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Transcript
Major Psychiatric Disorders

Psychoses eg schizophrenia

Affective disorders eg depression and
mania
Psychoses

False perceptions (Hallucinations)

False beliefs (Delusions)
Affective Disorders

Emotional disturbances:
Mood is very low (Depression)
Mood is very high (Mania)
Schizophrenia


Most common form of psychosis (1% of world
population)
Most typical features are :
-Delusions
-Hallucinations
-Disorganised thinking
-Emotional abnormalities
Types of Schizophrenia



Paranoid
Disorganised
Catatonic forms
Symptoms


Positive symptoms: agitation, delusions,
insomnia, disorganised speech, hallucinations
disorganised thinking
Result from excessive neuronal activity in
mesolimbic neuronal pathways
Negative symptoms: apathy, lack of
motivation,lack of pleasure, social isolation,
poverty of speech
Result from insufficient activity in mesocortical
neuronal pathways
Aetiology and pathogenesis





Children of two schizophrenic parents have
about 40% risk of disease
So heredity appears to have a major role
Dopamine hypothesis or= phamacocentric
hypothesis
Hypofrontality hypothesis
Linked hypothesis
Antipsychotic Drugs

Mechanisms of action
-competitive blockade of dopamine receptors
and serotonin receptors
-adverse effect result from blockade of different
receptors
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 SCh
Blockade of D2 receptors in the basal ganglia is
responsible for parkinsonian and other
extrapyramidal side effects of anti psychotic drugs
Atypical antipsychotic drugs


eg clozapine have a greater affinity for 5-HT2
receptors than for D2 receptors
Some atypical drugs have increased affinity for
D3 or D4 receptors
Three time-dependent changes in
dopamine neuroteransmission


Compensatory response (increase in
dopamine synthesis and release) to acute
blockade of postsynaptic dopamine receptors
Continued dopamine receptor blockade
Inactivation of dopaminergic neurons
reduced dopamine release from mesolimbic
and nigrostriatal neurons, So, alleviate
positive symptoms of schizophrenia and
cause extrapyramidal side effects.
Continued
Dopamine reduction causes dopamine upregulation and super sensitivity to dopamine
agonists and then delayed extrapyramidal side
effect called tardive dyskinesia.
 In mesocortical and nigrostriatal pathways, 5HT2 receptors mediate presynaptic inhibition of
dopamine release.
Blockade of 5-HT2 receptors by atypical drugs
increase dopamine release in these pathways.
Continued
In mesocortical pathway, this action alleviate
negative symptoms of Sch.
In nigrostriatal pathway, increased dopamine
release counteracts the extrapyramidal side
effects caused by D2 receptor blockade.
Drug Classification


Typical antipsychotic drugs
-Phenothiazines
-Thioxanthenes
-Butyrophenones
- some Azepines (eg loxapine)
Atypical antipsychotic drugs
-other Azepines (clozapine, olanzapine)
-Benzisoxasole (risperidone)
Phenothiazines





Chlorpromazine, Fluphenazine, Thioridazine,
Trifluoperazine
Similar therapeutic effects
Different potency and side effect
Chlo. And Thio. lower potency, more
autonomic side effects and fewer
extrapyramidal side effects than high potency
Flu. Higher potency
Mechanisms of therapeutic effects




Blockade of D2 receptors
Positive symptoms of Sch. Decrease in 1-3
weeks
Less agitated, fewer auditory hallucinations,
disappear of paranoid delusions
Behavioural improvement
Adverse effects
1- Extrapyramidal side effects
-Acute: 1- Akathisia
2- Pseudoparkinsonism
3- Dystonias
-Chronic: Tardive dyskinesia
continued
2- neuroleptic malignant syndrome
3-increase serum prolactin levels
4-impair thermoregulation cause poikilothermy
Treatment of adverse side effects
Acute extrapyramidal side effects
 Decrease dose
 Change to atypical drug
 Counteract with benztropine, diphenhydramine,
amantadine
Chronic extrapyramidal side effects
 Decrease dose
 Drug treatment
Continued
Neuroleptic malignant syndrome
 Supportive care
 Discontinuing of drug
 Administration of bromocryptine
 Change to atypical
Indication of Phenothiazines






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
Chlorpromazine and thioridazine



Thioridazine causes greater antichloinergic
activity
And so fewer extrapyramidal side effect
High doses of thioridazine cause pigmentary
retinopathy and cardiac arrythmia
Fluphenazine and trifluoperazine


In compare with thioridazine, cause fewer
autonomic side effect and more extrapyramidal
side effects
Fluphenazine is available in long-term depot
preparation
Thioxanthenes



Thiothixene has pharmacological effects
similar to trifluoperazine
It is used for schizophrenia
(Other thiothixenes in BNF are flupentixol
[depixol] zuclopentixol [clopixol].
Butyrophenones



Haloperidol has pharmacological effects similar
to fluphenazine.
It is available in a long-acting depot.
It is used for schizophrenia and Tourette’s
syndrome (corprolalia and echolalia).
Azepines




Loxapine (typical), clozapine, olanzapine
(atypical)
Loxapine properties are similar to phenothiazines
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.
Other atypical drugs are amisulpride, quetiapine,
risperidone and zotepine.
continued

Olanzapine is:
As effective as haloperidol in alleviating of
positive symptoms.
Superior to haloperidol in alleviating of
negative symptoms.
Fewer extrapyramidal side effects
At high doses may cause akathisia,
pseudoparkinsonism, and dystonias.
Risperidone


Its pharmacological effects are similar to
olanzapine.
But less sedation more orthostatic
hypotension, higher incidence of
extrapyramidal side effcts.
Antidepressant drugs
1.
2.
3.
4.
Tricyclic antidepressants
Selective serotonin reuptake inhibitors (SSRI)
Monamine oxidase inhibitors (MAOI)
Others
Tricyclic antidepressants




Amitriptyline, nortriptyline, imipramine,
clomipramine, desipramine
They block neuronal reuptake of NE and serotonin,
but at different degrees
Side effects:
Autonomic side effects by blocking muscarinic
and a-adrenergic receptors, sedation, induce
seizure, orthostatic hypotension
Overdose cause life-threatening cardiac arrythmia.
Indications




Depression
Phobic, panic and obsessive compulsive
disorder.
Sleep disorder (sleepwalking, night terrors,
enuresis).
Chronic pain syndrome
Selective serotonin reuptake
inhibitors (SSRI)





Fluoxetine, fluvoxamine, paroxetine, sertraline.
Most widely used drugs for depression and
anxiety disorders (panic & obsessive
compulsive disorders)
As effective as TCAs
But cause fewer autonomic side effects and
less sedation.
Following overdose, seldom cause cardiac
arrhythmia and less likely to induce seizure.
Mechanism and pharmacological
effects


They selectively block reuptake of serotonin.
(citalopram and escitalopram are newer SSRI
drugs)
Adverse effects





Fewer sedative, autonomic, cardiovascular
side effects.
They tend to increase alertness in patients.
Most common adverse effects are:
nervousness, dizziness, insomnia.
Should be used with caution in patients with
seizure and hepatic disorders, diabetes, bipolar
disorders.
Should not be used with MAOI, cause
serotonin syndrome.
Indications



Depression
Eating disorders (bulimia nervosa, anorexia
nervosa).
Panic, phobic and obsessive compulsive
disorders.
Monoamine oxidase inhibitors





They were among the first to be introduced clinically as
ADS.
They were replaced by TCAs and others whose clinical
efficacies were better and whose clinical side effects
were less than MAOI.
The main examples are Phenelzine, iproniazid and
tranylcypramine.
They cause irreversible inhibition of the enzyme and do
not distinguish between the two main isozymes.
Meclobamate acts as a specific inhibitor of MAOA.
Others (Atypical)

1.
2.
3.
4.
The main claims are:
Fewer side effects (sedation and
anticholinergic effects)
Lower acute toxicity in overdose
Action with less delay
Efficacy in patients non-responsive to TCA or
MAOI
Continued

1.
2.
They can be divided into two categories:
Non-tricyclic structures with similar
noradrenaline uptake blocking effects to TCA
such as nomifensine and maprotiline
Drugs that do not affect amine reuptake such
as mianserin, trazodone and bupropion
 Great minds discuss ideas.
 Average minds discuss events.
 Small minds discuss people.
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