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Neuroleptics - Antipsychotic Drugs - Major Tranquilizers - indications - Adverse/side effects - Pchizopherina treatment



Neuroleptics are antipsychotic drugs used for the treatment of schizophrenia. These are also called major tranquillizers. These drugs are also effective in the treatment of manic disorders, delusions and hallucinations.


DRUGS and Their Classification.

Typical Neuroleptics;

  1. Chlorpromazine
  2. Prochlorperazine
  3. Thioridazine
  4. Fluphenazine
  5. Haloperidol
  6. Thiothixene
Chlorpromazine, Prochlorperazine and Thioridazine are low potency drugs
Fluphenazine, Haloperidol and Thiothixene are high potency drugs.

Atypical Neuroleptics:
  1. Aripiprazole
  2. Clozapine
  3. Olanzapine
  4. Quetipine
  5. Paliperidone
  6. Risperidone
  7. Ziprasidone

Mechanism Of Action Of drugs:

Neuroleptic drugs act through several mechanisms. 
Typical neuroleptic drugs act through blocking Dopamine receptors such as D2 receptors. There are five types of Dopamine receptors from D1 - D5. clozapine blocks D4 receptor more than D2. 
Those drugs which block the D2 receptors are responsible for extrapyramidal effects and Parkinson disease-like effects in the patient.
e.g atypical neuroleptic drug clozapine has less affinity for D2 receptor and binds more avidly to D4 receptors and hence is likely to have less Extrapyramidal and Parkinson like effects.

Moreover, some typical and most of the atypical drugs act on the serotonin receptors. They inhibit serotonin receptors particularly 5HT2a receptor.

Actions And Effects:

1. Antipsychotic Effect.
                      All neuroleptic drugs reduce to symptoms of hallucinations and delusions. they have fewer effects on negative symptoms (anhedonia, lack of pleasure, apathy, impaired attention, cognitive impairment) 
However, some atypical neuroleptics such as clozapine has appeared to reduce these negative symptoms as well.

2. Extrapyramidal Effects.
                           These occur because of inhibition of D2 receptors in the brain.
EPE include dystonias, Parkinson like symptoms, motor restlessness, tardive dyskinesia.

3. Antiemetic effects.
                       These drugs have an antiemetic effect. This is because of the blockage of the D2 receptor in chemo-receptor trigger zone.

4. Antimuscarinic effects:
                       These are responsible for side effects as well as better effects.
drugs having more antimuscarinic action tend to have less extrapyramidal side effects. Thioridazine, clozapine, olanzapine, chlorpromazine have antimuscarinic actions. Thioridazine has the most.

5. Alpha receptor blockade.
                      Some drugs block alpha receptors and can cause postural hypotension and lightheadedness.

6. Antimuscarinic effects:
                     Some drugs block histamine receptors and cause sedation. e.g chlorpromazine, olanzapine, clozapine.
Indications:
  • Treatment of Schizophrenia
  • To Prevent Severe Nausea and Vomiting
  • Chronic Pain: used in combination with other analgesics.
  • Intractable hiccups: Chlorpromazine
  • Motor and phonic tics of Tourette's disorder. (pimozide)

Adverse/Side Effects:

  • Parkinson like symptoms
  • dyskinesia
  • bradykinesia ( difficulty in initiating movements)
  • akathisia ( restlessness )
  • Clozapine may cause agranulocytosis, bone marrow depression and cardiovascular side effects.
  • Tardive dyskinesia
  • neuroleptic malignant syndrome
  • Drowsiness
  • orthostatic hypotension
  • amenorrhea 
  • gynecomastia
  • galactorrhea
  • infertility (rare)
  • impotence (rare)
  • hyperlipidemia
Contraindications:
  • Epilepsy
  • Clozapine should be used with caution as it causes agranulocytosis.
  • agitation accompanying withdrawal from alcohol or other drugs may be aggravated by the neuroleptics.

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