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psychoterapeutic Drugs

Major Psychiatric Disorders


Psychoses eg schizophrenia
Affective

mania

disorders eg depression and

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 D 2


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-HT 2


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
Positive

of D2 receptors

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 Tourettes
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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