3031-002 Basic Concepts of Pharm: Antipsychotic Lecture

Antipsychotic Agents

- Chemically Diverse group of Compounds

What are antipsychotic agents used for?

Used for a diverse spectrum of psychotic disorders

•Schizophrenia, delusional disorders, bipolar disorders, depressive psychoses, and drug-induced psychoses

•Also used to suppress emesis and to treat Tourette's syndrome

Who should Antipsychotic Agents not be used to treat?

• Should not be used to treat dementia in the older adult

Therapeutic Uses of Antipsychotic Agents

•Schizophrenia is the primary indication for antipsychotic drugs

•These drugs suppress symptoms during acute psychotic episodes

•Continued use reduces the risk of relapse

Schizophrenia

• Disordered thinking and reduced ability to comprehend reality

Sypmtoms of Schizophrenia

Negative

Positive

Cognitive

Negative Symptoms of Schizophrenia

What is absent or reduced that should be present

•Loss or diminution of normal function

•Lack of motivation

•Poverty of speech

•Blunted affect

•Poor self-care

•Social withdrawal

Positive Symptoms of Schizophrenia

What is present that should not be.

Exaggeration or distortion of normal function

Hallucinations

Delusions

Agitation

Tension

Paranoia

Cognitive Symptoms of Schizophrenia

•Disordered thinking

•Reduced ability to focus attention

•Prominent learning and memory difficulties

•Subtle changes may appear years before symptoms become florid

•Florid changes: Thinking and speech may be completely incomprehensible to others

Schizophrenia Clinical Presentation: Acute Episodes

Delusions (fixed false beliefs)

Hallucinations are prominent

Schizophrenia Clinical Presentation: Residual Symptoms

•Suspiciousness; poor anxiety management; and diminished judgment, insight, motivation, and capacity for self-care

Schizophrenia Clinical Presentation: Long-Term Course

Acute exacerbations separated by intervals of partial remission

Schizophrenia Etiology

Exact cause is UNKNOWN

Could be caused by:

• Genetic

• Perinatal

• Neurodevelopmental

• Neuroanatomic factors

• Excessive activation of CNS receptors for dopamine

• Insufficient activation of CNS receptors for glutamate

Treatment of Psychosis: First-Generation Antipsychotics

• Older, well-established

• Side-effect profile is less well tolerated

How are First Generation Antipsychotics classified?

By potency (Low-potency vs. High-potency)

• Low-potency has more sedation, hypotension, and anticholinergic effects

• High-potency has more EPS

Treatment of Psychosis: 2nd Generation Antipsychotics

•Fewer side effects

•Better tolerated

MOA of First-Generation Antipsychotics

Blocks dopamine, acetylcholine, histamine, and norepinephrine receptors

Theory of First-Generation Antipsychotics

D-2 blockade in mesolimbic area responsible for therapeutic benefit

Usage of 1st Generation Antipsychotics

• Used during acute episodes and for chronic management

• Equally effective, drug choice based on side-effect profile

• More effective for positive symptoms than negative

Chlorpromazine (Thorazine)

1st Gen

Low-Potency:

Haloperidol (Haldol)

1st Gen

High Potency

Extrapyramidal Symptoms (EPS)

• Theory is caused by dopamine blockade

• Different types: Can occur with early-onset or long-term use of the medication

• Early onset is less common with low-potency agents

• Long-term occurs equally across FGA's

EPS: Acute Dystonia Onset

Symptoms within hours to 5 days after drug initiation

EPS: Acute Dystonia S/S

• Spasms of the tongue, face, neck, and back

• Laryngeal dystonia can impair respiration

•Differentiate between Acute Dystonia and Psychotic Hysteria

EPS: Acute Dystonia (Oculogyric Crisis)

Involuntary upward deviation of the eyes

EPS: Acute Dystonia (Opisthotonus)

Tetanic spasms of back muscles:

- Back arches forward while lower limbs and head thrust backward

Treatment of Acute Dystonia

Anticholinergic Drug:

Benztropine (Cogentin) or diphenhydramine

EPS: Pseudoparkinsonism Onset

5-30 Days after drug initiation

EPS: Pseudoparkinsonism S/S

Symptoms are the same as Parkinson's,

•Tremor

• Rigidity,

• Shuffling gait

• Bradykinesia

• Stooped posture

• Drooling

• Cogwheeling

Treatment of Parkinsonism

Pseudoparkinsonism Treatment

• Switch to SGA

• Anticholinergics (benztropine, diphenhydramine)

• Amantadine

What treatment should clients with Parkinsonism NOT receive?

Do NOT use Levodopa or direct dopamine agonists (counteracts the therapeutic effect of antipsychotics)

EPS: Akathisia Onset

Symptoms develop 5 to 60 days after drug initiation

EPS: Akathisia S/S

• Restlessness with the sensation of always needing to be in movement

• Pacing and squirming

• Think "restless legs" but on the whole body

Akathisia Treatment

Treatment of Akathisia:

• Reduce the dose or switch to a low-potency FGA

• Anticholinergics

• Benzodiazepines

• Beta blockers

EPS: Tardive Dyskinesia Onset

Symptoms develop months to years after drug initiation

• Irreversible

EPS: Tardive Dyskinesia S/S

• Involuntary choreoathetoid movements of tongue and face

• Twisting, writhing, worm-like movement of tongue and face

• Tongue flicks out in "fly-catching" movement

• Lip-smacking

• Eventually develops involuntary movements in limbs, toes, fingers, trunk

Tardive Dyskinesia Treatment

Reduce dose or switch to SGA

Ingrezza (Valbenazine)

Neuroleptic Malignant Syndrome (NMS) S/S

• Lead-pipe rigidity

• High fever

• Sweating

• Autonomic instability: dysrhythmias and fluctuating blood pressure

Neuroleptic Malignant Syndrome (NMS) Treatment

• Dantrolene

• Switch to SGA

Other Adverse Effects of 1st Gen Antipsychotics: Anticholinergic Effects:

Can't see

Can't Pee

Can't Spit

Can't Shit

Other Adverse Effects of 1st Gen Antipsychotics: Blood Pressure

• Orthostatic Hypotension (from alpha-1 blockade)

Other Adverse Effects of 1st Gen Antipsychotics: Sedation

Caused by Histamine Blockade

Other Adverse Effects of 1st Gen Antipsychotics: Seizures

Antispychotics lowers seizure threshold

Other Adverse Effects of 1st Gen Antipsychotics: Neuroendocrine Effects

• Increases Prolactin release: milk production

• Gynecomastia and galactorrhea

Other Adverse Effects of 1st Gen Antipsychotics: Dysrhythmias

• Prolonged QT, check ECG; use cautiously in older adults

• BLACK BOX WARNING: Delirium and Dementia!!!!!

Other Adverse Effects of 1st Gen Antipsychotics: NMS

• Notify provider immediately of fever; check CBC

Antipsychotic Toxicity (1st Gen)

• Conventional antipsychotic drugs are very safe

• Death by overdose is extremely rare

• Overdose produces hypertension, CNS depression, and EPS

Treatment for Antipsychotic Toxicity (1st Gen):

Treatment for Antipsychotic Toxicity (1st Gen):

•Intravenous fluids, alpha-adrenergic agonists, and gastric lavage

• Emetics are not effective: Neuroleptics block the antiemetic action

MOA: Second Generation Antipsychotics

Dopamine and Serotonin Blockade

Examples of Second-Generation Antipsychotics:

•Risperidone (Risperdal)

• Clozapine (Clozaril)

• Quetiapine (Seroquel)

2nd-Generation Antipsychotics Adverse Effects: Agranulocytosis

•Serial CBC to check white count and ANC

- Must be within the normal range to continue!

2nd-Generation Antipsychotics Adverse Effects: Metabolic Effects

• Weight gain

• Diabetes

• Dyslipidemia

Monitor labs, treat as needed

2nd-Generation Antipsychotics Adverse Effects: General

• Seizures

• EPS - less than with FGA's, but risk is not zero

• BLACK BOX WARNING in Dementia and Delirium

Antipsychotic Drug Therapy: Effectiveness

•Most FGAs and SGAs are equally effective, except for Clozapine, which is more effective than the rest

• FGAs: Significant risk of EPS

-- Cost less than SGAs

• SGAs: Risk of metabolic effects

Antipsychotic Drug Therapy: Nursing Interventions

• Promoting adherence

• Ensure that the medication is taken

• Encourage family members to oversee medication for outpatients

• Provide patients with instructions

• Inform patients and their families that antipsychotics must be taken on a regular schedule

Antipsychotic Drug Therapy: Nursing Considerations

• Inform patients about side effects of treatment

• Assure patients that antipsychotic drug use does not lead to addiction

• Establish a good therapeutic relationship with the patient

• Use an intramuscular depot preparation for long-term therapy

Psychotic Nondrug Therapy:

• Counseling for the patient and family

• Behavioral therapy

• Vocational training

A patient with schizophrenia is prescribed chlorpromazine oral concentrate. Which instruction should the nurse include in the teaching plan?

A. Sexual arousal may be enhanced with this medication.

B. Avoid direct skin contact with this medication.

C. The medication may cause excessive salivation.

D. Do not limit salt intake while taking the medication.

B. Avoid direct skin contact with this medication.

Rationale: Handling chlorpromazine (or other antipsychotics) can cause contact dermatitis in patients and healthcare personnel. Avoid direct contact with these drugs.

- Sexual dysfunction may occur; dry mouth may be an adverse effect, and sodium intake is not affected.

Which manifestations does the nurse associate with tardive dyskinesia?

A. Pacing and squirming, with an uncontrollable need for motion

B. Mask-like face with drooling, tremors, rigidity, and shuffling gait

C. Twisting, worm-like movements of the tongue and face

D. Sudden high fever, sweating, and blood pressure fluctuations

C. Twisting, worm-like movements of the tongue and face

Rationale: Tardive dyskinesia is characterized by involuntary twisting, writhing, worm-like movements of the tongue and face. Parkinsonism is characterized by a mask-like face with drooling, tremors, rigidity, and shuffling gait. Akathisia is characterized by pacing and squirming, with an uncontrollable need for motion. Neuroleptic malignant syndrome is characterized by sudden high fever, sweating, and fluctuations in blood pressure.

A patient is diagnosed with type 2 diabetes mellitus and schizophrenia. The nurse will closely monitor the blood sugar if the patient receives which medication for the treatment of schizophrenia?

A. Loxapine [Loxitane]

B. Clozapine [Clozaril]

C. Thiothixene [Navane]

D. Haloperidol [Haldol]

B. Clozapine [Clozaril]

Rationale: Second-generation antipsychotics such as clozapine carry a higher risk of serious metabolic effects (eg, diabetes and dyslipidemia) than first-generation antipsychotics (eg, loxapine, thiothixene, and haloperidol). Among the second-generation antipsychotics, the risk of metabolic effects is greatest with clozapine and olanzapine. Clozapine should be used with caution in patients with diabetes.

The nurse prepares to administer the first dose of an antipsychotic agent to a patient. One hour after administration, what is most important for the nurse to assess?

A. The range of motion of the upper and lower extremities

B. The orthostatic blood pressure measurements

C. The abdomen for distention and bowel sounds

D. The tympanic membrane with an otoscope

B. The orthostatic blood pressure measurements

Rationale: Antipsychotic drugs promote orthostatic hypotension. The blood pressure and pulses should be checked before dosing and 1 hour afterward. Measurements should be taken while the patient is lying down and again after the patient has been sitting or standing for 1 to 2 minutes. Hypotension is more likely with low-potency first-generation antipsychotics than with high-potency first-generation antipsychotics. Tolerance to hypotension develops after 2 to 3 months.