Antipsychotic fluphenazine

Three patients treated with various antipsychotics (fluphenazine, ha-loperidol, trifluoperazine, chlorpromazine) developed Stevens-Johnson syndrome within 8 to 14 days of starting to take carbamazepine. All 3 had erythema multiforme skin lesions and at least two mucous membranes were affected. After treatment, all 3 were restarted on all their previous drugs, except carbamazepine, without problems. Another case of Stevens-Johnson syndrome has been reported in a patient taking carbamazepine, lithium carbonate, haloperidol and trihexyphenidyl. The reasons are not understood. Stevens-Johnson syndrome with carbamazepine alone is rare, and the risk appears to be mostly confined to the first 8 weeks of treatment. It may be more common in patients being treated for conditions other than epilepsy. It is not possible to say whether the concurrent use of antipsychotics increases the risk of its development, but until more is known it would be prudent to monitor the outcome, particularly during the first 2 weeks of combined use. 

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

Of the antipsychotic drugs prescribed, 72% were typical antipsychotics, which included haloperidol, chlorpromazine, levomepromazine, sulpiride, trifluoperazine, fluphenazine, flupentixol, and bromperidol. Use of typical drugs was associated with longer hospitalization, male gender, and clinical reports of violence or aggression. Atypical drugs only accounted for 28% of antipsychotic drugs... 

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. 

Intramuscular (IM) Into skeletal muscle. This route is used to deliver depot antipsychotic drugs like fluphenazine and haloperidol decanoate, which are used in the treatment of schizophrenia. 

The answer is b. (Hardman, pp 282—283J Central dopamine receptors are divided into Dt and D2 receptors. Antipsychotic activity is better correlated to blockade of D2 receptors. Haloperidol, a potent antipsychotic, selectively antagonizes at Dz receptors. Phenothiazine derivatives, such as chlorpromazine, fluphenazine, and promethazine, are not selective for D2 receptors. Bromocriptine, a selective D2 agonist, is useful in the treatment of parkinsonism and hyperprolactinemia. It produces fewer adverse reactions than do nonselective dopamine receptor agonists... 

Depot antipsychotics (e.g., haloperidol decanoate, fluphenazine decanoate, and risperidone long-acting injection) can be used for maintenance therapy of bipolar disorder with noncompliance or treatment resistance. 

If partial or poor adherence is an issue, a long-acting or depot injectable antipsychotic should be considered (e.g., risperidone microspheres, halo-peridol decanoate, fluphenazine decanoate). 

If a change in antipsychotic therapy is required, risperidone, molindone, thioridazine, haloperidol, pimozide, trifluoperazine, and fluphenazine may be considered. 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

Fluphenazine (Prolixin). Fluphenazine is another high potency antipsychotic. It is widely used to treat psychosis and comes in oral, injectable, and long-acting injectable (depot) forms. Its side effect profile is typical of the other high potency antipsychotics. 

Risperidone (Risperdal). Risperidone was the second atypical antipsychotic released in the United States. It is actually quite different from clozapine, and, in general, members of the class of atypical antipsychotics are often not all that similar among themselves. Risperidone blocks D2 receptors as do haloperidol and fluphenazine, but it probably blocks a lower percentage of D2 receptors, more like clozapine than haloperidol. In addition to blocking dopamine D2 receptors, risperidone also blocks serotonin type 2 receptors. 

For patients in whom treatment noncompliance is a recurring problem, the snccess of maintenance therapy can greatly be enhanced by administering a depot formnlation of the antipsychotic. Depot formulations are currently available for haloperidol (which must be administered once every 4 weeks) and risperidone or fluphenazine (each of which must be administered once every 2 weeks). 

Typical Antipsychotics. Low doses of high potency typical antipsychotics such as haloperidol or fluphenazine (0.5-2mg given once or twice daily) are generally quite effective for psychotic symptoms after TBI. Unfortunately, as noted earlier, many post-TBl patients are susceptible to the extrapyramidal side effects of these medicines, especially if there was any injury to brain regions such as the basal ganglia. Low potency antipsychotics are not a viable alternative, because their anticholinergic and sedative effects are equally, if not more, problematic for patients who have suffered TBI. We recommend using typical antipsychotics, even for psychotic symptoms, as briefly as possible and in the lowest effective dose, if at all. Fortunately, there are now alternatives. 

From the chemical point of view antipsychotic drugs are subdivided into six chemical groups, as well as to the group of non-classifiable drugs. They are phenothiazines (chlorpromazine, promazine, triflupromazine, acetophenazine, fluphenazine, perphenazine, prochlorpherazine, trifluoperazine, mesoridazine, and thioridazine), thioxanthenes... 

Fluphenazine is an extremely strong antipsychotic drug. A stimulatory effect accompanies the neuroleptic effect. It is used in psychiatry for treating various forms of schizophrenia and other mental illnesses. The most common synonyms are fluorphenazine, moditen, dapotum, motival, permitil, and others. 

Compounds also found active include (among many others) tannins,145 the pharmaceutical products pyrimethamine (51, Scheme 15),146 ambroxol (52),147 the secre-tolytic ingredient in mucosolvan, or fluphenazine (53),147 an antipsychotic substance, as well as—and closer to real sugars—ascorbic acid derivatives (54).148... 

Fluphenazine (Prolixin, Permitil) [Antipsychotic/ Phenothiazine] Uses Schizophrenia Action Phenothiazine antipsychotic blocks postsynaptic mesolimbic dopamin gic brain receptors Dose 0.5-10 mg/d in % doses PO q6-8h, av age maint 5 mg/d or 1.25 mg IM, then... 

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. 

There are several antipsychotics that are substrates to CYP2D6 (von Bahr et ah, 1991 Jerling et ah, 1996 Ring et ah, 1996 (Fang and Gorrod, 1999 Flockhart and Oesterheld, 2000) (Table 26.3). Moreover, several antipsychotics may act as inhibitors of CYP2D6-mediated biotransformation. These include thioridazine, chlorpromazine, haloperidol, fluphenazine, and pimozide (Desta et ah, 1998 Shin et ah, 1999). Of particular salience is the fact that the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and paroxetine are metabolized to a significant extent by this isoenzyme. 

Acute angle closure and difficulty with accommodation can occur from the anticholinergic effects of antipsychotic agents. In addition, pigment deposits may develop in the cornea and lens. Pigmentary retinopathy has been reported with thioridazine. Keratopathy and corneal edema may occur occasionally during pharmacotherapy with chlorpromazine and fluphenazine... 

A high risk of relapse is inherent to schizophrenic psychoses. A relapse is often triggered by emotional stress. It is very important to prevent a relapse by either maintaining low-dose oral medication or by switching to a depot antipsychotic. In some cases, this cannot be avoided. Especially when compliance is a problem, a depot medication may help to keep the patient free of psychotic symptoms. Frequently used depot antipsy-chotics are haloperidol-decanoate, fluphenazine-decanoate, and fluspirilene, which are given in relatively low dosages (see Table 41.4). In EOS, relapse prevention is more important than in adulthood, as the majority of patients have not yet finished school or started a professional career. 

Most conventional antipsychotics are associated with a dose-depen-dent risk of a lowered seizure threshold, although the incidence of seizures with most of these drugs is quite small (Devinsky et al. 1991). Of all the conventional antipsychotics, molindone and fluphenazine have been shown most consistently to have the lowest potential for this side effect (ltd and Soldatos 1980 Ohver et al. 1982). The atypical antipsychotic clozapine is associated with a dose-dependent risk of seizure. 

For patients with chronic psychotic symptoms who do not comply with a daily medication regimen, a long-acting depot preparation should be considered after stabilization with oral medication. Fluphenazine, haloperidol, and risperidone are the only long-acting injectable antipsychotic medications currently available in the United States. 

Pharmacodynamics, antipsychotics also differ in their pharmacodynamics, i.e. their pharmacological and clinical profiles of action. A rough distinction is made between highly sedative, hypnotic antipsychotics (e.g. clopenthixol, levomepromazine) and other products with weaker initial sedative action (e.g. fluphenazine and haloperidol). Sedative antipsychotics are prescribed for states of major unrest, often combined with insomnia, whereas the less sedative antipsychotics are preferred for patients suffering from delusions and hallucinations but in whom heavy sedation during daytime is undesirable. 

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). 

Several longitudinal studies have also found that patients stabilized on depot fluphenazine relapsed when switched to an oral antipsychotic preparation ( 264). Mirror-image studies also found depot fluphenazine (decanoate or enanthate) reduced the incidence of relapse, as well as the number of days hospitalized, when compared with oral therapy. These open, crossover studies switched patients from oral to depot forms, and the outcome with each approach was evaluated. 

Kane et al. (266) point out that some studies may not have effectively evaluated the potential benefit of depot fluphenazine. Thus, patients volunteering for such studies are those who might be compliant whether they took oral or depot medications therefore, these studies may underrepresent the noncompliant population. In addition, inasmuch as relapse may not occur for 3 to 7 months after medications have been completely discontinued, a 1-year study period may not be long enough to evaluate the relative effectiveness of a depot versus oral antipsychotic. 

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