ANTIPSYCHOTICS

Jonathan M. Paghubasan, MD
4th Year
Emergency Medicine
ANTIPSYCHOTICS
ANTIPSYCHOTICS

first-generation (typical) antipsychotics-

effective against the positive features of
psychosis (e.g., delusions, hallucinations,
disorganized thought) but provided no
treatment for the negative features (e.g.,
avolition, alogia, social withdrawal)

second-generation (atypical) antipsychotics

& third generation- work on both the p tive
and negative symptoms and, when taken at
therapeutic doses, are associated with fewer
extrapyramidal effects than the first-
generation antipsychotics
 PHARMACOKINETICS

After oral administration, absorption occurs rapidly, the drugs undergo significant first-
pass metabolism, and peak plasma concentrations typically occur within 1 to 6 hours.

intramuscular injection, peak plasma concentrations typically occur within 60 minutes for
immediate-release products but can be delayed up to 1 day with depot preparations.

have high protein binding and a large volume of distribution.

Metabolism is primarily through the cytochrome P450 enzyme system.

 CLINICAL FEATURES

CNS depression is frequent but is less severe in patients receiving long-term therapy

CNS effects range from lethargy, ataxia, dysarthria, and confusion to coma with respiratory depression
in cases of severe overdose.

Paradoxical agitation and delirium may occur in mixed overdoses, especially those involving agents
with antimuscarinic properties.

Seizures occur in approximately 1% of individuals after overdose

patients can manifest signs or symptoms that are consistent with antimuscarinic toxicity, including
tachycardia, dry mucous membranes, dry skin, decreased bowel sounds, urinary retention, agitation,
delirium, and hyperthermia.
most common cardiovascular manifestations of antipsychotic overdose are
sinus tachycardia and orthostatic hypotension.

ECG changes also include QT prolongation (highest rate with amisulpride and
thioridazine), QRS widening (usually with large ingestions), and nonspecific T-
wave abnormalities. 9,10 Ventricular dysrhythmias are rare, 11with the
exception of amisulpride overdoses.12
DIAGNOSIS

include basic chemistry tests and a

pregnancy test for women of childbearing
age. Test for co-ingestants, including
acetaminophen and salicylate levels, in all
intentional overdoses. Perform an ECG to
assess the conduction intervals. Obtain
complete blood counts for patients who
develop a fever while taking clozapine or
chlorpromazine.
 TREATMENT

Treatment for patients with antipsychotic poisoning is largely supportive.

Seizures should be treated with a benzodiazepine such as lorazepam.

Treat hypotension with IV fluid resuscitation; adults without previously known or

suspected cardiac disease should receive at least 1 to 2 L of crystalloid and
children should receive 20 to 40 mL/kg.

direct-acting α-adrenergic agonists, such as phenylephrine or norepinephrine,

are the preferred vasopressors for treatment
regardless of the serum magnesium level, adults with a QT c interval of >500 milliseconds
should receive magnesium sulfate, 2 grams IV over 10 minutes.

Patients with torsades de pointes should receive 2 grams of magnesium sulfate as a bolus,
followed by an infusion of 2 to 4 milligrams/min, regardless of the magnesium concentration.

Patients with an intraventricular conduction delay (e.g., prolonged QRS complex) and
ventricular dysrhythmias should be treated with sodium bicarbonate, 1 to 2 mEq/kg IV bolus,
followed by intermittent boluses or a continuous infusion

Lidocaine is an acceptable alternative or second-line agent for ventricular dysrhythmias.

Avoid using class Ia (e.g., quinidine, procainamide), Ic (e.g., propafenone), III (e.g.,
amiodarone), and IV antiarrhythmics in patients with cardiac conduction disturbances or
ventricular dysrhythmias
 DISPOSITION AND FOLLOW-UP

observe the patient for at least 6 hours.

patient can be judged to be free of toxicity if there are no mental status changes, pulse and
blood pressure abnormalities, orthostatic hypotension, and QT c interval prolongation after 6
hours of observation from the time of ingestion.

evidence of toxicity (e.g., sinus tachycardia or QT interval prolongation) should be admitted

to a monitored bed for observation.

Patients who develop severe symptoms (e.g., seizure, respiratory depression, hypotension,
acidosis) during the observation period in the ED should be admitted to an intensive care
unit.
ADVERSE EFFECTS OF THERAPEUTIC
DOSING

CARDIOVASCULAR- affect myocardial

conduction and repolarization.

usually evidenced by prolongation of the QT

interval.
 EXTRAPYRAMIDAL SYMPTOMS

four extrapyramidal syndromes include acute dystonia, akathisia, drug-induced parkinsonism, and tardive
dyskinesia.

Acute dystonias manifest as hyperkinetic movements characterized by intermittent, uncoordinated,

involuntary contractions of the muscles of the face, tongue, neck, trunk, or extremities

Akathisias are a subjective sensation of motor restlessness

typically encountered early after starting therapy (or increasing the dose of a drug) and can be reversed
with diphenhydramine (25 to 50 milligrams IV) or benztropine (1 to 2 milligrams IV).

Diphenhydramine, 25 to 50 milligrams PO three or four times a day, or benztropine, 1 to 2 milligrams PO

twice a day, should be continued for 2 to 3 days after parenteral treatment because of the prolonged
effects of the dystonia-inducing agent
 OTHER ADVERSE EFFECTS

type 2 diabetes mellitus and diabetic ketoacidosis

P azines are associated with leukopenia in up to 0.8% and agranulocytosis in

0.05% of patients.

Seizures have been associated with several antipsychotics, primarily

chlorpromazine, loxapine, and clozapine.
NEUROLEPTIC MALIGNANT SYNDROME

Neuroleptic malignant syndrome typically

develops over a period of 1 to 3 days and is
characterized by the tetrad of altered mental
status, muscular rigidity, fever, and
sympathetic nervous system lability.

described as lead pipe and cogwheel rigidity,

similar to that observed with parkinsonism

present first with altered mental status,

followed by rigidity, then fever, and lastly
sympathetic nervous system lability
two other features embody important concepts about this syndrome: recent
dopamine antagonist exposure or dopamine agonist withdrawal and negative
evaluation for other causes

differential diagnosis of neuroleptic malignant syndrome includes infectious,

endocrine, toxicologic, and metabolic disorders.

common disorder creating diagnostic confusion is serotonin syndrome- a more

rapid onset (2 to 24 hours), shivering, hyperreflexia, myoclonus, nausea,
vomiting, diarrhea, and less intense muscle rigidity and fever.