ANTIPSYCHOTIC

DRUGS

PRESENTATION BY- SUMAIYA

SADAF
 ANTIPSYCHOTICS

Psychotropic drugs are those having

primary effects on Psyche (mental
processes) and are used for treatment
Of Psychiatric disorders.

One of the primary psychotic disorders in

which the Antipsychotics works is the,
Psychosis
 Psychosis:

These are severe psychiatric

Illness with serious distortion
of thought, behavior, capacity
to recognize reality and of
perception (delusions and
hallucinations).

Psychosis can be broadly

Categorized in to four groups:
1. Acute and chronic organic brain syndromes (cognitive disorders)
such as, Delirium and dementia, prominent features of confusion,
disorientation, defective memory and disorganized behavior.

2. Functional disorders such as, memory and orientation mostly

retained by emotion, thought, reasoning and behavior are altered.

3. Schizophrenia (split mind) i.e. splitting of perception and

interpretation from reality- hallucination, inability to think coherently.
Schizophrenia is often described in terms of positive or negetive
(deficit) symptoms..

4. Paranoid state i.e. fixed delusions (false beliefs) and loss of insight in
to abnormality.
Antipsychotic drugs are also
known as Neuroleptics, Ataractic,
Major Tranquilizer and Anti-
Schizophrenic drugs. A first
generation of antipsychotics,
known as Typical antipsychotics,
was discovered in the 1950s. Most
of the drugs in the second
generation, known as Atypical antipsychotics,
have been developed more recently.
 Classification:

A. Typical Antipsychotics:
1.Phenothiazines:
a. Aliphatic side chain: Chlorpromazine, Triflupromazine
b. Piperidine side chain: Thioridazine
c. Piperazine side chain: Trifluoperazine, Fluphenazine
 
2.Butyrophenones: Haloperidol, Trifluperidol, Penfluridol
 
3.Thioxanthenes: Flupenthixol
 
  4. Other heterocyclics: Pimozide, Loxapine
 
B. Atypical neuroleptics: Clozapine, Risperidone,
Olanzapine, Quetiapine, Aripiprazole, Ziprasidone.
 Mechanism of Action:

-Antipsychotic blocks D₂
receptors in the brain's
Dopaminergic pathway.

-Some also block or partially

block serotonin receptors
(particularly 5HT2A, C and
5HT1A receptors)
 
-But antipsychotic drugs can also
block wide range of receptor
targets.
Dopaminergic pathway in Brain:

Mesolimbic- mesocortical:
Control behavior, cognitive
funtion regulated by D₂
Receptor.
Nigrostriatal: Control
Voluntary Movement
regulated by D₁ and D₂
receptor.
Tuberoinfundibular:
Control prolactin secretion
Regulated by D₂ receptor.
 In the Mesolimbic- Mesocortical and
Nigrostriatal pathway Antipsychotic blocks:
In the Tuberoinfundibular pathway
Antipsychotics block:

Dopamine released
at this site regulates
the secretion
of prolactin
from anterior
the pituitary gland.
Antipsychotics
blocks D₂ receptor
at this site.
 Some also block or partially block 
Antipsychotic blocks D₂ receptors serotonin receptors
 Pharmacology of Antipsychotics:
Typical Antipsychotics
Phenothiazine Absorption Concentration Metabolism Vd Dose

Chlorpromazine More Highly bound to Metabolized in Large Acute single

(CPZ) consistent plasma and liver by 20 dose lasts 6-8
effect in IV tissue protein CYP2D6 L/kg hours t⅟₂ is
and IM enzyme 18-30 hrs
administration
Triflupromazine More potent -- -- --
than CPZ

Thioridazine Low potency -- -- --

with
anticholinergic
action
Trifluoperazine, High potency -- -- -- Depot IM inj
Fluphenazine with every 2-4
Autonomic weeks (25
action mg/ml )
Butyrophenones Potency t⅟₂ Dose

Haloperidol Potent antipsychotic 24 hours. --

Produces few
autonomic effects

Trifluperidol Similar to -- --
Haloperidol but
slightly more potent

Penfluridol Exceptional long -- 20-60 mg , once

acting neuroleptic, weekly
used for chronic
Schizophrenia,
affective withdrawl
and social mal-
adjustment
Thioxanthenes

Flupenthixol Less sedative than CPZ, indicated for

Schizophrenia and other Psychoses.

Other t⅟₂
heterocyclics

Pimozide Specific DA antagonist with little 48-60 hrs. (after

adrenergic or cholinergic blocking single dose)
activity. Used in Gilles de la Tourett’s
syndrome and ticks.
Long Duration of action.
 Atypical Antisychotic drugs

These are newer 2nd

Generation antipsychotics
that have weak D₂ receptor
blocking but potent 5-HT₂
antagonistic activity. They
May improve the impaired
Cognitive function in
psychotics.
Atypical Blocking activity Metabolism t⅟₂ and
(Enzyme) Dose

Clozapine A very potent D₂, D₄, 5HT₂, α receptors By CYP3A4 t⅟₂ - 12

antipsychotic hours

Risperidone -- Combination of D₂+5HT₂ , -- Dose - Low

High affinity for α₁, α₂ and dose <6
H₁ receptors mg/day

Olanzapine Potent antipsychotic Monoaminergic (D₂, 5HT₂, By CYP1A2 and t⅟₂ -

Broader spectrum of α₁, α₂) as well as muscarinic Glucuronyl 24-30 hours
efficacy and H₁ receptors transferase

Quetiapine New short- acting 5HT₁А, 5HT₂, D₂, α₁, α₂ and By CYP3A4 --
antipsychotic H₁ receptor

Aripiprazole Unique antipsychotic 5HT₂ By CYP2D6 and t⅟₂ - 3days

which is partial agonist CYP3A4
at D₂ and 5HT₁А

Ziprasidone Latest antipsychotic , Combination D₂+5HT₂A/₂C -- t⅟₂ - 8 hours

moderately potent +H₁ + α₁,
inhibitor. Na reuptake
 Adverse effects:

• On CNS: - Drowsiness
- lethargy
- mental confusion
- seizure.
• CVS: - Postural hypotension
- palpitation
- arrythmia in elderly
• Anticholinergic: - Dry mouth
- blurring of vision
- constipation
- urinary inconsistency
• Endocrine: - Hyperprolactinemia
- amenorrhoea
- infertility
- gelactorrhoea and gynaecomastia.
• Extrapyramidal disorders: - Parkinsonism
- Acute muscular dystonias
- Akathisia
- Malignant Neuroleptic Syndrome
- Tardive dyskinesia
• Miscellaneous: - Weight gain
- Blood sugar – lipid rise
- worsening of diabetes.