Antipsychotic Drugs Psych

TRUE/FALSE The first-generation antipsychotics are most effective in treating POSITIVE symptoms of schizophrenia

TRUE

Which antipsychotics has the highest risk of QT prolongation?

Thioridazine (typical) ziprasidone and iloperidone also have cautions (atypicals)

First-Generation (typical) Antipsychotics MOA

competitive inhibitors at a variety of receptors Antipsychotic effects reflection of competitive blocking of dopamine D2 receptors

Which second-generation antipsychotic is a partial agonist at D2 and 5-HT1A receptors, as well as an antagonist of 5-HT2A receptors

Aripiprazole

Which First-Generation Antipsychotic has less associated movement disorders? Why?

Chlorpromazine (lowest of typicals) Movement disorders are less likely with medications that bind weakly **but it still has a MUCH HIGHER risk of EPS than the ATYPICALS

What is the drug of choice for refractory schizophrenia patients?

Clozapine

Which medication has a high affinity for D1, D4, 5-HT2, muscarinic, and α-adrenergic receptors, but it is also a weak dopamine D2 receptor antagonist.?

Clozapine

Second Generation (Atypical) Antipsychotics IND

First-line therapy for schizophrenia Minimize the risk of debilitating EPS

What are some classic movements associated with Tardive dyskinesia?

bilateral and facial jaw movements "fly-catching" motions of the tongue

FIRST-GENERATION ANTIPSYCHOTICS (high potency)

Fluphenazine Haloperidol Loxapine Perphenazine Pimozide Prochlorperazine Thiothixene Trifluoperazine

List the Long-acting injectable (LAI) antipsychotic formulations

Fluphenazine decanoate haloperidol decanoate risperidone microspheres paliperidone palmitate aripiprazole monohydrate olanzapine pamoate therapeutic duration of action of up to 2 to 4 weeks often used to treat outpatients and individuals who are non-adherent

Second Generation (Atypical) Antipsychotics

Lower incidence of EPS than the first-generation agents Higher risk of metabolic side effects, such as diabetes, hypercholesterolemia, and weight gain

Can tardive dyskinesia be reversed?

NO its irreversible, BUT.... A prolonged holiday from antipsychotics may cause the symptoms to diminish or disappear within a few months Traditional anti-EPS medications may actually worsen this condition

Which is antipsychotic is used for schizoaffective disorder?

Paliperidone (Atypical)

Which First-Generation Antipsychotic has increased AE? Why?

haloperidol Binds tightly to dopaminergic neuroreceptors

Which medications produce extrapyramidal effects MORE frequently? and why?

haloperidol and fluphenazine Because they exhibit low anticholinergic activity and preferential blocking of dopaminergic transmission

What can be given to cholinergic activity is blocked and this minimize extrapyramidal effects?

the anticholinergic drug, benztropine The therapeutic trade-off is a lower incidence of EPS in exchange for the side effect of muscarinic receptor blockade

Which medications produce LESS extrapyramidal effects?

those with strong anticholinergic activity thioridazine

Which two medications are known to blocks 5-HT2A receptors to a greater extent than it does D2 receptors?

Risperidone & Olanzapine (Atypicals)

Most of the second generation agents appear to exert part of their unique action through inhibition of which serotonin receptors?

5-HT2A receptors

What is Neuroleptic malignant syndrome?

A potentially fatal reaction to antipsychotic drugs characterized by muscle rigidity, fever, altered mental status and stupor, unstable blood pressure, and myoglobinemia

SECOND-GENERATION ANTIPSYCHOTICS

Aripiprazole ABILIFY Asenapine Clozapine Iloperidone Lurasidone Olanzapine Paliperidone Quetiapine SEROQUEL Risperidone RISPERDAL Ziprasidone GEODON

Which antipsychotics are most often used for treatment of refractory depression?

Aripiprazole and Quetiapine (Atypicals) used adjunctively with antidepressants

Which antipsychotic can be used for intractable hiccups?

Chlorpromazine

FIRST-GENERATION ANTIPSYCHOTICS (low potency)

Chlorpromazine Thioridazine

Which medication has the highest affinity for D1 receptors?

Clozapine

Which one of the following antipsychotics has been shown to be a partial agonist at the dopamine D2receptor? A.Aripiprazole. B.Clozapine. C.Haloperidol. D.Risperidone. E.Thioridazine.

Correct answer = A. Aripiprazole is the agent that acts as a partial agonist at D2 receptors. Theoretically, the drug would enhance action at these receptors when there is a low concentration of dopamine and would block the actions of high concentrations of dopamine. All of the other drugs are only antagonistic at D2 receptors, with haloperidol being particularly potent.

Which antipsychotic agent has been most associated with significant QT interval prolongation and should be used with caution in patients with preexisting arrhythmias or patients taking other drugs associated with QT prolongation? A.Thioridazine. B.Risperidone. C.Asenapine. D.Lurasidone. E.Aripiprazole.

Correct answer = A. Of the antipsychotic drugs listed, thioridazine has the highest risk for causing QT interval prolongation. Although this is a general warning for all antipsychotics, thioridazine has been issued a "black box warning," suggesting that it is associated with the greatest risk.

A 21-year-old male has recently begun pimozide therapy for Tourette disorder. His parents bring him to the emergency department. They describe that he has been having "different-appearing tics" than before, such as prolonged contraction of the facial muscles. While being examined, he experiences opisthotonos (type of extrapyramidal spasm of the body in which the head and heels are bent backward and the body is bowed forward). Which of the following drugs would be beneficial in reducing these symptoms? A.Benztropine. B.Bromocriptine. C.Lithium. D.Prochlorperazine. E.Risperidone.

Correct answer = A. The patient is experiencing EPS due to pimozide, and a muscarinic antagonist such as benztropine would be effective in reducing the symptoms. The other drugs would have no effect or, in the case of prochlorperazine and risperidone, might increase the symptoms.

Which of the following antipsychotic agents is considered to be the most potent and, thus, have the highest risk of extrapyramidal symptoms? A.Thioridazine. B.Fluphenazine. C.Quetiapine. D.Chlorpromazine. E.Clozapine.

Correct answer = B. Among the older, conventional, or typical antipsychotics on this list, fluphenazine is the most potent and would thus be expected to have the highest incidence of EPS. The atypical antipsychotics listed (quetiapine and clozapine) could be considered low potency based on their common dosing and are considered to have the lowest risk for EPS.

Which antipsychotic has the most sedative potential and is sometimes questionably used as a hypnotic agent in certain clinical settings? A.Fluphenazine. B.Thiothixene. C.Quetiapine. D.Haloperidol. E.Iloperidone.

Correct answer = C. Quetiapine has strong antihistaminergic effects causing sedation and is sometimes used at low doses as a sedative-hypnotic, even though this use is considered off-label. The other antipsychotic agents listed are weaker at blocking the histamine receptor and therefore are not as sedating.

Which of the following antipsychotic agents is most associated with the possibility of a hematological dyscrasia such as agranulocytosis in a patient being treated for schizophrenia? A.Chlorpromazine. B.Buspirone. C.Lithium. D.Clozapine. E.Asenapine.

Correct answer = D. Clozapine is the only antipsychotic medication that has a black box warning and a risk of agranulocytosis in approximately 1% of the patients treated. This requires regular monitoring of white blood cell counts. Although other antipsychotics have case reports of blood dyscrasias, clozapine is considered to have the highest risk.

A 28-year-old woman with schizoaffective disorder (combination of mood and psychotic symptoms) reports difficulty falling asleep. Which of the following would be most beneficial in this patient? A.Lithium. B.Chlorpromazine. C.Haloperidol. D.Paliperidone. E.Ziprasidone.

Correct answer = D. Paliperidone is the only agent that is FDA approved for schizoaffective disorder. Chlorpromazine has significant sedative activity as well as antipsychotic properties and is the drug most likely to alleviate this patient's major complaint of insomnia. Although other antipsychotics may benefit this patient's disorder, paliperidone has the indication for this disorder, and if the underlying disorder is improved, then the symptom of insomnia may also improve without risking other, unwanted adverse effects, such as the anticholinergic effects of chlorpromazine.

An adolescent male is newly diagnosed with schizophrenia. Which of the following antipsychotic agents may have the best chance to improve his apathy and blunted affect? A.Chlorpromazine. B.Fluphenazine. C.Haloperidol. D.Risperidone. E.Thioridazine.

Correct answer = D. Risperidone is the only antipsychotic on the list that has some reported benefit in improving the negative symptoms of schizophrenia. It is a second-generation antipsychotic, and the other drugs listed are firstgeneration antipsychotic agents. All of the agents have the potential to diminish the hallucinations and delusional thought processes (positive symptoms).

A 30-year-old male patient who is treated with haloperidol for his diagnosis of schizophrenia is considered to be well-managed symptomatically for his psychotic symptoms. However, he is reporting restlessness, the inability to sit still at the dinner table, and his family notices that he is pacing up and down the hallway frequently. Of the following, which is the best medication to treat this antipsychotic-induced akathisia? A.Benztropine. B.Dantrolene. C.Amoxapine. D.Bromocriptine. E.Propranolol.

Correct answer = E. Propranolol, a β-blocker, is considered the drug of choice for the management of antipsychotic-induced akathisia. Benztropine is more effective for pseudoparkinsonism and acute dystonias. Amoxapine is an antidepressant that has been associated with EPS. Bromocriptine is more effective for Parkinson-like symptoms Dantrolene is a muscle relaxant that is best reserved for managing some symptoms of neuroleptic malignant syndrome.

Which of the following antipsychotic agents is available in a LAI formulation that may be useful for patients with difficulty adhering to therapy? A.Asenapine. B.Chlorpromazine. C.Clozapine. D.Quetiapine. E.Risperidone.

Correct answer = E. Risperidone is available in a LAI formulation containing risperidone microspheres. The other agents listed do not have LAI formulations. Aripiprazole, fluphenazine, haloperidol, olanzapine, and paliperidone are other antipsychotics that are available in LAI formulations.

Other common AE of antipsychotics

Drowsiness Confusion Potent antimuscarinic activity:dry mouth, urinary retention, constipation, and loss of visual accommodation α-adrenergic receptors blockers: lowered blood pressure and orthostatic hypotension Depressed hypothalamus: affects thermoregulation causing amenorrhea, galactorrhea, gynecomastia, infertility, and erectile dysfunction Significant weight gain: Glucose and lipid profiles should be monitored due to the potential for the second generation agents to increase these laboratory parameters QT prolongation

Which medication has the highest affinity for D2 receptors?

Haloperidol

Cautions/Contraindications associated with antipsychotics

Lower the seizure threshold-->use cautiously in pts with seizure disorders or those with an increased risk for seizures such as withdrawal from alcohol When used in pts with mood disorders monitor for worsening of mood and SI WARNING: increased risk for mortality when used in elderly patients with dementia-related behavioral disturbances and psychosis

Which antipsychotics are most often used for bipolar depression?

Lurasidone and Quetiapine (Atypicals)

First-Generation (typical) Antipsychotics AE

Movement disorders Extrapyramidal symptoms (EPS)

Which antipsychotics can be used for motor and phonic tics of Tourette disorder?

Pimozide is primarily indicated (typical) Risperidone (Atypical) Haloperidol (typical)

Which Atypical blocks D2 receptors more potently than 5-HT2A receptors but is relatively weak at blocking either receptor

Quetiapine Its low risk for EPS may also be related to the relatively short period of time it binds to the D2 receptor.

Which antipsychotics can be used for management of disruptive behavior and irritability secondary to autism?

Risperidone and Aripiprazole (Atypicals)

TRUE/FALSE Atypicals are most effective in treating the negative symptoms of schizophrenia

TRUE they also treat positive sx

When does Tardive dyskinesia occur?

Within Months to Years

Which antipsychotics have increased absorption is increased with food?

Ziprasidone and Paliperidone (Atypicals) These agents readily pass into the brain and have a large volume of distribution

Second Generation (Atypical) Antipsychotics MOA

blockade of both serotonin and dopamine in the brain and the periphery

What are some of the unique AE of Clozapine?

bone marrow suppression, seizures, orthostasis, severe agranulocytosis Its clinical use is limited to refractory patients because of serious adverse effects.

How do you treatment Neuroleptic malignant syndrome?

discontinuation of the antipsychotic agent supportive therapy Administration of dantrolene or bromocriptine (may be helpful)

What causes Extrapyramidal effects?

inhibitory effects of dopaminergic neurons are normally balanced by the excitatoryactions of cholinergic neurons excess cholinergic influence causes extrapyramidal motor effects

What causes Tardive dyskinesia?

long-term treatment with antipsychotics This makes the neuron super-sensitive to the actions of dopamine, and it allows the dopaminergic input to this structure to overpower the cholinergic input, causing excess movement in the patient.

Which drug is an active metabolite of risperidone?

paliperidone (if a pt fails paliperidone, they will likely fail risperidone)

Which typical is used most commonly for the prevention of nausea and vomiting?

prochlorperazine

When does Akathisias occur?

within Days to Weeks

When to symptoms such as bradykinesia, rigidity, and tremor begin to occur?

within Weeks to Months

When does Dystonia occur?

within hours to days

What drugs do Akathisias respond better too?

β blockers (for example, propranolol) or benzodiazepines rather than anticholinergic medications.