3. Schizophrenia
Schizophrenia is a mental disorder
characterized by abnormal social behavior and
failure to understand what is real.
Common symptoms include false beliefs,
unclear or confused thinking, hearing voices
that others do not, reduced social
engagement and emotional expression and a
lack of motivation.
4.
5. Pathogenesis of schizophrenia is unknown
Dopamine Hypothesis of schizophrenia:
Excessive dopaminergic activity plays a role in the
schizophrenic disorder developments
This hypothesis is supported by following evidences
1. Many antipsychotic drugs strongly block postsynaptic
D2 receptors in CNS
2. Drugs that increase dopaminergic activity, such as
levodopa, amphetamines and apomorphine either
aggravate schizophrenia or produce psychosis
6. 3. Dopamine receptor density have been found
to be increased in postmortem reports in the
brains of schizophrenic patients
4. Positron emission tomography (PET) has
shown increased dopamine receptor density
in both treated and untreated schizophrenic
patients as compared to non schizophrenic
patients
7. Dopamine hypothesis is far from complete
If an abnormality of dopamine physiology
were completely responsible for the
pathogenesis of schizophrenia, antipsychotic
drugs would do a much better job of treating
patients
However, they are only partially effective for
the most of the patients and ineffective for
some patients
10. D2 receptorD2 receptor
Typical
-
Atypical
-
5-HT2A receptor
Atypical
-
Typical is D2 antagonist Atypical is serotonin-dopamine antagonist
high affinity to D2 high affinity to 5-HT2ALow affinity to D2
Binding to D2 receptor
(tight)
Binding to D2 receptor
(loose)
Atypical dissociate rapidly from D2 receptor
11. • first-generation ('typical') antipsychotics (e.g.
chlorpromazine, haloperidol, fluphenazine and
thioridazine)
• second-generation ('atypical') antipsychotics (e.g.
clozapine, risperidone, quetiapine, aripiprazole etc.).
• Distinction between typical and atypical groups is not
clearly defined but following difference is significant
• Incidence of extrapyramidal side effects (less in atypical
group)
12. Typical antipsychotic drugs
They have an equal or greater affinity for D2
receptors than for 5-HT2 receptors
Antagonism of D2 receptors in mesolimbic
pathways suppress the positive symptoms of
Schizophrenia
Blockade of D2 receptors in the basal ganglia
is responsible for parkinsonian and other
extrapyramidal side effects of anti psychotic
drugs
13. Phenothiazines
• Chlorpromazine, Fluphenazine, Thioridazine
• Similar therapeutic effects
• Different potency and side effect
• Chlorpromazine And Thioridazine lower
potency, more autonomic side effects and
fewer extrapyramidal side effects than high
potency drugs
• Fluphenazine has Higher potency
14. Phenothiazines
Blockade of D2 receptors
Positive symptoms of Schizophrenia Decrease
in 1-3 weeks
Less agitated, fewer auditory hallucinations
It causes Behavioural improvement
15. Indication of Phenothiazine
• Schizophrenia
• Drug-induced psychosis
• Psychosis associated with the manic phase of
bipolar disorder.
• Dementia
• Severe mental retardation
• Some of them for management of nausea and
vomiting
16. Butyrophenones (Haloperidone)
• Haloperidol has
pharmacological effects
similar to fluphenazine.
• It is available in a long
acting depot.
• It is used for treatment
of schizophrenia and
Tourette’s syndrome .
Tourette’s syndrome is a
neurological disorder
characterized by
repetitive, stereotyped,
involuntary movements
and vocalizations called
tics
17. Atypical antipsychotic drugs
These includes;
Clozapine
Olanzapine
Ziprasidone
Risperidone
quetiapine
They have a greater affinity for 5-HT2
receptors than for D2 receptors
18. Olanzapine
Olanzapine is superior to haloperidol in
alleviating of negative symptoms.
Fewer extrapyramidal side effects
At high doses may cause akathisia,
pseudoparkinsonism, and dystonias.
19. Risperidone
• Its pharmacological effects are similar to
olanzapine.
• But less sedation more orthostatic
hypotension, higher incidence of
extrapyramidal side effects.
20. Clozapine
Clozapine has fewer extrapyramidal side effect
and greater activity against negative
symptoms and its use is with 1.3% first year
incidence of potentially fatal agranulocytosis.
21. Other Actions of Antipsychotic drugs
Antiemetic effects:
With the exceptions of aripiprazole and
thioridazine most of neuroleptics have
antiemetic effects mediated by blocking of D2
receptors of chemoreceptor trigger zone of
medulla.
Antimuscarinic effects:
Some of neuroleptics such as thioridazine,
chlorpromaine, cloapine and olanapine produces
anticholinergic effects
22. Other Effects of Neuroleptics
Alpha-1 adrenergic blocking effects causing
orthostatic hypotension
They also alter temperature regulation
mechanism
Elevation of prolactin level
Atypical neuroleptics less likely cause
elevation of prolactin level
They also have H1 blocking effects thus
causing sedation
23. Therapeutic Uses of Neuroleptics
Treatment of schizophrenia
Prevention of nausea and vomiting
They can be used as tranquilizers to manage
agitation secondary to other disorders
24. Adverse side effects of anti-psychotics
Common side effects are;
Tremors
Postural hypotension
Constipation
Urinary retention
Confusion
Sexual dysfunctions
25. Adverse effects
1- Extrapyramidal side effects
-Acute:
Akathisia (Motor restlessness)
Pseudoparkinsonism
Dystonias (Sustained contraction
of muscles leading to twisting
distorted postures)
-Chronic:
Tardive dyskinesia (Involuntary
movements of lips, neck, trunk,
tongue and libs)
Tardive dyskinesia
26. Dystonias Akathisia
• Akathisia is a movement
disorder characterized by a
feeling of inner restlessness
and a compelling need to be
in constant motion, as well
as by actions such as
rocking while standing or
sitting, lifting the feet as if
marching on the spot, and
crossing and uncrossing the
legs while sitting.