(also called antischizophrenic drugs, antipsychotic drugs...

29
Neuroleptic drugs (also called antischizophrenic drugs, antipsychotic drugs or major tranquilizers)

Upload: others

Post on 20-Jun-2020

11 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Neuroleptic drugs

(also called antischizophrenic drugs, antipsychotic drugs or

major tranquilizers)

Page 2: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Psychosis—severe mental disorder character. By

disordered though processes, inappropriate emotional

responses, bizarre behavior, agitation, aggressiveness,

hostility, social withdrawal, deterioration in occupational and

social functioning, hallucinations and paranoid delusions.

Page 3: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

The most important types of psychosis are:

Schizophrenia

Affective disorders (e.g. depression, mania)

Organic psychoses (mental disturbances caused by head injury, alcoholism, or other kinds of organic disease).

Page 4: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Schizophrenia is a particular type of psychosis, that is, a mental disorder caused by some inherent dysfunction of the brain. It is characterized by delusions, hallucination (often in the form of voices), and thinking or speech disturbances.

Page 5: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Hallucinations—sensory perceptions of people or objects

that are not present. Unable to distinguish between

false perceptions and reality.

In schizophrenia or bipolar disorder, usually auditory; in

delirium, usually visual or tactile; in dementia usually

are visual.

Delusions are false beliefs that persist in absence of

reason or evidence. May believe others control their

thoughts, feelings or seek to harm them.

Page 6: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Psychosis may be acute or chronic.

When acute—may be confusion or delirium. Can be

precipitated by illness, drug effects or superimposed on

chronic dementias.

Page 7: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Positive symptoms: CNS stimulation, agitation, behavioral

disturbances, delusions, hallucinations, insomnia, and paranoia.

Negative symptoms: anhedonia, lack of motivation, blunted

affect, poor hygiene, poor social skills and social withdrawal.

Schizophrenia:

Symptoms

Page 8: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Etiology of Schizophrenia- Evidence indicates abnormal neurotransmission systems

in the dopaminergic, serotonergic, and glutaminergic

systems. Also, seems to be interplay between the systems

so one system may affect others.

- Imbalance in amount of neurotransmitters, most notably

dopamine. Overactivity accounts for the positive symptoms

of schizophrenia and underactivity in another part of the

brain may account for the negative symptoms.

- Glutamatergic dysfunction may be genetically linked as

well as causative in the cognitive impairments and negative

symptoms of this disorder.

Page 9: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Dopamine Receptor Subtypes• D1, D5: Gs coupled - increase cAMP

• D2, D3, D4: Gi coupled - decrease

cAMP

• D2 mediates much of „typical APD‟

therapeutic action and side effects

Page 10: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Classification of Antipsychotic drugs

– Typical antipsychotics

Phenothiazines (chlorpromazine, perphenazine,

fluphenazine, thioridazine et al)

Thioxanthenes (Thiothixene, flupenthixol, clopenthixol)

Butyrophenones (haloperidol, droperidol)

– Atypical antipsychotics (e.g. clozapine, risperidone,

sulpiride, olanzapine)

Page 11: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Mode of action

All of the neuroleptic drugs block dopamine receptors in the brain and in the periphery.

The neuroleptic drugs bind to receptors to varying degrees; however, the clinical efficacy of the traditional neuroleptic drugs correlates closely with their relative ability to block D2 receptors in the mesolimbic system.

Page 12: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Mode of action

The newer “atypical” agents appear to exert part of their unique action through inhibition of serotonin (5-HT) receptors.Thus, Clozapine has high affinity for D1 and D4, 5-HT2, M-cholinergic and α-adrenergic receptors, but it is also a dopamine D2-receptor antagonist. Another new agent, Risperidone, blocks 5-HT2 receptors to a greater extent than it does D2 receptors. Both of these drugs exhibit a low incidence of exrapyramidal side effects.

Page 13: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Atypical antipsychotics

Relative receptor-binding of atypical antipsychotics

Drug D1 D2 5-HT2 1 M1 H1

Clozapine ++ ++ +++ +++ +++ +

Risperidone - +++ +++ +++ - +

Olanzapine ++ ++ +++ ++ +++ ++

Quetiapine - + ++ +++ + +

Ziprasidone +/- ++ +++ ++ - +

Aripiprazole + +++ ++ ++ - +

Page 14: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Actions

The antipsychotic actions of neuroleptic drugs reflect blockade at dopamine and/ or serotonin receptors. However, many of these drugs block cholinergic, adrenergic, and histamine receptors, causing a variety of side effects.

Page 15: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Actions

1. Antipsychotic actions.This effect is differ in normal and psychotic individuals.In normal individuals neuroleptic drugs produce indifference to surroundings, psychomotor slowing, emotional quietening, reduction in initiative and tendency to go off to sleep from which the subject is easily arousable. This has been refered to as the «neuroleptic syndrome».In a psychotic individuals neuroleptic drugs reduse agitation and aggressiveness and controls psychotic symptomatology. Hyperactivity,hallucinations and delusions are supressed.

Page 16: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Actions

2. Extrapyramidal effects.

Neuroleptic drugs block dopamine receptors in the nigrostriatal pathway and may cause Parkinsonian symptoms, akathisia (motor restlessness), and tardive dyskinesia (inappropriate postures of the neck, trunk and limbs), which occur with chronic treatment.

Page 17: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs
Page 18: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Actions

3. Antiemetic effect.

Most of the neuroleptic drugs (with the exception of Thiordazine) block D2 dopaminergic receptors of the chemoreceptor trigger zone of the medulla and have antiemetic effects.

Page 19: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Actions

4. Antimuscarinic effects.

All of the neuroleptic drugs, particularly Thioridazine and Chlorpromazine, cause anticholinergic effects, including blurred vision, dry mouth, sedation, confusion, and inhibition of gastrointestinal and urinary smooth muscle, leading to constipation and urinary retention.

Page 20: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Actions

5. Other effects.The neuroleptic drugs produce orthostatic hypotension and lightheadedness, because they block α-adrenergic receptors. The reflex tachycardia may occur.The neuroleptic drugs alter temperature-regulating mechanisms and can produce poikilothermia (body temperature varies with the environment).In the pituitary, neuroleptics block D2receptors, leading to an increase in prolactin release, reduce gonadotropin secretion and decrease on release of ADH (this may result in an increase in urine volume).

Page 21: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Chlorpromazine is a more potent a local anestheticthan Procaine.

However, it is not used for this pupose because of its irritant action. Other have weaker membrane stabilizing action.

Neuroleptic drugs have no effect on muscle fibres or neuromuscular transmission. They reduce certain types of spasticity: the site of action being in the basal ganglia or medulla ablongata. Spinal reflexes are

not affected.

Page 22: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Therapeutic uses1. Treatment of schizophrenia.

The traditional neuroleptics are most effective in treating positive symptoms. The newer agents are effective in many patients resistant to the traditional agents, especially in treating negative symptoms of schizophrenia.

2. Other psycoses3. Prevention of severe nausea and vomiting.4. Neuroleptanalgesia (droperidol and fentanil)5. Malignant hyperthermia6. Hypertensive crisis (droperidol)7. Bipolar Affective Disorders8. Hiccups

Page 23: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Adverse effects

All neuroleptics may cause:

1) Drowsiness;

2) Confusion;

3) Postural hypotension, palpitation;

4) Amenorrhea, galactorrhea, infertility and impotence;

5) Dry mouth, blurring of vision, constipation, urinary retention 6) Parkinsonian effects (extrapyramidal disturbances).

Page 24: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Adverse effects

a) Parkinsonism with typical manifestations: rigidity, tremor, hypokinesia, mask like facies. It often responds to central anticholinergic drugs.

b) Acute muscular dystonias: bizarre muscles spasms, mostly involving linguo-facial muscles – grimacing, torticollis. It lasts one to few hours and then resolves spontaneously.

c) Tardive dyskinesia. It occurs late in the therapy, sometimes even after withdrawal of the neuroleptics: manifests as purposeless involuntary facial and limb movements.

Page 25: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Blockade Of D2 Receptors

D2

ANTAGONIST

Mesolimbic pathway

dramatic therapeutic action on positive

psychotic symptoms

Tuberoinfundibular pathway

hyperprolactinemia (lactation, infertility,

sexual dysfunction)

Nigrostriatal pathway

extrapyramidal side effects (EPS) and

tardive dyskinesia

Mesocortical pathway

enhanced negative and cognitive

psychotic symptoms

Page 26: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Diabetes

Lowered seizure threshold

Myocarditis

Neutropenia and other blood dyscrasias

Agitation and anxiety

Photosensitivity

Neuroleptic malignant syndrome (NMS)

Jaundice

Cerebral edema

Weight gain

Other side effects

Page 27: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Neuroleptic Malignant Syndrome

An idiosyncratic, life-threatening neurological disorder associated

with antipsychotic therapy

Idiosyncrasy: An unusual or unexpected sensitivity of an individual

to a particular food or drug. Idiosyncrasy is usually determined

genetically and it may be due to a biological deficiency (e.g. an

inability to metabolize a drug).

Page 28: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Clinical manifestations include:

Encephalopathy, Hyperpyrexia, delirium

Autonomic instability (vitals unstable)

Rigidity of muscles

Elevated creatine phosphokinase (CPK) due to

increased muscular activity and rhabdomyolysis

(destruction of muscle tissue)

Neuroleptic Malignant Syndrome

Page 29: (also called antischizophrenic drugs, antipsychotic drugs ...do.rsmu.ru/fileadmin/user_upload/pf/Antipsikhotiki_MF.pdf · (also called antischizophrenic drugs, antipsychotic drugs

Thanks!