Antipsychotic

What should 1st generation and 2nd generation antipsychotic drugs NOT be used to treat?

Dementia in the older adult

Positive Symptoms of Schizophrenia

Hallucinations, delusions, agitation

Negative Symptoms of Schizophrenia

Social withdrawal, lack of motivation, loss of normal function, blunt affect

Cognitive Symptoms of Schizophrenia

Disordered thinking, reduced focus, thinking and speech may be incomprehensible to others

Causes of Schizophrenia

Excessive dopamine synthesis, decreased dopamine breakdown, increased post-synaptic dopamine receptors

1st Generation Antipsychotic Drug Example (FGA)

Haloperidal

2nd Generation Antipsychotic Drug Example (SGA)

Clozapine, Olanzapine, Quetiapine

1st Generation Antipsychotics

Block dopamine receptors (D2) in the mesolimbic area  (can cause extrapyramidal symptoms)

2nd Generation Antipsychotics

Produced moderate blockade of dopamine receptors (D2), stronger blockade for serotonin (5HT2)

2nd Generation Antipsychotics lack EPS effects but cause?

Undesirable metabolic side effects (hyperglycaemia, new-onset diabetes, hyperlipidaemia) 

Antipsychotic Action of Antipsychotic Drugs

Reduction of hallucinations + agitations, produces calming effect (all FGAs are equally effective as SGAs)

Extrapyramidal Syndrome of Antipsychotic Drugs

D/t blockade of dopamine receptors in nigro-striatal pathway (atypical drugs have lower incidence of EPS)

Antiemetic Effect of Antipsychotics

Prevents nausea and vomiting d/t blockade of D2 receptors of the chemoreceptor trigger zone (CTZ)

Antimuscarinic Effect of Antipsychotics

L/t anticholinergic effects (can’t see, can’t poop, can’t pee, can’t cry)

Other Effects of Antipsychotics

Orthostatic hypotension, poikilothermic, increase in prolactin release (most common with FGAs)

Antipsychotics Pharmacokinetics

Parenteral injection useful for treating difficult/non-compliant patients

Extrapyramidal Motor Symptoms (EPS)

Induced by excessive cholinergic influence l/t tardive dyskinesia, pseudoparkinsomism, akathisia, dyskinesia, dystonia, NMS

Tardive Dyskinesia

Involuntary and fragmented movements of the mouth, young jaw (early signs include vermicular tongue movements)

Management of Tardive Dyskinesia

Prolonged drug holiday, provide benzodiazepines, reduce dose of FGA, switch to SGA, provide valbenazine and deutetrabenazine

Pseudoparkinsonism

Decreased dopamine and increased AcH l/t resting tremor, bradykinesia, rigidity

Management of Pseudoparkinsonism

Observe within few days to 1st month, switch to SGA, administer amantadine

Akathisia

Motor restlessness, inability to sit/lie still, agitation, insomnia, involuntary tapping of feet (occurs more frequently with FGAs)

Management of Akathisia

Nurse should observe within few days/months of therapy, administer b-receptor blockers, benzodiazepines + anticholinergic drugs

Dyskinesia + Dystonias

Broad bizarre movements of arms/legs/face/neck/tongue, oculogyric crisis, opisthotonos (may begin after a single dose of drug)

Management of Dyskinesia + Dystonias

Nurse should monitor a few hours to 5 days after 1st dose, if laryngeal spasms occur = respiration compromised

Neuroleptic Malignant Syndrome (NMS)

Catatonia, high fever, most common with FGAs, can be fatal (nurse must recognize symptoms and report immediately)

Management of NMS

Stop medication, provide dantrolene + bromocriptine, monitor vital signs, wait 2 weeks before resuming therapy

Black Box Warning for FGAs + SGAs

Increased risk of death in elderly patients with dementia

Non-Motor Side Effects of Antipsychotic Drugs

Sedation, sexual dysfunction, agranulocytosis, orthostatic hypotension

Physical + Psychological Dependence of Antipsychotic Drugs

Dependence is rare (but abrupt withdrawal can precipitate mild abstinence syndrome)

Drug Interactions of Antipsychotic Drugs

Intensify anticholinergic effect, intensify CNS depressant effect (more for FGAs), levodopa + dopamine agonist counteract antipsychotic effect

Therapeutic Uses of FGAs

Used for schizophrenia, acute psychotic episodes, continued use reduces risk of relapse

Therapeutic Uses of SGAs

FDA-approved for use in bipolar disorders, primarily used for schizophrenia

Although initially assumed to be relatively safe, SGAs increase the risk of

Weight gain, new-onset of diabetes, dyslipidemia

Clozapine

Inhibits dopamine + serotonin receptors (has low risk for EPS + tardive dyskinesia), most effective antipsychotic drug available

Side Effect of Clozapine

Associated with agranulocytosis, providers must enroll in REMS to prescribe clozapine, weight gain, anticholinergic effect

What are providers instructed to conduct when providing Clozapine?

•WBC Count + Neutrophil Count (ANC)

Black Box Warning of Clozapine

Increased risk of death in elderly patients with dementia, fatal agranulocytosis, seizure activity

Risperidone

Can be included among first-line drugs (compared to FGAs, it has low potential for EPS + TD)

Side Effects of Risperidone

Weight gain, orthostatic hypotension, decreased sexual function

Compared to risperidone, clozapine has more…

Anti-muscarinic effects, more sedating effects, and may cause agranulocytosis

Cariprazine Therapeutic Uses

First-line treatment option for schizophrenia, acute manic attack associated with bipolar, bipolar depression in adults

Side Effects of Cariprazine

Hyperglycemia, weight gain, EPS, orthostatic hypotension

What has the most significant risk of EPS?

FGAs

What has the highest risk of metabolic effects such as weight gain, new-onset of diabetes, dyslipidemia?

SGAs