Drug Therapy for Psychotic Disorders

Psychotic Disorders Overview

• Psychotic disorders are characterized by a range of symptoms and cognitive disruptions:
  • Hallucinations/Delusions: Perception of stimuli that are not present or fixed false beliefs.
  • Paranoia: Extreme suspicion or distrust of others.
  • Aggression: Hostile or violent behavior.
  • Lack of Inhibition: Reduced social or personal restraint.
• The condition in schizophrenia is thought to be most likely related to an increased level of activity of the neurotransmitter Dopamine.

Drug Therapy Classifications

Drug therapy for psychosis is divided into two primary categories:

• First-generation ("typical") antipsychotics: Includes phenothiazines and non-phenothiazines.
• Second-generation ("atypical") antipsychotics: Generally have different receptor binding profiles and side effect profiles compared to first-generation drugs.

First-Generation (Typical) Antipsychotics: Phenothiazines

Chlorpromazine (Thorazine)

• Mechanism of Action: Blocks the postsynaptic dopamine receptors in the brain.
• Administration: Administered via Intramuscular (IM) and Oral (PO) routes.
• Contraindications: There are many contraindications associated with this medication.
• Black Box Warning (BBW): Usage in older adults with dementia-related psychosis treated with antipsychotic drugs could lead to death.
• Adverse Effects:
  • CNS Effects: Depression, slurred speech, impaired mobility, and impaired mental processes.
  • Extrapyramidal Effects (EPS): Tardive dyskinesia, akathisia, dystonia, and drug-induced parkinsonism.
  • Neuroleptic Malignant Syndrome (NMS).
  • Cardiovascular: Alterations in cardiac rhythm/function.
  • Hematologic: Agranulocytosis and pancytopenia.

First-Generation (Typical) Antipsychotics: Non-Phenothiazines

Haloperidol (Haldol)

• Mechanism of Action: Blocks the postsynaptic dopamine receptors in the brain.
• Administration: Administered via Intramuscular (IM) and Oral (PO) routes.
• Contraindications: There are many contraindications for use.
• Black Box Warning (BBW): Older adults who suffer from dementia and dementia-related psychosis and receive haloperidol have an increased risk of death.
• Adverse Effects:
  • Cardiovascular/Respiratory: Cardiac rhythm changes, tachycardia, bronchospasm, and laryngospasm.
  • CNS: Akathisia, hyperthermia, dystonia, EPS, Neuroleptic Malignant Syndrome, parkinsonism, seizures, and vertigo.
  • Dermatologic: Photosensitivity, hyperpigmentation, contact dermatitis, and alopecia.
  • Genitourinary/Reproductive: Urinary retention, sexual dysfunction, amenorrhea, and breast enlargement.
  • Metabolic: Hyperglycemia, hypoglycemia, and hyponatremia.

Neuroleptic Malignant Syndrome (NMS)

NMS is a life-threatening reaction to antipsychotic medication characterized by the acronym FEVER:

• F – Fever: Hyperthermia.
• E – Encephalopathy: Confusion, agitation, stupor, or coma.
• V – Vitals unstable: Changes in Blood Pressure (BP), Heart Rate (HR), and Respiratory Rate (RR).
• E – Elevated creatine kinase.
• R – Rigidity of muscles: Severe muscle stiffness.

Second-Generation (Atypical) Antipsychotics

Selected Medications:

• clozapine (Clozaril)
• quetiapine (Seroquel)
• olanzapine (Zyprexa)
• risperidone (Risperdal)
• aripiprazole (Abilify)

Pharmacodynamics:

• Block dopamine receptors in the brain, thereby depressing the reticular activating system.
• Block serotonin and glutamate receptors.
• Possess anticholinergic, antihistamine, and alpha-adrenergic blocking abilities.
• Associated with many Boxed Warnings.

Adverse Effects:

• Cardiovascular: Orthostatic hypotension, tachycardia, ECG changes, myocardial infarction, pericarditis, cardiomyopathy, mitral insufficiency, heart failure, and pericardial effusion.
• CNS: Seizures.
• Hematologic: Agranulocytosis and neutropenia.
• Metabolic: Hyperglycemia and weight gain.

Nursing Implications and Medication Administration

General Administration Guidelines:

• Initial Assessments: Obtain a baseline ECG for patients starting chlorpromazine.
• Injection Site: Give IM injections in a large muscle (e.g., the ventrogluteal or gluteus maximus).
• Oral Timing (Chlorpromazine): Give the PO dose $1$ to $2$ hours before bedtime.
• Oral Timing (Haloperidol): Take PO doses with a full glass of water ($240\,mL$).
• GI Protection: Administer with food if Gastrointestinal (GI) upset occurs.
• Liquid Forms: Mix liquid formulations of chlorpromazine with $60\,mL$ of fruit juice.
• Skin Safety: Avoid contact with the skin when handling liquid medications to prevent contact dermatitis.
• Positioning: Ensure slow position changes to manage orthostatic hypotension.
• Safety Precautions: Do not drive or operate heavy machinery while on these medications.
• Tapering: Medications must be tapered gradually to prevent extrapyramidal effects and avoid withdrawal; do not stop taking abruptly.

Monitoring and Communication:

• Healthcare Provider (HCP) Notification: Notify the HCP before starting new prescriptions or over-the-counter (OTC) supplements, and before/during pregnancy.
• Infection Signs: Monitor for lethargy, weakness, or flu-like symptoms which may indicate hematologic issues.
• Laboratory Tests:
  • Obtain baseline White Blood Cell (WBC) and neutrophil counts (especially for clozapine).
  • Monitor blood glucose levels regularly for metabolic changes.
• Systemic Monitoring: Monitor for signs of Neuroleptic Malignant Syndrome.
• Adherence: Follow the prescribed medication regimen strictly.

Questions & Discussion

Q: A nurse understands that schizophrenia is most likely related to an increased level of activity of what neurotransmitter?A: Dopamine.

Q: The nurse observes that a patient with a long history of chlorpromazine therapy demonstrates lip smacking and appears to be chewing continually. What is the likely adverse effect?A: Tardive dyskinesia (an EPS characterized by involuntary movements of the tongue, lips, and face).

Q: In order to reduce the patient's risk of extrapyramidal effects during the transition from haloperidol to an atypical antipsychotic, what intervention should be implemented?A: Gradually taper the dose of haloperidol.

Q: Following the administration of haloperidol for an acute psychotic episode, what therapeutic effect should the nurse initially assess?A: Decreased agitation and combativeness.

Q: A patient is prescribed clozapine. What laboratory test is most important during the introduction of the medication regimen?A: Regular complete blood counts (to monitor for agranulocytosis/neutropenia).