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Schizophrenia
• Pathogenesis is unknown.
• Onset of schizophrenia is in the late teens -early ‘20s.
• Genetic predisposition -- Familial incidence.
• Multiple genes are involved.
• Afflicts 1% of the population worldwide.
• Athought disorder
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Schizophrenia
Positive Symptoms.Hallucinations, delusions, paranoia, ideas of reference.
Negative Symptoms. Apathy, social withdrawal, anhedonia, emotional blunting,
cognitive deficits, lack of motivation to interact with the environment.
These symptoms are progressive and non-responsive to medication.
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Schizophrenia
• Drugs currently used in the prevention of psychosis.
** These drugs are not a cure **
• Schizophrenics must be treated with medications indefinitely, in as much as the disease in lifelong and it is preferable to prevent the psychotic episodes than to treat them.
SCHIZOPHRENIA IS FOR LIFE
There is no remission
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Dopamine Theory of Schizophrenia
Many lines of evidence point to the aberrant increased activity of the dopaminergic system as being critical in the symptomatology of schizophrenia.
There is a greater occupancy of D2 receptors by dopamine => greater dopaminergic stimulation
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Classification of Antipsychotic drugs
• Main categories are:
– Typical antipsychotics
Phenothiazines (chlorpromazine, perphenazine,
fluphenazine, thioridazine et al)
Thioxanthenes (flupenthixol, clopenthixol)
Butyrophenones (haloperidol, droperidol)
– Atypical antipsychotics (e.g. clozapine, risperidone, sulpiride, olanzapine)
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Classification of Antipsychotic drugs
• Distinction between ‘typical’ and ‘atypical’ groups is not clearly defined, but rests on:
– Incidence of extrapyramidal side-effects (less in ‘atypical’ group)
– Efficacy in treatment-resistant group of patients
– Efficacy against negative symptoms.
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First Generation Antipsychotic Drugs
CompoundSeda-
tion
Hypo-
tension
Motor
(EP)
Effects
Phenothiazines
Chlorpromazine
Fluphenazine
Haloperidol
+++ ++ ++
+ + ++++
+ + ++++
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Second Generation Antipsychotic Drugs
Compound Sedation Hypo-
tension
Motor
effects
++ ++++/++Dose
dependent
Clozapine
Clozaril
++ ++ -
Risperidone
0/+ 0/+ 0/+Aripiprazole
Abilify
Risperdal
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Pharmacological effects of antipsychotic drugs: blockade of
DA action
Area What
dopamine
does
What
antipsychotic
drug does
Drug profile
Basal ganglia Control of
movement
Extrapyramidal
(motor) side
effects: DA
deficiency
Less with 2nd gen. None
with clozapine or quetiapine.
Limbic and
frontal cortex
Affective
behavior;
cognition
Site of
antipsychotic
action
Most equally efficacious,
ex. Clozapine &
olanzapine
Hypothalamus
& endocrine
Temp.
regulation;
prolactin
prolactin
1st Generation and
risperidone
Chemoreceptor
trigger zone
Nausea,
emesis
Reduce nausea,
emesis
1st Generation and
risperidone
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Tolerance and dependence to
antipsychotic drugs
• Not addicting
• Relapse in psychosis if discontinued
abruptly
• Tolerance develops to sedative effects
• No tolerance to prolactin secretion
• No tolerance to antipsychotic effect
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Withdrawal-like syndrome
1. Symptoms: nausea, vomiting, insomnia, and headache
2. Symptoms may persist for up to 2 weeks.
3. Symptoms can be minimized with a tapered reduction
of drug dosage.
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Clozapine and
olanzapine
• VERY low EPS
• Blocks D1, D2, D4, -
adrenergic, 5HT2, muscarinic,
and histamine H1 receptors
• May show greater efficacy
against negative symptoms than
other antipsychotic drugs
• Agranulocytosis is a potentially
fatal side effect for clozapine
Both drugs have high efficacy, but cause significant weight gain
and diabetes
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Aripiprazole
• Partial agonist at D2 receptor
• Intrinsic activity depends on synaptic levels of DA
• Affinity for muscarinic, α1-adrenergic, serotonin and histamine receptors
• Good oral absorption, 3-5 hr to peak plasma concentration, long elimination half life
• Few extrapyramidal side effects
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Tardive dyskinesia
comprises mainly involuntary movements of
face and tongue, but also of trunk and
limbs, appearing after months or years of
antipsychotic treatment due to accumulation
of the drug.
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Risperidone
Endocrine effect One of the most prescribed drugs in Jordan.
In women, these disturbances include:
galactorrhea
loss of libido
delayed ovulation and menstruation or amenorrhea.
In men, these disturbances include:
gynecomastia
impotence.