Week 10 - Chapter 31 Antipsychotic Drugs and Their Use in Schizophrenia Flashcards Preview

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Flashcards in Week 10 - Chapter 31 Antipsychotic Drugs and Their Use in Schizophrenia Deck (31)
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1
Q

Akathisia

A

Akathisia is characterized by pacing and squirming brought on by an uncontrollable need to be in motion. This profound sense of restlessness can be very disturbing. The syndrome usually develops within the first 2 months of treatment. Like other early EPS, akathisia occurs most frequently with high-potency FGAs.

  • -Three types of drugs have been used to suppress symptoms: beta blockers, benzodiazepines, and anticholinergic drugs. Although these drugs can help, reducing antipsychotic dosage or switching to a low-potency FGA may be more effective.
  • -It is important to differentiate between akathisia and exacerbation of psychosis. If akathisia were to be confused with anxiety or psychotic agitation, it is likely that antipsychotic dosage would be increased, thereby making akathisia more intense.
2
Q

Atypical Antipsychotics

a.k.a Second-Generation (Atypical) Antipsychotics (SGA)

A

The SGAs produce moderate blockade of receptors for dopamine and much stronger blockade of receptors for serotonin. Because dopamine receptor blockade is only moderate, the risk of EPS is lower than with the FGAs. However, although the SGAs carry a reduced risk of EPS, they carry a significant risk of metabolic effects—weight gain, diabetes, and dyslipidemia—that can cause cardiovascular events and early death.
–Furthermore, like the FGAs, the SGAs can cause sedation and orthostatic hypotension, and can increase the risk of death when used to treat dementia-related psychosis in older adults. Finally, even though SGAs have no clear clinical advantage over FGAs, the SGAs cost 10 to 20 times as much.

3
Q

Butyrophenones

A

Butyrophenones are 1 of 4 major categories of FGAs. They are the family to which haloperidol belongs. Haloperidol is the prototype of the high-potency FGAs

4
Q

Cognitive Symptoms

A

Cognitive symptoms include disordered thinking, reduced ability to focus attention, and prominent learning and memory difficulties. Subtle changes may appear years before symptoms become florid, when thinking and speech may be completely incomprehensible to others. Cognitive symptoms may respond equally to FGAs and SGAs.

5
Q

Conventional Antipsychotics

a.k.a First-generation antipsychotics (FGAs)

A

First-generation antipsychotics can be classified as low potency, medium potency, or high potency (Table 31–2). The low-potency drugs, represented by chlorpromazine, and the high-potency drugs, represented by haloperidol, are of particular interest.

  • -It is important to note that, although the FGAs differ from one another in potency, they all have the same ability to relieve symptoms of psychosis. Recall that the term potency refers only to the size of the dose needed to elicit a given 320response; potency implies nothing about the maximal effect a drug can produce.
  • -Although these agents produce identical antipsychotic effects, they differ significantly in side effects. Hence, by knowing the potency category to which a particular neuroleptic belongs, we can better predict its undesired responses.
6
Q

Depot Preparation of Drug

A

Depot antipsychotics are long-acting, injectable formulations used for long-term maintenance therapy of schizophrenia. The objective is to prevent relapse and maintain the highest possible level of functioning. As a rule, the rate of relapse is lower with depot therapy than with oral therapy. Depot preparations are valuable for all patients who need long-term treatment—not just for patients who have difficulty with adherence.
–Following the injection, active drug is slowly absorbed into the blood. Because of this slow, steady absorption, plasma levels remain relatively constant between doses. The dosing interval is 2 to 4 weeks.

7
Q

Dopamine System Stabilizers (DDS)

A
A unique class of antipsychotic drugs with the ability to modulate the activity of dopamine receptors—rather than simply cause receptor activation or blockade. At synapses where transmitter concentrations are high, DDSs will compete with the transmitter for receptor binding, and hence will reduce receptor activation. Approved indications are schizophrenia, acute bipolar mania, major depressive disorder, agitation associated with schizophrenia or bipolar mania, and irritability associated with autism spectrum disorder. 
-Aripiprazole is the most common type of DDS that has a more favorable safety profile than any other SGA, but may be less effective than some.
8
Q

Dystonia (Acute)

A

Typically, the patient develops severe spasm of the muscles of the tongue, face, neck, or back. Oculogyric crisis (involuntary upward deviation of the eyes) and opisthotonus (tetanic spasm of the back muscles causing the trunk to arch forward, while the head and lower limbs are thrust backward) may also occur. Severe cramping can cause joint dislocation. Laryngeal dystonia can impair respiration.

9
Q

Extrapyramidal Symptoms

A

Three of these reactions—acute dystonia, parkinsonism, and akathisia—occur early in therapy and can be managed with a variety of drugs. The fourth reaction—tardive dyskinesia—occurs late in therapy and has no satisfactory treatment.
–SAFTEY ALERT: For many patients, EPS are uncomfortable, disturbing, and sometimes, dangerous. Some manifestations of EPS, such as tardive dyskinesia, are irreversible. It is crucial for the RN to monitor patients treated with antipsychotic medications for evidence of EPS, and to report this immediately if present.

10
Q

High-Potency Agents

A

Compared with the low-potency FGAs, the high-potency FGAs cause more early EPS, but cause less sedation, orthostatic hypotension, and anticholinergic effects. Because they cause fewer side effects, high-potency agents are generally preferred for initial therapy.
Haloperidol is an example of this type of agent.

11
Q

Low-Potency Agents

A

The risk of early extrapyramidal reactions (dystonia, akathisia, parkinsonism) is relatively low. However, the risk of TD is the same as with all other FGAs. Chlorpromazine lowers seizure threshold.

12
Q

Negative Symptoms

A
  • Social withdrawal
  • Emotional withdrawal
  • Lack of motivation
  • Poverty of speech
  • Blunted affect
  • Poor insight
  • Poor judgment
  • Poor self-care
13
Q

Neuroleptic Malignant Syndrome

A

Neuroleptic malignant syndrome (NMS) is a rare but serious reaction that carries a 4% risk of mortality—down from 30% in the past, thanks to early diagnosis and intervention. Primary symptoms are “lead pipe” rigidity, sudden high fever (temperature may exceed 41°C), sweating, and autonomic instability, manifested as dysrhythmias and fluctuations in blood pressure. Level of consciousness may rise and fall, the patient may appear confused or mute, and seizures or coma may develop. Death can result from respiratory failure, cardiovascular collapse, dysrhythmias, and other causes. NMS is more likely with high-potency FGAs than with low-potency FGAs.
SAFETY ALERT: Neuroleptic malignant syndrome can be fatal if not treated promptly. The RN must recognize the signs and symptoms of NMS and report them immediately. Treatment with dantrolene and bromocriptine may be ordered by the provider.

14
Q

Parkinsonism

A

ntipsychotic-induced parkinsonism is characterized by bradykinesia, mask-like facies, drooling, tremor, rigidity, shuffling gait, cogwheeling, and stooped posture. Symptoms develop within the first month of therapy and are indistinguishable from those of idiopathic PD.
Neuroleptics cause parkinsonism by blocking dopamine receptors in the striatum.
–Neuroleptic-induced parkinsonism is treated with some of the drugs used for idiopathic PD. Specifically, centrally acting anticholinergic drugs (eg, benztropine, diphenhydramine) and amantadine [Symmetrel] may be employed. Levodopa and direct dopamine agonists (eg, bromocriptine) should be avoided because these drugs activate dopamine receptors, and might thereby counteract the beneficial effects of antipsychotic treatment.
–Use of antiparkinsonism drugs should not continue indefinitely. Antipsychotic-induced parkinsonism tends to resolve spontaneously, usually within months of its onset.

15
Q

Phenothiazines

A

Phenothiazines were the first modern antipsychotic agents. Chlorpromazine, our prototype of the low-potency neuroleptics, belongs to this family.

16
Q

Positive Symptoms

A
  • Hallucinations
  • Delusions
  • Disordered thinking
  • Disorganized speech
  • Combativeness
  • Agitation
  • Paranoia
17
Q

Seizure Threshold

A

Neuroleptics reduce seizure threshold, thereby increasing the risk of seizures, especially in patients with epilepsy and other seizure disorders. For patients with seizure disorders, adequate doses of antiseizure medication must be employed. Monitor the patient for seizure activity; if loss of seizure control occurs, dosage of antiseizure medication must be increased.

  • -First-generation agents can reduce seizure threshold, thereby increasing the risk of seizure activity. The risk of seizures is greatest in patients with seizure disorders. These patients should be monitored, and, if loss of seizure control occurs, the dosage of their antiseizure medication must be increased.
  • -Chlorpromazine lowers seizure threshold.
18
Q

Tardive Dyskinesia

A

Occurs late in therapy and has no satisfactory treatment.

  • -TD, the most troubling EPS, develops in 15% to 20% of patients during long-term therapy with FGAs. The risk is related to duration of treatment and dosage size. For many patients, symptoms are irreversible.
  • -TD is characterized by involuntary choreoathetoid (twisting, writhing, worm-like) movements of the tongue and face. Patients may also present with lip-smacking movements, and their tongues may flick out in a “fly-catching” motion. One of the earliest manifestations of TD is slow, worm-like movement of the tongue. Involuntary movements that involve the tongue and mouth can interfere with chewing, swallowing, and speaking. Eating difficulties can result in malnutrition and weight loss. Over time, TD produces involuntary movements of the limbs, toes, fingers, and trunk. For some patients, symptoms decline following a dosage reduction or drug withdrawal. For others, TD is irreversible.
  • -The cause of TD is complex and incompletely understood.
19
Q

Haloperidol

Actions and uses

A

Haloperidol [Haldol], a member of the butyrophenone family, is the prototype of the high-potency FGAs. Principal indications are schizophrenia and acute psychosis. In addition, haloperidol is a preferred agent for Tourette’s syndrome. The drug can also be used to control severe behavior problems in children (eg, combative, explosive hyperexcitability unrelated to any immediate provocation), but only as a last resort. Haloperidol is used more than other FGAs.

20
Q

Haloperidol

Pharmacokinetics

A

Haloperidol may be administered PO or IM. Oral bioavailability is about 60%. Hepatic metabolism is extensive. Parent drug and metabolites are excreted in the urine.

21
Q

Haloperidol

Adverse effects

A

Early extrapyramidal reactions (acute dystonia, parkinsonism, akathisia) occur frequently, whereas sedation, hypotension, and anticholinergic effects are uncommon. Note that the incidence of these reactions is opposite to that seen with the low-potency agents. However, the incidence of TD is the same as with all other FGAs. Neuroendocrine effects—galactorrhea, gynecomastia, menstrual irregularities—are seen occasionally. NMS, photosensitivity, convulsions, and impotence are rare.
Haloperidol can prolong the QT interval, and hence may pose a risk of serious dysrhythmias, especially when given IV and/or in high doses. The drug should be used with caution in patients with dysrhythmia risk factors, including long QT syndrome, hypokalemia or hyperkalemia, or a history of dysrhythmias, heart attack, or severe heart failure. Combined use with other QT-prolonging drugs (eg, amiodarone, erythromycin, quinidine) should be avoided.

22
Q

Clozapine

Description

A

Clozapine [Clozaril, FazaClo, Versacloz] was the first SGA and will serve as our prototype for the group—even though other SGAs are now used more widely. This drug is our most effective agent for schizophrenia, the only indication it has. However, because clozapine can cause agranulocytosis, it should be reserved for patients who have not responded to safer alternatives.

23
Q

Clozapine

Mechanism of Action

A

Antipsychotic effects result from blockade of receptors for dopamine and serotonin (5-hydroxytryptamine [5-HT]). Like the FGAs, clozapine blocks D2 dopamine receptors, but its affinity for these receptors is relatively low. In contrast, the drug produces strong blockade of 5-HT2 serotonin receptors. Combined blockade of D2 receptors and 5-HT2 receptors is thought to underlie therapeutic effects. Low affinity for D2 receptors may explain why SGAs cause fewer EPS than do the FGAs. In addition to blocking receptors for dopamine and serotonin, clozapine blocks receptors for norepinephrine (alpha1), histamine, and acetylcholine.

24
Q

Clozapine

Therapeutic Use

A
  • Schizophrenia

- Levodopa-Induced Psychosis.

25
Q

Clozapine

Pharmacokinetics

A

Clozapine is rapidly absorbed following oral administration. Plasma levels peak in 3.2 hours. About 95% of the drug is bound to plasma proteins. Clozapine undergoes extensive metabolism by hepatic cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2D6, and CYP3A4), followed by excretion in the urine and feces. The half-life is approximately 12 hours.

26
Q

Clozapine

Adverse Effects and Interactions

A

Common adverse effects include sedation and weight gain (from blocking histamine1 [H1] receptors); orthostatic hypotension (from blocking alpha-adrenergic receptors); and dry mouth, blurred vision, urinary retention, constipation, and tachycardia (from blocking muscarinic cholinergic receptors). Neuroendocrine effects (galactorrhea, gynecomastia, amenorrhea) and interference with sexual function are minimal. Compared with the FGAs, clozapine carries a low risk of extrapyramidal effects, including TD.

27
Q

Aripiprazole

Despricption

A

Aripiprazole is the first representative of a unique class of antipsychotic drugs, referred to by some as dopamine system stabilizers (DSSs).

28
Q

Aripiprazole

Therapeutic uses

A

Approved indications are schizophrenia, acute bipolar mania, major depressive disorder, agitation associated with schizophrenia or bipolar mania, and irritability associated with autism spectrum disorder. Aripiprazole has a more favorable safety profile than any other SGA, but may be less effective than some.

29
Q

Aripiprazole

Mechanism of Action

A

Like other antipsychotic drugs, aripiprazole can affect multiple receptor types. It blocks H1, 5-HT2, and alpha1 receptors, and has mixed effects on 5-HT1 and D2 receptors. The drug does not block cholinergic receptors.
As with other SGAs, therapeutic effects are believed to result from interaction with dopamine and serotonin receptors.

30
Q

Aripiprazole

Pharmacokinetics

A

Aripiprazole is well absorbed following oral administration, both in the presence and absence of food. Plasma levels peak 3 to 5 hours after dosing. Protein binding in blood is high—more than 99%. In the liver, aripiprazole undergoes metabolism by CYP3A4 and CYP2D6. Aripiprazole and its active metabolite—dehydro-aripiprazole—have prolonged half-lives: 75 hours and 94 hours, respectively. Because elimination is slow, (1) dosing can be done once a day and (2) about 14 days (four half-lives) are required to achieve steady-state (plateau) plasma drug levels.

31
Q

Aripiprazole

Adverse effects

A

Aripiprazole is generally well tolerated. The most common side effects are headache, agitation, nervousness, anxiety, insomnia, nausea, vomiting, dizziness, and somnolence. The incidence of EPS is very low. Only a few cases of NMS have been reported. Among the SGAs, aripiprazole (along with ziprasidone) poses the lowest risk of weight gain, diabetes, and dyslipidemia.

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