Antipsychotics

High Potency D2 Receptor Antagonists

Fluphenazine (Prolixin) Trifluoperazine (Stelazine) Thiothixene (Navane) Haloperidol (Haldol)

2. A pt on an antipsychotic drug develops acute dystonia. Which drug will most likely be prescribed for this reaction? A. 5-HT3 blocker B. Anticholinergic C. Neuroleptic D. Tricyclic

B. Anticholinergic

6. The preferred agent for the treatment of Tourette's syndrome is: A. loxapine B. chlorpromazine C. haloperidol D. perphenazine

C. haloperidol

Positive symptoms of schizophrenia

Hallucinations, Delusions, Disordered thinking, Disorganized speech, Combativeness, Agitation, Paranoia

10. A pt on an antipsychotic agent suddenly becomes febrile, develops "lead-pipe" rigidity, and appears confused. You should suspect: A. tardive dyskinesia B. acute dystonia C. neuroleptic malignant syndrome D. Parkinsonism

C. neuroleptic malignant syndrome

18. Which of the following side effects of antipsychotic drugs should be treated immediately? A. mild slowing of gait B. production of breast milk in non-nursing women C. neuroleptic malignant syndrome D. constipation

C. neuroleptic malignant syndrome

Schizophrenia Drug Therapy Steps

Initial therapy Maintenance therapy Adjunctive drugs: Benzodiazepines, Antidepressants

"psychotropic"

capable of affecting the mind, emotions, and behavior.

Phenothiazines Extrapyramidal symptoms (EPS)

CNS Effects [contd.] Iatrogenic Parkinsonism (akinesia, tremors, rigidity) Akathisia Dystonias Tardive Dyskinesia a slow or belated onset, a disorder resulting in involuntary, repetitive body movements; from long-term or high-dose use of antipsychotic drug

Olanzapine (Zyprexa)

"Atypical" Antipsychotic Agents Antagonist at 5-HT2A and antagonizes types 1,2, and 4 dopamine receptors (as well as alpha-adrenergic, muscarinic, and histaminic receptors) Effective for both positive and negative symptoms of schizophrenia As with other "atypicals", it has a lower incidence of EPS and hyperprolactinemia and perhaps less cardiovascular reactions compared to typical antipsychotics. Appears to have low potential for drug interactions and neutropenia.

Risperidone (Risperdal)

"Atypical" Antipsychotic Agents Combined 5-HT2A and D2 antagonist (as well as alpha-adrenergic, muscarinic, and histaminic receptors) Broad efficacy; claimed more effective in decreasing negative symptoms Produces EPS and hypotension, especially with higher doses

Clozapine (Clozaril)

"Atypical" Antipsychotic Agents Indicated for patients not responding to traditional antipsychotics and/or those who can't tolerate their extrapyramidal side effects. Antagonism of D4>>>D2 so less EPS; also blocks 5-HT2A receptors as well as alpha-adrenergic, muscarinic and histamine receptors. Major disadvantage is agranulocytosis (potentially fatal and occurs in up to 1-3 %) and seizures (~ 3%).

Thioxanthenes

Chlorprothixene (Taractan)

Dibenzodiazepines

Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel)

Butyrophenones

Haloperidol (Haldol) Droperidol (Inapsine)

Three depot preparations available

Haloperidol decanoate (Haldol Decanoate) Fluphenazine decanoate (Prolixin Decanoate) Risperidone microspheres (Risperdal Consta)

Dibenzoxazepines

Loxapine (Loxitane)

Indoles

Molindone (Moban)

Diphenylbutylpiperidines

Pimozide (Orap)

Benzisoxazoles

Risperidone (Risperdal)

Summary of the Pharmacologic Effects of the Phenothiazine-Type Antipsychotic Drugs

"Sedation" (tranquilizing/calming effect)--> decrease mild to moderate anxiety in severe agitation. Antipsychotic - first, patient's rxn to such symptoms of psychosis as hallucinations and delusions and later helps to improve the patient's disturbed behavior. Potentiation of the effects of opioid analgesics and of general depressant drugs. Antiemetic - control of nausea and vomiting. Autonomic blockade

Phenothiazines: CNS Effects

"Sedation"; sleepiness: May decrease mental performance in non-psychotic subjects; Mental performance in psychotics may improve as symptoms decrease. Antipsychotic (neuroleptic effect): Symptoms may start to resolve within 1-2 days, but the full therapeutic response develops gradually over several weeks Antiemetic effect- action on CTZ chemoreceptor trigger zone Central skeletal muscle relaxation Temperature regulation: Hypothalamus - disrupts thermoregulatory mechanisms Neuroendocrine effects: Blockade of prolactin inhibitory factor ("PIF" or DA) resulting in release of prolactin; may result in amenorrhea-galactorrhea, altered libido, infertility; Decrease gonadotropin release; Increase in MSH (melanocyte stimulating hormone). Neurophysiological effects: EEG changes 1st appear in subcortical sites; Activate EEG in epileptic patients; May produce seizures in patients with no history of seizures (EPS)

Schizophrenia Drug Therapy Dosing and routes

Dosing: Highly individualized, Elderly patients require relatively small doses Size and timing likely to be changed over course of therapy Routes: Oral (preferred), Intramuscular

Medium Potency D2 Receptor Antagonists

Droperidol (Inapsine) Loxapine (Loxitane) Molindone (Moban) Perphenazine (Trilafon) Prochlorperazine (Compazine)

34. Which of the following actions distinguishes newer (atypical) antipsychotics from typical phenothiazine-like antipsychotics? A. Low incidence of EPS B. Potent antiemetic actions C. Much greater effect on alleviating positive symptoms of schizophrenia D. None of the above

A. Low incidence of EPS

13. When considering an antipsychotic agent for a pt with a cardiac disorder, which characteristic would most affect the decision to use haloperidol rather than risperidone? A. Q-T prolongation B. positive symptoms C. HTN D. tachypnea

A. Q-T prolongation

3. Which of the following best describes the extrapyramidal effects of antipsychotic drugs called acute dystonias that may develop early in therapy? A. Severe spasms of the muscles of the tongue, face, neck, or back B. Pacing and squirming and urge to move C. Involuntary upward deviation of the eyes D. Cramping causing joint dislocation

A. Severe spasms of the muscles of the tongue, face, neck, or back

A patient with schizophrenia is prescribed chlorpromazine (Thorazine) oral concentrate. Which of the following discharge instructions should the nurse complete? A. Sexual arousal may be enhanced with this medication. B. Avoid direct skin contact with the medication. C. The medication may cause excessive salivation. D. Do not limit salt intake while taking the medication.

A. Sexual arousal may be enhanced with this medication

20. Tardive dyskinesia is thought to result from which of the following? A. dopamine receptor supersensitivity B. depolarization blockade of mesolimbic DA neurons C. blockade of serotonin D. anticholinergic properties of the drug

A. dopamine receptor supersensitivity

17. A pt is actively hallucinating and delusional. Which term would most accurately document these findings? A. positive symptoms B. negative symptoms C. affective flattening D. attention impairment

A. positive symptoms

22. African Americans experience a high incidence of adverse effects from antipsychotic drugs. A. true B. false

A. true

23. Tardive dyskinesia may occur with long term use of typical antipsychotic drugs A. true B. false

A. true

26. Quetiapine (Seroquel) relieves both positive and negative symptoms of psychosis A. true B. false

A. true

27. Clozapine (Clozaril) is indicated for clients with schizophrenia, including those that have exhibited recurrent suicidal behavior. A. true B. false

A. true

EPS Dystonic Reactions

Adverse Effects Onset: 1-5 days post exposure Risk Factors: Male, young age, history of acute dystonia, cocaine use Presentation: oculogyric (eyeball movement) crisis, torticollis (head persistently turned to one side, often associated with painful muscle spasms), grimacing, opisthotonus (spasm of the muscles causing backward arching of the head, neck, and spine), tortipelvis (distortions of the spine and hip produced by a disorder marked by irregular muscular contractions of the trunk and extremities), laryngeal dystonia Treatment: anticholinergics (diphenhydramine, benztropine), benzodiazepines

EPS Parkinsonism (iatrogenic)

Adverse Effects Onset: 5-30 days or longer; within 72 days of therapy Mechanism: Antagonism of dopamine Presentation: bradykinesia, shuffling gait, resting tremor, rigidity, masked facies, perioral tremor Treatment: may respond to reduction of neuroleptic dose, anticholinergics

EPS Akathisia

Adverse Effects Onset: 5-60 days post exposure Risk Factors: Often affects elderly Presentation: inability to sit still, restlessness, muscular discomfort Treatment: reduction of neuroleptic dose, anticholinergics, benzodiazepines, propranolol

EPS Tardive Dyskinesia

Adverse Effects: [ Note- different than other EPS] Onset: months to years (often when neuroleptic is removed and dopaminergic activity increases) Mechanism: Upregulation of DA receptors in striatum caused by chronic neuroleptic use Risk Factors: Older females (dyskinesia), younger males (dystonia) Presentation: involuntary buccolingual-masticatory movements, may be permanent Treatment: stop offending drug, add or increase neuroleptic dose, switch to another drug (clozapine; quetiapine), prevent with drug holidays?, discontinue anticholinergic agents (botulinum toxin injections?), tetrabenazine (Nitoman®) or reserpine

Phenothiazines

Aliphatic: Chlorpromazine (Thorazine) Piperazine: Prochlorperazine (Compazine) Piperidine: Thioridazine (Mellaril)

Phenothiazines: Peripheral Effects

Alpha-adrenergic block, dopamine antagonism, central sympatholytic effects. Anticholinergic effects Antihistamine effects Local anesthetic-like effects

Tricyclic Structures

Anticholinergic actions Tachycardia; cardiac toxicity Orthostatic hypotension Weight gain Seizures [except for carbamazepine]

4. A pt complains of lightheadedness on standing since the initiation of an antipsychotic drug. Select the best response to the patient. A. This is an unfortunate and permanent effect of this class of drugs B. Get up slowly. Tolerance to this effect should develop in 2 to 3 month. C. The drug must be discontinued immediately to avoid injury D. This probably means that you are not getting enough of the drug

B. Get up slowly. Tolerance to this effect should develop in 2 to 3 month.

28. Most common antipsychotic neurological side effect: A. pseudoparkinsonism B. akathisia C. perioral tremor D. tardive dyskinesia E. neuroleptic malignant syndrome

B. akathisia

21. antipsychotic drugs are frequently used in clients who are critically ill. A. true B. false

B. false

24. Extrapyramidal effects are more likely to occur with newer atypical agents A. true B. false

B. false

25. Intramuscular injections of antipsychotic drugs require double the dose of oral dosages A. true B. false

B. false

14. Chlorpromazine and similar phenothiazines have been associated with the development of: A. breast cancer B. gynecomastia and galactorrhea C. ovarian hypertrophy D. multiple sclerosis

B. gynecomastia and galactorrhea

8. A depot preparation of an antipsychotic drug is prescribed. What information would be included in counseling this patient? A. depot agents are associated with a higher rate of relapse B. the drug will be administered by injection every 2 to 4 weeks C. there is an increased incidence of neuroleptic malignant syndrome D. this agent may be associated with a higher incidence of tardive dyskinesia

B. the drug will be administered by injection every 2 to 4 weeks

16. Clozapine is prescribed for a pt with a schizophreniform disorder. Which information would be the most important to include in the teaching plan for this patient? A. strategies to manage breast enlargement and nipple discharge B. the importance of promptly reporting flu-like symptoms C. contraceptive measures and expected changes in menstruation D. the meaning of various components of a white blood cell count

B. the importance of promptly reporting flu-like symptoms

31. Effective in managing rapidly cycling bipolar disorder in lithium or carbamazepine non-responding pt populations: A. triazolam (Halcion) B. valproic acid (Depakene, Depakote) C. dexamethasone (Decadron) D. all of the above

B. valproic acid (Depakene, Depakote)

29. Least EPS effects: A. Aliphatic phenothiazine- Chlorpromazine (thorazine) B. Dibenzodiazepine- Olanzapine C. Diabenzodiazepine-Clozapine D. Piperazine phenothiazine- Prochlorperazine E. Benzisoxazoles- Risperidone

C. Diabenzodiazepine-Clozapine

Which assessment best determines tardive dyskinesia in a patient taking antipsychotic agents? A. Pacing and squirming with an uncontrollable need for motion B. Mask-like face with drooling, tremors, rigidity, and shuffling gait C. Twisting, writhing, worm-like movements of the tongue and face D. Sudden high fever, sweating, and fluctuations in blood pressure

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

33. MM returns to the pharmacy a week later complaining she is still experiencing psychotic symptoms. The most appropriate reply of the pharmacist would be: A. You may need a different type of antipsychotic and the MD should be called to see if an atypical antipsychotic could be substituted for fluphenazine B. You probably have not been taking them correctly C. Your medication works very slowly and may take 2-3 weeks or longer to produce optimal effects D. Quetiapine may be countering the effectiveness and the MD should be called to see if it could be discontinued. E. You may be experiencing tardive dyskinesia so you should contact your physician

C. Your medication works very slowly and may take 2-3 weeks or longer to produce optimal effects

1. Haloperidol is classified as: A. a low-potency antipsychotic drug B. A medium-potency antipsychotic drug C. a high-potency antipsychotic drug D. an atypical antipsychotic drug

C. a high-potency antipsychotic drug

11. A pt on clozapine is being monitored. Which lab parameter is the most crucial to monitor on a weekly basis? A. renal function studies B. Hepatic function studies C. complete blood count D. serum clozapine levels

C. complete blood count

Phenothiazines: Pharmacokinetics

CPZ (Chlorpromazine) well absorbed orally and readily enter BBB. Long plasma halflives permit once-daily dosing Parenteral dosage forms available for rapid initiation of therapy [Delayed onset for antipsychotic effects] Lipophilic (accumulate in fatty tissues) Lack of correlation with dose, t-1/2, serum levels and clinical efficacy Metabolites may be detected in urine for weeks (especially phenothiazines)

Low Potency D2 Receptor Antagonists

Chlorpromazine (Thorazine) Chlorprothixene (Taractan) Thioridazine (Mellaril) Mesoridazine (Serentil)

5-HT2A & D2 Antagonists

Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal)

Neuroleptic History

Currently in US, 10-15% of prescriptions are for psychiatric disorders "Neuroleptic" -DA receptor antagonist These drugs suppress spontaneous movement and may cause complex EPS movement disorders Atypical vs Conventional Neuroleptics-Clozapine is an antipsychotic with fewer EPS effects-but we will still use the word "neuroleptic"

5. For how long after an acute episode of psychosis should one expect a patient to take an entipsychotic medication? A. at least 12 months B. life C. 2 weeks D. 6 months

D. 6 months

15. A pt receiving perphenazine, a traditional antipsychotic medication is assessed. The examiner notices the patient is shifting in the chair, rocking back and forth, and tapping both feet constantly. Select the most accurate term for the documentation of these findings. A. Dystonia B. CNS effects C. Alexithymia D. Akathisia

D. Akathisia

32. MM is a 20yo pt diagnosed with schizophrenia. She presents two prescriptions to the pharmacist. The prescribing psychiatrist had told her that the first prescription, fluphenazine (Prolixin), was to treat her schizophrenia symptoms but now MM wants to know why she had been given the second prescription written for Quetiapine (Seroquel). Which of the following statements regarding AN's two prescriptions is most correct? A. Quetiapine was probably prescribed to prevent allergic reactions from fluphenazine B. Quetiapine will enhance the antipsychotic actions of fluphenazine C. Fluphenazine causes excessive orthostatic hypotension that will be alleviated by quetiapine D. Quetiapine was probably prescribed to decrease the likelihood of fluphenazine causing eps such as akathisias, dystonic rxns, tremors, or rigidity E. Quetiapine will prevent fluphenazine-induced tardive dyskinesias

D. Quetiapine was probably prescribed to decrease the likelihood of fluphenazine causing eps such as akathisias, dystonic rxns, tremors, or rigidity

12. When comparing the effects of olanzapine with those of clozapine, which statement is correct? A. Olanzapine produces more tardive dyskinesia B. Olanzapine does not cause somnolence C. Clozapine has fewer serious side effects D. The drugs are similar in structure and actions

D. The drugs are similar in structure and actions

19. Which of the following are correct regarding typical antipsychotic drugs? A. clinical potency correlates with binding to D2 receptors B. long-term treatment may result in the supersensitivity of dopamine receptors C. the drugs differ more in potency than in efficacy D. a, b, and c are correct

D. a, b, and c are correct

30. Antipsychotic most appropriate in elderly pts with prostatic hypertrophy and chronic constipation. A. thioridazine (Mellaril) B. haloperidol (Haldol) C. chlorpromazine (Thorazine) D. clozapine (Clozaril)

D. clozapine (Clozaril)*

9. Which statement is correct regarding the use of atypical antipsychotic agents? A. they affect only the positive symptoms of schizophrenia B. they affect only the negative symptoms of schizophrenia C. they cause more extrapyramidal symptoms D. they commonly cause weight gain

D. they commonly cause weight gain

7. A pt on fluphenazine elixir should be instructed that: A. the drug can be diluted in any beverage B. it is acceptable to mix the drug with apple juice C. mixing the drug with tea can decrease some of the side effects D. water or orange juice can be used to dilute the elixir

D. water or orange juice can be used to dilute the elixir

Dopamine antagonism MOA

DA receptor block--> blocks postsynaptic DA receptors but also increases DA turnover (compensatory mechanism); after about 12 weeks of therapy, get inactivation (depolarization blockade) of DA neurons; correlates with antipsychotic effects.

Depot Preparations

Depot antipsychotics - long-acting, injectable formulations used for long-term maintenance therapy of schizophrenia No evidence that depot preparations pose an increased risk of side effects

Summary of Adverse Effects of the Phenothiazine-Type Antipsychotics: Central Nervous System Side Effects

Drowsiness, lethargy, feelings of fatigue and weakness. Extrapyramidal motor system reactions: Pseudoparkinsonism - akinesia, masklike facies, shuffling gait, tremors, rigidity. Akathisia - motor restlessness marked by feelings of inner tension or an inability to sit still or sleep. Acute dyskinesia or dystonic - contractions of small muscle groups resembling tics and of large muscle groups resembling convulsions. Tardive dyskinesias continued movements of the lips, tongue, and jaws may make speech and swallowing difficult. Muscles of upper and lower extremities may twitch and jerk continuously. Seizures Recognized as a complication from chlorpromazine but rarely seen with high potency drugs (However, may occur in 2-4% of those treated with clozapine)

Schizophrenia Drug Therapy: 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 Inform patients about side effects of treatment Assure patients that antipsychotic drug use does not lead to addiction Establish a good therapeutic relationship with patient Use an IM depot preparation for long-term therapy

Summary of Adverse Effects of the Phenothiazine-Type Antipsychotics Hypersensitivity-Type Reactions

Hematologic: blood dyscrasias reported include leukopenia and agranulocytosis; hemolytic anemia; thrombocytic purpura; and pancytopenia. Hepatic: cholestatic jaundice in which laboratory tests of liver function give results resembling extrahepatic obstruction. Dermatologic: urticaria, contact dermatitis, photosensitivity, erythema, exfoliative dermatitis

Summary of Adverse Effects of the Phenothiazine-Type Antipsychotics Neuroleptic Malignant Syndrome [NMS]

Life-threatening disorder in patients with extreme sensitivity to EPS of antipsychotics; occurs more commonly with high than low potency agents. Initial symptom is muscle rigidity; also fever, autonomic instability, seizures, coma, respiratory and cardiac failure can occur. Treatment includes use of dopamine agonists (bromocriptine) and direct-acting skeletal muscle relaxants (dantrolene)

"Atypical" Antipsychotic Agents

May benefit treatment-resistant patients Produce less extrapyramidal toxicities May involve different antipsychotic mechanism of action than D-2 antagonism by "typical" antipsychotics Varying degrees wt gain & diabetes Increased mortality of elderly patients with dementia Sedation & orthostatic hypotension QTc prolongation

Summary of Adverse Effects of the Phenothiazine-Type Antipsychotics Endocrine Disorders

Menstrual irregularities, including amenorrhea and false positive pregnancy tests. Gynecomastia and lactation. [hyperprolactinemia] Change in libido (sex drive). Weight gain with increased appetite and edema. Hyperglycemia and glycosuria (also hypoglycemia).

Neuroleptic Drug Classes (Structural)

Phenothiazines Thioxanthenes Butyrophenones Indoles Dibenzoxazepines Diphenylbutylpiperidines Dibenzodiazepines Benzisoxazoles

Summary of Adverse Effects of the Phenothiazine-Type Antipsychotics Cardiovascular and Other Autonomic Reactions

Postural (orthostatic) hypotensio; minimized by keeping the patient lying with head low and legs raised. Development of shock-like state may require administration of vasopressor drugs but not epinephrine. Cardiac palpitations, changes in ECG; possible sudden death due to cardiac arrest. Cholinergic blockade type: mouth dryness; blurring of vision; constipation, or obstipation and paralytic ileus; urinary retention; failure of sweating followed by fever. Adrenergic blockage type (in addition to orthostatic hypotension) includes: nasal stuffiness; inhibition of ejaculation.

Conventional Antipsychotics; Phenothiazines & related neuroleptics: Some Medical, Surgical, and Obstetrical Indications

Preanesthetic sedation Postoperative vomiting control In labor to reduce dosage of analgesics In management of cancer patients to potentiate narcotic analgesics and prevent vomiting induced by antineoplastic agents.

Dopamine (DA) hypothesis of schizophrenia

Schizophrenia associated with overactivity of DA in mesolimbic- frontal system Most antipsychotics block postsynaptic D2 receptors; Increasing DA activity with levodopa, amphetamines, or DA agonist drugs --> schizophrenia in some patients Postmortem studies have revealed increased DA receptor density in schizophrenic brains. The DA hypothesis does not explain why antipsychotics, which block DA receptors, are only partially effective for most patients and ineffective for others. Subtypes of DA receptors (D1-5) - provides hope that drugs that are more specific will produce fewer EPS. Newer atypical antipsychotics (eg, clozapine) have much less activity on D2 receptors and are still effective which may implicate a role for other DA receptors, and even non- DA receptors (eg, 5-HT2) in schizophrenia.

Conventional Antipsychotic Agents; Phenothiazines & related neuroleptics Psychiatric Indications

Schizophrenia- acute and chronic: Psychotic symptoms: hallucinations, delusions. Cognitive impairment: incoherence, looseness of symptoms, thought disorders, impaired attention or information processing. Negative symptoms: restricted affect, poverty of speech, loss of interests and sense of purpose, diminished social drive Manic phase of bipolar affective disorder (BAD). Confusional agitated states and psychoses. Organic brain syndrome with psychoses. Psychotic aspects of schizoaffective disorders. Tourette's syndrome (repetitive, stereotyped, involuntary movements and vocalizations called tics) Control disturbed behavior of patients with senile dementia of the Alzheimer type.

Antiemetic Drugs

Serotonin antagonist: Odansetron [Zofran] Anticholinergic: Scopolamine Antihistamine: diphenhydramine [Benadryl] DA antagonist: Prochlorperazine [Compazine] Cannabinoids: Dronabinol [Marinol]

Negative symptoms of schizophrenia

Social withdrawal, Emotional withdrawal, Lack of motivation, Poverty of speech, Blunted affect, Poor insight, Poor judgment, Poor self-care

Schizophrenia Drug Therapy

Three major objectives (1) Suppression of acute episodes (2) Prevention of acute exacerbations (3)Maintenance of the highest possible level of functioning Route: Oral (tablets, capsules, liquids), Intramuscular Most FGAs and SGAs ["atypicals] are equally effective - except for clozapine, which is more effective than the rest FGAs - significant risk of EPS. SGAs - risk of metabolic effects. FGAs - cost 10 times less than SGAs FGA/SGA: first/second-generation antipsychotic

"schizophrenia"

common type of psychosis with disorders in perception & thought, hallucinations & delusions, & withdrawal.