Revision of previous lecture• Depression • Not only psychiatrics prescribe antidepressant drugs…

oncologist, pediatric • SSRI=specific=less side effects=reduction in sexual ability• Always describe drug according to the side effect not the

efficacy• SNRI= main side effect is hypertension• After 8 weeks of Tx of 100 pt= only 50 will respond to the

Tx=only 20 of those have remission+ only 20 of those have reduction in symptoms

• Most serious problem in depressant pt is suicide

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.• A thought disorder

SchizophreniaMainly In males esp. in second decade. smoking is a risk

factor.Increase dopamine In CNS.

... بتقل اجتماعية عالقات وعمل التكلم على القدرة تقل االدراكية القدرة

Positive Symptoms.Hallucinations, delusions, paranoia, ideas of reference.

Negative Symptoms. (some say bcz of decrease dopamine in some parts in the brain or increase serotonin!!!)

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.Pt may cure in his own…with cognitive TxPlacebo is very effective as antipsychotic and anti

depressant (35%).

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

Dopamine Theory of SchizophreniaMany 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

Effect of drug appears after 9 weeksAll antipsychotic drugs should be taken before

sleep bcz of sedative effect

Classification of Antipsychotic drugs• Main categories are:

– Typical antipsychotics :dopamine antagonists( induce extrapyrimidal side effect (Tardive dyskinesia: irreversible) and Parkinson)

Phenothiazines (chlorpromazine, perphenazine, fluphenazine, thioridazine et al) Thioxanthenes (flupenthixol, clopenthixol) Butyrophenones (haloperidol, droperidol)– Atypical antipsychotics: serotonin antagonists– (e.g. clozapine, risperidone>>> في انتشارا أكثر

الثمن غالي (sulpiride, olanzapine ,(األردن

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:حفظ

Fluphenazine

Haloperidol: most effective حفظ

+++ ++ ++

+ + ++++

+ + ++++

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Second Generation Antipsychotic Drugs

Compound Sedation Hypo-tension

Motor effects

++ +++ +/++Dose dependent

Clozapine مهم

Clozaril

++ ++ -

Risperidone:maximum dose:6mg مهم جدا

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

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 gainand 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• Efficacy is less than others• Little hypotension

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. Irreversible side effect

You should follow your pt over years of the Tx

RisperidoneEndocrine 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. Ultra-rapid metabolizes (13% of the Jordanians)

need higher dose

• Patients on antipsychotic drugs have low cognitive and complex motor abilities.

• In psychiatry, we start the drug on high dose to relieve the primary symptom, then reduce the dose.