

Hemodialysis: Chapter 5, Dialyzers Overview - Dr.Gawad
Hemodialysis: Chapter 5, Dialyzers Overview - Dr.GawadHemodialysis: Chapter 5, Dialyzers Overview - Dr.Gawad
Hemodialysis: Chapter 5, Dialyzers Overview - Dr.Gawad
 
Ear and its clinical correlations By Dr. Rabia Inam Gandapore.pptx
Ear and its clinical correlations By Dr. Rabia Inam Gandapore.pptxEar and its clinical correlations By Dr. Rabia Inam Gandapore.pptx
Ear and its clinical correlations By Dr. Rabia Inam Gandapore.pptx
 
Pharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and AntagonistPharmacology of 5-hydroxytryptamine and Antagonist
Pharmacology of 5-hydroxytryptamine and Antagonist
 
Abortion PG Seminar Power point presentation
Abortion PG Seminar Power point presentationAbortion PG Seminar Power point presentation
Abortion PG Seminar Power point presentation
 
K CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấu
K CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấuK CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấu
K CỔ TỬ CUNG.pdf tự ghi chép, chữ hơi xấu
 
Top Travel Vaccinations in Manchester
Top Travel Vaccinations in ManchesterTop Travel Vaccinations in Manchester
Top Travel Vaccinations in Manchester
 
vonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentationvonoprazan A novel drug for GERD presentation
vonoprazan A novel drug for GERD presentation
 
Travel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International TravelersTravel Clinic Cardiff: Health Advice for International Travelers
Travel Clinic Cardiff: Health Advice for International Travelers
 
DECLARATION OF HELSINKI - History and principles
DECLARATION OF HELSINKI - History and principlesDECLARATION OF HELSINKI - History and principles
DECLARATION OF HELSINKI - History and principles
 
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptx
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptxMuscles of Mastication by Dr. Rabia Inam Gandapore.pptx
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptx
 
CHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdf
CHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdfCHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdf
CHEMOTHERAPY_RDP_CHAPTER 6_Anti Malarial Drugs.pdf
 
Cervical Disc Arthroplasty ORSI 2024.pptx
Cervical Disc Arthroplasty ORSI 2024.pptxCervical Disc Arthroplasty ORSI 2024.pptx
Cervical Disc Arthroplasty ORSI 2024.pptx
 
Tests for analysis of different pharmaceutical.pptx
Tests for analysis of different pharmaceutical.pptxTests for analysis of different pharmaceutical.pptx
Tests for analysis of different pharmaceutical.pptx
 
The Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of RespirationThe Nervous and Chemical Regulation of Respiration
The Nervous and Chemical Regulation of Respiration
 
June 2024 Oncology Cartoons By Dr Kanhu Charan Patro
June 2024 Oncology Cartoons By Dr Kanhu Charan PatroJune 2024 Oncology Cartoons By Dr Kanhu Charan Patro
June 2024 Oncology Cartoons By Dr Kanhu Charan Patro
 
Complementary feeding in infant IAP PROTOCOLS
Complementary feeding in infant IAP PROTOCOLSComplementary feeding in infant IAP PROTOCOLS
Complementary feeding in infant IAP PROTOCOLS
 
CLEAR ALIGNER THERAPY IN ORTHODONTICS .pptx
CLEAR ALIGNER THERAPY IN ORTHODONTICS .pptxCLEAR ALIGNER THERAPY IN ORTHODONTICS .pptx
CLEAR ALIGNER THERAPY IN ORTHODONTICS .pptx
 
10 Benefits an EPCR Software should Bring to EMS Organizations
10 Benefits an EPCR Software should Bring to EMS Organizations   10 Benefits an EPCR Software should Bring to EMS Organizations
10 Benefits an EPCR Software should Bring to EMS Organizations
 
CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1
CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1
CHEMOTHERAPY_RDP_CHAPTER 2 _LEPROSY.pdf1
 
Chapter 11 Nutrition and Chronic Diseases.pptx
Chapter 11 Nutrition and Chronic Diseases.pptxChapter 11 Nutrition and Chronic Diseases.pptx
Chapter 11 Nutrition and Chronic Diseases.pptx
 

Antipsychotic drug

  • 1. Writing prescription is easy, understanding people is hard Franz Kafka, (1883-1924)
  • 2.  History  Introduction  Different hypothesis for schizophrenia  Classification  Mechanism of action  Uses  Adverse effects  Recent advances
  • 3.  1931 Sen and Bose – publish therapeutic effect of reserpine in Hypertension and Insanity  Hans Laborit – note the antipsychotic effect of chlorpromazine, which was being tried as preanesthetic medication  1950 - Jean Delay and Piere Deniker conducted trial  1960-1970: identification of D2 blockade as the key mechanism, development of these first- generation of antipsychotic agents  Janssen introduced Haloperidol & Pimozide
  • 4.  Neuroleptics/ Major tranquillisers/ Dopamine antagonist  Psychoses and Neuroses  Psychotic disorders – Schizophrenia, severe forms of depression and mania
  • 5.
  • 6. Positive symptoms: the presence of inappropriate behaviors Delusions Hallucinations Disorganized talking Movements Negative symptoms: the absence of appropriate behaviors Flat affect Anhedonia Catatonia
  • 7.  Excessive dopaminergic activity: • Drugs which increase dopamine activity • Postmortem – receptor density high in nucleus accumbens, caudate, putamen • Imaging studies – amphetamine – high dopamine in striated areas  Diminished dopaminergic activity • Cortical/hippocampal – cognitive and negative • Postmortem – cortical, limbic, nigral, striatal
  • 8.  5HT2A and 5HT2C – hallucination  5HT2A- depolarization of glutamate receptors stabilization of NMDA  5HT 2C- inhibition of cortical dopamine release  5HT1C- anxiolytic effect, exert procognitive effects in schizophrenia
  • 9.  Hypofunctioning of NMDA receptors located on GABAergic interneurons, leading to diminished inhibitory influence on neuron function  GABA ergic activity  induce disinhibiton of downstream glutamate activity hyperstimulation of cortical neuron through non NMDA receptor  NMDA requires glycine  In schizophrenia, glycine site is not fully occupied
  • 11. Phenothiazines With aliphatic tertiary amine side chain Chlorpromazine With piperadine moiety in side chain Thioridazine With piperazine moiety in side chain Trifluperazine, fluphenazine
  • 13. Typical or first generation antipsychotics (FGA) Atypical antipsychotics or second generation antipsychotics (SGA) D2 receptor blockade 5HT and Dopamine receptor block Less effective against negative symptoms More effective against negative symptoms Not effective in refractory cases Effective in refractory cases More side effects (EPS) Less side effects profile Clozapine Olanzapine Quetiapine Zotepine Risperidone Ziprasidone Paliperidone Aripiprazole Sertindole
  • 14. Increased dopamine Rise in Number of brain D2 receptors Receptor supersensitivity Excess availability of dopamine due to over production Reduced destruction through enzyme deficiency SCHIZOPHRENIA
  • 15.  Typical/ FGA – D2 antagonist  Initially – increased synthesis of DA – later decreases  HVA and DOPAC level in blood & urine  Molindone, loxapine, sulpiride and amisulpiride  In between typical and atypical antipsychotics
  • 16.
  • 17.  Most of the antipsychotics are given orally but incompletely absorbed.  Significant first-pass metabolism.  Bioavailability is 25-65%.  Most are highly lipid soluble.  Most are highly protein bound (92-98%).  High volumes of distribution (>20 L/Kg).
  • 18.  Plasma half life • Quetiapine – 7h • Clozapine – 12h • Fluphenazine- 20h (depot – 14.3days) • Haloperidol – 24-48h (depot – 21days) • Olanzapine – 33h  Depot preparation – 2-4 weeks  Measurable plasma concentration with I.M route is seen within 15-30min
  • 19. Most antipsychotics are almost completely metabolized- phase 1 and subsequent phase 2 Exceptions are asenapine(phase 2), ziprasidone(aldehyde oxidase system) and paliperidone(oxidized metabolite) Most metabolites- inactive. Chlorpromazine – 160 metabolites, 70 have been identified.
  • 20.  Psychiatric indication: • Schizophrenia – advantage V/s disadvantage • First psychotic episode – start with atypical • Olanzapine (10mg), risperidone (4mg), quetiapine (25mg) • 2 weeks later increase the dose • Previously treated with typical – continue • Long acting depot preparations – haloperidol, fluphenazine • Rapid tranquillizers – lorazepam – 1-2mg i.v • Haloperidol – 2-10mg i.m Drug Dose Maximum Chlorpromazine 25-100mg TDS 1g/day Thioridazine 50-100mg TDS 800mg/day Fluphenazine 1-3mg TDS 20mg/day Trifluoperazine 2-5mg BD 40mg/day Flupenthixol 3-9mg TDS 18mg/day Zuclopenthixol 20-50 mg daily 200mg I.M depot Haloperidol 0.5-5mg TDS 60mg /day Penfluridol 20-60mg once a week 250mg once a week Pimozide 2-4mg /day 12mg/day Loxapine 10-25mg BD 75mg/day Drug Dose Maximum dose Sulpiride 400-800mg Amisulpride 200-400mg/day 1g/day Levosulpride 200-300mg/day Aripiprazole 10-15mg/day 30mg/day Clozapine 12.5mg OD/BD 300mg/day Olanzapine 5-10mg/day 20mg/day Risperidone 1mg BD 3mg BD Paliperidone 6mg/day 12mg/day Ziprasidone 20mg BD 80mg BD Quetiapine 25mg BD 300mg BD
  • 21. • Drug induced psychoses –LSD , amphetamine • Schizo-affective disorder – schizo part – antipsychotic, affective part – anti depressant or lithium  Neuro psychiatric indication • Tourette’s syndrome – haloperidol or pimozide • Huntington’s disease – haloperidol or chlorpromazine  Non psychiatric indication: • Antiemetic – D2 block at CTZ,GIT – prochlorperazine, domperidone • Preanaesthetic medication - promethazine • Intractable hiccups – parenteral haloperidol, CPZ
  • 22.  CNS side effects: • Behavioral effects – sedation more with phenothiazines, thioxanthenes, olanzapine Less with butyrophenones, pimozide • Tolerance and dependence – tolerance develops to sedation and autonomic side effects
  • 23. Treatment: Promethazine, Diphenhydramine Treatment: non selective b-blocker like Propranolol Treatment: Trihexyphenidyl, Procyclidine Treatment: withdraw neuroleptic drug and add diazepam
  • 24. *Parkinsonism • Due to disturbance in DA-Ach imbalance • Treatment with anticholinergic- antiparkinsonian drugs •Trihexyphenyidyl, procyclidine •DO NOT START WITH LEVODOPA *Neurolept malignant syndrome •Hyperpyrexia, muscle rigidity, fluctuating BP, increase CK, myoglobin •Central mechanism •Peripheral mechanism •Stop neuroleptic •Supportive care •Dantrolene •Diazepam, bromocriptine
  • 25.  Autonomic (ANS) side effects: • Alpha adrenergic blockade- Postural hypotension • Antimuscarinic effects- dryness of mouth, constipation etc. (except clozapine)  Endocrinal side effects: chlorpromazine, thioxanthene  Agranulocytosis - clozapine  Photosensitivity – UV rays oxidizes phenothiazines – accumulates in melanin containing tissues  Retinal pigmentation, , corneal opacities- thioridazine  Epileptogenic effects- clozapine, chlorpromazine  Poikilothermic effects- impair the ability of hypothalamic thermoregulation
  • 26. Mechanism Therapeutic effects Adverse effects α1 block -- Dizziness, orthostatic hypotension, reflex tachycardia. D2 block +ve symptom ↓ EPS & ↑ Prolactin D1 & D4 block -ve symptom & EPS ↓ -- H1 block Sedation Drowsiness & ↑ appetite & weight M block -- Dry mouth, etc. 5-HT2 block -ve symptom & EPS ↓ Anxiety & insomnia
  • 27.  Thioridazine: ventricular arrythmias, cardiac conduction block, sudden death  Pimozide, ziprasidone: prolong QT, hypokalemia  Quetiapine: cataract formation, priapism, peripheral edema, hyperventilation
  • 28. Drug Effects Antacids Decrease absorption of antipsychotics Anticholinergics Increased anticholinergic effect Alcohol More sedation Antithyroid drugs Agranulocytosis Barbiturates Decreased effect but more sedation Carbamazepines and phenytoin Decreased effect but lower threshold Chloroquine May precipitate EPS Lithium Enhancement of neurotoxicities Levodopa Decrease efficacy Oral contraceptives Hyperprolactinemia Cigarette smoking Increased metabolism
  • 29.  Aspirin  Minocycline  Raloxifene  Estrogen  N-acetyl cysteine
  • 30.
  • 31. Raloxifene  Exhibit agonistic and protective action on the brain by modulating the monoaminergic neurotransmission of dopamine, serotonin and GABA Addition of Raloxifene (60 mg/day) to regular antipsychotic treatment ↓ negative, positive & general psychopathological symptoms in comparison with women receiving antipsychotic medication alone (Usall et al., 2011)
  • 32. *Short term  Rapid membrane effects by altering functional activity in the dopaminergic synapse (Di Paolo, 1994) *Long term  Modifies synthesis in dopamine receptors (Di Paolo, 1994) *Estrogen alters serotonergic system (Moses et al., 2000) *Estrogen promotes neuronal regeneration & blocks mechanisms of neuronal death (DonCarlos et al., 2009)
  • 33. Glutathione is a major antioxidant that protects cells against oxidative stress (Meister and Anderson, 1983) Glutathione potentiates NMDA receptors (Choi and Lipton, 2000)
  • 34. * Targeted gene therapy  Dysbindin, Neurogelin 1, COMT, DISC1 * Enhancement of BDNF * Targets  GSK 3, PKC , GABAA receptor * PDE inhibitors (particularly at PDE1B) *Cannabinoid receptor antagonist *Currently glycine transport inhibitors are in trials *Preliminary study with LY2140023 (agonist at glutamate receptor) is also been tried