Antipsychotic Drugs PDF

11/27/23, 3:45 AM Realizeit for Student Antipsychotic Drugs Antipsychotic drugs, formerly known as neuroleptics, are used to treat the symptoms of psychosis, such as the delusions and hallucinations seen in schizophrenia, schizoaffective disorder, and the manic phase of bipolar disorder. Off-label...

11/27/23, 3:45 AM Realizeit for Student Antipsychotic Drugs Antipsychotic drugs, formerly known as neuroleptics, are used to treat the symptoms of psychosis, such as the delusions and hallucinations seen in schizophrenia, schizoaffective disorder, and the manic phase of bipolar disorder. Off-label uses of antipsychotics include treatment of anxiety and insomnia; aggressive behavior; and delusions, hallucinations, and other disruptive behaviors that sometimes accompany Alzheimer disease. Antipsychotic drugs work by blocking receptors of the neurotransmitter dopamine. They have been in clinical use since the 1950s. They are the primary medical treatment for schizophrenia and are also used in psychotic episodes of acute mania, psychotic depression, and drug-induced psychosis. Clients with dementia who have psychotic symptoms sometimes respond to low dosages of conventional antipsychotics. Second-generation antipsychotics can increase mortality rates in elderly clients with dementia-related psychosis. Shortterm therapy with antipsychotics may be useful for transient psychotic symptoms such as those seen in some clients with borderline personality disorder. Mechanism of Action The major action of all antipsychotics in the nervous system is to block receptors for the neurotransmitter dopamine; however, the therapeutic mechanism of action is only partially understood. Dopamine receptors are classified into subcategories (D1, D2, D3, D4, and D5), and D2, D3, and D4 have been associated with mental illness. The conventional, or first-generation, antipsychotic drugs are potent antagonists (blockers) of D2, D3, and D4. This not only makes them effective in treating target symptoms but also produces many extrapyramidal side effects (discussion to follow) because of the blocking of the D2 receptors. Newer, atypical or second-generation antipsychotic drugs, such as clozapine (Clozaril), are relatively weak blockers of D2, which may account for the lower incidence of extrapyramidal side effects. In addition, second-generation antipsychotics inhibit the reuptake of serotonin, as do some of the antidepressants, increasing their effectiveness in treating the depressive aspects of schizophrenia. Paliperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), and lurasidone (Latuda) are the newest second-generation agents. Paliperidone (Invega) is chemically similar to risperidone (Risperdal); however, it is an extendedrelease preparation. This means the client can take one daily dose in most cases, which may be a factor in increased compliance. Asenapine (Saphris) is a sublingual tablet, so clients must avoid food or drink for 10 to 15 minutes after the medication dissolves. The third generation of antipsychotics, called dopamine system stabilizers, is being developed. These drugs are thought to stabilize dopamine output; that is, they preserve or enhance dopaminergic transmission when it is too low and reduce it when it is too high. This results in control of symptoms without some of the side effects of other antipsychotic medications. Aripiprazole (Abilify), the first drug of this type, was approved for use in 2002. Cariprazine (Vraylar) and https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 1/25 11/27/23, 3:45 AM Realizeit for Student brexpiprazole (Rexulti) are newer third-generation antipsychotics. These drugs are used for schizophrenia, manic episodes, and as adjunct medication in both bipolar disorder and depression. The most common side effects are sedation, weight gain, akathisia, headache, anxiety, and nausea (Stahl, 2017). Six antipsychotics are available in depot injection, a time-release form of intramuscular medication for maintenance therapy. Two first-generation antipsychotics use sesame oil as the vehicle for these injections, so the medication is absorbed slowly over time; thus, less frequent administration is needed to maintain the desired therapeutic effects. Decanoate fluphenazine (Prolixin) has a duration of 7 to 28 days, and decanoate haloperidol (Haldol) has a duration of 4 weeks. After the client’s condition is stabilized with oral doses of these medications, administration by depot injection is required every 2 to 4 weeks to maintain the therapeutic effect. Risperidone (Risperdal Consta), paliperidone (Invega Sustenna), and olanzapine pamoate (Zyprexa Relprevv), second-generation antipsychotics, encapsulate active medication into polymer-based microspheres that degrade slowly in the body, gradually releasing the drug at a controlled rate. Risperdal Consta, 25 mg, is given every 2 weeks. Invega Sustenna, 117 mg, is given every 4 weeks. Zyprexa Relprevv can be given 210 mg every 2 weeks or 405 mg every 4 weeks. Zyprexa Relprevv has the potential to cause postinjection delirium/sedation syndrome, including sedation, confusion, disorientation, agitation, and cognitive impairment that can progress to ataxia, convulsions, weakness, and hypertension, which can lead to arrest. For that reason, the client must be directly observed by a health care professional for 3 hours after the injection and must be alert, oriented, and symptom-free before he or she can be released (Meyers et al., 2017). Aripiprazole (Abilify Maintena), a thirdgeneration antipsychotic, is slowly absorbed into the bloodstream because of insolubility of aripiprazole particles (Otsuka America Pharmaceuticals, 2018). After initiation with oral medication, Abilify Maintena 400 mg is given monthly. WARNING - Atypical Antipsychotics Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk for death. Causes of death are varied, but most appear to be either cardiovascular or infectious in nature. Side Effects Extrapyramidal Side Effects Extrapyramidal symptoms (EPSs), serious neurologic symptoms, are the major side effects of antipsychotic drugs. They include acute dystonia, pseudoparkinsonism, and akathisia. Although often collectively referred to as EPSs, each of these reactions has distinct features. One client can https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 2/25 11/27/23, 3:45 AM Realizeit for Student experience all the reactions in the same course of therapy, which makes distinguishing among them difficult. Blockade of D2 receptors in the midbrain region of the brain stem is responsible for the development of EPSs. First-generation antipsychotic drugs cause a greater incidence of EPSs than do second-generation antipsychotic drugs, with ziprasidone (Geodon) rarely causing EPSs (Virani, Bezchlibnyk-Butler, & Jeffries, 2017). WARNING - Geodon Contraindicated in patients with a known history of QT prolongation, recent myocardial infarction, or uncompensated heart failure, it should not be used with other QT-prolonging drugs. Therapies for acute dystonia, pseudoparkinsonism, and akathisia are similar and include lowering the dosage of the antipsychotic, changing to a different antipsychotic, or administering anticholinergic medication (discussion to follow). While anticholinergic drugs also produce side effects, atypical antipsychotic medications are often prescribed because the incidence of EPSs associated with them is decreased. Acute dystonia includes acute muscular rigidity and cramping, a stiff or thick tongue with difficulty swallowing, and, in severe cases, laryngospasm and respiratory difficulties. Dystonia is most likely to occur in the first week of treatment, in clients younger than 40 years, in males, and in those receiving high-potency drugs such as haloperidol and thiothixene. Spasms or stiffness in muscle groups can produce torticollis (twisted head and neck), opisthotonus (tightness in the entire body with the head back and an arched neck), or oculogyric crisis (eyes rolled back in a locked position). Acute dystonic reactions can be painful and frightening for the client. Immediate treatment with anticholinergic drugs, such as intramuscular benztropine mesylate (Cogentin) or intramuscular or intravenous diphenhydramine (Benadryl), usually brings rapid relief. Drug-induced parkinsonism, or pseudoparkinsonism, is often referred to by the generic label of EPS. Symptoms resemble those of Parkinson disease and include a stiff, stooped posture; masklike facies; decreased arm swing; a shuffling, festinating gait (with small steps); cogwheel rigidity (ratchetlike movements of joints); drooling; tremor; bradycardia; and coarse pill-rolling movements of the thumb and fingers while at rest. Parkinsonism is treated by changing to an antipsychotic medication that has a lower incidence of EPS or by adding an oral anticholinergic agent or amantadine, which is a dopamine agonist that increases transmission of dopamine blocked by the antipsychotic drug. Akathisia is reported by the client as an intense need to move about. The client appears restless or anxious and agitated, often with a rigid posture or gait and a lack of spontaneous gestures. This feeling of internal restlessness and the inability to sit still or rest often leads clients to discontinue https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 3/25 11/27/23, 3:45 AM Realizeit for Student their antipsychotic medication. Akathisia can be treated by a change in antipsychotic medication or by the addition of an oral agent such as a beta-blocker, anticholinergic, or benzodiazepine. Akathisia Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome (NMS) is a potentially fatal idiosyncratic reaction to an antipsychotic (or neuroleptic) drug. The major symptoms of NMS are rigidity; high fever; autonomic instability such as unstable blood pressure, diaphoresis, and pallor; delirium; and elevated levels of enzymes, particularly creatine phosphokinase. Clients with NMS are usually confused and often mute; they may fluctuate from agitation to stupor. All antipsychotics seem to have the potential to cause NMS, but high dosages of high-potency drugs increase the risk. NMS most often occurs in the first 2 weeks of therapy or after an increase in dosage, but it can occur at any time. Dehydration, poor nutrition, and concurrent medical illness all increase the risk for NMS. Treatment includes immediate discontinuance of all antipsychotic medications and the institution of supportive medical care to treat dehydration and hyperthermia until the client’s physical condition stabilizes. After NMS, the decision to treat the client with other antipsychotic drugs requires full discussion between the client and the physician to weigh the relative risks against the potential benefits of therapy. Tardive Dyskinesia Tardive dyskinesia (TD), a syndrome of permanent involuntary movements, is most commonly caused by the long-term use of conventional antipsychotic drugs. About 20% to 30% of patients on long-term treatment develop symptoms of TD, and the pathophysiology is still unclear. The symptoms of TD include involuntary movements of the tongue, facial and neck muscles, upper and lower extremities, and truncal musculature. Tongue thrusting and protruding, lip smacking, blinking, grimacing, and other excessive unnecessary facial movements are characteristic. After it has developed, TD is irreversible, although decreasing or discontinuing antipsychotic medications can arrest its progression. Unfortunately, antipsychotic medications can mask the beginning symptoms of TD; that is, increased dosages of the antipsychotic medication cause the initial symptoms to disappear temporarily. As the symptoms of TD worsen, however, they “break through” the effect of the antipsychotic drug. In 2017, the FDA approved valbenazine (Ingrezza) and deutetrabenazine (Austedo, Teva) as the first drugs to treat TD. These drugs are vesicular monoamine transporter 2 (VMAT2) inhibitors. It is believed that these drugs decrease activity of monoamines, such as dopamine, serotonin, and norepinephrine, thereby decreasing the abnormal movements associated with Huntington chorea and TD. Valbenazine has a dosage range of 40 to 80 mg daily, and deutetrabenazine ranges from 12 https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 4/25 11/27/23, 3:45 AM Realizeit for Student to 48 mg daily. Both drugs cause somnolence, QT prolongation, akathisia, and restlessness. In addition, valbenazine can cause nausea, vomiting, headache, and balance disturbances. Deutetrabenazine can also cause NMS and increased depression and suicidality in patients with Huntington chorea (Kim, Baker, & Levien, 2018). Preventing TD is the primary goal when administering antipsychotics. This can be done by keeping maintenance dosages as low as possible, changing medications, and monitoring the client periodically for initial signs of TD using a standardized assessment tool such as the Abnormal Involuntary Movement Scale. Clients who have already developed signs of TD but still need to take an antipsychotic medication are often given one of the atypical antipsychotic drugs that have not yet been found to cause or therefore worsen TD. Anticholinergic Side Effects Anticholinergic side effects often occur with the use of antipsychotics and include orthostatic hypotension, dry mouth, constipation, urinary hesitance or retention, blurred near vision, dry eyes, photophobia, nasal congestion, and decreased memory. These side effects usually decrease within 3 to 4 weeks but do not entirely remit. The client taking anticholinergic agents for EPSs may have increased problems with anticholinergic side effects. Using calorie-free beverages or hard candy may alleviate dry mouth, and stool softeners, adequate fluid intake, and the inclusion of grains and fruit in the diet may prevent constipation. Other Side Effects Antipsychotic drugs also increase blood prolactin levels. Elevated prolactin may cause breast enlargement and tenderness in men and women; diminished libido, erectile and orgasmic dysfunction, and menstrual irregularities; and increased risk for breast cancer. It can also contribute to weight gain. Weight gain can accompany most antipsychotic medications, but it is most likely with the secondgeneration antipsychotic drugs, with ziprasidone (Geodon) being the exception. Weight increases are most significant with clozapine (Clozaril) and olanzapine (Zyprexa). Since 2004, the FDA has made it mandatory for drug manufacturers that atypical antipsychotics carry a warning of the increased risk for hyperglycemia and diabetes. Though the exact mechanism of this weight gain is unknown, it is associated with increased appetite, binge eating, carbohydrate craving, food preference changes, and decreased satiety in some clients. Prolactin elevation may stimulate feeding centers, histamine antagonism stimulates appetite, and there may be an as yet undetermined interplay of multiple neurotransmitter and receptor interactions with resultant changes in appetite, energy intake, and https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 5/25 11/27/23, 3:45 AM Realizeit for Student feeding behavior. Penninx and Lange (2018) found that genetics can also make clients more prone to weight gain and metabolic syndrome. Metabolic syndrome is a cluster of conditions that increase the risk for heart disease, diabetes, and stroke. The syndrome is diagnosed when three or more of the following are present: Obesity—excess weight, increased body mass index (BMI), and increased abdominal girth because of fat deposits Increased blood pressure High blood sugar level High cholesterol—with at least 150 mg/dL of triglyceride; less than 40 mg/dL of high-density lipoprotein for women and 50 mg/dL for men Obesity is common in clients with schizophrenia, further increasing the risk for type 2 diabetes mellitus and cardiovascular disease. In addition, clients with severe, persistent mental illness are less likely to exercise or eat low-fat nutritionally balanced diets; this pattern decreases the likelihood that they can minimize potential weight gain or lose excess weight. The increased risk of heart disease results in a shorter life expectancy (Penninx & Lange, 2018). It is recommended that clients taking antipsychotics be involved in an educational program to control weight and decrease BMI. However, it can be a difficult task. Gill, Zechner, Zambo, Swarbrick, and Murphy (2016) found that clients had greater success when staff provided information and practical support when it was needed. Information about healthy eating and the need for physical activity was modified to account for the client’s cognitive difficulties where they existed. Community-based social support was provided to help clients make necessary changes over time in their home environments. Most antipsychotic drugs cause relatively minor cardiovascular adverse effects such as postural hypotension, palpitations, and tachycardia. Certain antipsychotic drugs, such as thioridazine (Mellaril), droperidol (Inapsine), and mesoridazine (Serentil), can also cause a lengthening of the QT interval. A QT interval longer than 500 ms is considered dangerous and is associated with lifethreatening dysrhythmias and sudden death. Although rare, the lengthened QT interval can cause torsade de pointes, a rapid heart rhythm of 150 to 250 beats/minute, resulting in a “twisted” appearance on the electrocardiogram (hence the name “torsade de pointes”). Thioridazine and mesoridazine are used to treat psychosis; droperidol is most often used as an adjunct to anesthesia or to produce sedation. Sertindole (Serlect) was never approved in the United States to treat psychosis but was used in Europe and was subsequently withdrawn from the market because of the number of cardiac dysrhythmias and deaths that it caused. WARNING - Droperidol, Thioridazine, and Mesoridazine https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 6/25 11/27/23, 3:45 AM Realizeit for Student May lengthen the QT interval, leading to potentially life-threatening cardiac dysrhythmias or cardiac arrest. Clozapine produces fewer traditional side effects than do most antipsychotic drugs, but it has the potentially fatal side effect of agranulocytosis. This develops suddenly and is characterized by fever, malaise, ulcerative sore throat, and leukopenia. This side effect may not manifest immediately and can occur up to 24 weeks after the initiation of therapy. Initially, clients needed to have a weekly white blood cell (WBC) count above 3,500/mm3 to obtain the next week’s supply of clozapine. Currently, all clients must have weekly WBCs drawn for the first 6 months. If the WBC is 3,500/mm3 and the absolute neutrophil count (ANC) is 2,000/mm3, the client may have these labs monitored every 2 weeks for 6 months and then every 4 weeks. This decreased monitoring is dependent on continuous therapy with clozapine. Any interruption in therapy requires a return to more frequent monitoring for a specified period of time. After clozapine has been discontinued, weekly monitoring of the WBC and ANC is required for 4 weeks. WARNING - Clozapine May cause agranulocytosis, a potentially life-threatening event. Clients who are being treated with clozapine must have a baseline WBC count and differential before initiation of treatment and a WBC count every week throughout treatment and for 4 weeks after discontinuation of clozapine. Client Teaching The nurse informs clients taking antipsychotic medication about the types of side effects that may occur and encourages clients to report such problems to the physician instead of discontinuing the medication. The nurse teaches the client methods of managing or avoiding unpleasant side effects and maintaining the medication regimen. Drinking sugar-free fluids and eating sugar-free hard candy ease dry mouth. The client should avoid calorie-laden beverages and candy because they promote dental caries, contribute to weight gain, and do little to relieve dry mouth. Methods to prevent or relieve constipation include exercising and increasing water and bulk-forming foods in the diet. Stool softeners are permissible, but the client should avoid laxatives. The use of sunscreen is recommended because photosensitivity can cause the client to sunburn easily. Clients should monitor the amount of sleepiness or drowsiness they feel. They should avoid driving and performing other potentially dangerous activities until their response times and reflexes seem normal. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 7/25 11/27/23, 3:45 AM Realizeit for Student If the client forgets a dose of antipsychotic medication, he or she can take the missed dose if it is only 3 or 4 hours late. If the dose is more than 4 hours overdue or the next dose is due, the client can omit the forgotten dose. The nurse encourages clients who have difficulty remembering to take their medication to use a chart and to record doses when taken or to use a pillbox that can be prefilled with accurate doses for the day or week. Treatment Psychopharmacology Antipsychotic medications, also known as neuroleptics, are prescribed primarily for their efficacy in decreasing psychotic symptoms. They do not cure schizophrenia; rather, they are used to manage the symptoms of the disease. The conventional, or first-generation, antipsychotic medications are dopamine antagonists. The atypical, or second-generation, antipsychotic medications are both dopamine and serotonin antagonists. The first-generation antipsychotics target the positive signs of schizophrenia, such as delusions, hallucinations, disturbed thinking, and other psychotic symptoms, but have no observable effect on the negative signs. The second-generation antipsychotics not only diminish positive symptoms but also lessen the negative signs of lack of volition and motivation, social withdrawal, and anhedonia for many clients. Maintenance Therapy Six antipsychotics are available as long-acting injections (LAIs), formerly called depot injections, for maintenance therapy. They are the following: Fluphenazine (Prolixin) in decanoate and enanthate preparations Haloperidol (Haldol) in decanoate Risperidone (Risperdal Consta) Paliperidone (Invega Sustenna) Olanzapine (Zyprexa Relprevv) Aripiprazole (Abilify Maintena) The vehicle for the first two conventional antipsychotic injections is sesame oil; therefore, the medications are absorbed slowly over time into the client’s system. The effects of the medications last 2 to 4 weeks, eliminating the need for daily oral antipsychotic medication. The duration of action https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 8/25 11/27/23, 3:45 AM Realizeit for Student is 7 to 28 days for fluphenazine and 4 weeks for haloperidol. The other four second-generation antipsychotics are contained in polymer-based microspheres that degrade slowly in the body. It may take several weeks of oral therapy with these medications to reach a stable dosing level before the transition to depot injections can be made. Therefore, these preparations are not suitable for the management of acute episodes of psychosis. They are, however, useful for clients requiring supervised medication compliance over an extended period. In addition, some studies have shown that the second-generation LAIs are more effective than oral forms of the medication in controlling negative symptoms and improving psychosocial functioning (Kane & Corell, 2017). Yet, clinicians may be reluctant to prescribe the LAIs because they assume patients are reluctant to have injections. Side Effects The side effects of antipsychotic medications are significant and can range from mild discomfort to permanent movement disorders. Because many of these side effects are frightening and upsetting to clients, they are frequently cited as the primary reason that clients discontinue or reduce the dosage of their medications. Serious neurologic side effects include extrapyramidal side effects (EPSs) (acute dystonic reactions, akathisia, and parkinsonism), tardive dyskinesia, seizures, and neuroleptic malignant syndrome (NMS; discussion to follow). Nonneurologic side effects include weight gain, sedation, photosensitivity, and anticholinergic symptoms, such as dry mouth, blurred vision, constipation, urinary retention, and orthostatic hypotension. Extrapyramidal Side Effects EPSs are reversible movement disorders induced by neuroleptic medication. They include dystonic reactions, parkinsonism, and akathisia. Dystonic reactions to antipsychotic medications appear early in the course of treatment and are characterized by spasms in discrete muscle groups, such as the neck muscles (torticollis) or eye muscles (oculogyric crisis). These spasms may also be accompanied by protrusion of the tongue, dysphagia, and laryngeal and pharyngeal spasms that can compromise the client’s airway, causing a medical emergency. Dystonic reactions are extremely frightening and painful for the client. Acute treatment consists of diphenhydramine (Benadryl) given either intramuscularly or intravenously, or benztropine (Cogentin) given intramuscularly. Pseudoparkinsonism, or neuroleptic-induced parkinsonism, includes a shuffling gait, masklike facies, muscle stiffness (continuous) or cogwheeling rigidity (ratchet-like movements of joints), drooling, and akinesia (slowness and difficulty initiating movement). These symptoms usually appear in the first few https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1up… 9/25 11/27/23, 3:45 AM Realizeit for Student days after starting or increasing the dosage of an antipsychotic medication. Treatment of pseudoparkinsonism and prevention of further dystonic reactions are achieved. Akathisia is characterized by restless movement, pacing, inability to remain still, and the client’s report of inner restlessness. Akathisia usually develops when the antipsychotic is started or when the dose is increased. Clients are typically uncomfortable with these sensations and may stop taking the antipsychotic medication to avoid these side effects. Beta-blockers such as propranolol have been most effective in treating akathisia, and benzodiazepines have provided some success as well. The early detection and successful treatment of EPSs is important in promoting the client’s compliance with medication. The nurse is most often the person who observes these symptoms or the person to whom the client reports symptoms. To provide consistency in assessment among nurses working with the client, a standardized rating scale for EPSs is useful. The Simpson–Angus scale for EPS is one tool that can be used. Tardive Dyskinesia Tardive dyskinesia, a late-appearing side effect of antipsychotic medications, is characterized by abnormal, involuntary movements such as lip smacking, tongue protrusion, chewing, blinking, grimacing, and choreiform movements of the limbs and feet. These involuntary movements are embarrassing for clients and may cause them to become more socially isolated. Tardive dyskinesia is irreversible once it appears, but decreasing or discontinuing the medication can arrest the progression. In addition, newly approved medications to treat tardive dyskinesia, valbenazine (Ingrezza) and deutetrabenazine (Austedo, Teva), are now available. Clozapine (Clozaril), an atypical antipsychotic drug, has not been found to cause this side effect, so it is often recommended for clients who have experienced tardive dyskinesia while taking conventional antipsychotic drugs. Screening clients for late-appearing movement disorders such as tardive dyskinesia is important. The Abnormal Involuntary Movement Scale (AIMS) is used to screen for symptoms of movement disorders. The client is observed in several positions, and the severity of symptoms is rated from 0 to 4. The AIMS can be administered every 3 to 6 months. If the nurse detects an increased score on the AIMS, indicating increased symptoms of tardive dyskinesia, he or she should notify the physician so that the client’s dosage or drug can be changed to prevent advancement of tardive dyskinesia. Abnormal Involuntary Movement Scale Examination Procedure Client identification: ________________________________________________________________________ Date: _________________ https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 10/25 11/27/23, 3:45 AM Realizeit for Student Rated by: ________________________________________________________________________________ Either before or after completing the examination procedure, observe the client unobtrusively at rest (e.g., in waiting room). The chair to be used in this examination should be a hard, firm one without arms. After the client is observed, he or she may be rated on a scale of 0 (none), 1 (minimal), 2 (mild), 3 (moderate), and 4 (severe) according to the severity of symptoms. Ask the client if there is anything in his or her mouth (i.e., gum, candy), and if there is, ask him or her to remove it. Ask the client about the current condition of his or her teeth. Ask the client if he or she wears dentures. Do teeth or dentures bother the client now? Ask the client whether he or she notices any movement in mouth, face, hands, or feet. If yes, ask to describe and ask to what extent the movements currently bother the client or interfere with his or her activities. 0 1 2 3 4 Have the client sit in chair with hands on knees, legs slightly apart, and feet flat on floor. (Look at entire body for movements while in this position.) 0 1 Ask the client to sit with hands hanging unsupported. If male, hands between legs; if 2 3 female and wearing a dress, hands hanging over knees. (Observe hands and other body 4 areas.) 0 1 2 3 Ask the client to open the mouth. (Observe tongue at rest within mouth.) Do this twice. 4 0 1 2 3 4 Ask the client to protrude the tongue. (Observe abnormalities of tongue movement.) Do this twice. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 11/25 11/27/23, 3:45 AM Realizeit for Student 0 1 Ask the client to tap the thumb with each finger as rapidly as possible for 10 to 15 2 3 seconds: separately with right hand, then with left hand. (Observe facial and leg 4 movements.) 0 1 2 3 Flex and extend the client’s left and right arms. (One at a time.) 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 Ask the client to stand up. (Observe in profile. Observe all body areas again, hips included.) Ask the client to extend both arms outstretched in front with palms down. (Observe trunk, legs, and mouth.) Have the client walk a few paces, turn, and walk back to the chair. (Observe hands and gait.) Do this twice. Seizures Seizures are an infrequent side effect associated with antipsychotic medications. The incidence is 1% of people taking antipsychotics. The notable exception is clozapine, which has an incidence of 5%. Seizures may be associated with high doses of the medication. Treatment is a lowered dosage or a different antipsychotic medication. Neuroleptic Malignant Syndrome NMS is a serious and frequently fatal condition seen in those being treated with antipsychotic medications. It is characterized by muscle rigidity, high fever, increased muscle enzymes (particularly, creatine phosphokinase), and leukocytosis (increased leukocytes). It is estimated that 0.1% to 1% of all clients taking antipsychotics develop NMS. Any of the antipsychotic medications can cause NMS, which is treated by stopping the medication. The client’s ability to tolerate other antipsychotic medications after NMS varies, but use of another antipsychotic appears possible in most instances. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 12/25 11/27/23, 3:45 AM Realizeit for Student Agranulocytosis Clozapine has the potentially fatal side effect of agranulocytosis (failure of the bone marrow to produce adequate white blood cells). Agranulocytosis develops suddenly and is characterized by fever, malaise, ulcerative sore throat, and leukopenia. This side effect may not be manifested immediately but can occur as long as 18 to 24 weeks after the initiation of therapy. The drug must be discontinued immediately. Clients taking this antipsychotic must have weekly white blood cell counts for the first 6 months of clozapine therapy and every 2 weeks thereafter. Clozapine is dispensed every 7 or 14 days only, and evidence of a white blood cell count above 3,500 cells/mm3 is required before a refill is furnished. Drug Therapy Overall, the goal of drug treatment is to relieve symptoms with minimal or tolerable adverse effects. In patients with acute psychosis, the goal during the first week of treatment is to decrease symptoms (e.g., aggression, agitation, combativeness, hostility) and normalize patterns of sleeping and eating. The next goals may be increased ability for self-care and increased socialization. Therapeutic effects usually occur gradually, over 1 to 2 months. Long-term goals include increasing the patient’s ability to cope with the environment, promoting optimal functioning in self-care and activities of daily living, and preventing acute episodes and hospitalizations. With drug therapy, patients often can participate in psychotherapy, group therapy, or other treatment modalities; return to community settings; and return to their preillness level of functioning. Schizophrenia in children is often characterized by more severe symptoms and a more chronic course than in adults. Drug therapy in children has been largely empiric. However, research establishing an evidence base for treatment decisions in children and adolescents is growing. Dosage regulation is difficult because children may require lower plasma levels for therapeutic effects, but they also metabolize antipsychotic drugs more rapidly than do adults. The American Academy of Child and Adolescent Psychiatry has updated established practice guidelines that advocate for high-quality assessment of the child or adolescent receiving antipsychotic medications. The purpose of the practice guidelines is to promote the appropriate use of antipsychotic medications and to enhance safety in the pediatric population. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 13/25 11/27/23, 3:45 AM Realizeit for Student As a class, antipsychotics are also effective in the treatment of acute agitation, bipolar mania, and other psychiatric conditions. These drugs may be broadly categorized as (1) “typical,” “conventional,” or first-generation agents and (2) “atypical” or second-generation agents. Typical antipsychotic drugs fall into five different major chemical categories, including two that are discussed in this module—the phenothiazines, such as chlorpromazine, and older nonphenothiazines, such as haloperidol. In addition, the typical, first-generation drugs can be classified by potency. The level of potency refers to the size of the dose needed to produce a given response; all first-generation antipsychotics have the same ability to relieve symptoms of psychosis. Second-generation drugs, including clozapine and other related drugs, generally have lower risk of extrapyramidal adverse effects and tardive dyskinesia compared with the typical first-generation antipsychotics. Both generations of these drugs bind to D2 dopamine receptors and block the action of dopamine. However, binding to the receptors does not account for antipsychotic effects because binding occurs within a few hours after a drug dose, and antipsychotic effects may not occur until the drugs have been given for a few weeks. Prescribers caring for patients with psychosis have a greater choice of drugs than ever before. Some general factors to consider include the patient’s age and physical condition, the severity and duration of illness, the frequency and severity of adverse effects produced by each drug, the patient’s use of and response to antipsychotic drugs in the past, the supervision available, and the prescriber’s experience with a particular drug. People with schizophrenia usually need to take antipsychotics for years because there is a high rate of relapse (acute psychotic episodes) when drug therapy is discontinued, most often by patients who become unwilling or unable to continue taking their medication. With wider use of maintenance therapy and the newer, better-tolerated antipsychotic drugs, patients may experience fewer psychotic episodes and hospitalizations. Most antipsychotics are available in oral formulations. Patients who are unable or unwilling to take daily doses of an antipsychotic may receive periodic injections of long-acting forms of aripiprazole, fluphenazine, haloperidol, olanzapine, risperidone, or paliperidone. These long-acting injectable (LAI) antipsychotics may be an important therapeutic option for patients with schizophrenia; it allows a prescriber to tailor pharmacotherapy to each patient’s needs. The LAI form may serve to replace oral medications for patients who may have difficulty with medication adherence. These first- and second-generation antipsychotic LAIs are administered via “depot” injections. Depot refers to the way the drug is deposited and stored in the muscle before being absorbed. The injected drug takes time to move out of the muscle into the bloodstream, extending its action. However, extrapyramidal symptoms may be more problematic with depot injections of antipsychotics. Although some LAIs are https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 14/25 11/27/23, 3:45 AM Realizeit for Student expensive because they have been recently approved for use, they potentially reduce the financial burden of schizophrenia and improve quality of life. QSEN Alert: Safety All antipsychotics are identified in the Beers criteria as potentially inappropriate medications in patients 65 years and older with dementia. Antipsychotics should be avoided because they increase risk of mortality and cerebrovascular accidents as well as lead to a greater rate of cognitive decline. First-Generation Antipsychotics Health care providers have used the first-generation antipsychotics, including phenothiazines and nonphenothiazines, to treat psychosis since the 1950s. Although these drugs are historically significant, their usage and clinical importance have waned in recent years. Two drugs are identified as prototypes in this module. Chlorpromazine hydrochloride is the prototype drug of the phenothiazine groups, and Haloperidol (Haldol) is the prototype nonphenothiazine first-generation antipsychotic. Pharmacokinetics Chlorpromazine is well absorbed and distributed to most body tissues, and it reaches high concentrations in the brain. After oral administration, the onset of action is 30 to 60 minutes, with a peak of 2 to 4 hours and a duration of 4 to 6 hours. After intramuscular (IM) administration, the onset of action is 10 to 15 minutes, with a peak at 15 to 20 minutes and a duration of 4 to 6 hours. The half-life is 2 to 30 hours. The drug is metabolized in the liver and excreted in urine. Action The mechanism of action of chlorpromazine is not fully understood. When the drug produces antipsychotic effects, it blocks the postsynaptic dopamine receptors in the brain. Use The major clinical indication for chlorpromazine and other phenothiazine antipsychotics is schizophrenia. Other uses include treatment of psychotic symptoms associated with brain impairment induced by head injury, tumor, stroke, alcohol withdrawal, overdoses of CNS stimulants, and other disorders. It is necessary to individualize the dosage and route of administration of chlorpromazine according to the patient’s condition and response; in some cases, prescribers may exceed the recommended maximum dosage approved by the U.S. Food and Drug Administration (FDA). Use in Children https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 15/25 11/27/23, 3:45 AM Realizeit for Student Chlorpromazine is administered for the treatment of psychosis. The drug is not routinely administered to children under the age of 6 months. It is also used preoperatively for the control of restlessness and apprehension. In addition, it is administered rectally or intramuscularly for the control of nausea and vomiting. Use in Older Adults Chlorpromazine should be administered cautiously to older adults. The dosage of chlorpromazine should be started at one fourth to one third of the level for younger adults. Older adults are more likely to have problems for which chlorpromazine and other antipsychotic agents are contraindicated (e.g., severe cardiovascular disease, liver damage, Parkinson’s disease) or must be used very cautiously (diabetes mellitus, glaucoma, prostatic hypertrophy, peptic ulcer disease, chronic respiratory disorders). Use in Patients With Renal Impairment Excretion of chlorpromazine takes place in the kidneys, and therefore caution is necessary when using the drug in patients with impaired renal function. It is necessary to monitor renal function periodically during long-term therapy and lower the dosage or discontinue the drug altogether if test results (e.g., blood urea nitrogen) become abnormal. Use in Patients With Hepatic Impairment Chlorpromazine undergoes extensive hepatic metabolism, which means that caution is warranted in patients with hepatic impairment. In the presence of liver disease (e.g., cirrhosis, hepatitis), metabolism may be slowed and drug elimination half-lives prolonged, with resultant accumulation and increased risk of adverse effects. Use in Patients With Critical Illness Antipsychotic medications have been used for decades to treat symptoms associated with delirium in critically ill patients. Undesirable adverse effects caused by chlorpromazine include anticholinergic symptoms, hypotension, tachycardia, cardiac dysrhythmias, and extrapyramidal symptoms, which limit its use (see Adverse Effects). In addition, chlorpromazine has been shown to lower the seizure threshold. Because of these serious problems, chlorpromazine is generally not recommended for critically ill patients. There are other antipsychotic medications that have a lower adverse effect profile that may be more effective. Use in Patients Receiving Home Care People with chronic mental illness, such as schizophrenia, are among the most challenging in the caseload of the home care nurse. Major recurring problems include failure to take antipsychotic medications as prescribed and the concurrent use of alcohol and other drugs of abuse. Either https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 16/25 11/27/23, 3:45 AM Realizeit for Student problem is likely to lead to acute psychotic episodes and hospitalizations. The nurse must assist and support caregivers’ efforts to administer medications and manage adverse effects, other aspects of daily care, and follow-up psychiatric care. In addition, the nurse may need to coordinate the efforts of several health and social service agencies or providers. Adverse Effects Chlorpromazine has several adverse effects, including CNS effects: excessive sedation, with drowsiness, lethargy, fatigue, slurred speech, impaired mobility, and impaired mental processes. Extrapyramidal effects may also occur. Symptoms include movement disorders such as tardive dyskinesia, akathisia, dystonia, and drug-induced parkinsonism. Tardive dyskinesia occurs as the result of long-term chlorpromazine use. Patients may experience lip smacking, tongue protrusion, and facial grimaces and may have choreic movements of trunk and limbs. This condition is usually irreversible, and there is no effective treatment. Akathisia (motor restlessness and inability to be still), the most common extrapyramidal reaction, may occur about 5 to 60 days from the start of drug therapy. Dystonias are uncoordinated bizarre movements of the neck, face, eyes, tongue, trunk, or extremities. These adverse effects may occur suddenly 1 to 5 days after drug therapy is started and may be misinterpreted as seizures or other disorders. Drug-induced parkinsonism is loss of muscle movement (akinesia), muscular rigidity and tremors, shuffling gait, masked facies, and drooling. Neuroleptic malignant syndrome is a rare but potentially fatal reaction, which may occur hours to months after initial drug use. Symptoms of fever, muscle rigidity, respiratory failure, and confusion develop rapidly. Cardiovascular effects: prolonged QT and PR interval, T-wave blunting, and depression of the ST interval. Hematologic effects: agranulocytosis and pancytopenia. Other effects: antiadrenergic effects, such as hypotension, dizziness, fatigue, and faintness, as well as respiratory depression, endocrine effects, photosensitivity, and difficulty with temperature regulation. Contraindications Because of wide-ranging adverse effects, chlorpromazine may cause or aggravate a number of conditions. Contraindications include liver damage, coronary artery disease, cerebrovascular disease, parkinsonism, bone marrow depression, severe hypotension or hypertension, coma, and severely depressed states. Caution is warranted in seizure disorders, diabetes mellitus, glaucoma, prostatic hypertrophy, peptic ulcer disease, and chronic respiratory disorders, as well as in pregnancy, especially during the first trimester. Nursing Implications Preventing Interactions https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 17/25 11/27/23, 3:45 AM Realizeit for Student Many medications interact with chlorpromazine, increasing or decreasing its effects. The combination of the herbal supplement with kava results in increased dystonia. Administering the Medication For acute psychotic episodes, therapy with chlorpromazine may require IM administration and hospitalization. Control of symptoms usually occurs within 48 to 72 hours, after which the person takes the oral drug. It is necessary to obtain a baseline electrocardiogram (ECG) prior to administering the drug, because of associated risk of alterations in the cardiac rhythm. The nurse needs to check doses carefully, especially when starting or stopping an antipsychotic drug or substituting one for another. The dosages are often changed during the course of treatment. When the drug is started, it is usually necessary to titrate initial doses upward over days or weeks and then reduce them for maintenance. Discontinuation of the drug requires a gradual reduction in dosage. For IM administration, the nurse adheres to the following guidelines: Determine the dose, which is approximately half of an oral dose. IM doses avoid first-pass metabolism and produce serum drug levels approximately double those of oral doses. Change the needle after filling the syringe with the injectable medication. Give the injection in the ventrogluteal muscle with a 1½-inch needle. Have the patient lie down for 30 to 60 minutes after the injection to prevent orthostatic hypotension. Watch for idiopathic edema and muscle necrosis, which may occur with IM administration. For oral administration, the nurse adheres to the following guidelines: Give doses 1 to 2 hours before bedtime; peak sedation occurs in about 2 hours. Mix liquid concentrations with at least 60 mL of fruit juice. Avoid contact with skin because the liquid forms can cause contact dermatitis. Administer the oral preparation with food to reduce gastric upset. Use divided doses. Assessing for Therapeutic Effects With acute psychotic episodes, the nurse observes for decreased agitation, combativeness, and psychomotor activity. The sedative effects of chlorpromazine, considered to be therapeutic, occur within 48 to 72 hours. With acute or chronic psychosis, the nurse observes for decreased psychotic behaviors, such as decreased hallucinations and delusions. Assessing for Adverse Effects The nurse assesses the fluid and electrolyte status for a possible fluid volume deficit. It is also necessary to measure the patient’s weight daily and assess for signs of dehydration. In addition, the nurse assesses for increased anticholinergic effects, such as diminished fluid status and urinary retention. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 18/25 11/27/23, 3:45 AM Realizeit for Student The nurse assesses for aspiration related to depressed cough reflex. It is important to monitor renal and hepatic function along with the complete blood count. A depression in white blood cell count requires discontinuation of the medication. The nurse monitors for increased CNS depression that could result in falls or altered safety. He or she assesses for extrapyramidal effects such as dystonia, tardive dyskinesia, and akathisia. First-Generation Nonphenothiazines Nonphenothiazines include the first-generation antipsychotics, which are similar to phenothiazines in many ways. They were introduced approximately 50 years ago and are effective in treating acute psychosis, chronic psychotic disorders, and other psychiatric conditions. They are effective in treating both psychotic disorders and nonpsychotic depression. The first-generation antipsychotic medication Haloperidol (Haldol) is the prototype “typical” nonphenothiazine. This butyrophenone is a frequently used, long-acting antipsychotic. Pharmacokinetics Haloperidol is well absorbed after oral or IM administration. For the oral drug, the onset of action is 2 hours, with a peak of 2 to 6 hours and a duration of 8 to 12 hours. For the IM drug, the onset of action is 20 to 30 minutes, with a peak of 30 to 45 minutes and a duration of 4 to 8 hours. The halflife of the drug is 21 to 24 hours. It is metabolized in the liver and is excreted in urine and bile. Action The mechanism of action of haloperidol is not fully understood, but experts believe that the drug produces antipsychotic effects by blocking the postsynaptic dopamine receptors in the brain. Use Prescribers order haloperidol to control the symptoms of schizophrenia and psychotic disorders. Use in Children The FDA has issued a BLACK BOX WARNING ♦ regarding extrapyramidal and withdrawal symptoms in newborns who have been exposed to haloperidol. Withdrawal symptoms occur in newborns born to women who take haloperidol during the third trimester of pregnancy. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 19/25 11/27/23, 3:45 AM Realizeit for Student Use in Older Adults It is important to note that the FDA has not approved haloperidol for treatment of dementia-related psychosis. A BLACK BOX WARNING ♦ alerts health care practitioners that older patients who suffer from dementia and dementia-related psychosis and receive haloperidol have an increased risk of death compared with those patients who receive a placebo. (The deaths were related to cardiovascular or infectious diseases.) Use in Patients With Renal Impairment Excretion of haloperidol takes place in the kidneys, and therefore caution is necessary when using the drug in patients with impaired renal function. It is necessary to monitor renal function periodically during long-term therapy and lower the dosage or discontinue the drug altogether if test results (e.g., blood urea nitrogen) become abnormal. Use in Patients With Hepatic Impairment Haloperidol undergoes extensive hepatic metabolism. In the presence of liver disease (e.g., cirrhosis, hepatitis), metabolism may be slower, with resultant accumulation and increased risk of adverse effects. Thus, caution is necessary. Use in Patients With Critical Illness Haloperidol has relatively weak sedative effects and does not cause respiratory depression. However, it can cause hypotension in patients who are volume depleted or receiving antihypertensive drugs. It can also cause cardiac dysrhythmias, including life-threatening torsade de pointes, in patients who are receiving large doses (greater than 50 mg/day) or who have abnormal serum electrolyte levels (e.g., calcium, potassium, magnesium). Patients should be on a cardiac monitor, and it is necessary to check the ECG for a prolonged QT interval. Use in Patients Receiving Home Care Major recurring challenges face patients with psychosis and their caregivers in the home. Supporting efforts to stabilize positive and negative symptoms and cognitive function, take medications as prescribed, manage adverse effects, and follow-up psychiatric care may require the coordinated efforts of several health and social service agencies or providers. Adverse Effects Haloperidol has several adverse effects, including the following: Cardiovascular effects: abnormal T waves, prolonged ventricular depolarization, QT prolongation, torsade de pointes, tachycardia, and sudden death CNS effects: akathisia, hyperthermia, dystonia, extrapyramidal symptoms, neuroleptic malignant syndrome, parkinsonism, seizures, and vertigo Dermatologic effects: photosensitivity, hyperpigmentation, contact dermatitis, and alopecia https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 20/25 11/27/23, 3:45 AM Realizeit for Student Genitourinary effects: anticholinergic adverse effects such as urinary retention, sexual dysfunction, amenorrhea, breast engorgement and galactorrhea (women), and priapism and gynecomastia (men) Metabolic effects: hyperglycemia, hypoglycemia, and hyponatremia Respiratory effects: bronchospasm or laryngospasm Contraindications Contraindications to haloperidol include Parkinson's disease, seizure disorders, and severe mental depression. Nursing Implications Preventing Interactions Many medications and herbs interact with haloperidol, increasing or decreasing its effects. Administering the Medication Oral administration of haloperidol tablets requires taking the tablets with a full glass of water or milk. People should take them with food to decrease gastric upset. IM administration of haloperidol decanoate requires that the nurse gives the drug intramuscularly deep in the ventrogluteal muscle. (The amount injected should not exceed 3 mL.) During administration of the IM preparation, the patient should be in the recumbent position and remain recumbent for 1 hour following the administration. It is necessary to keep the preparation in a light-protected container. When discontinuing haloperidol, it is essential to taper the dosage to prevent extrapyramidal symptoms. If the medication is abruptly discontinued, the patient is at risk for this condition. Assessing for Therapeutic Effects When haloperidol is given for acute psychotic episodes, the nurse observes for sedation, decreased agitation, combativeness, and psychomotor activity. When the drug is given for acute or chronic psychosis, he or she observes for decreased psychotic behaviors, such as decreased hallucinations and delusions. Assessing for Adverse Effects The nurse assesses the ECG for tachycardia and other abnormalities. Also, he or she assesses the patient’s temperature for the onset of neuroleptic malignant syndrome. In addition, the nurse assesses for laryngospasm. Finally, it is necessary to monitor for the development of parkinsonism and extrapyramidal signs and symptoms, most notably tardive dyskinesia. Second-Generation “Atypical” Antipsychotics The “atypical” antipsychotics are the drugs of choice, especially for patients who are newly diagnosed with schizophrenia. These second-generation antipsychotics differ from first-generation https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 21/25 11/27/23, 3:45 AM Realizeit for Student agents in that they have a broader range of action due to their effects on the serotonergic, noradrenergic, and dopaminergic systems. They may be more effective in relieving some symptoms, they usually produce milder adverse effects, and patients seem to take them more consistently. Better adherence to the drug regimen helps prevent acute episodes of psychosis and repeated hospitalizations, thereby reducing the overall cost of health care, according to studies. A major drawback is the high cost of these drugs, which may preclude their use in some patients. Clozapine (Clozaril, Versacloz) is the prototype “atypical” antipsychotic. Pharmacokinetics Clozapine is an oral drug. Its onset of action is unknown, with a peak of 1 to 6 hours and a duration of weeks. The half-life is 12 hours. Clozapine crosses the placenta and enters the breast milk. The drug is metabolized in the liver, and it is excreted in the urine and in the feces. Action The mechanism of action of clozapine is not clearly understood. Apparently, the drug blocks the dopamine receptors in the brain, depressing the reticular activating system. It also blocks the serotonin and glutamate receptors. In addition, clozapine has anticholinergic, antihistamine, and alpha-adrenergic blocking activity. Use Clinicians consider clozapine and other “atypical” antipsychotics to be first-line therapy for schizophrenia. Prescribers use the drug to manage patients with severe schizophrenia who have not responded to standard antipsychotic medications. Other uses in psychosis include reducing the risk of recurrent suicidal behavior in patients with schizophrenia or with schizoaffective disorder. Clozapine is available only through a distribution system that ensures monitoring of white blood cell count and absolute neutrophil count. Use in Children Despite the wide range of benefits associated with clozapine treatment, use of this drug has been reserved for treatment-resistant children and adolescents because of its greater propensity to cause serious hematologic adverse events (agranulocytosis) compared with other first- and secondgeneration antipsychotic medications. The safety and effectiveness of clozapine in children have not been established. Use in Older Adults The FDA has issued a Black Box Warning related to the administration of clozapine and other second-generation antipsychotics to elderly patients with dementia. The risk of death is increased in these patients. The FDA has not approved the drug for use in dementia-related psychosis. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IVD5YOX6GjyN8BXsE5kBD64UN3Harx67qLkpTVXS1u… 22/25 11/27/23, 3:45 AM Realizeit for Student Use in Patients With Renal Impairment Although renal complications of clozapine use are very rare, it is essential that psychiatrists using clozapine are aware of the potent