Antipsychotic Drugs and Antimanic Drugs

Antipsychotic Drugs and Antimanic Drugs: Haloperidol, Lithium

Synonym/acronym: Antipsychotic drugs: haloperidol (Dozic, Fortunan, Haldol, Haldol Decanoate, Haloneural, Serenace); antimanic drugs: lithium (Cibalith-S, Eskalith, Lithane, Lithobid, Lithonate, Lithotabs, PFI-Lith, Phasal).

Common use

To assist in monitoring subtherapuetic, therapeutic, or toxic drug levels related to medical interventions.

Specimen

Serum (1 mL) collected in a red-top tube.

Drug	Route of Administration	Recommended Collection Time
Haloperidol	Oral	Peak: 3–6 hr
Lithium	Oral	Trough: at least 12 hr after last dose; steady state occurs at 90–120 hr

Normal findings

(Method: Chromatography for haloperidol; ion-selective electrode for lithium)

Drug	Therapeutic Range Conventional Units	Conversion to SI Units	Therapeutic Range SI Units	Half-Life (hr)	Volume of Distribution (L/kg)	Protein Binding (%)	Excretion
Haloperidol	6–24 ng/mL	SI units = Conventional Units × 2.66	16–64 nmol/L	15–40	18–30	90	Hepatic
Lithium (chronic)	0.6–1.2 mEq/L	SI units = Conventional Units × 1	0.6–1.2 mmol/L	18–24	0.7–1	0	Renal

Description

Haloperidol is an antipsychotic tranquilizer used for treatment of acute and chronic psychotic disorders, Tourette’s syndrome, and hyperactive children with severe behavioral problems. Frequent monitoring is important due to the unstable relationship between dosage and circulating steady-state concentration. Lithium is used in the treatment of manic depression. Daily monitoring of lithium levels is important until the proper dosage is achieved. Lithium is cleared and reabsorbed by the kidney. Clearance is increased when sodium levels are increased and decreased in conditions associated with low sodium levels; therefore, patients receiving lithium therapy should try to maintain a balanced daily intake of sodium. Lithium levels affect other organ systems. A high incidence of pulmonary complications is associated with lithium toxicity. Lithium can also affect cardiac conduction, producing T-wave depressions. These electrocardiographic (ECG) changes are usually insignificant and reversible and are seen in 10% to 20% of patients on lithium therapy. Chronic lithium therapy has been shown to result in enlargement of the thyroid gland in a small percentage of patients. Other medications indicated for use as mood stabilizers include carbamazepine, lamotrigine, and valproic acid. Detailed information is found in the monograph titled “Anticonvulsant Drugs.”

Many factors must be considered in effective dosing and monitoring of therapeutic drugs, including patient age, patient weight, interacting medications, electrolyte balance, protein levels, water balance, conditions that affect absorption and excretion, and the ingestion of substances (e.g., foods, herbals, vitamins, and minerals) that can either potentiate or inhibit the intended target concentration. Peak collection times should be documented carefully in relation to the time of medication administration.

The metabolism of many commonly prescribed medications is driven by the cytochrome P450 (CYP450) family of enzymes. Genetic variants can alter enzymatic activity that results in a spectrum of effects ranging from the total absence of drug metabolism to ultrafast metabolism. Impaired drug metabolism can prevent the intended therapeutic effect or even lead to serious adverse drug reactions. Poor metabolizers (PM) are at increased risk for drug-induced side effects due to accumulation of drug in the blood, while ultra-rapid metabolizers (UM) require a higher than normal dosage because the drug is metabolized over a shorter duration than intended. Other genetic phenotypes used to report CYP450 results are intermediate metabolizer (IM) and extensive metabolizer (EM). Genetic testing can be performed on blood samples submitted to a laboratory. The test method commonly used is polymerase chain reaction. Counseling and informed written consent are generally required for genetic testing. CYP2D6 is a gene in the CYP450 family that metabolizes drugs such as antipsychotics like haloperidol, tricyclic antidepressants like nortriptyline, and beta blockers. Testing for the most common genetic variants of CYP2D6 is used to predict altered enzyme activity and anticipate the most effective therapeutic plan. Incidence of the PM Phenotype is estimated to be 10% of Caucasians and Hispanics, 2% of African Americans, and 1% of Asians.

Important note: These medications are metabolized and excreted by the liver and kidneys and are therefore contraindicated in patients with hepatic or renal disease. Caution is advised for patients with renal impairment. Information regarding medications must be clearly and accurately communicated to avoid misunderstanding of the dose time in relation to the collection time. Miscommunication between the individual administering the medication and the individual collecting the specimen is the most frequent cause of subtherapeutic levels, toxic levels, and misleading information used in calculation of future doses. If administration of the drug is delayed, notify the appropriate department(s) to reschedule the blood draw and notify the requesting health-care (HCP) if the delay has caused any real or perceived therapeutic harm.

This procedure is contraindicated for

N/A

Indications

Assist in the diagnosis and prevention of toxicity
Monitor compliance with therapeutic regimen

Potential diagnosis

Level	Response
Normal levels	Therapeutic effect
Subtherapeutic levels	Adjust dose as indicated
Toxic levels	Adjust dose as indicated
Haloperidol	Hepatic impairment
Lithium	Renal impairment

Critical findings

It is important to note the adverse effects of toxic and subtherapeutic levels. Care must be taken to investigate signs and symptoms of not enough medication and too much medication. Note and immediately report to the HCP any critically increased or subtherapeutic values and related symptoms.
It is essential that a critical finding be communicated immediately to the requesting HCP. A listing of these findings varies among facilities.
Timely notification of a critical finding for lab or diagnostic studies is a role expectation of the professional nurse. The notification processes will vary among facilities. Upon receipt of the critical finding the information should be read back to the caller to verify accuracy. Most policies require immediate notification of the primary HCP, hospitalist, or on-call HCP. Reported information includes the patient’s name, unique identifiers, critical finding, name of the person giving the report, and name of the person receiving the report. Documentation of notification should be made in the medical record with the name of the HCP notified, time and date of notification, and any orders received. Any delay in a timely report of a critical finding may require completion of a notification form with review by Risk Management.

Haloperidol: Greater Than 42 ng/mL (SI: Greater Than 112 nmol/L)

Signs and symptoms of haloperidol toxicity include hypotension, myocardial depression, respiratory depression, and extrapyramidal neuromuscular reactions. Possible interventions include emesis (contraindicated in the absence of gag reflex or central nervous system depression or excitation) and gastric lavage followed by administration of activated charcoal.

Lithium: Greater Than 2 mEq/L (SI: Greater Than 2 mmol/L)

Signs and symptoms of lithium toxicity include ataxia, coarse tremors, muscle rigidity, vomiting, diarrhea, confusion, convulsions, stupor, T-wave flattening, loss of consciousness, and possible coma. Possible interventions include administration of activated charcoal, gastric lavage, and administration of intravenous fluids with diuresis.

Interfering factors

Blood drawn in serum separator tubes (gel tubes).
Haloperidol may increase levels of tricyclic antidepressants and increase the risk of lithium toxicity.
Drugs that may increase lithium levels include angiotensin-converting enzyme inhibitors, some NSAIDs, and thiazide diuretics.
Drugs and substances that may decrease lithium levels include acetazolamide, osmotic diuretics, theophylline, and caffeine.

Nursing Implications and Procedure

Pretest

Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
Patient Teaching: Inform the patient this test can assist in monitoring subtherapeutic, therapeutic, or toxic drug levels.
Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
These medications are metabolized and excreted by the kidneys and liver. Obtain a history of the patient’s genitourinary and hepatobiliary systems, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus). Note the last time and dose of medication taken.
Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
Note that there are no food, fluid, or medication restrictions unless by medical direction.

Intratest

Potential complications:
Lack of consideration for the proper collection time relative to the dosing schedule can provide misleading information that may result in erroneous interpretation of levels, creating the potential for a medication-error-related injury to the patient.
Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Consider recommended collection time in relation to the dosing schedule. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection, noting the last dose of medication taken. Perform a venipuncture.
Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
Promptly transport the specimen to the laboratory for processing and analysis.

Post-Test

Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
Nutritional Considerations: Include avoidance of alcohol consumption.
Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Explain to the patient the importance of following the medication regimen and instructions regarding drug interactions.
Instruct the patient receiving haloperidol to immediately report any unusual symptoms (e.g., arrhythmias, blurred vision, dry eyes, repetitive uncontrolled movements) to his or her HCP. Instruct the patient receiving lithium to immediately report any unusual symptoms (e.g., anorexia, nausea, vomiting, diarrhea, dizziness, drowsiness, dysarthria, tremor, muscle twitching, visual disturbances) to his or her HCP. Answer any questions or address any concerns voiced by the patient or family.
Instruct the patient to be prepared to provide the pharmacist with a list of other medications he or she is already taking in the event that the requesting HCP prescribes a medication.
Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

Related laboratory tests include albumin, BUN, calcium, creatinine, ECG, glucose, magnesium, osmolality urine, potassium, sodium, T₄, and TSH.
See the Genitourinary and Hepatobiliary systems tables at the end of the book for related tests by body system.