The human brain can react and adapt to many different types of drugs.

In this paper I will try to explain one such class of drug, called phenothiazine. It is better known that phenothiazine class drugs are the largest in between the eleven classes of neuroleptic antipsychotic drugs. The paper is interrelated into our class by the fact that phenothiazine class drugs are the most common class of drugs used by psychiatrics in treatments for patients who suffer from disorders such as schizophrenia. As with many drugs in the medical world, phenothiazine class drugs have their pros and cons as well, even though antipsychotic pharmaceutical phenothiazines are not prone to compulsive abuse. To better understand any disorder, it is very important to understand the drugs, which will be used in the patients treatment. This whole paper will be based upon the study/usage of the phenothiazine class, their side effects, and also how it alters a human's state of consciousness. Neuroleptic or antipsychotic drugs radically diminish the concentration of psychotic symptoms such as hallucinations, delusions, paranoid suspiciousness, disordered thinking, and confused speech in many mental patients especially those with schizophrenia. The most extensively used antipsychotic drugs are the phenothiazines, of which the first chlorpromazine that was sold as Thorazine in the United States and as Largactil in Canada and the United Kingdom has been accepted. Another neuroleptic drug known as haloperidol was put on the market as Haldol is about as helpful as the phenothiazines, but this drug brings on less sedation, which is needed for these types of patients (Julien 356). Clinicians may need to administer another type of neuroleptic drug to their patients when they do not respond to antipsychotic pharmaceutical phenothiazines (Schatzberg, Cole, & DeBattista 139). There are signs of improvement in

60 to 70 percent of the patients that receive the antipsychotic pharmaceutical phenothiazines, but there are approximately 30 percent of these patients who do not respond well enough to continue this type of treatment (Freedman 408). An altered state of consciousness is needed for most people who have schizophrenia, and therefore, the treatment of schizophrenia has long been the administering of the antipsychotic pharmaceutical phenothiazines. While the antipsychotic pharmaceutical phenothiazines have been used for other purposes such as the treatment for nausea and vomiting, most clinicians will agree that the antipsychotic pharmaceutical phenothiazines primary purpose in the clinic setting has been to sedate patients and to manage hallucinations (DeLeon, Fox, Newman, Sammons, Dunivin, and Baker 297). The antipsychotic pharmaceutical phenothiazines are absorbed from the gastrointestinal tract, and therefore, clinicians often administer them orally unless an intramuscular injection is needed to alter the conscious state of the patient by sedating them (DeLeon, Fox, Newman, Sammons, Dunivin, and Baker 297). The clinician is often advised that the patients state of mind will be altered four to ten times faster when antipsychotic pharmaceutical phenothiazines are administered through the bloodstream rather than reaching the patient through digestive system. The levels of antipsychotic pharmaceutical phenothiazines are usually found in trace amounts in the brain especially compared to the levels found in other body tissues, the highest concentrations are found in the lungs, live, adrenal glands and the spleen (DeLeon, Fox, Newman, Sammons, Dunivin, and Baker 297). The antipsychotic pharmaceutical phenothiazines have half-lives of 24 to 48 hours, and they are slowly metabolized in the liver (DeLeon, Fox, Newman, Sammons, Dunivin, and

Baker 298). The clinical effects of a single dose persist for at least 24 hours. It is for this reason, that clinicians will administer the daily dose at bedtime because they have an excessive sedation effect, and it also minimizes certain side effects. The antipsychotic pharmaceutical phenothiazines become extensively bound to body tissues, which partially accounts for their slow rate of elimination. Metabolites of some of the antipsychotic pharmaceutical phenothiazines can be detected for several months after the pharmaceutical has been discounted. Due to slow elimination, the residue of the pharmaceutical can contribute to the slow rate of recurrence of psychotic episodes during the cessation of the pharmaceutical therapy. Most patients experience an altered state of consciousness because the antipsychotic pharmaceutical phenothiazines block the dopamine-2 receptors as well as blocking acetylcholine, histamine, and norepinephrine receptors (Keltner and Folks 520). Most patients will experience an altered state of consciousness with the blockade of the acetylcholine as well as dry mouth, dilated pupils, blurred vision, constipation, urinary retention, and tachycardia. Specific to an altered state of consciousness, the blockade of norepinephrine and histamine receptors usually causes patients to feel sedated or in a state of hypotension (Keltner and Folks 520). Most patients will experience an altered state of consciousness as the antipsychotic pharmaceutical phenothiazines block the dopamine-2 receptors and the dopamine secreting neurons which are located in the central midbrain portion of the brain stem that send axonal projections to the parts of the patients limbic system that regulates emotional expressions as well as to the limbic forebrain areas, were thought and emotions are integrated (Keltner and Folk 522). Clinicians will find the hypothesized patient

response optimal for patients with schizophrenia because of an increased sensitivity of dopamine receptors in those areas may be responsible for the positive symptomatology of schizophrenia (Carpenter 71). The antipsychotic pharmaceutical phenothiazines are believed to decrease most patients paranoia, fear, hostility, and agitation as well the intensity of schizophrenic delusions and hallucinations. The antipsychotic pharmaceutical phenothiazines are also thought to dramatically relieve the agitation, restlessness, and the hyperactivity associated with patients that show symptoms of an acute schizophrenia attack (Green, Kern, and Heaton 34). The delusions and hallucinations are particularly sensitive to the antipsychotic pharmaceutical phenothiazines treatment. Chlorpromazine is the best-known representative of the antipsychotic pharmaceutical phenothiazines. Although it is considered to be a low potency agent, it is still frequently used (Keltner and Folks 525). It is one of the most sedative antipsychotic pharmaceutical phenothiazines and is therefore very effective in the treatment of agitated and violent schizophrenic patients. Extrapyramidal effects are seen with a rather low incidence. However, it displays marked anticholinergic activity. There have been reports of hepatotoxicity, also in patients with previously normal hepatic functions due to chlorpromazine. Alimemazine and triflupromazine are other pharmaceuticals from this group that can be used in the treatment of schizophrenic patients. The piperazines include fluphenazine, trigluoperazine, prochlorperazine, perazine and perphenazine (Keltner and Folks 525). They are agents with a high antipsychotic potency with less pronounced anticholinergic effects. However, their potential to produce extrapyramidal effects is more pronounced. Fluphenazine is a short agent that can be used in the management of agitated and

potentially violent patients (Keltner and Folks 525). The hydrochloride formulation of fluphenazine is frequently used for parenteral administration. Fluphenazine decanoate is a widely used depot. Although its principle pharmacological activities are similar to those of other antipsychotic pharmaceutical phenothiazines, fluphenazine displays only weak sedative action and it shows little anticholinergic and hypotensive effects. Trifluoperazine is also a more potent antipsychotic than chlorpromazine with only minor sedative, anticholinergic and cardiovascular activity (Keltner and Folks 525). The impact on the brain stem from the antipsychotic pharmaceutical phenothiazines more than likely will trigger an altered state of consciousness in most patients because it is through the actions on the brain stem that the antipsychotic pharmaceutical phenothiazines suppress the centers involved in behavioral arousal (the ascending reticular activating center) and vomiting (the chemoreceptor trigger zone) (Carpenter 71). The antipsychotic pharmaceutical phenothiazines suppress activity in the reticular as well as induce an indifference to external stimuli, which reduces the inflow of sensory stimuli that would otherwise reach higher brain centers. Unfortunately, up to 90 percent of patients who receive treatment with antipsychotic pharmaceutical phenothiazines experience the syndromes of acute extrapyramidal reactions early on, and tardive dyskinesia, which occurs later during and even after the cessation of the antipsychotic pharmaceutical phenothiazines treatment (Carpenter 72). These symptoms occur when the concentration of dopamine in the nuclei of the basal ganglia (caudate nucleus, putamen, and globus pallidus) decreases to about twenty percent of normal. Here the neuroleptic pharmaceutical induced blockade of dopamine receptors in excess of eighty percent occupancy produces side effects. The antipsychotic pharmaceutical

phenothiazines produce these two main kinds of motor disturbances, which comprise both the most bothersome and the most serious side effects associated with the use of these agents. Acute extrapyramidal side effects are threefold: akathesia, dystonia, and neurolepticinduced Parkinson (Andreasen and Olsen 792). Akathesia is a syndrome where patients experience feelings of anxiety that are often accompanied by restlessness, pacing, constant rocking back and forth, and other repetitive purposeless actions. Dystonia is characterized when patients experience involuntary muscle spasms and sustained abnormal, bizarre postures of the limbs, trunk, face, and tongue. NeurolepticInduced Parkinson, which resembles idiopathic Parkinsons disease. Neuroleptic-induced Parkinson is characterized when patients exhibit symptoms of tremor at rest, rigidity of the limbs, and slowing of the movement with a reduction in spontaneous activity (Andreasen and Olsen 792). But the tardive dyskinesia is a much more puzzling and serious form of movement disorder. Unfortunately, some patients will exhibit involuntary hyperkinetic movements, often of the face and tongue but also of the trunk and limbs, which can be severely disabling. In addition, some patients will exhibit the characteristics of sucking and smacking of the lips, lateral jaw movements, and darting, pushing or the twisting of the tongue. Patients may also exhibit choreiform movements of the extremities. The tardive dyskinesia syndrome appears a few months to several years after the beginning of neuroleptic treatment, which leads clinicians to the description of tardive being irreversible (Andreasen and Olsen 792). The incidence of tardive dyskinesia has been estimated at more than 10 percent of patients who are treated with antipsychotic pharmaceutical phenothiazines, but this side effect depends greatly on

the dosage used by the patient, and the age of the patient as it is most common in patients older than 50 and particular type of pharmaceutical used. Clinicians may find it difficult to adequately control tar dive dyskinesia, and it may necessitate restarting the antipsychotic pharmaceutical phenothiazines or increasing the dosage, which is a problem if the Parkinson side affects are troublesome. It is likely that patients receiving treatment with antipsychotic pharmaceutical phenothiazines will experience emotions, eating and drinking, and sexual behavior due to the secretion of some pituitary hormones (Carpenter 72). Clinicians will want to know that when patients are given antipsychotic pharmaceutical phenothiazines, they trigger pathways of dopamine-secreting neurons that extend from the hypothalamus to the pituitary gland. The suppressing of the function of the hypothalamus caused by the antipsychotic pharmaceutical phenothiazines interrupts the functions of emotions, eating and drinking as well as sexual behavior (Fadem 24). By suppressing the appetite, food intake may be reduced. By suppressing the temperature-regulating centers of the hypothalamus, body temperature fluctuates widely with changes in room temperature. In addition, several body hormones are affected. This can result in breast enlargement in males and lactation in females. The antipsychotic pharmaceutical phenothiazines also reduce the release of hormones from the pituitary gland, which regulates the secretion of sex hormones (Corcoran, Walker, Huot, Mittal, Tessner, and Kestler, 673). For this reason, many male patients may experience the blocking of ejaculation, and in female patients, the libido may be decreased, ovulation may be blocked, and normal menstrual cycles may be suppressed, which would ultimately lead to infertility. Since the antipsychotic pharmaceutical phenothiazines have as side actions the blockade

of cholinergic receptors (an anticholinergic action) and histamine receptors (an antihistaminic effect), these actions may contribute to the patients decline in cognitive abilities as histamine blockade produces sedation and cholinergic blockade results in the interference with memory (Keltner and Folks 524). Yet there is a difference between the typical and atypical agents in antipsychotic, which do relate to the effects on the patients cognitive abilities. The atypical agents improve cerebral cortical acetylcholine function by inducing acetylcholine release from neurons. Since acetylcholine is necessary for the formation for memory, this action may contribute to positive effects on cognition. As with almost every kind of pharmaceutical drugs, clinicians are well aware that antipsychotic pharmaceutical phenothiazines do produce side effects in some patients, and these side effects can include dry mouth and dizziness to symptoms that are similar to Parkinsons disease. Symptoms similar to Parkinsons disease include muscle rigidity, restlessness, tremors, and slowed movement. Yet clinicians should also take into consideration that some of these side effects can be treated with medication. Clinicians should also understand that twenty-five percent of the patients that take chlorpromazine or haloperidol for several years develop an irreversible movement disorder called tardive dyskinesia. Tardive dyskinesia causes uncontrollable, repetitive actions that are demonstrative in the twitching of the face, the flaying of arms and legs, and the thrusting of the tongue (McEvoy 288). Currently there are also the atypical neuroleptic pharmaceuticals that are considered a newer generation of antipsychotic drugs. One such atypical neuroleptic pharmaceuticals is known as Clozarill, which has effects like those of the antipsychotic pharmaceutical phenothiazines, and it is less likely to cause movement disorders (Schatzberg, Cole, &

DeBattista 140). Clozapinehas helped many patients who do not respond to antipsychotic pharmaceutical phenothiazines even though they are no more effective. Still, patients who take clozapine have a slight risk of developing a fatal blood disease called agraulocytosis. Clinicians will want to recommend that patients who are treaded with clozapine should also be given weekly blood tests to detect early signs of this disease. In this way, clinicians often shy away using clozapine for treatment because of the increased costs and inconvenience. Clinicians usually prescribe clozapine when patients have not responded well to antipsychotic pharmaceutical phenothiazines or if a patient is not willing to have their blood drawn frequently. Several other atypical neuroleptic pharmaceuticals have recently been introduced such as Risperdal, Zyprexa, Seroquel, Geodon, and Abilify. Unfortunately, these pharmaceuticals are expensive, but they do have fewer side effects than clozapine, and they do not cause agranulocytosis (Schatzberg, Cole, and Debattista 141). Like clozapine, these newly released atypical neuroleptic pharmaceuticals reduce the negative symptoms of schizophrenia, such as lack of emotion, social withdrawal and reduced speech. There is some doubt though as to whether these newest atypical neuroleptic pharmaceuticals are significantly more effective than the antipsychotic pharmaceutical phenothiazines. One other side effects that may cause patients to resist the use of the atypical neuroleptic pharmaceuticals is that eighty percent of the patients may stop taking them due to weight gain, nervous tics, and other bothersome side effects.

The therapeutic use of antipsychotic pharmaceutical phenothiazines invariably leads to many side effects. Much of the art of managing schizophrenic patients being treated with

a phenothiazine lies in diagnosing and managing side effects (Keltner and Folks 524). In general, the high-potency phenothiazines, fluphenazine, trifluoperazine, and perphenazine cause less sedation, fewer anticholinergic side effects, less postural hypotension, and more extrapyramidal side effects than the low-potency phenthiazines chlorpromazine and thioridazine. The antipsychotic pharmaceutical phenothiazines can be divided in the aliphatic phenothiazines with a dimethylaminopropyl group, those with a piperazine structure and agents with a piperidine structure (Keltner and Folks 525).

The piperidines of thioridazine, pipothiazine and pericyazine have the lowest potential to cause extrapyramidal effects (Keltner and Folks 526). Piperidines are just organic compounds which include the molecular formula (CH2)5NH. Thioridazine is one of the most sedative antipsychotic pharmaceutical phenothiazines, and it is known to decrease inotropic activity of digitalis by its quinidine-like action, which can cause myocardial depression, decreased efficiency of repolarization and increased risk of tachyarrhythmia. With thioridazine pharmaceuticals, there is the possibility that a patient could experience sexual dysfunction and especially cardio toxicity with prolongation of the QT-interval is more frequently seen than with other antipsychotic pharmaceutical phenothiazines. For this reason, thioridazine has been withdrawn from the market in many countries. Anticholinergic properties are highest in the aliphatic and piperidine groups and are lowest in the piperazine pharmaceuticals.

In conclusion, phenothiazine class drugs are the most common used in treatment for patients who suffer from schizophrenia. It is still amazing how this class of drugs have

the power to help patients who suffer from this disorder, which left untreated can lead to bigger issues such as Parkinsons or Huntingtons disease. Perhaps one of the few positive and distinctive attributes of these antipsychotic pharmaceutical phenothiazines is that they are not prone to compulsive abuse. They do not produce tolerance, physical dependence, or psychological dependence (Keltner and Folks 525). Schizophrenic patients may take antipsychotic pharmaceutical phenothiazines for years without increasing their dose because of tolerance, if a dose is increased; it is usually done to increase the control of psychotic episodes.

Works Cited

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Corcoran, C., Walker, E. F., Huot, R., Mittal, V. A, Tessner, K., and Kestler, K. (2003). The stress cascade and schizophrenia: Etiology and onset. Schizophrenia Bulletin, 29 (4), 671-692. Print.

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Green, M. F., Kern, R. S., & Heaton, R. K. 2004. Longitudinal Studies of Cognition and Functional Outcome in Schizophrenia. Schizophrenia Research, 72, 41-51. Print.

Keltner, Norman, and David Folks. 2008. Psychotropic drugs. Ann Arbor: University of Michigan. Print.

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Schatzberg, A. F., J. O. Cole, and C. DeBattista. 2007. Manual of Clinical Psychopharmacology Washington, D.C., American Psychiatric Press. Print.