Antipsychotics flupenthixol

Across the sites, an average of 15% of inpatients received depot antipsychotic drugs (Sim etal, 2004b). This was most common in Singapore (75%) followed by Taiwan (20%), Japan and China (6%). The depot antipsychotic drugs used were fluphenazine decanoate, flupenthixol decanoate, zuclopenthixol decanoate, haloperidol decanoate, pipothiazine palmitate, and fluphenazine enanthate. 

The intramuscular administration of antipsychotics acting for weeks prevents this independent action and improves compliance on the other hand, only highly potent antipsychotics such as fluphenazine, flupenthixol and haloperidol are suitable for depot administration and it is precisely these medicines that lead more frequently to EPS and dysphoric mood (van Putten et al, 1984). 

One common denominator of all antipsychotics is the biockade of centrai dopamine (DA) receptors. As a result, extrapyramidal reactions, particularly parkinsonian symptoms, are a major adverse effect of many of these drugs, as well as an important clue to their mechanism of action. True Parkinson s disease is caused by a DA deficiency in the nigrostriatal system. Further, crystallographic data have demonstrated that CPZ s molecular configuration is similar to that of DA, which could explain its ability to block this neurotransmitter s receptors. Drugs with similar structures that do not block DA receptors (e.g., promethazine, imipramine) do not have antipsychotic activity. Another example is the isomer of flupenthixol, which blocks DA receptors is an effective antipsychotic, but the isomer that does not is ineffective (7). The other family of dopamine receptors, D and Dg, have not yet been implicated in psychosis. 

Thioxanthenes, such as flupenthixol and clopenthixol, are similar in structure to the phenothiazines. The therapeutic effects are similar to those of the piperazine group. Antipsychotic thioxanthenes are thought to benefit psychotic conditions by blocking postsynaptic dopamine receptors in the brain. They also produce an alpha-adrenergic blocking effect and depress the release of most hypothalamic and hypophyseal hormones. However, the concentration of prolactin is increased due to blockade of prolactin inhibitory factor (PIF), which inhibits the release of prolactin from the pituitary gland. 

Antipsychotics are also referred to as neuroleptic drugs, such as haloperi-dol, phenothiazines (e.g. chlorpromazine, promazin and thioridazine) and thioxanthines (e.g. flupenthixol). All theses agents are used in treating the symptoms and are mostly successful with positive symptoms. 

ANTIPSYCHOTICS (e.g. flupenthixol) may also be used, at a much lower dose, as antidepressants. 

The so-called typical antipsychotics, such as chlorpromazine (Largactil, Thorazine) and trifluperazine (Stelazine) were introduced into psychiatric practice in the 1950 s. Other drugs in this category are, thioridazine (Mel-leril), and haloperidol (Haldol, Serenace). In addition, fluphenazine (Motile ate), flupenthixol (Depixol) and haloperidol (Haldol decoanate), which... 

I a- but not p-flupenthixol has antipsychotic activity greater than placebo (only the a isomer is antagonist at D2 receptors) (Fig. 3.2). 

Figure 3.2 Efficacy of a- and f-flupenthixol in schizophrenia. The a-isomer caused a greater improvement in symptomatology than placebo while the f-isomer was without antipsychotic efficacy. Source Reproduced with permission from Johnstone et al. 1978.

The documentation is limited. The manufacturers of flupentixoP and haloperidol warn that, in common with other antipsychotic drugs, the effects of alcohol maybe enhanced. Warn patients that if they drink alcohol while taking chlorpromazine, and to a lesser extent flupenthixol, sulpiride or thioridazine (probably other related drugs as well), they may become very drowsy, and should not drive or handle other potentially dangerous machinery. Some risk is possible with any antipsychotic that causes drowsiness, including those used as antiemetics, such as prochlorperazine. 

When the occurrence of flip-flop kinetics is not recognised it may compromise the interpretation of results from studies on the pharmacokinetic behaviour of slow release dosage forms. Flip-flop pharmacokinetics may occur with any extravascularly administered parenteral slow release dosage form. Intramuscular depot injectimis of antipsychotics such as fluphenazine decanoate, haloperidol decanoate or flupenthixol decanoate show this behaviour. It also occurs after the administration of oral slow release products of active substances such as isoxuptine, carbamazepine, diclofenac, valproic acid, morphine and theophylline. 

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