Neuroleptics high doses

In Chapter 1 of this book, psychopharmaceuticals were introduced as effective medicines that primarily have a symptomatic action but are problematic in several respects. Antipsvchotics can cause serious side effects and antidepressants often exert their therapeutic effects only after a delay of weeks and in many cases have unpleasant side effects. With anxiolytics, hypnotics and, in particular, psychostimulants, there are problems with habituation and the potential of dependency. It is therefore not surprising that psychopharmaceuticals do not enjoy a very high reputation among many doctors and the general public (see Box 8.1) and have been given names such as chemical strait-jackets for the older neuroleptics (Szasz, 1957) or chemical blinkers for the mind for tranquillizers. Elomaa (1993) even posed the question of whether the long-tom use of conventional antipsychotics should be considered a crime against humanity. 

Repeated high i.m. doses over several days are inadvisable inasmuch as most patients do not require such aggressive intervention, and this strategy may increase the risk for severe EPS and the neuroleptic malignant syndrome (NMS). Finally, it is preferable to switch patients to oral treatment as quickly as possible to manage the remainder of an acute episode. 

It is well known that typical neuroleptics, all of which have a high affinity for dopamine receptors (particularly D2 receptors), do not effectively treat all schizophrenic patients and have only limited beneficial effects on the negative symptoms of the illness. Furthermore, neither typical nor atypical neuroleptics have an immediate effect on the positive symptoms even though it can be shown by both experimental studies in animals and by imaging methods in schizophrenic patients that neuroleptics rapidly bind to dopamine receptors. Thus factors other than an overactive dopaminergic system are probably operative in this disorder. The question is which of the numerous neurotransmitters and modulatory neuropeptides are responsible for both the negative symptoms and the delay in onset of the therapeutic effects of neuroleptics on the positive symptoms ... 

Etorphine is a high-efficacy opioid which, combined with a neuroleptic, is used to immobilise animals in veterinary practice. The doses used in large animals are enough to kill an adult human if, in a struggle, the drug is splashed on skin or mucous membrane, or there is a needle scratch. A competitive antagonist, naloxone (or diprenorphine which accompanies veterinary formulations, and is labelled for use in animals only) should be used at once in man in this urgent situation (do not delay to fetch an official human formulation death has occurred where this was done). Wash a splashed site copiously at once. 

Pimozide is available as an antipsychotic limited to use as an alternate to haloperidol in the treatment of Tourette s syndrome (TS). It is indicated for patients with severe symptoms who cannot tolerate or do not respond to haloperidol. The adverse reaction profile is similar to that of other neuroleptics however, serious ventricular arrhythmias can occur sudden unexpected deaths have been reported with high doses. 

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