DRUG TREATMENT OF
PSYCHOSIS
Psychiatric illness
Psychosis Neurosis
OCD
Phobia
Anxiety
PTSD
Schizophrenia
Mania Depression Bipolar
Psychosis: Pt is not...
Psychosis
• Psychosis is a thought disorder
characterized by :
• Disturbances of reality and perception
• Impaired cogniti...
• Earlier: termed as major tranquilizers
• USA: Antipsychotics
• Europe: Neuroleptics (both antipsyo + EPS)
Schizophrenia
• Pathogenesis is unknown.
• Onset of schizophrenia is in the late teens
early twenties.
• Genetic predispos...
Schizophrenia
• It is a thought disorder.
• The disorder is characterized by a divorcement from
reality in the mind of the...
• Negative
– Poor socialization
– Emotional blunting
– Introvert behaviour
– Lack of motivation
– Congnitive deficits (lac...
Psychosis Producing Drugs
1) Levodopa
2) CNS stimulants
a) Cocaine
b) Amphetamines
c) Khat, cathinone, methcathinone
3) Ap...
Role of DA in psychosis
• Positron emission tomographic (PES) DA receptor density
• Postmortem  DA density
• Inc DA by L...
Central Dopaminergic pathway
• Ultra short Periglomular cells in olfactory bulb
• Intermediate  Ventral hypothalamus  r...
Parkinson’s  dec. DA in
basal ganglia
Scizopherenia  Over activity
of DA in Mesolimbic
Mesocortical Mesofrontal
There ar...
• 5HT2 agonist visual hallucinations and
sensory disturbance , which are similar to
psychosis
• 5HT has a modulator role...
Glutamate
• Glutamate exerts excitatory, while DA exerts inhibitory role
over GABA ergic striatal neurons which projects t...
Dopamine Synapse
DA
L-DOPA
Tyrosine
Tyrosine
Antipsychotic treatments
 In 1940’s Phenothiazenes were isolated and were
used as pre-anesthetic medication, but quickly
...
Antipsychotic/Neuroleptics
Three major groups :
1. Phenothiazines
2. Thioxanthine
3. Butyrophenones
OLDER DRUGS
Antipsychotic/Neuroleptics
1) Phenothiazines
Chlorpromazine Thioridazine Fluphenazine
Trifluopromazine Piperacetazine Perf...
Antipsychotic/Neuroleptics
2) Thioxanthines
Thiothixene
Chlorprothixene
Closely related to phenothiazines
Antipsychotic/Neuroleptics
3) Butyrophenones
Haloperidol
Droperidol*
*Not marketed
Atypical Antipsychotic
Pimozide
Atypical Antipsychoitcs
Loxapine
Clozapine
Olanzapine
Quetiapine
Indolones
Sertindole
Zipr...
Classification of antipsychotic drugs:
Atypical Antipsychotic Drugs:
Clozapine,
Olanzapine,
Risperidone,
Ziprasidone
Typic...
Antipsychotics/Neuroleptics
• The affinities of
most older
“classical” “Typical”
agents for the D2
receptors correlate
wit...
Typical
• 1st generation
• Agitation, Acute mania
• More extrapyramidal
symptom
• Less efficacy
• addicitive
• Difficulty ...
Antipsychotics/Neuroleptics
Presynaptic Effects
Blockade of D2 receptors

Compensatory Effects
 Firing rate and activity...
Antipsychotic/Neuroleptics
Chlorpromazine: 1 = 5-HT2 = D2 > D1 > M > 2
Haloperidol: D2 > D1 = D4 > 1 > 5-HT2 >H1>M = 2...
Thioridazine
• Least incidence of EPS
• Low D2 blocking preset central anticholinergic
activity
– Interferes male sexual b...
Trifluperazine, fluphenazine, Haloperidol
• High potency drugs and have least α blocking,
anticholinergic , sedative, Caus...
A typical antipsychotics
• Unique receptor profile
• Effective against the negative as well as
positive schizophrenia
• Le...
• 5HT2, and D4 high affinity
• Besides α1, M1, H1, D2
• No singal receptor action best predict
Clozapine 5-HT2 >H1=M1= 1 ...
Clozapine:
• weak D2 blocking action
• 5HT2, α, D4
• Positive and negative schizophrenia
• Dyskinesia rare
• Reserve drug,...
Risperidone: 5HT2, α, D2
• EPS at high dose , less precipitation of seizures
Olanzapine: 5HT2, α, D2, M more action
• Anti...
PK
• Oral BV vary largely
• IM inj 10 fold inc BV
• IM Oil depot longer acting
• Highly lipophilic
• Highly protein bindin...
Non psychotics Uses
• Antiemetics:D2 block in CTZ
• Preanaesthetic (Promethazine) Anti H, Anti
Choli, Antiemetic
• Hunting...
Antipsychotic/Neuroleptics
Clinical Problems with antipsychotic drugs
include:
1) Failure to control negative effect
2) Si...
Neurological effects
• Acute dystonia- Spasms of muscles of tongue, neck
and face (ACh)IM anticholinergic
• Akasthisia – ...
Tardive Dyskinesia (TD)
• Repetitive involuntary movements, lips, jaw,
and tongue
• Choreiform quick movements of the extr...
ADR/Anticholinergic
 Some antipsychotics have effects at
muscarinic acetylcholine receptors:
• Dry mouth
• Blurred vision...
ADR/CVS
 Some antipsychotics have effects at -
adrenergic receptors:
Chlorpromazine
Thioridazine
Postural hypotension, P...
ADR/CNS
 Drowsiness, Lethargy, confusion (typical)
 Other side effects are increased appetite
 Sedation (RAS)
 Weight ...
ADR/ Endocrinal
 Blockade of D2 receptors in lactotrophs in
breast increase prolactin concentration
 Galactorrhea in fem...
ADR/ Metabolic
 Elevation of blood sugar (insulin resistance)
 Triglyceride levels
 Low potency drug high risk
Antipsychotics/Neuroleptics
• Antipsychotics produce catalepsy (reduce motor activity).
– BLOCKADE OF DOPAMINE RECPTORS IN...
• Postural hypotension (α blocking)
• Weight again ( except haloperidol)
• Retinal damage ( Thioridazine)
• Agranulocytosi...
THANK Q
Etiology of Schizophrenia
Idiopathic
Biological Correlates
1) Genetic Factors
2) Neurodevelopmental abnormalities.
3) Envi...
Treatment of psychosis
Treatment of psychosis
Treatment of psychosis
Upcoming SlideShare
Loading in...5
×

Treatment of psychosis

324

Published on

TREATMENT OF PSYCHOSIS

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
324
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
3
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Treatment of psychosis

  1. 1. DRUG TREATMENT OF PSYCHOSIS
  2. 2. Psychiatric illness Psychosis Neurosis OCD Phobia Anxiety PTSD Schizophrenia Mania Depression Bipolar Psychosis: Pt is not aware of illness and refers to treatment Neurosis: Less serious and insight present (Obsessive compulsive disorder, Post traumatic stress disorder)
  3. 3. Psychosis • Psychosis is a thought disorder characterized by : • Disturbances of reality and perception • Impaired cognitive functioning • Inappropriate or diminished affect (mood) • Psychosis denotes many mental disorders.  Schizophrenia is a type of functional psychosis in which severe personality changes and thought disorders
  4. 4. • Earlier: termed as major tranquilizers • USA: Antipsychotics • Europe: Neuroleptics (both antipsyo + EPS)
  5. 5. Schizophrenia • Pathogenesis is unknown. • Onset of schizophrenia is in the late teens early twenties. • Genetic predisposition -- Familial incidence. • Multiple genes are involved. • Afflicts 1% of the population worldwide. • May or may not be present with anatomical changes.
  6. 6. Schizophrenia • It is a thought disorder. • The disorder is characterized by a divorcement from reality in the mind of the person (psychosis). • Symptoms positive or negative. • Positive: – visual and auditory hallucinations – Delusions – Thought disorders – Irrational conclusions – Control by external forces (paranoia),
  7. 7. • Negative – Poor socialization – Emotional blunting – Introvert behaviour – Lack of motivation – Congnitive deficits (lack of attention and loss of memory)
  8. 8. Psychosis Producing Drugs 1) Levodopa 2) CNS stimulants a) Cocaine b) Amphetamines c) Khat, cathinone, methcathinone 3) Apomorphine 4) Phencyclidine
  9. 9. Role of DA in psychosis • Positron emission tomographic (PES) DA receptor density • Postmortem  DA density • Inc DA by L Dopa , Amphetamine, Apomorphin  precipitate the symptoms • Most antipsychotic drugs blocking D2 in CNS  Mesolimbic, frontal • Inc Homovalinic acid (HVA) • Drug should absolutely  rather then partially, ineffective
  10. 10. Central Dopaminergic pathway • Ultra short Periglomular cells in olfactory bulb • Intermediate  Ventral hypothalamus  role in prolactin release, Hypothalamic-hypophyseal functions • Long : most IMP. Cover SN, Ventral Tegmental areas to Limbic system, amygdala, Caudate, Putamen
  11. 11. Parkinson’s  dec. DA in basal ganglia Scizopherenia  Over activity of DA in Mesolimbic Mesocortical Mesofrontal There are four major pathways for the dopaminergic system in the brain: I. The Nigro-Stiatal Pathway: Voluntary movements II. The Mesolimbic Pathway.: Behaviour III. The Mesocortical Pathway: Behaviour IV. The Tuberoinfundibular Pathway: Prolactin release
  12. 12. • 5HT2 agonist visual hallucinations and sensory disturbance , which are similar to psychosis • 5HT has a modulator role on DA pathway • After has fall off because • 5HT Visual • Schizo  Auditory predominate
  13. 13. Glutamate • Glutamate exerts excitatory, while DA exerts inhibitory role over GABA ergic striatal neurons which projects to thalamus and serves as sensory gate. • Inc Glu, or Dec DA disturbed the Gate t allow uninhibited sensory inputs to cortex. • Hallucination and thought disorders.
  14. 14. Dopamine Synapse DA L-DOPA Tyrosine Tyrosine
  15. 15. Antipsychotic treatments  In 1940’s Phenothiazenes were isolated and were used as pre-anesthetic medication, but quickly were adopted by psychiatrists to calm down their mental patients.  In 1955, chlorpromazine was developed as an antihistaminic agent by Rhone-Pauline Laboratories in France.  In-patients at Mental Hospitals dropped by 1/3.
  16. 16. Antipsychotic/Neuroleptics Three major groups : 1. Phenothiazines 2. Thioxanthine 3. Butyrophenones OLDER DRUGS
  17. 17. Antipsychotic/Neuroleptics 1) Phenothiazines Chlorpromazine Thioridazine Fluphenazine Trifluopromazine Piperacetazine Perfenazine Mesoridazine Acetophenazine Carphenazine Prochlorperazine Trifluoperazine • Aliphatic Piperidine Piperazine* * Most likely to cause extrapyramidal effects.
  18. 18. Antipsychotic/Neuroleptics 2) Thioxanthines Thiothixene Chlorprothixene Closely related to phenothiazines
  19. 19. Antipsychotic/Neuroleptics 3) Butyrophenones Haloperidol Droperidol* *Not marketed
  20. 20. Atypical Antipsychotic Pimozide Atypical Antipsychoitcs Loxapine Clozapine Olanzapine Quetiapine Indolones Sertindole Ziprasidone Olindone Molindone Risperidone
  21. 21. Classification of antipsychotic drugs: Atypical Antipsychotic Drugs: Clozapine, Olanzapine, Risperidone, Ziprasidone Typical Antipsychotic Drugs: Phenothiazines: Chlorpromazine, Thioridazine , Trifluperazine, Fluphenazine. Butyrophenones: Haloperidol Benperidol. Thioxanthenes: Thiothixene Others: Pimozide Loxapine
  22. 22. Antipsychotics/Neuroleptics • The affinities of most older “classical” “Typical” agents for the D2 receptors correlate with their clinical potencies as antipsychotics Dopamine Synapse DA L-DOPA Tyrosine Tyrosine dopamine receptor antagonist D2
  23. 23. Typical • 1st generation • Agitation, Acute mania • More extrapyramidal symptom • Less efficacy • addicitive • Difficulty to discontinue • Slow excret Atypical • 2nd generation • Depression, bipolar, mania • Less extrapyramidal symptom • Efficacy is more • Less addicitive • Easier discontinue • Fast excret (relapse)
  24. 24. Antipsychotics/Neuroleptics Presynaptic Effects Blockade of D2 receptors  Compensatory Effects  Firing rate and activity of nigrostriatal and mesolimbic DA neurons.  DA synthesis, DA metabolism, DA release. Postsynaptic Effects Depolarization Blockade Inactivation of nigrostriatal and mesolimbic DA neurons.  Receptor Supersensitivity The acute effects of antipsychotics do not explain why their therapeutic effects are not evident until 4-8 weeks of treatment.
  25. 25. Antipsychotic/Neuroleptics Chlorpromazine: 1 = 5-HT2 = D2 > D1 > M > 2 Haloperidol: D2 > D1 = D4 > 1 > 5-HT2 >H1>M = 2 Clozapine: D4 = 1 > 5-HT2 = M > D2 = D1 = 2 ; H1 Quetiapine: 5-HT2 = D2 = 1 = 2 ; H1 Risperidone: 5-HT2 >> 1 > H1 > D2 > 2 >> D1 Sertindole: 5-HT2 > D2 = 1
  26. 26. Thioridazine • Least incidence of EPS • Low D2 blocking preset central anticholinergic activity – Interferes male sexual by inhibiting ejaculation – It can cause cardical arry. (Prolong QT interval) – Retinal damage limits long term admnistration
  27. 27. Trifluperazine, fluphenazine, Haloperidol • High potency drugs and have least α blocking, anticholinergic , sedative, Cause jaundice, • Penfluridol: long acting anti psychotic • Pimozidine : Selective D2, long duration, inc QT
  28. 28. A typical antipsychotics • Unique receptor profile • Effective against the negative as well as positive schizophrenia • Lesser liability for inducing Extra pyramidal • Effectiveness in patient refractoru to typical neuroleptics
  29. 29. • 5HT2, and D4 high affinity • Besides α1, M1, H1, D2 • No singal receptor action best predict Clozapine 5-HT2 >H1=M1= 1 =D4>D2=D1 olanzapine 5-HT2 >H1=M1=D4> 1 =D2=D1 Risperidone 5-HT2 > 1 = D2>D4>H1>D1 Quetiapine 1 =H1>D2=5-HT2 =M1>D1
  30. 30. Clozapine: • weak D2 blocking action • 5HT2, α, D4 • Positive and negative schizophrenia • Dyskinesia rare • Reserve drug,(Risk of precipitation of seizures and agranulocytosis) • Risk of EPS • Risks of intestinal dysfunction, weight gain, uncontrol BP, hyperlipidemia,
  31. 31. Risperidone: 5HT2, α, D2 • EPS at high dose , less precipitation of seizures Olanzapine: 5HT2, α, D2, M more action • Anti cholinergic side effects • Can cause seizures, weight gain, • Mania, bipolar disorder Ziprasidone: Inc QT, arrhythmias Quetiapine : Cataract formation , short half life Aripiprazole: partial agonist 5HT1a, D2, antagonist at 5HT2a/. DA, 5HT stabilizer
  32. 32. PK • Oral BV vary largely • IM inj 10 fold inc BV • IM Oil depot longer acting • Highly lipophilic • Highly protein binding • Metab cyto p-450
  33. 33. Non psychotics Uses • Antiemetics:D2 block in CTZ • Preanaesthetic (Promethazine) Anti H, Anti Choli, Antiemetic • Huntington’s disease (Haloperidol)
  34. 34. Antipsychotic/Neuroleptics Clinical Problems with antipsychotic drugs include: 1) Failure to control negative effect 2) Significant toxicity a) Neurological effects b) Autonomic effects c) Endocrine effects d) Cardiac effects 3) Poor Concentration
  35. 35. Neurological effects • Acute dystonia- Spasms of muscles of tongue, neck and face (ACh)IM anticholinergic • Akasthisia – Uncontrolled motor restlessness • Parkinsonism • Neuroleptic Mallignant Syndrome dantrolene, Diazepam • Rabbit syndrome (perioral tremors)Anti choliner • Tardive dyskinesia Piperazines Butyrophenones
  36. 36. Tardive Dyskinesia (TD) • Repetitive involuntary movements, lips, jaw, and tongue • Choreiform quick movements of the extremities • As with Parkinson’s, movements stop during sleep • May get worse when medications discontinued, No effective treatment
  37. 37. ADR/Anticholinergic  Some antipsychotics have effects at muscarinic acetylcholine receptors: • Dry mouth • Blurred vision • Urinary retention • Constipation Clozapine Chlorpromazine Thioridazine
  38. 38. ADR/CVS  Some antipsychotics have effects at - adrenergic receptors: Chlorpromazine Thioridazine Postural hypotension, Palpitation, Inhibition of ejaculations, Q-T prolongation ( Tiori) Excess cardiovascular mortality Phenothiazine
  39. 39. ADR/CNS  Drowsiness, Lethargy, confusion (typical)  Other side effects are increased appetite  Sedation (RAS)  Weight gain  Aggravation of seizures
  40. 40. ADR/ Endocrinal  Blockade of D2 receptors in lactotrophs in breast increase prolactin concentration  Galactorrhea in females  Males Gynaeocmastia  Dec FSH, LH  amenorrhoea Riseridone
  41. 41. ADR/ Metabolic  Elevation of blood sugar (insulin resistance)  Triglyceride levels  Low potency drug high risk
  42. 42. Antipsychotics/Neuroleptics • Antipsychotics produce catalepsy (reduce motor activity). – BLOCKADE OF DOPAMINE RECPTORS IN BASAL GANGLIA. • Antipsychotics reverse hyperkinetic behaviors (increased locomotion and stereotyped behaviour). – BLOCKADE OF DOPAMINE RECPTORS IN LIMBIC AREAS. • Antipsychotics prevent the dopamine inhibition of prolactin release from pituitary. – BLOCKADE OF DOPAMINE RECEPTORS IN PITUITARY.  hyperprolactinemia
  43. 43. • Postural hypotension (α blocking) • Weight again ( except haloperidol) • Retinal damage ( Thioridazine) • Agranulocytosis ( Clozapine) • Cataract formation ( Quetiapine) • Cholestatic jaundice ( Chlorpormazine) • Dryness mouth, blurred vision(max thioridazine )
  44. 44. THANK Q
  45. 45. Etiology of Schizophrenia Idiopathic Biological Correlates 1) Genetic Factors 2) Neurodevelopmental abnormalities. 3) Environmental stressors.
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×