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Home , Fluphenazine

FLUPHENAZINE

Dana Bartlett, RN, BSN, MSN, MA, CSPI

Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU and ER experience and over 20 years of as a poison control center information specialist. Dana has published numerous CE and journal articles, written NCLEX material, written textbook chapters, and done editing and reviewing for publishers such as Elsevier, Lippincott, and Thieme. He has written widely on the subject of toxicology and was a contributing editor, toxicology section, for Critical Care Nurse journal. He is currently employed at the Rocky Mountain Poison Control Center.

ABSTRACT

Fluphenazine is an that is used for the treatment of patients who have a psychotic disorder. It is used off-label to treat chorea associated with Huntington’s disease, chronic tic disorders, and and agitation associated with . Fluphenazine is a . The are a class of medications that are used as antiemetics and to treat psychiatric disorders. Fluphenazine’s mechanism of action is not completely understood but its antipsychotic effect is likely mediated through selective blockade of receptors in the brain. Fluphenazine may also affect peripheral alpha- receptors, receptors, and muscarinic receptors but fluphenazine’s ability to block these receptors is considered limited.

Policy Statement

1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 2.5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content is 2.5 hours.

Statement of Learning Need

Health clinicians need to know the indications, uses, contraindications and potential side effects of fluphenazine. An awareness of fluphenazine benefits and risks in oral and depot forms is necessary for clinicians to prescribe and monitor outcomes safely, and to prevent both side effects and relapse of symptoms in the setting of chronic mental illness.

Course Purpose

To inform health clinicians of practical learning points for the use of fluphenazine that clinicians can include in everyday practice, as well as the potential for side effects or overdose that may occur with fluphenazine.

Target Audience

2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Dana Bartlett, RN, BSN, MSN, MA, CSPI, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – All have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.

1. Fluphenazine is a piperazine phenothiazine and a first-generation

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a. . b. antipsychotic. c. mood stabilizer. d. .

2. Fluphenazine should be used cautiously in patients who have asthma, glaucoma or other visual problems because

a. of its cholinergic effects. b. it stimulates the neurotransmitter acetylcholine. c. it has a high potential to cause anticholinergic effects. d. of its possible anticholinergic effects.

3. Fluphenazine has an off-label use for the treatment of

a. chorea associated with Huntington’s disease. b. anticholinergic symptoms. c. severe central nervous system (CNS) . d. subcortical brain damage.

4. If a patient has hepatic impairment,

a. fluphenazine should be used cautiously. b. the adult dosage for fluphenazine may still be used. c. using fluphenazine is contraindicated. d. there are no specific dosing recommendations for fluphenazine.

5. A US Box Warning warns ______, who receive (such as fluphenazine) for the treatment of dementia-related psychosis, that they are at an increased risk for death.

a. elderly patients b. renally impaired patients c. patients with hepatic impairment d. patients with Huntington’s chorea

Introduction

4 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Fluphenazine is an antipsychotic that is used for the treatment of patients who have a psychotic disorder. Antipsychotic medications are typically the initial treatment for and fluphenazine has been successfully used to treat delusions and hallucinations. Fluphenazine is widely used to treat psychosis and may be administered in an oral and intramuscular (long acting) form. There are extensive possible adverse effects, which need to be reviewed with the patient when studying the drug profile and evaluating risks to the patient.

Pharmacological Profile

The information presented here is summarized from prescribing information and current published information relative to the basic pharmacological profile of fluphenazine. The clinical pearls section of drug use, which includes in-depth information on topics initially covered in the basic pharmacological profile, and a review of fluphenazine overdose will be covered in the next sections.

Category

First generation, ; phenothiazine derivative.2

Mechanism of Action

Fluphenazine is a piperazine phenothiazine. The phenothiazines are a class of medications that are used as antiemetics and to treat psychiatric disorders. Fluphenazine’s mechanism of action is not completely understood, but its antipsychotic effect is likely mediated through selective blockade of dopamine receptors in the brain. Phenothiazines have some effect on peripheral alpha-adrenergic receptors, histamine receptors, and muscarinic

5 nursece4less.com nursece4less.com nursece4less.com nursece4less.com receptors but fluphenazine’s ability to block these receptors is considered limited.2

Labeled Use

Treatment of patients who have a psychotic disorder.2

Off-Label Uses

Chorea of Huntington’s disease, chronic tic disorders, and psychosis and agitation associated with dementia.2

Dosing

Oral Tablets: The initial dose is 2.5 mg – 10 mg a day given in three-four divided doses. The maintenance dose is 1 mg – 5 mg a day and may be given as one dose.2

Intramuscular Injection - Fluphenazine Hydrochloride:

Initial dose is 1.25 mg, however some patients may need 2.5 mg – 10 mg a day and divided doses should be used every 6-8 hours. When the symptoms have stabilized, a switch may be made to the oral tablets.2

IM Injection - Fluphenazine Decanoate:

Intramuscular (IM) or subcutaneous (SQ) injection, 6.25 mg – 25 mg every 2 weeks. Once the patient has stabilized the effects of a dose may last for 4 - 6 weeks.2 Fluphenazine decanoate 12.5 mg given every three weeks is approximately equivalent to 10 mg of oral fluphenazine hydrochloride given daily.2

Available Forms

6 nursece4less.com nursece4less.com nursece4less.com nursece4less.com ● Oral concentrate: 5 mg/mL

● Oral elixir: 2.5 mg/5 mL

● Oral tablets: 1 mg, 2.5 mg, 5 mg, and 10 mg

● Fluphenazine decanoate injection: 25 mg/mL

● Fluphenazine hydrochloride injection: 2.5 mg/mL

All of the above are generic names for fluphenazine. The brand name is Prolixin.

US Boxed Warning

Elderly patients who receive antipsychotics for the treatment of dementia- related psychosis are at an increased risk for death. 2 Analyses of 17 placebo-controlled trials (most of the patients were taking atypical antipsychotics) found that the risk of death in the treated patients was 1.6 – 1.7 times that of the patients who received a placebo. The rate of death in the patients receiving an antipsychotic was 4.5%, for the placebo group it was 2.6%. Most of the deaths appeared to be from cardiovascular causes.

Contraindications

Contraindications include hypersensitivity to fluphenazine or to any of the components of the product. Fluphenazine is contraindicated if the patient has a blood dyscrasia, is comatose or has severe central nervous system (CNS) depression. Fluphenazine is also contraindicated if the patient is receiving large amounts of hypnotics, has hepatic disease, or subcortical brain damage. 2

Dosing Adjustment: Geriatric Patients

7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Oral: The initial dose should be 1 to 2.5 mg daily.2 The antipsychotics are identified by the Beers criteria as potentially inappropriate for patients 65 years or older.2 This issue will be discussed further in the Clinical Pearls section.

Dosing Adjustment: Hepatic Impairment

The use of fluphenazine is contraindicated if the patient has hepatic impairment.2

Dosing Adjustment: Renal Impairment

There are no specific dosing recommendations for fluphenazine for patients who have renal impairment.2

Adverse Effects

The incidence of the adverse effects of fluphenazine has not been reported in the prescribing information. Adverse effects of the typical antipsychotics (discussed more fully under the next section) may include: 1) Anticholinergic effects, 2) Blood dyscrasias, 3) Falls, 4) Central nervous system depression, , and seizures, 5) Metabolic effects: elevated level, and weight gain, 6) Orthostatic hypotension and QT interval prolongation, and 7) Neuroleptic malignant syndrome.2

Warning and Precautions

Anticholinergic Effects:

Fluphenazine can cause anticholinergic effects like blurred vision, constipation, urinary retention, and xerostomia but its potential for causing this adverse effect is considered low. Regardless, given the possibility of

8 nursece4less.com nursece4less.com nursece4less.com nursece4less.com anticholinergic effects occurring, fluphenazine should be used cautiously in patients who have asthma, benign prostatic hypertrophy (BPH), glaucoma or other visual problems, decreased gastric motility, or urinary retention.2

Cardiovascular:

Fluphenazine may cause orthostatic hypotension, and this can cause an angina attack, falls, and other adverse effects. Because of this possible adverse effect, fluphenazine should be used cautiously for patients who have cardiovascular (CV) disease, cannot tolerate orthostatic hypotension, such as elderly patients, have cerebrovascular disease, are taking other medications that may cause bradycardia or hypotension, or are volume depleted.2

Cardiac conditions such as QT prolongation, torsades de pointes, and sudden death have been associated with the use of fluphenazine and all the typical antipsychotics. Fluphenazine should be used cautiously if the patient has any condition with a predisposition to QT prolongation or torsades de pointes, including concurrent use of a medication that can cause prolonged QT interval, electrolyte abnormalities (hypocalcemia, hypokalemia, or hypomagnesemia) family history of prolonged QT, hypothyroidism, or a cardiac abnormality that puts the patient at risk for QT prolongation or torsades de pointes.2 The use of fluphenazine is not recommended if a patient has congenital long QT syndrome; this would put the patient at risk for torsade de pointes.3

Prior to starting therapy with fluphenazine, serum electrolytes should be measured, and a 12-lead ECG should be done. The QT interval is measured from the start of the Q wave to the end of the T wave. It consists of the QRS complex, the ST segment, and the T wave, and it measures the amount of time of ventricular depolarization and repolarization. The QTc is the

9 nursece4less.com nursece4less.com nursece4less.com nursece4less.com corrected QT interval, a measurement that adjusts for heart rate and provides a more accurate assessment of the risk for arrhythmias than the QT interval. The QTc interval can vary, but for men it is usually 470 msec or less and for women it is 480 msec or less.

Central Nervous System:

Fluphenazine may cause central nervous system depression. Extrapyramidal symptoms (EPS) are a common adverse effect of fluphenazine. These symptoms include acute dystonic reactions, akathisia, parkinsonism, and tardive . The risk of developing EPS appears to be specific to the EPS type or motor movement, and is possibly related to age, high doses, female gender, the patient’s response to antipsychotic medication, and the presence of comorbidities like alcoholism, brain injury, and diabetes.2 The presence of Parkinson disease is also a risk factor for developing EPS.2

Falls:

Fluphenazine can cause somnolence, motor instability, and orthostatic hypotension, all of which increase the risk for falling.2

Gastrointestinal:

Fluphenazine has been associated with esophageal dysmotility, dysphagia, and aspiration, and there is increased risk in patients > 75 years of age.2

Hematologic:

Agranulocytosis (sometimes fatal), leukopenia, and neutropenia have been reported during the clinical trials and during post-marketing experience with the typical antipsychotics.1,2 Patients who have a low white blood cell (WBC) count prior to taking fluphenazine or patients who have drug-induced

10 nursece4less.com nursece4less.com nursece4less.com nursece4less.com leukopenia may have an increased risk for these hematologic adverse effects.1,2 If a patient is taking fluphenazine and the WBC count is < 1000 mm3, the drug use should be discontinued and the WBC monitored.1

Hepatic:

Cholestatic jaundice and liver damage have been reported in association with the use of fluphenazine.1,2

Neuroleptic Malignant Syndrome:

Fluphenazine may cause neuroleptic malignant syndrome (NMS), a rare and potentially fatal adverse drug reaction characterized by autonomic instability, hyperthermia, muscle rigidity, and neurological changes.1,2

Ophthalmic:

The use of fluphenazine may cause pigmentary retinopathy, and lenticular and corneal deposits. The risk of such an adverse effect may be increased by prolonged use of the drug.1

Prolactin Levels:

Fluphenazine may increase serum prolactin levels.1,2

Renal:

Fluphenazine should be used cautiously if the patient has renal impairment and clinicians should consider discontinuing its use if there is evidence of renal damage.2

Seizure Disorder:

11 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Fluphenazine may lower the seizure threshold, and it should be used cautiously if the patient has a seizure disorder or a history of seizures.1,2

Temperature Regulation:

Fluphenazine may affect thermoregulation, and if a patient taking fluphenazine is exposed to high ambient temperatures, exercises strenuously, becomes dehydrated, or is taking another drug that has anticholinergic properties, an elevated temperature may develop.1,2

Venous Thromboembolism:

Antipsychotics have been associated with venous thromboembolism and pulmonary embolism.1

Withdrawal/Discontinuation:

The dose of an antipsychotic should be gradually tapered. Abrupt discontinuation of drug use can cause withdrawal signs and symptoms.1,2

Pregnancy and Breastfeeding

Pregnancy:

Fluphenazine has been classified as a pregnancy risk category C drug. Category C means that studies involving animals demonstrated harm to the fetus, there are no well-controlled studies of its effects on humans, and the benefits of using the drug during pregnancy may outweigh the risks.

The potential of a drug to cause fetal harm has been categorized by a system developed by the Food and Drug Administration (FDA). The system used five categories, A, B, C, D, and X. A drug would be considered category C if data from animal studies had shown adverse fetal effects, there were no

12 nursece4less.com nursece4less.com nursece4less.com nursece4less.com well controlled studies in humans, and the potential benefits of the drug may outweigh the risk of its use during pregnancy.

The A-X system is still widely used, albeit informally. However, the FDA has required manufacturers to no longer use the A-X system in prescribing information and to change package inserts to comply with the FDA’s Pregnancy and Lactation Labeling Rule (PLLR). Using the PLLR rule, the prescribing information must provide data about a pregnancy registry for the drug (if one exists), a risk summary, and clinical considerations. The FDA link for information about the PLLR may be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfor mation/Guidances/UCM450636.pdf.

Breastfeeding:

It is not known if fluphenazine is excreted in breast milk.

Drug Interactions

If a patient is taking fluphenazine, clinicians should check with a pharmacist or a reliable drug information source before administering anticholinergic drugs, anti-Parkinson drugs, CNS depressant drugs, drugs that lower the seizure threshold, CYP2D6 inhibitors (which can decrease the metabolism of fluphenazine) and drugs that can cause prolonged QT interval.4 Cross- reactivity with other phenothiazines may occur.

Clinical Pearls: Fluphenazine

13 nursece4less.com nursece4less.com nursece4less.com nursece4less.com The Clinical Pearls section is designed to provide practical learning points that clinicians can include in everyday practice. This section expands upon the earlier discussion on the drug Pharmacological Profile by focusing more specifically on the current research and case studies that inform clinicians on fluphenazine use, benefits and risks.

Fluphenazine and other similar drugs are often referred to as first- generation or typical antipsychotics because they were developed before the so-called second-generation antipsychotics like and . These drugs and the second-generation antipsychotics both share the same basic mechanism of action but the first-generation antipsychotics are more likely to cause side effects that were considered specific to and typical of that class of drugs. The typical antipsychotics are also called conventional antipsychotics, major tranquilizers, or neuroleptics.

The typical antipsychotics currently available in the U.S. include those in Table I below (trade names are in parentheses). The typical antipsychotics are sometimes referred to as high-potency or low-potency.1 The high- potency typical antipsychotics include fluphenazine, , , , , thiothixene, and ; they are used in doses from 1 mg and higher, and they have a high risk for EPS. These drugs have low activity at histaminic and muscarinic receptors so anticholinergic effects and sedation are less likely to occur.1

The low-potency typical antipsychotics, and , are dosed from 100 mg and they have a low risk for EPS. Low-potency typical antipsychotics have a high level of activity at histaminic and muscarinic receptors, so anticholinergic effects and sedation are likely to occur.1 Table 1: Typical Antipsychotics and Level of Potency

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Chlorpromazine (Thorazine): Low Potency Fluphenazine (Prolixin): High Potency Haloperidol (Haldol): High Potency Loxapine (Adasuve) Perphenazine (Trilafon) Pimozide (Orap) Thioridazine (Mellaril) Thiothixene (Navane) Trifluoperazine (Stelazine)

Labeled Uses

Psychosis:

Psychosis can be usefully, albeit somewhat broadly defined as loss of contact with reality.5 Psychosis is typically characterized by agitation, delusions, hallucinations, and thought disorganization, but the clinical presentation varies considerably.5 The three primary causes of psychosis are mental illness, substance-induced psychosis, and psychosis caused by a medical or neurological condition.5 Psychosis is very common in people who have schizophrenia. Specific treatment for psychosis will depend on the underlying cause, but the antipsychotics are often recommended to reduce symptoms like agitation, delusions, and hallucinations and to keep the patient safe until a definitive diagnosis can be made.5

The typical antipsychotics are considered essentially equivalent in effectiveness, and fluphenazine has been proven to produce a good response to treatment.1,6,7 When choosing which typical antipsychotic to use, primary consideration should be given to the adverse effect profile, the potential use of an intramuscular (IM) depot form (discussed later) and the appropriateness of drug use for a patient.

15 nursece4less.com nursece4less.com nursece4less.com nursece4less.com US Boxed Warning

In 2005 the Food and Drug Administration (FDA) issued a boxed warning stating that the atypical antipsychotics were associated with an increased risk for mortality when used to treat behavioral problems in elderly patients who had dementia. In 2008, the FDA extended this warning and confirmed that typical antipsychotics were associated with a risk of death in elderly patients through a randomized, placebo-controlled trial and a separate meta-analysis. Using these three sources the absolute increased risk for death was reported to be 1%-2%, but a more recent (2015) retrospective analysis concluded that the risk was higher, reporting an increased mortality risk of 2.0% (with ) to 3.8% (with haloperidol).8 Other research has also found that haloperidol has the highest risk for increased mortality.8 The number of patients in these studies who were taking fluphenazine was comparatively small; for example, in one of the three studies there were 26 patients taking fluphenazine and 8940 taking loxapine.

It is not clear why the antipsychotics were associated with an increased risk of mortality in this patient population.9 Most of the deaths were caused by myocardial infarction, pneumonia, and other morbidities that would not be unexpected given the age of the patients, but these diseases did not account for all the difference in mortality between the treated groups and the placebo groups.9

Behavioral and neuropsychiatric signs or symptoms are common in elderly patients who have dementia.10 The antipsychotics may be useful for managing behavioral and neuropsychiatric symptoms, but the evidence that supports their effectiveness for such symptoms is considered weak. These drugs have an adverse effect profile that, aside from the increased risk of death, makes them problematic for elderly, demented patients. In terms of

16 nursece4less.com nursece4less.com nursece4less.com nursece4less.com efficacy and safety they do not compare well with other medications or with behavioral interventions as a treatment for behavioral problems in elderly patients who have dementia, and authoritative sources recommend their use only when other treatments have been unsuccessful.8,10,11

Contraindications

Fluphenazine is contraindicated if the patient has a blood dyscrasia, is comatose or has severe central nervous system depression, is receiving large amounts of hypnotics, has hepatic disease, or has subcortical brain damage.2 Fluphenazine can cause CNS depression so its use would obviously be contraindicated in patients who had severe CNS depression, subcortical brain damage, or are receiving large amounts of hypnotics. The issues of fluphenazine use, blood dyscrasias and hepatic damage are discussed later.

Dosing Adjustment: Geriatric Patients

The antipsychotics are identified by the Beers Criteria as potentially inappropriate for patients 65 years or older.2 The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, commonly called the Beers Criteria, is a list produced by the American Geriatrics Society. The Beers Criteria, named after one of its founders, Dr. Mark Beers, identifies medications that should be avoided in older adults or used with caution and close monitoring because of an increased risk of harmful adverse effects in elderly patients.

The 2015 Beers Criteria categorizes the typical and atypical antipsychotics as potentially inappropriate for patients 65 years and older who have dementia because their use in this population is associated with an increased risk for stroke and a greater rate of cognitive decline and mortality. The Beers Criteria recommends that antipsychotics be used to treat behavioral

17 nursece4less.com nursece4less.com nursece4less.com nursece4less.com problems in elderly patients who have dementia only if non-pharmacologic therapies have not been effective and the problematic behaviors represent a risk to the patient or to others.11

Dosing Adjustment: Hepatic Impairment

The use of fluphenazine is contraindicated if the patient has hepatic impairment. Elevations of liver functions tests (LFTs) are a common occurrence in patients who are on long-term therapy with a phenothiazine,12 but the LFT abnormalities are usually mild (< 3 times the upper limit of normal), the patient is asymptomatic, and the LFTs return to normal, even if the patient continues to take the drug.12

Cholestatic jaundice associated with fluphenazine has rarely been reported (no published cases in the last 30 years), and this is an adverse effect associated with all the phenothiazines. Aside from chlorpromazine, serious liver injury from these drugs is very uncommon, and the mechanism of injury is unknown.1,12 However, cases of liver damage associated with phenothiazines have been reported that may have been caused by a hypersensitivity reaction.12 An authoritative review and prescribing information mention that cross-reactivity between phenothiazines may occur.2,12,13

Dosing Adjustment: Renal Impairment

There are no specific dosing recommendations for fluphenazine for patients who have renal impairment.2 The risk for acute kidney injury from the typical antipsychotics, and fluphenazine in particular, is very low.2,14 The anticholinergic effects of the antipsychotics can cause urinary retention, and the antipsychotics are strongly sedating; those that have a strong effect could cause urinary incontinence in debilitated patients.

18 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Warning and Precautions

Anticholinergic Effects:

Fluphenazine can cause anticholinergic effects like blurred vision, constipation, urinary retention, and xerostomia, but its potential for causing this adverse effect is considered low. Regardless, given the possibility of anticholinergic effects, fluphenazine should be used cautiously in patients who have asthma, benign prostatic hypertrophy, glaucoma or other visual problems, decreased gastric motility, or urinary retention.2

The visceral organs like the bladder, the bronchioles, the eyes, and the gastrointestinal tract are innervated by fibers of the parasympathetic and sympathetic divisions of the autonomic nervous system. The parasympathetic and sympathetic divisions act synergistically, but antipsychotic binding to muscarinic receptors prevents these receptors from being activated by acetylcholine, and the balance of sympathetic or parasympathetic activation is disrupted.

Muscarinic receptors are called cholinoreceptors because they are activated by acetylcholine. A medication that is a competitive inhibitor at muscarinic receptors is said to be have anticholinergic properties, and its use may cause a group of signs and symptoms that are called the anticholinergic syndrome. An example of this is stimulation of the muscarinic receptors in the urinary sphincter, which causes the sphincter to relax, whereas stimulation of the sympathetic receptors causes the urinary sphincter to contract. A medication that has anticholinergic properties can cause urinary retention and these drugs should be used cautiously in patients who have benign prostatic hypertrophy or urinary retention.

Orthostatic Hypotension:

19 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Fluphenazine has some peripheral alpha-adrenergic activity so it may cause orthostatic hypotension. Orthostatic hypotension is defined as an abnormal decrease in blood pressure after moving from a lying to a standing position. After five minutes of being supine the blood pressure is measured after the patient has been standing quietly for two to five minutes. At that point orthostatic hypotension is present if the systolic blood pressure has decreased ≥ 20 mmHg, the diastolic blood pressure has decreased ≥ 10 mmHg, or both.15

Moving from lying to standing can cause 500 – 1000 mL of blood to pool in the lower extremities and in the splanchnic circulation, decreasing both blood pressure and cardiac output and if the patient is volume depleted or cannot tolerate a sudden decrease in perfusion to the brain or the heart, orthostatic hypotension can cause serious consequences.15 Because of this possible adverse effect, fluphenazine should be used cautiously for patients who have cardiovascular disease, have cerebrovascular disease, are taking other medications that may cause bradycardia or hypotension, are volume depleted, and cannot tolerate orthostatic hypotension (elderly patients).2 Elderly patients are more likely to have orthostatic hypotension, probably due to decreased baroreceptor sensitivity.15

Cardiovascular - QT Prolongation:

Cardiovascular conditions of QT prolongation, torsades de pointes, and sudden death have been associated with the use of fluphenazine and all the typical antipsychotics. A prolonged QT interval, either drug-induced or congenital, is a risk factor for the development of torsades de pointes (also

20 nursece4less.com nursece4less.com nursece4less.com nursece4less.com called polymorphic ventricular tachycardia), a potentially lethal ventricular arrhythmia.

Drug-induced QT prolongation is defined as a QTc interval that is > 500 msec or a

QTc interval increase ≥ 60 msec of the patientʼs baseline QTc interval.17 Drug- induced acquired QT interval prolongation is relatively common, but medication-induced torsades de pointes is rare, and the use of a drug that prolongs the QT interval or a prolonged QT interval alone are seldom enough by themselves to cause torsades de pointes.18 Risk factors are almost always present when this arrhythmia occurs, and not all medications that prolong the QT interval will cause torsades de pointes. A drug-induced QT interval prolongation is not consistently predictive for torsades de pointes.19 Factors that prolong the QT interval and increase the risk for torsades de pointes in patients who have drug-induced, acquired QT prolongation may include those listed in Table 2.18

Table 2: Risk Factors for Torsades De Pointes

Advanced age Baseline prolonged QT interval Bradycardia Cardiovascular disease, hepatic disease, renal disease Electrolyte abnormalities, specifically hypocalcemia, hypokalemia, and hypomagnesemia Female gender High doses of a drug that prolongs the QT interval Overdose of a drug that can prolong the QT interval The use of drugs that inhibit the metabolism of a drug that causes prolonged QT interval. The use of multiple drugs that cause prolonged QT interval

21 nursece4less.com nursece4less.com nursece4less.com nursece4less.com The incidence of QTc prolongation and torsades de pointes caused by fluphenazine is not known, but regardless of the level of risk, a prudent clinician should carefully evaluate a patient before prescribing fluphenazine, determine the presence of risk factors, and carefully monitor the patient

during use. Jibson (2018) advised that high-risk typical antipsychotics should not

be given to a patient who has a QTc greater than 450 msec, and an

electrocardiogram (ECG) should be done at least once a year in patients who are

taking a high-risk typical antipsychotic, whenever the dose is changed, and for any

change in the patientʼs cardiac condition. If the QTc interval is > 500 msec or if the

QTc is ≥ 60 msec from baseline, the dose should be reduced or a different drug

prescribed.1 Clinicians can decide if they want to apply these standards for patients taking fluphenazine.

Fluphenazine should be used cautiously if the patient has any condition predisposing to QT prolongation or torsades de pointes, including concurrent use of a medication that can cause prolonged QT interval, electrolyte abnormalities (hypocalcemia, hypokalemia, or hypomagnesemia), family history of prolonged QT, hypothyroidism, or a cardiac abnormality that puts the patient at risk for QT prolongation or torsades de pointes.2

The use of fluphenazine is not recommended if the patient has congenital long QT syndrome as this may cause torsade de pointes.3 Prior to starting therapy with fluphenazine, serum electrolytes should be measured, and a 12-lead ECG should be done.

Central Nervous System

22 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Extrapyramidal symptoms are movement disorders that are caused by an interference with dopamine transmission in the nigrostriatal tract, an area of the brain that controls motor movements. Extrapyramidal symptoms are a well-known and common adverse effect of the typical antipsychotics, and the EPS symptoms that are caused by the typical antipsychotics include acute dystonic reactions, akathisia, Parkinsonism, and .1,20,21

Acute dystonic reactions are involuntary muscle movements that are caused by simultaneously occurring contractions of agonist and antagonist muscle groups. The muscle movements of a dystonic reaction are often repetitive, rhythmic, and patterned. Examples of dystonic reactions include , opisthotonos, and torticollis.

Dystonic reactions are a common adverse effect of the phenothiazines. Nguyen, et al. (2016) examined data from an adverse drug reaction database and found that among all the antipsychotics there were more dystonic reactions caused by haloperidol than by any other antipsychotic, typical and non-typical, but fluphenazine can be a cause, as well.22 Tardy, et al. (2014) compared fluphenazine with low-potency antipsychotics and reported dystonia had an incidence of 5% in patients taking fluphenazine.23

Akathisia is characterized by subjective feelings of restlessness, an intense feeling of a need to move, and observable movements like fidgeting and pacing. Akathisia develops within hours or days after beginning therapy with an antipsychotic, but akathisia can be delayed in onset (tardive akathisia), it can be acute or chronic (lasting > 3 months), and it has also been associated with discontinuation of an antipsychotic.23,24 In the review by Tardy, et al. (2014) the incidence of akathisia caused by fluphenazine was 15%,22 and akathisia caused by the antipsychotics has been reported to

23 nursece4less.com nursece4less.com nursece4less.com nursece4less.com have an overall prevalence of 18.5%.23 The frequency of acute akathisia caused by antipsychotics has been reported to be 8% - 76%, and chronic or tardive akathisia 0.1% - 41%.25

Drug-induced Parkinsonism causes signs and symptoms like those of the clinical presentation of Parkinson disease, such as bradykinesia, rigidity, and resting tremor. Parkinsonism typically begins within days to weeks after beginning therapy with an antipsychotic or after an increase in dose, but an onset of several months is possible.26 In most cases Parkinsonism will resolve when use of the drug is discontinued, but occasionally the signs and symptoms worsen, and they may persist.26

Parkinsonism is the most common EPS caused by the antipsychotics with a reported prevalence of up to 72%.26 There is little information about fluphenazine and Parkinsonism, but Nguyen, et al. (2016) found that fluphenazine is less likely to cause Parkinsonism than most of the other antipsychotics.22

Tardive dyskinesia is a late occurring EPS with an onset of months to years after beginning therapy with an antipsychotic; occasionally, it can occur after the patient has stopped taking the offending drug.27 Tardive dyskinesia is characterized by choreoathetoid movements of the extremities, face, mouth, tongue, or trunk; lip smacking, tongue thrusting, and facial grimacing are common and obvious forms of tardive dyskinesia.

The true incidence of tardive dyskinesia caused by antipsychotics is not known, however estimates range from > 20% - 32.4%, with a yearly increase of 5%.27-29 Given the severity of this adverse effect and that tardive dyskinesia is often irreversible, even a lesser degree of risk would still have

24 nursece4less.com nursece4less.com nursece4less.com nursece4less.com serious implications.27,30 The risk of tardive dyskinesia associated with fluphenazine is not known.

Factors that may increase the risk for developing tardive dyskinesia are listed in Table 3.21,27

Table 3: Risk Factors, Tardive Dyskinesia, and Antipsychotics

African American ethnicity or substance abuse Anticholinergic or Anti-Parkinson drugs Cognitive disturbance Diabetes Development of other EPS Early onset of EPS High dose and long duration of use HIV positive Female gender Mood disorder Older age Typical antipsychotics

As mentioned previously, the risk of developing EPS appears to be different for the specific EPS or abnormal motor movement, and is possibly related to age, high doses, female gender, use of an antipsychotic medication, and the presence of comorbidities like alcoholism, brain injury, diabetes, and Parkinson disease.2 Patients who are taking fluphenazine should be closely monitored for the development of EPS. Marder and Stroup (2018) recommended that when beginning therapy with an antipsychotic the patient should have weekly assessments for EPS until the same dose is taken for at

25 nursece4less.com nursece4less.com nursece4less.com nursece4less.com least two weeks, and biweekly assessments should be done whenever the dose is increased.21

Clinicians are encouraged to use standardized, validated assessment tools like the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Scale, and the Simpson-Angus Scale. The Simpson-Angus Scale is an assessment tool for detecting Parkinsonism.1,21 The AIMS test, the Barnes Akathisia Scale and the Simpson-Angus Scale are widely available online.

Falls:

Fluphenazine can cause somnolence, motor instability, and orthostatic hypotension, all of which increase the risk for falling.2 No specific information was located on the risk or incidence of falls associated with the use of fluphenazine, but the use of antipsychotics is associated with an increased risk for developing osteoporosis, falls, and fractures.31,32 In 2017 the FDA issued a warning that antipsychotic drugs may cause falls and fractures and advised that before initiating therapy with an antipsychotic, a fall risk assessment should be done and the assessment should be periodically repeated.1

Gastrointestinal:

Dysphagia is a well-documented, albeit very uncommon adverse effect of the typical antipsychotics and antipsychotic use has been associated with an increased risk of aspiration pneumonia.33,34 A 2018 study reported an incidence of aspiration pneumonia in 1.2% of hospitalized patients who were taking an antipsychotic, and 0.3% incidence in unexposed patients.35 The exact cause is unknown, but dysphagia in patients who are taking an antipsychotic may be an EPS that occurs by itself or with other EPS but is

26 nursece4less.com nursece4less.com nursece4less.com nursece4less.com not recognized as such.33 The incidence of, and risk for dysphagia and aspiration caused by fluphenazine is not known.

Hematologic:

Agranulocytosis, leukopenia, and neutropenia have been reported as rare adverse effects of all the typical antipsychotics.1,2,36 The incidence of, and risk for blood dyscrasias caused by fluphenazine is not known; there have been very few published reports on this topic and all of them are > 30 years old. There is limited information that suggests that blood dyscrasias caused by a typical antipsychotic resolve when use of the medication is stopped.36

Ophthalmic:

The use of fluphenazine may cause pigmentary retinopathy, and lenticular and corneal deposits. The risk of these adverse effects may be increased by prolonged use of the drug.1,2 Ocular adverse effects caused by the typical antipsychotics appear to be very rare and associated primarily with chlorpromazine and thioridazine; only one case report (2004) linking the use of fluphenazine to an ocular disorder (maculopathy) was found.

Neuroleptic Malignant Syndrome:

Neuroleptic malignant syndrome is a well-known and well-documented adverse effect of all antipsychotics, typical and atypical, and it can occur with normal use and also when therapy with an antipsychotic is abruptly discontinued.37,38 The onset of signs and symptoms usually begin within two weeks of starting therapy with an antipsychotic, and almost all cases of NMS occur within 30 days of the first dose.37,38 NMS can occur, however, after the first dose or after years of taking the same drug at the same dose, and the risk of developing NMS appears to be independent of the dose of

27 nursece4less.com nursece4less.com nursece4less.com nursece4less.com antipsychotic that is being taken.38 The pathophysiology of NMS is not understood, but is at least in part likely to be due to blockade.37,38

Neuroleptic malignant syndrome is a diagnosis of exclusion. Its presence cannot be confirmed by clinical tests and the four signs that have traditionally been used as the diagnostic criteria for NMS are altered consciousness (usually confusion), autonomic dysfunction (changes in blood pressure and pulse), hyperthermia, and muscular rigidity.37,38 Neuroleptic malignant syndrome is an idiosyncratic drug reaction and it is rare. Because it is a clinical diagnosis of exclusion the true incidence of NMS is not known, but has been estimated to be 0.01% - 3% of all patients who are taking an antipsychotic; the higher figure is from older research and the and more recent research estimated an incidence of 0.2%.37-39 The risk of developing NMS has been reported to be essentially the same for the typical and atypical antipsychotics. In an analysis of 111 cases of NMS, haloperidol was the cause of 49 cases (44% incidence of NMS).37 The mortality rate of NMS is reported to be 5.9% - 21%.38,40

The risk and incidence of NMS caused by fluphenazine is not known. Eleven case reports of NMS caused by fluphenazine were located in the medical literature, none were current (within the past five years) and most were published 25-30 years prior. Most case reports involved fluphenazine decanoate, and in some of the cases the patient had been taking several antipsychotics. If the patient has NMS, use of the offending drug should be discontinued.38

Treatment of NMS is primarily supportive, but the drugs and and the muscle relaxer dantrolene can be

28 nursece4less.com nursece4less.com nursece4less.com nursece4less.com effective.38 Restarting treatment with an antipsychotic after NMS has resolved is complicated and risky. Recurrence of NMS after restarting therapy with an antipsychotic has been reported to occur in 10%-90% of all patients who had an episode of NMS, and reoccurrence of NMS is unpredictable.38,40 Widjicks (2017) advised that the following steps may decrease the risk for recurrent NMS.38

● Wait at least two weeks after an episode of NMS has resolved before restarting therapy with an antipsychotic.

● Use a lower potency drug rather than high-potency one, for example, use thioridazine instead of haloperidol. ● Start with a low dose and increase the dose slowly, ● Make the sure the patient is well hydrated. ● Avoid the use of , if possible. Concurrent use of fluphenazine and lithium has been reported to cause NMS. ● Monitor the patient carefully and closely for signs or symptoms of NMS.

Prolactin Levels:

Prolactin is a hormone that is secreted by the pituitary gland. It is involved in hundreds of physiological processes, but it is most prominent for its role in lactation, ovulation, and breast development. Although there is inter- individual variability, the normal serum prolactin level is 10-20 ng/mL for men and 10-25 ng/mL for women.

Elevated prolactin levels are a common adverse effect of all the typical antipsychotics, occurring in approximately 40% - 90% of patients who are taking these drugs.41,42 Elevated prolactin levels caused by a typical antipsychotic increase the risk for ejaculatory and , , infertility, loss of libido, and menstrual abnormalities, and

29 nursece4less.com nursece4less.com nursece4less.com nursece4less.com these adverse effects can cause patients to stop taking the medication. Risk factors for antipsychotic-induced hyperprolactinemia may include the use of high-potency antipsychotics, high doses, female gender, and use during adolescence.42

Elevated prolactin levels caused by an antipsychotic often persist, but for some patients they will over time return to normal, and elevated prolactin levels have been shown to be present in up to 33% of patients with schizophrenia before beginning therapy with an antipsychotic.42 If the patient has an elevated prolactin level and is symptomatic, treatment with the drug can be discontinued and the serum prolactin level should return to normal within several day. The dose can also be reduced, and a low-potency antipsychotic can be used as a replacement, or the patient can continue to take the offending drug and a full or partial can be prescribed.42

Seizure Disorder:

The typical antipsychotics lower the seizure threshold, and the use of medium-potency and high-potency antipsychotics in patients who have affective disorders, dementia, or schizophrenia has been associated with a 59.1% incidence of seizures per 10,000 patient years versus 11.7% in non-users.43 The risk and incidence of seizures associated with fluphenazine is not known.

Venous Thromboembolism:

The use of antipsychotics increases the risk for developing venous thromboembolism (VTE) and pulmonary embolism (PE); the incidence of these adverse effects has been reported to be 1.2% - 20.8%.44 This wide range is caused in part by differences in patient populations, the pattern of

30 nursece4less.com nursece4less.com nursece4less.com nursece4less.com drug use, and by differences in study and research design, but regardless, this adverse effect was observed soon after the typical antipsychotics were first used and it has been well-documented. The risk appears to be highest in the first three months of treatment, and there is no evidence that conclusively shows any of the antipsychotics is more likely than the others to cause VTE or PE.44

Withdrawal/Discontinuation:

Withdrawal is a common occurrence when the use of a psychotropic medication is stopped, and abrupt withdrawal of an antipsychotic can cause significant signs and symptoms like psychosis, withdrawal tardive dyskinesia and signs and symptoms related to the histaminergic and cholinergic activity of the drug.45,46

Pregnancy and Breastfeeding

There is no evidence that prenatal exposure to typical antipsychotics increases the incidence of congenital malformations, and their use during pregnancy does not appear to cause low birth weight, premature delivery, or perinatal mortality or have a negative effect on behavioral, cognitive, or emotional development.48-50 Maternal use of typical antipsychotics has been associated with signs and symptoms of withdrawal in neonates.50 There is no published information on the use of fluphenazine during breastfeeding.47

Long-Acting Injectable Antipsychotics:

Approximately 60% of patients taking an oral antipsychotic do not adhere to the therapy regimen, putting them at risk for relapse.51 The long-acting

31 nursece4less.com nursece4less.com nursece4less.com nursece4less.com injectable antipsychotics have been proven to be effective, they are convenient for the patient (injection every few weeks instead of taking a tablet several times), their use guarantees that the patient is receiving the medication, and, if a patient has symptom relapse, non-compliance is generally not an indication of cause.

Changing from oral to injectable fluphenazine should be based on the premise that 1 mg of oral fluphenazine given daily is equivalent to 1.25 mg of long-acting fluphenazine given every three weeks.51 Lauriello (2017) recommended that when switching from oral fluphenazine to injectable the patient should continue taking the tablets for at least a week after receiving the first injection.51

Fluphenazine Overdose

Most cases of typical antipsychotic overdose do not cause significant harm or life-threatening toxicity.52 Commonly seen signs and symptoms are CNS depression, anticholinergic effects like mydriasis and tachycardia, EPS, and orthostatic hypotension.52,53 A large overdose however can cause arrhythmias, coma, and seizures.52,53 The toxic dose of fluphenazine is not known.

Treatment is symptomatic and supportive.52,53 Serum calcium, magnesium, and potassium should be measured, and a 12-lead electrocardiogram (ECG) should be done. There is no antidote for fluphenazine overdose but antidotal therapy can be used if the patient develops EPS (, ), QT prolongation (IV magnesium) or NMS. The typical antipsychotics have a high volume of distribution, they are lipophilic, and they are highly protein bound so extracorporeal removal would not be helpful.52,53

32 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

Case Study: Fluphenazine

The following case study was obtained from a PubMed search and discusses the case of a 34-year-old Japanese woman with schizophrenia, paranoid type who developed rhabdomyolysis after receiving fluphenazine decanoate injection.54 The authors of the case study explained that “rhabdomyolysis is a potentially life-threatening condition of skeletal muscle damage with degradation of cellular components and subsequent transfer of toxic intracellular material into the blood circulation”.54 Rhabdomyolysis may occur following muscle trauma, ischemia, drugs, toxins, metabolic disorders, and infections. Neuroleptic malignant syndrome is one of the leading causes of rhabdomyolysis in patients prescribed neuroleptics, however, NMS is often difficult to distinguish from other disorders.

The authors in this study reported that the patient had been admitted to a psychiatric unit for the evaluation of left hip pain coinciding with elevated levels of creatine phosphokinase (CPK). For the preceding 3 years, the patient had received fluphenazine decanoate (50 mg) intramuscularly every 4 weeks. Her last injection of fluphenazine was given 25 days before admission to hospital, and she had tolerated the injection without any alteration to mental status. The patient was reported to appear alert.

A physical examination was performed that revealed the patient had no symptoms of muscular rigidity and autonomic dysfunction. Body temperature was reported to be 99.5°F (37.5°C) and the patient reported left hip pain and swelling with gradual onset that had become progressively worse over 3 days. A CPK level was obtained with a result of 21,113 IU/L. The patient was reported to be in acute renal failure and showing evidence of liver dysfunction. Leukocytosis and myoglobinuria were not evident.

33 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

Initial treatment included intravenous fluid replacement. The patient’s serum CPK and creatinine levels gradually returned to normal values after approximately one and half weeks. A computed tomography (CT) scan was performed approximately 2 weeks later to evaluate prolonged left hip pain and swelling. The contrast-enhanced CT images revealed “marked enlargement of the left gluteus maximus muscle with a low-density area located where she had last been injected with fluphenazine decanoate”.54 The authors reported not performing a muscle biopsy. In this case, a patient with schizophrenia undergoing neuroleptic treatment developed a marked CPK elevation, and was first suspected of having NMS. However, she was afebrile and lacking expected symptoms, such as EPS. The authors pointed out that patients with variant NMS sometimes show vague clinical manifestations, however this patient was completely asymptomatic and NMS was ruled out.

Rhabdomyolysis without NMS believed to be induced by antipsychotic use have been reported in studies, indicating that neuroleptics could have direct toxic effects on skeletal muscle. Such cases are extremely rare, and the underlying pathophysiology is not yet known. In this case, localized rhabdomyolysis in the left gluteus maximus muscle was revealed by contrast-enhanced CT, corresponding to the last injection site.

Discussion

The authors of this case study claimed that this was the first reported case of rhabdomyolysis without NMS following an of fluphenazine decanoate. Whether this was a traumatic or myotoxic process causing myonecrosis of the muscle tissue was uncertain, but the delayed

34 nursece4less.com nursece4less.com nursece4less.com nursece4less.com rhabdomyolysis made the injection trauma appear less likely. The increased serum CPK following intramuscular injection appeared acutely.

The cause of the delayed appearance of rhabdomyolysis in this patient appeared related to a toxic effect of the injected drug or an ingredient in the injection. The authors noted that fluphenazine decanoate intramuscular injection, slowly releases over a month, and had been shown to elicit oxidative damage in rat skeletal muscle. They cautioned clinicians to consider the risk of late-onset rhabdomyolysis when using long-acting injectable antipsychotics. Summary

Fluphenazine has a labeled use as a treatment for psychosis. It is used off- label to treat chorea associated with Huntington’s disease, chronic tic disorders, and psychosis and agitation associated with dementia. The incidence of the adverse effects of fluphenazine are not reported in the prescribing information but similar to other first generation antipsychotics, elderly patients who receive antipsychotics, such as fluphenazine, for the treatment of dementia-related psychosis are at an increased risk for death.

The use of fluphenazine is contraindicated if the patient has hepatic impairment, blood dyscrasia, is comatose or has severe central nervous system depression. Fluphenazine is also contraindicated if the patient is receiving large amounts of hypnotics or if the patient has subcortical brain damage. Finally, clinicians have been cautioned in the included study to consider the risk of late-onset rhabdomyolysis when using long-acting injectable antipsychotics. Rhabdomyolysis without neuroleptic malignant syndrome in the setting of antipsychotic use have been reported in studies, and neuroleptics are believed to have direct toxic effects on skeletal muscle

35 nursece4less.com nursece4less.com nursece4less.com nursece4less.com in rare cases. Further study is needed to understand the underlying pathophysiology involved.

Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation.

Completing the study questions is optional and is NOT a course requirement.

36 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. Fluphenazine is a piperazine phenothiazine and a first-generation

a. anticonvulsant. b. antipsychotic. c. mood stabilizer. d. antidepressant.

2. Fluphenazine should be used cautiously in patients who have asthma, glaucoma or other visual problems because

a. of its cholinergic effects. b. it stimulates the neurotransmitter acetylcholine. c. it has a high potential to cause anticholinergic effects. d. of its possible anticholinergic effects.

3. Fluphenazine has an off-label use for the treatment of

a. chorea associated with Huntington’s disease. b. anticholinergic symptoms. c. severe central nervous system (CNS) depression. d. subcortical brain damage.

4. If a patient has hepatic impairment,

a. fluphenazine should be used cautiously. b. the adult dosage for fluphenazine may still be used. c. using fluphenazine is contraindicated. d. there are no specific dosing recommendations for fluphenazine.

5. A US Box Warning warns ______, who receive antipsychotics (such as fluphenazine) for the treatment of dementia-related psychosis, that they are at an increased risk for death.

a. elderly patients b. renally impaired patients c. patients with hepatic impairment d. patients with Huntington’s chorea

6. In patients with renal impairment,

a. fluphenazine doses should be reduced 50%. b. the adult dosage for fluphenazine may not be used. c. using fluphenazine is contraindicated.

37 nursece4less.com nursece4less.com nursece4less.com nursece4less.com d. there are no specific dosing recommendations for fluphenazine.

7. True or False: Phenothiazines have some effect on peripheral alpha-adrenergic receptors, histamine receptors, and muscarinic receptors but fluphenazine’s ability to block these receptors is considered limited.

a. True b. False

8. The use of fluphenazine is not recommended if a patient has congenital long QT syndrome; this would put the patient at risk for

a. extrapyramidal symptoms. b. blurred vision c. torsade de pointes. d. xerostomia.

9. The risk of ______appears to increase in patients > 75 years of age who use fluphenazine.

a. esophageal dysmotility b. dysphagia c. aspiration d. All of the above

10. If a patient is taking fluphenazine and the patient’s white blood cell (WBC) count is < 1000 mm3, the drug use or dosage

a. should be discontinued and the WBC monitored. b. may be continued but the WBC should be monitored. c. should be adjusted to 50% of the adult dosage. d. should be discontinued only if the patient is symptomatic.

11. Fluphenazine may cause ______, a rare and potentially fatal adverse drug reaction characterized by autonomic instability, hyperthermia, muscle rigidity, and neurological changes.

a. subcortical brain damage b. neuroleptic malignant syndrome (NMS) c. extrapyramidal symptoms (EPS) d. anticholinergic symptoms

38 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12. The Beers Criteria recommends that antipsychotics be used to treat behavioral problems in elderly patients who have dementia only if the behavior poses a risk to the patient or others and

a. the patient does not have a comorbidity. b. the patient has a high seizure threshold. c. non-pharmacologic therapies have failed. d. All of the above

13. True or False: Fluphenazine may decrease serum prolactin levels.

a. True b. False

14. Prenatal exposure to typical antipsychotics

a. does not have a negative effect on behavioral, cognitive, or emotional development in an infant. b. increases the incidence of congenital malformations. c. causes low birth weight. d. causes premature delivery.

15. In cases of typical antipsychotic overdose, extracorporeal removal would not be helpful because

a. typical antipsychotics have a high volume of distribution. b. they are not lipophilic. c. they do not bind to proteins. d. most cases of typical antipsychotic overdose are life-threatening.

39 nursece4less.com nursece4less.com nursece4less.com nursece4less.com References

The References below include published works and in-text citations of published works that are intended as helpful material for your further reading.

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