Antipsychotic Agents and Their

Use in Schizophrenia
Objectives:
At the end of the chapter, the student is expected to:
1. Characterize schizophrenia
2. Describe the various antipsychotic drugs
3. Determine the role of anti-psychotic drugs
to schizophrenia
 Schizophrenia
• Is a chronic psychotic state characterized by
disordered thinking and an inability to accurately
comprehend reality.
• A mental disorder caused by some inherent
dysfunction of brain
• A particular kind of psychosis characterized mainly by
a clear sensorium but a marked thinking disturbance.
A. Positive symptoms are an exaggeration or
distortion of normal function and includes:
1. Hallucinations and delusions
2. Agitation
3. Tension
4. Paranoia( grandiosity)
B. Negative symptoms represent a loss of
normal function and include:
1. Lack of motivation
2. Poverty of speech
3. Blunted affect
4. Poor self care
5. Social withdrawal
C. Current antipsychotics are more effective at
relieving the positive symptoms of
schizophrenia
D. Acute episodes are characterized by fixed false beliefs,
hallucinations and delusion (often religious, grandiose or
persecusatory in nature).
1. Auditory hallucinations are more common than visual ones.
2. Patient often feels controlled by outside influences
3. Rational conversation is often impossible
4. Hostility and lack of cooperation
5.Disheveled and dirty appearance
6. Impaired/altered sleep and eating patterns.

E. Exact etiology is unknown but may have a biologic basis as

well as genetic, developmental and neuroanatomic
involvement.
Antipsychotic Drugs
Antipsychotic drugs (Narcoleptic drugs)
• Major tranquilizer
• Used primarily to treat schizophrenia, but they are also
effective in other psychotic state.
Mode of Action
1. Dopamine Receptor-blocking activity in the brain
- All of the older and most of the newer neuroleptic
drugs block dopamine receptors in the brain and the
periphery
2. Serotonin Receptor-blocking activity in the brain
- Most of the newer atypical agent appears to exert
part of their unique action through inhibition of
serotonin receptor (5-HT), particularly 5-HT2A receptors
Neuroleptic drugs block at dopaminergic and serotonergic receptors as well
as at adrenergic, cholinergic and histamine- binding receptor
Dopamine- blocking actions of neuroleptic drugs
Action
1. Antipsychotic action
2. Extrapyramidal effects
3. Antiemetic effects
4. Antimuscarinic effects
5. Others: orthostatic hypotension and light
headedness
Therapeutic uses
1.Schizophrenia
2. Bipolar disorder
3. Tourette’s syndrome
4. Antiemetic
5. Dementia, delusional disorder, Huntington’s
chorea
Conventional Antipsychotic Agents
Classification by Potency
1. Low
2. Medium
3. High potency
Only concerns how much of a particular drug must be
given to achieve a desired effect (i.e. Haldol is high
potency while Thorazine is low potency but both are
quite effective)
 Adverse effects

1. Extrapyramidal symptomes (EPS)

2. Anticholinergic effects
3. Sedation
4. Neuroendocrine effects
- Amenorrhea, Galactorrhea (female)
- Impotence, Gynecomastia (male)
5. Seizures
6. Sexual dysfunction
7. Tardive diskinesia
Drug interactions are possible
including:
1. Anticholinergic drugs
2. CNS depressants.
3. Levodopa.
NEUROLEPTIC DRUGS
TYPICAL NEUROLEPTIC
(Low Potency)
Chlorpromazine
Prochlorperazine
Thioridazine
TYPICAL NEUROLEPTIC
(High Potency)
Haloperidol
Fluphenazine
Pimozide
Thiothixene

ATYPICAL NEUROLEPTIC
Aripiprazole Quetiapine
Clozapine Paliperidone
Olanzapine Risperidone
Ziprasidone
Low potency agents
1. Chlorpromazine (Thorazine)
- Prototype
- Therapeutic uses include schizophrenia and other psychotic
disorder
- It is the first neuroleptic drug used to treat schizoprenia
 IM, PO or Suppository
 well absorbed but undergoes extensive first pass effect
 Oral bioavailability is only 30 %
- Adverse effects
Most common are orthostatic hypotension, sedation and
anticholinergic side effects and can also lower the seizure
threshold.
2. Prochlorperazine
3. Thioridazine
High potency agent
1. Haloperidol (Haldol)
-prototype
a. High potency agent are more likely to cause EPS and
TD but less sedation, orthostatic hypotension and
anticholinergic effects.
b. Principal indications are schizophrenia and acute
psychosis
c. Can be given PO or IM
2. Fluphenazine
3. Pimozide
4. Thiothixene
Depot preparations
1. Long acting injectable drugs used for
maintenance therapy in schizophrenia and
psychosis
2. Most commonly used depot drugs are
haloperidol and fluphenazine (Prolixin)
Atypical Antipsychotic agents
Drugs in this class include
1. Clozapine ( Clozaril)
a. indicated for use in patients who have not
responded well to the conventional agents or those
who cannot tolerate the EPS
b. major adverse effect is agranulocytosis despite
close monitoring which is the main limiting factor
regarding its use
Other commonly used atypical antipsychotics
include:
2. Resperidone ( Resperdal)
3. Olanzapine (Zyprexa)
4. Quetiapine ( Seroquel)
5. Aripiprazole
6. Paliperidone
7. Ziprasidone
 Drug Class Drug Advantages Disadvantages
Phenothiazines
Aliphatic Chlorpromazine Generic Many adverse effects
Piperidine (Thorazine) Slight extrapyramidal 800 mg/d limit: no
Thioridazine (Mellaril) syndrome parenteral form;
cardotoxicity
Piperazine Fluphenazine ( Permitil, Depot form also Increase tardive
Prolixin) available ( enanthate, dyskinesia
decanoate)
Thioxanthene Thiothixene (Navane) Parenteral form also Uncertain
available;(?) tardive
dyskinesia.
Butyrophenone Haloperidol (Haldol) Parenteral form also Severe extrapyramidal
available syndrome
Dibenzoxazepine Loxapine (Loxitane) (?) No weight gain Uncertain

Dihydroindoline Molindone (Moban) (?) No weight gain Uncertain

Dibenzodiazepine Clozapine (Clozaril) May benefit treatment may cause

–resistant patient; little agrannulocytosis in up
extrapyramidal to 3% of patient
syndrome
References:
Cagayan, M.S. & Jimeno, C.A. (2009).
Pharmacology for Beginners. 1st ed.
Educational Publishing House. Manila. pp.215-
220

Katzung,B.G. (1992). Basic and Clinical

Pharmacology. 6th ed., Paramount Publishing
Business and Professional Group. Philadelphia
pp. 432-451