Acute Symptoms

Antipsychotic drugs are used mainly in schizophrenia to control the acute symptoms, to prevent relapses and, less effectively, to ameliorate chronic schizophrenic symptoms. They are also used to combat the symptoms of mania such as exhausting overactivity, euphoria, garrulousness and delusions of grandeur and to help in the management of organic syndromes such as brain damage and dementia. The antipsychotic action of these drugs may be attributable to anti-dopaminergic activity in the limbic system. Blockade of this transmitter in other brain areas is also responsible for the adverse effects of extrapyramidal reactions and hyperprolactinaemia. Antipsychotics interact to varying degrees with a wide range of other neuroreceptors in the CNS. The degree of interaction may be responsible for many of the different adverse effects associated with these agents (see below).

Phenothiazines can be divided into 3 groups:

1. Aliphatic compounds (characterised by pronounced sedative effects and moderate extrapyramidal and autonomic effects).
2. Piperidines (characterised by moderate sedative effects, fewer extrapyramidal but more autonomic effects).
3. Piperazines (characterised by fewer sedative effects, pronounced extrapyramidal but less autonomic effects).

Other Classes of antipsychotics include the thioxanthenes and butyrophenones whose action resembles the piperazine phenothiazines, and the substituted benzamides which may be less sedative and may have a reduced incidence of tardive dyskinesia. This may be related to a slightly different profile of dopamine blocking activity seen with these drugs.

The tricyclic dibenzoxazepine, loxapine is pharmacologically similar to phenothiazines, butyrophenones and thioxanthines, but is thought to have a lower incidence of extrapyramidal side effects. The exact mechanism of action is unknown but it may act by reducing the firing thresholds of CNS neurons acting in polysynaptic pathways.

Atypical Antipsychotics

The dibenzodiazepine, clozapine has serotonergic, alpha adrenergic and histaminergic blocking activity with a minimal central antidopaminergic activity, and hence has a low potential for producing extrapyramidal effects. Clozapine has been shown to be effective in relieving both positive and negative schizophrenic symptoms in patients refractory to classical antipsychotics. Patients should be carefully monitored due to the risk of agranulocytosis.

The phenylindole sertindole produces an improvement in both the positive and negative symptoms of schizophrenia. It has a greater effect in the limbic system than the substantia nigra and is therefore less likely to produce extrapyramidal side effects than classical antipsychotics.

The benzisoxazole derivative, risperidone has antagonist activity at both serotonergic (5HT2) and dopaminergic (D2) receptors, and produces fewer extrapyramidal side effects than classical antipsychotics. It has also been shown to be effective against both the positive and negative symptoms of schizophrenia.

The thienobenzodiazepine, olanzapine, has potent antagonist activity at 5HT2 D1 D2, H1 and alpha receptors, as well as antimuscarinic activity. It improves the positive and negative symptoms and affective component of schizophrenia, but has a low potential to cause extrapyramidal effects.

Note : Antipsyqhotics

Drugs Interactions :

CNS depressants, alcohol analgesics, anti hypertensives, antidepressants, anticonvulsants, antidiabetics, levodopa.

Adverse Drug Reaction :

Acute dystonias (spasms of eye, face, neck and back muscles), akathisia (motor restlessness), parkinsonism-like syndrome (rigidity and tremor), and tardive dyskinesia, dry mouth, nasal stuffiness, difficulty in micturition, tachycardia, constipation, blurring of vision, hypotension, weight gain, impotence, galactorrhoea, hypothermia (a problem in the elderly), gynaecomastia, amenorrhoea, benign obstructive jaundice, blood dyscrasias and dermatitis, ECG irregularities, drowsiness, lethargy, fatigue, epileptiform seizures.

Butyrophenone

Butyrophenone. .25mg white tablet

Indications :

Control of deviant and anti-social sexual behaviour.

Adults :

0.25-1.5 mg in divided doses.

Children :

Not recommended.

Contraindications :

Pyramidal or extrapyramidal symptoms.

Special Precautions :

Pregnancy, lactation. Regular blood counts and liver function tests during prolonged therapy.

Thioxanthene

Thioxanthene. Zuclopenthixol hydrochlor. 2 mg pink; 10 mg light brown; 25 mg brown

Indications :

Psychoses, especially schizophrenia.

Adults :

Initially 20-30 mg daily in divided doses. Maintenance 20-50 mg daily; max. 150 mg daily.

Children :

Not recommended.

Also Injection Depot thioxanthene. Zuclopenthixol decanoate 200 mg/ml oily inj.; amps. 10 x 1 ml, 232-25.

Adults:

Usually200-400 mg by deep; i.m. injection. every two to four weeks; maximum., 600 mg a week.

Children:

Not recommended.

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