High antipsychotics

Haloperidol is one of the most actively used modem neuroleptics. Its high antipsychotic activity is combined with a moderate sedative effect. It effectively stops various types of psychomotor excitement. It is used for schizophrenic psychoses, manic, paranoid, and delirious conditions, depression, psychomotor excitement of various origins, and for delirium and hallucinations of different origin. The most common synonyms are haldol, vezadol, linton, and others. 

The piperazines include fluphenazine, trifluoperazine, prochlorperazine, perazine and perphenazine. They are agents with a high antipsychotic potency with less pronounced anticholinergic effects. However their potential to produce extrapyramidal effects is more pronounced. 

Which of the following agents possesses pharmacological actions characterized by high antipsychotic potency, high potential for extrapyramidal toxicity, and a low likelihood of causing sedation ... 

Many earlier reports considered extrapyramidal side effects unavoidable when treating patients with neuroleptics. There appeared to he a parallel between antipsychotic action and the incidence of unwanted neurological effects. However, the development of newer neuroleptics has changed this view. Drugs like clozapine have a high antipsychotic potency and yet produce few neurological problems. It has therefore been proposed that the DA receptors involved in the beneficial actions of neuroleptics in the treatment of psychiatric disorders are situated in mesolimbic areas, such as the nucleus accumbens, whereas the extrapyramidal effects are mediated by striatal receptors. 

Correlation between clinical effectiveness and receptor affinities, however, can be seen with other receptors in addition to the dopamine D2 receptor. These include other dopaminergic receptors, as well as noradrenergic and serotonergic receptors. For example, most antipsychotics also have high affinity for a -adrenoceptors and 5-HT2 receptors (225). Some antipsychotics have been shown to be selective for the adrenoceptor versus the a -adrenoceptor, for example, spiperone [749-02-0] (226) and risperidone (61) (221]... 

More interesting is the mechanism of action of atypical antipsychotics, particularly clo2apine (60). It is also probably the least selective antipsychotic used in the clinic, having high affinity for numerous receptors including 5-HT2, 5-HT, and dopamine D, D3) and receptors ... 

It has been suggested that high affinity for certain 5-HT receptors is a possible method for reducing extrapyramidal side effects observed with antipsychotics. LiabiUty for extrapyramidal side effects has been hypothesi2ed to be related to the ratio of the affinity between dopamine receptor... 

The advent of novel atypical antipsychotic drugs has sharpened the debate in the UK about the cost burden of schizophrenia to the National Health Service (NHS) and the relative cost-effectiveness of these drugs. Schizophrenia has a prevalence of about 0.5% and a lifetime risk of 1%. Because the disease affects adolescents and has a lifetime course associated with a high degree of hospital and social... 

Although atypical antipsychotic agents may cost several times as much as traditional antipsychotics, drug costs in schizophrenia account for only 1-4% of the total treatment cost (Knapp, 1997). The argument then is that a small increase in drug costs— say to 10% of total cost—may result in disproportionate savings in the highly expensive direct hospital costs, if clinical trial... 

Since early detection and intervention in schizophrenia is important for maximizing outcomes, treatment with antipsychotic medications should begin as soon as psychotic symptoms are recognized. Antipsychotic medications are the cornerstone of therapy for people with schizophrenia, and most patients are on lifelong therapy since non-adherence and discontinuation of antipsychotics are associated with high relapse rates. If other symptoms are present such as depression and anxiety, these symptoms should also be aggressively treated. Additionally, psychosocial treatments should be used concomitantly to improve patient outcomes. 

High-potency antipsychotics include haloperidol, fluphenazine, thiothixine, and pimozide. 

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

Thirty-five to eighty-seven percent of the patients studied received antiparkinson drugs. Compared to other countries, Japan and Singapore used the most of these antidotes for drug-induced extrapyramidal symptoms. This is most likely related to the frequent use of high-dosage antipsychotic drugs and poly-antipsychotics (see Table 12.3). 

Sim, K., Su, A., Leong, J. Y. et al. (2004a). High dose antipsychotic use in schizophrenia findings of the REAP (research on East Asia psychotropic prescriptions) study. Pharmacopsychiatry, 37(4), 175-9. 

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