SADIA NOREEN ROLL # 09 ADCP

ANTIPSYCHOTIC DRUGS (NEUROLEPTICS)

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SOME DEFINITIONS• Antipsychotics (also known as neuroleptics or major tranquilizers) are a class of medication used  manage psychosis (including delusions, hallucinations, or disordered thought), in particular in schizophrenia and bipolar disorder, and are increasingly being used in the management of non-psychotic disorders (ATC code N05A). The word neuroleptic originates from the Greek word lepsis ("seizure" or "fit").

– Typical neuroleptic: older agents fitting this description

– Atypical neuroleptic: newer agents: antipsychotic efficacy with reduced or no neurologic side effects

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Medical uses

Schizophrenia Bipolar disorder Dementia Unipolar Depression Other

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All neuroleptics are equally effective in treating psychoses, including schizophrenia, but differ in their tolerability.

All neuroleptics block one or more types of DOPAMINE receptor, but differ in their other neurochemical effects.

All neuroleptics show a significant delay before they become effective. All neuroleptics produce significant adverse effects.

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GENERAL CHARACTERISTICS OF TYPICAL NEUROLEPTICS

The older, typical neuroleptics are effective antipsychotic agents with neurologic side effects involving the extrapyramidal motor system.

Typical neuroleptics block the dopamine-2 receptor.

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Typical neuroleptics do not produce a general depression of the CNS, e.g. respiratory depression

Abuse, addiction, physical dependence do not develop to typical neuroleptics.

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Typical neuroleptics are generally more effective against positive (active) symptoms of schizophrenia than the negative (passive) symptoms.

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Positive/active symptoms include thought disturbances, delusions, hallucinations

Negative/passive symptoms include social withdrawal, loss of drive, diminished affect, paucity of speech. impaired personal hygiene

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THERAPEUTIC EFFECTS OF TYPICAL NEUROLEPTICS

Relapse, recurrence of symptoms is common ( approx. 50% within two years).

Noncompliance is common.

Adverse effects are common.

11/02/14PELTON-C-2 Constellation

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ADVERSE EFFECTS OF TYPICAL NEUROLEPTICS

• Anticholinergic (antimuscarinic) side effects:– Dry mouth, blurred vision, constipation, urinary

retention(release), impotence (power less)

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RECEPTOR BLOCKADE IN THE BASAL GANGLIA RESULTS IN EXTRAPYRAMIDAL MOTOR SIDE EFFECTS (EPS).

DYSTONIANEUROLEPTIC MALIGNANT SYNDROMEPARKINSONISMTARDIVE DYSKINESIA

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Increased prolactin secretion (common with all; from dopamine blockade)

Weight gain (common, antihistamine effect)

Photosensitivity (v. common w/ phenothiazines)

Lowered seizure threshold (common with all)

Leucopenia (rare; w/ phenothiazines)

Retinal pigmentopathy (rare; w/ phenothiazines

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MECHANISMS OF ACTION OF TYPICAL NEUROLEPTICS

DOPAMINE-2 receptor blockade in meso-limbic and meso-cortical systems for antipsychotic effect.DOPAMINE-2 receptor blockade in basal ganglia (nigro-striatal system) for EPSDOPAMINE-2 receptor supersensitivity in nigrostriatal system for tardive dyskinesia

LONG TERM EFFECTS OF D2 RECEPTOR BLOCKADE:LONG TERM EFFECTS OF D2 RECEPTOR BLOCKADE:

Dopamine neurons reduce activity.Postsynaptic D-2 receptor numbers increase (compensatory response).When D2 blockade is reduced, DA neurons start again firing and stimulate increased no. of receptors tardive dyskinesia

MANAGEMENT OF EPS(extera pyramidalSymptoms)

oDystonia and parkinsonism: anticholinergic antiparkinson drugs

oNeuroleptic malignant syndrome: muscle relaxants, DA agonists, supportive

oAkathisia:( an often distressing sense of inner restlessness). benzodiazepines, propranolol

oTardive dyskinesia: increase neuroleptic dose; switch to clozapine

GENERAL CHARACTERISTICS OF ATYPICAL NEUROLEPTICS

Effective antipsychotic agents with greatly reduced or absent EPS, esp. reduced Parkinsonism and tardive dyskinesia

All atypical neuroleptics block dopamine and serotonin receptors; other neurochemical effects differ

Are effective against positive and negative symptoms of schizophrenia;

and in patients refractory to typical neuroleptics

Blockade of alpha-1 adrenergic receptorsBlockade of muscarinic cholinergic receptorsBlockade of histamine-1 receptors

oSame therapeutic effectivenessoSame side effect profile

HYPOTHESIZED MECHANISMS OF ACTION OF ATYPICAL NEUROLEPTICS

Combination of Dopamine-4 and Serotonin-2 receptor blockade in cortical and limbic areas.

Combination of Dopamine-2 and Serotonin-2 receptor blockade (esp. risperidone)

Antipsychotics are prescribed one at a time. In

cases in which single antipsychotics are tried alone, and when one of those three cases was Clozapine (Clozapine is usually used only in patients that have not responded to other anti-psychotic treatments ) if possible, then two antipsychotics may be prescribed at the same time.

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