1. psychoterapeutic Drugs

2. Major Psychiatric Disorders
Psychoses eg schizophrenia
Affective disorders eg depression and mania

3. Psychoses
False perceptions (Hallucinations)
False beliefs (Delusions)

4. Affective Disorders Emotional disturbances:
Mood is very low (Depression)
Mood is very high (Mania)

5. Schizophrenia Most common form of psychosis (1% of world population)
Most typical features are :
-Delusions
-Hallucinations
-Disorganised thinking
-Emotional abnormalities

6. Types of Schizophrenia
Paranoid
Disorganised
Catatonic forms

7. 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

8. 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

9. Antipsychotic Drugs Mechanisms of action
-competitive blockade of dopamine receptors and serotonin receptors
-adverse effect result from blockade of different receptors

10. 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

11. 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

12. 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.

13. Continued
Dopamine reduction causes dopamine up-regulation and super sensitivity to dopamine agonists and then delayed extrapyramidal side effect called tardive dyskinesia.
In mesocortical and nigrostriatal pathways, 5-HT2 receptors mediate presynaptic inhibition of dopamine release.
Blockade of 5-HT2 receptors by atypical drugs increase dopamine release in these pathways.

14. 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.

15. Drug Classification Typical antipsychotic drugs -Phenothiazines
-Thioxanthenes
-Butyrophenones
- some Azepines (eg loxapine)
Atypical antipsychotic drugs
-other Azepines (clozapine, olanzapine)
-Benzisoxasole (risperidone)

16. 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

17. 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

18. Adverse effects 1- Extrapyramidal side effects -Acute: 1- Akathisia
2- Pseudoparkinsonism
3- Dystonias
-Chronic: Tardive dyskinesia

19. continued 2- neuroleptic malignant syndrome
3-increase serum prolactin levels
4-impair thermoregulation cause poikilothermy

20. Treatment of adverse side effects
Acute extrapyramidal side effects
Decrease dose
Change to atypical drug
Counteract with benztropine, diphenhydramine, amantadine
Chronic extrapyramidal side effects
Drug treatment

21. Continued Neuroleptic malignant syndrome Supportive care
Discontinuing of drug
Administration of bromocryptine
Change to atypical

22. 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

23. Chlorpromazine and thioridazine
Thioridazine causes greater antichloinergic activity
And so fewer extrapyramidal side effect
High doses of thioridazine cause pigmentary retinopathy and cardiac arrythmia

24. 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

25. Thioxanthenes
Thiothixene has pharmacological effects similar to trifluoperazine
It is used for schizophrenia
(Other thiothixenes in BNF are flupentixol [depixol] zuclopentixol [clopixol].

26. 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).

27. 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.

28. 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.

29. Risperidone Its pharmacological effects are similar to olanzapine.
But less sedation more orthostatic hypotension, higher incidence of extrapyramidal side effcts.

33. Antidepressant drugs Tricyclic antidepressants
Selective serotonin reuptake inhibitors (SSRI)
Monamine oxidase inhibitors (MAOI)
Others

34. 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.

35. Indications Depression
Phobic, panic and obsessive compulsive disorder.
Sleep disorder (sleepwalking, night terrors, enuresis).
Chronic pain syndrome

36. 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.

37. Mechanism and pharmacological effects
They selectively block reuptake of serotonin.
(citalopram and escitalopram are newer SSRI drugs)

38. 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.

39. Indications Depression
Eating disorders (bulimia nervosa, anorexia nervosa).
Panic, phobic and obsessive compulsive disorders.

40. 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.

41. Others (Atypical) 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

42. Continued 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

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