Antipsychotics thiothixene

Thioridazine (Mellaril) Antipsychotic Thiothixene (Navane) Antipsychotic Tiagabine (Gabatril) Anticonvulsant... 

The answer is b. (Katzung, p 4822) Haloperidol, a butyrophenone, is by far the most likely antipsychotic to produce extrapyramidal toxicides Other agents, such as piperazine (an aromatic phenothiazine), thiothixene (a thioxanthene), and pimozide (a diphenylbutyropiperidine) are comparitively less likely to produce extrapyramidal toxicity than haloperi-dol. The antagonism of dopamine in the nigrostriatal system might explain the Parkinson-like effects Both haloperidol and pimozide act mainly on D2 receptors, whereas thioridazine and piperazine act on ooadrenergie receptors, and have a less potent but definite effect on D2 receptors. 

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. 

Thiothixene (Navane). Thiothixene is sometimes grouped with the medium potency and at other times with the high potency antipsychotics. Its potency is actually about halfway between these two groups. Thiothixene is available in both oral and injectable forms. It should be initiated at doses of about 5mg/day and can be... 

Limited evidence indicates that carbamazepine plus an antipsychotic may also benefit some schizophrenic patients. This is an interesting possibility in view of the similar antimanic properties of lithium and carbamazepine (375). This area requires further research, especially to clarify the indications for combining anticonvulsants with an antipsychotic. For example, mania complicated by psychotic features may benefit from lithium, valproate, or carbamazepine augmented by antipsychotics. Because carbamazepine induces the metabolism of at least some antipsychotics (e.g., haloperidol, thiothixene), dose adjustment based on TDM may be necessary to achieve the optimal effect. 

In one single-blind study, 17 schizotypal patients were given a modest dose of halopehdol (i.e., 2 to 12 mg per day), which produced some benefit, although many were sensitive to the adverse effects of this drug (216). The study by Goldberg et al. (217) also found that thiothixene benefited both schizotypal disorder and borderline personality disorder (BPD). Similarly, low-dose antipsychotics had a modest effect in patients with both schizotypal and obsessive-compulsive personality disorders (218). 

After dopamine was identified as a neurotransmitter in 1959, it was shown that its effects on electrical activity in central synapses and on production of the second messenger cAMP by adenylyl cyclase could be blocked by antipsychotic drugs such as chlorpromazine, haloperidol, and thiothixene. This evidence led to the conclusion in the early 1960s that these drugs should be considered dopamine-receptor antagonists and was responsible for the dopamine hypothesis of schizophrenia described earlier in this chapter. The antipsychotic action is now thought to be produced (at least in part) by their ability to block dopamine in the mesolimbic and mesocortical systems. 

Patients with inadequate responses to atypical antipsychotics may benefit from a trial of augmentation with a conventional antipsychotic such as thiothixene or from switching to a conventional antipsychotic such as thiothixene... 

However, long-term polypharmacy with a combination of a conventional antipsychotic such as thiothixene with an atypical antipsychotic may combine their side effects without cieariy augmenting the efficacy of either... 

Other, chemically distinct dopamine blockers were then developed, such as thiothixene, haloperidol, loxapine, molindone, and pimozide. All of these antipsychotics are potent dopamine blockers and collectively were called neuroleptics because they inadvertently cause certain neurological side effects (discussed below). More recently, atypical antipsychotic medications have been developed (clozapine and risperidone), which are effective antipsychotics yet are weak dopamine blockers and cause minimal neurological side effects. This group is discussed separately below. 

Thiothixene, USP. The thioxantheiic system differs from the phenothiazine sy.stem by replacement of the N-H moiety with a carbon atom doubly bonded to the propylidcnc side chain. With the. sub.stitucnt in the 2 position. Z and E isomers me produced. In accordance with the concept that the presently useful antipsychotics can be. superimposed on DA. the Z isomers arc the ntorc active antipsychotic isonters. The compounds of the group arc very. similar in pharmaco-... 

Antipsychotic drugs currently approved for clinical use in the United States are summarized in Table 10.1. Drugs classified as typical include the following several phenothiazine derivatives (1-9), the thioxanthene, thiothixene (10), the butyrophenone, haloperidol(ll),... 

Navane [Pfizer]. TM for the cis isomer of iV,iV-dnnethyl-9[3-4-methyl-l-piperazinyl-pro-pylidene]-thioxanthene-2-sulfonamide. An antipsychotic drug (thiothixene) said to be as effective as most of the phenothiazines. Approved by the FDA. 

After first trimester carbamazepine, lamotrigine, oxcarbazepine, or valproate Second choice benzodiazepine (lorazepam) Third choice calcium channel blocker With psychosis first choice adjunctive high-potency typical antipsychotic (haloperidol, perphenazine, thiothixene, or trifluoperazine)... 

I Drug-Drug Interactions. Carbamazepine induces the hepatic cytochrome P450 isoenzymes (1A2, 3A4, 2C9/10, and 2D6), which increases the metabolism of many medications, such as anticonvulsants (i.e., lamotrigine, topiramate, and valproate), antidepressants (i.e., tricyclics and bupropion), antipsychotics (i.e., clozapine, haloperi-dol, fluphenazine, olanzapine, and thiothixene), benzodiazepines, oral contraceptives, and protease inhibitors. " Women who receive carbamazepine require higher dosages of oral contraceptives or alternative contraceptive methods." ... 

At the clinical level various obstacles to improved therapy also exist. One in particular is the widespread myth (or misconception) that the antipsychotic drugs are interchangeable. Since patient responses to different antipsychotics can actually differ substantially, the belief of some clinicians that they do not must invariably result in suboptimal treatment for many patients. In fact, it has been shown that the overlap area of responding patients to CPZ, fluphenazine, and trifluoperazine is very small, while perphenazine shows little or no overlapping response at all. In one comparison it was found that 89% of patients improved with thioridazine while only 59% did so when treated with thiothixene. Thiothixene also produced a higher rate of worsening effects (15% vs. 4%). 

Thiothixene (2 mg t.i.d. in mild cases) is indicated in the management of psychotic disorders. Thiothixene and chlor-prothixene are thioxanthene antipsychotics. Their select pharmacological properties are compared with chlorprom-azine and haloperidol and are shown in Table 2. 

Haloperidol is a member of the butyrophenone class of drugs. It thus has greater potency and less autonomic effects than thiothixene, a member of the thioxanthene class of antipsychotics. 

A. Classification The major chemical subgroups of antipsychotic drugs are the phenothiazines (eg, chlorpromazine, thioridazine, fluphenazine) the thioxanthenes (eg, thiothixene) and the butyrophenones (eg, halopeiidol). 

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