Antipsychotic and Parkinson's drug questions

First generation and second generation antipsychotics differ in terms of their common side effects. Which of the following would be more likely observed in a patient taking either clozapine or olanzapine? A) diabetes B) endocrine side effects C) extrapyramidal symptoms D) hyperprolactemia E) tardive dyskinesia

A) Metabolic syndrome-related symptoms (diabetes, weight gain, dyslipidemia) are side effects associated with 2nd generation antipsychotics, and are believed to be primarily caused by antagonism of serotonin & histamine receptors The other side affects are more commonly produced by potent D2 antagonists (e.g. haloperidol & 1st generation antipsychotics)

Which of the following cardiovascular pathologies is NOT associated with use of a second generation antipsychotic agents? A. Cardiac myxoma B. Myocarditis C. QT prolongation D. Torsades de pointes

A. Cardiac myxomas are the most common primary heart tumor and are most often found in the left atrium. Second generation antipsychotics are not known to increase the risk of developing cardiac myxomas. B. Clozapine is associated with myocarditis and cardiomyopathy. Patients taking clozapine should be monitored for clinical signs of myocarditis, electrocardiogram changes, troponin level elevation, as well as rise in inflammatory markers (erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)). Echocardiogram can be used to diagnose clozapine induced cardiomyopathy. C. Atypical antipsychotics are known to prolong the QT interval. Ziprasidone carries the highest risk of QT prolongation amongst the members of its class. Prolonged QT interval can increase the risk of torsade de pointes as well as other dangerous arrhythmias. Patients should be evaluated with a electrocardiogram prior to initiating any new antipsychotic medication. D. Torsades de pointes is a form of ventricular tachyarrhythmia which can precipitate ventricular fibrillation. All antipsychotic medications are known to prolong the QT interval and predispose to torsades de pointes.

Which of the following agents is considered a low potency antipsychotic? A. Chlorpromazine B. Fluphenazine C. Haloperidol D. Trifluoperazine

A. Chlorpromazine and thioridazine are both considered low potency first generation antipsychotics. Low potency antipsychotics block dopamine-2 receptors as well as histamine-1 receptors, alpha-1 receptors and muscarinic receptors. Fluphenazine, Haloperidol, and Trifluoperazine are all high-potency first generation antipsychotic. Like others in this class, it exhibits a greater degree of D2 dopaminergic blockade compared to low potency agents. So, while these agents are associated with little sedation, weight gain, or anticholinergic activity, they confer a high risk for extrapyramidal side effects.

Patients prescribed clozapine should undergo routine monitoring of which of the following laboratory studies? A. Complete blood cell count B. Serum creatinine C. Serum sodium D. serum creatine kinase

A. Clozapine is known to cause agranulocytosis, a severe condition in which granulocytes production sharply declines. Patients taking clozapine should be closely monitored with complete blood count to ensure adequate white blood cell counts. Recall that carbamazepine, colchicine, and methimazole are also associated with a risk of agranulocytosis B. Clozapine is not commonly known to cause renal disease and routine monitoring of serum creatinine is not necessary. C. There is no strong link between the use of atypical antipsychotic and hyponatremia. Routine monitoring of serum sodium is not required with use of clozapine. D. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition associated with antipsychotic use. NMS is known to cause profound elevations in serum creatine kinase leading to rhabdomyolysis. Routine monitoring of creatine kinase is not required in patients taking clozapine, but clinicians should have a low threshold for checking creatine kinase in patients who present clinically with symptoms of NMS.

Which of the following statements regarding first generation antipsychotics is most accurate? A. First generation antipsychotic medications can be used treat delirium B. First generation antipsychotics are used to target negative symptoms of schizophrenia C. Low potency antipsychotics are less effective in treating psychosis than high potency antipsychotics D. The half-life of most first generation antipsychotics is relatively short

A. Delirium is characterized by change in level of consciousness often accompanied by hallucinations. Delirium is a common cause of altered mental status in hospitalized patients and is usually precipitated by infection, metabolic derangement or other illnesses. Antipsychotic agents (e.g. haloperidol) can effectively treat acute psychosis in many conditions, including psychotic mania in bipolar disorder, major depressive disorder with psychotic features, delirium, and even psychosis in Parkinson's disease and Alzheimer's disease. Antipsychotics are also used to manage patients during times of acute agitation or aggression.

Regarding long-term use of levodopa in patients with Parkinson's disease, which of the following statements is least accurate? A. Dyskinesias are uncommon B. Gastrointestinal side effects tend to improve C. Response fluctuations develop over time D. Therapeutic window narrows with disease progression

A. Dyskinesias are common with long-term use of levodopa and occur in up to 80% of patients on treatment for more than 10 years. Choreoathetosis, characterized by uncomfortable, involuntary movement of the face and extremities, is the most common presentation. B. Gastrointestinal upset including nausea, vomiting, and diarrhea are the most common side effects associated with levodopa. These adverse effects are thought to result from peripheral conversion to dopamine by DOPA decarboxylase. Fortunately, these symptoms generally improve over time. C. Long-term use of levodopa is also associated with response fluctuations to the medication. Patients who have used levodopa for long terms may experience "wearing-off reaction" as well as "on-off phenomena." D. As Parkinson's Disease progresses, the therapeutic window for levodopa narrows unpredictably. Even small fluctuations in the serum levodopa level can cause motor fluctuations—too much dopamine results in dyskinesia and uncoordinated movements, whereas not enough dopamine results in bradykinesia and rigidity. Patients may begin to experience an "on-off phenomenon" with fluctuations in symptoms that are unrelated to the timing of the levodopa dose. In this phenomenon, "OFF" periods of marked akinesia alternate over the course of a few hours with "ON" periods of improved mobility.

A severely agitated and aggressive patient is treated with the high potency antipsychotic haloperidol. High potency antipsychotics are more likely to precipitate which adverse effect when compared with low potency antipsychotics? A. Neuroleptic malignant syndrome B. Sedation C. Tourette syndrome D. Urinary retention

A. High potency antipsychotic medications are more likely to precipitate neuroleptic malignant syndrome (NMS). NMS is characterized by altered mental status, fever, autonomic instability, rhabdomyolysis and "lead-pipe" rigidity. Patients with NMS can be treated with dantrolene (a muscle relaxant) and bromocriptine (a dopamine agonist) B. Low potency antipsychotics are more likely to cause sedation since low potency antipsychotics are more likely to block H1 histaminergic receptors C. High potency antipsychotic medications can be used to treat Tourette syndrome. High potency antipsychotic medications are not known to precipitate Tourette syndrome. D. Low potency antipsychotics have higher affinity for muscarinic receptors and are more likely to cause antimuscarinic adverse effects including dry mouth, constipation, blurred vision and urinary retention.

A man with Parkinson's disease who is taking levodopa begins to experience hallucinations and severe agitation. Which of the following management strategies would be least likely to alleviate this patient's psychiatric symptoms? A. Add carbidopa to levodopa B. Initiate low-dose quetiapine C. Minimize environmental stimuli and provide verbal reassurance D. Reduce the dose of levodopa

A. This patient is most likely experiencing hallucinations and agitation secondary to excess dopaminergic activity in the central nervous system. Carbidopa prevents peripheral conversion of levodopa to dopamine by the enzyme DOPA decarboxylase. Addition of carbidopa to levodopa would allow more levodopa to cross the blood brain barrier and undergo conversion to dopamine in the central nervous system. Consequently, the addition of carbidopa would enhance central dopaminergic transmission and thereby exacerbate this man's symptoms of hallucinations and agitation. B. Quetiapine is an atypical antipsychotic medication that antagonizes D2 dopaminergic receptors in the central nervous system. In addition to reducing the dose of levodopa, addition of a low-dose antipsychotic may be effective for treating hallucinations and agitation resulting from centrally-acting dopaminergic agents C. Non-pharmacological measures can be effective in alleviating agitation in patients experiencing acute psychological distress. Such measures include removal of upsetting stimuli, provision of verbal reassurance, and reorientation as needed. D. Hallucinations and agitation result from excess dopaminergic activity in the brain. Reducing the dose of levodopa would alleviate his symptoms of hallucination and agitation.

Like many other drugs used in treating different psychiatric disorders, atyipcal "antipsychotics" have been approved for treating more than one type of psychiatric disorder. Which other condition are these drugs commonly used for? A) dementia B) depression C) diabetes D) Parkinson's disease

B) Many atypical antidepressants have been approved for treating major depressive disorder that is resistant to more traditional SSRIs and SNRIs, and as an alternative to lithium for treating bipolar disorder A) Antipsychotics as a drug class have a Black Box warning concerning the increased risk of death if used to treat dementia-related psychosis in elderly patients. C) Atypical antipsychotics are associated with an increased risk for weight gain, hyperlipidemia and type 2 diabetes. D) Drugs that are D2 receptor antagonists have no role in treating a disorder caused by death of dopaminergic neurons such as Parkinson's disease.

A 27-year-old man with a history of paranoid schizophrenia is hospitalized after exhibiting severe symptoms attributed to non-adherence to therapy with haloperidol. During the taking of his history he states that he "stopped taking that damned drug" because it caused breast enlargement. He also complained about delayed ejaculations, which became much less of a problem after stopping haloperidol for two weeks. What mechanism was most likely responsible for causing this patient's side effects? A) autonomic side effects B) endocrine side effects C) extrapyramidal side effects D) hypoprolactemia

B) endocrine side effects. Dopamine is the normal inhibitory regulator of prolactin release. As a result, potent D2 receptor antagonists produce "hyperprolactemia" which results in amenorrhea in women, infertility in both sexes, and breast development in men A and C) While these side effects are associated with 1st generation antipsychotics, they can't account for his major complaints D) First generation antipsychotics do not cause a reduction in prolactin release

Which of the following statements regarding aripiprazole is most accurate? A. Aripiprazole exhibits agonist activity at 5-HT2A serotonin receptors B. Aripiprazole is a dopamine-2 receptor partial agonist C. Aripiprazole is contraindicated in patients with Tourette syndrome D. Aripiprazole is the only antipsychotic medication which is not associated with extrapyramidal symptoms

B. Aripiprazole is a second generation antipsychotic (SGA). Most first generation antipsychotic agents and SGAs exhibit antagonist activity at D2 dopamine receptors. Aripiprazole is unique in that it is a dopamine-2 receptor partial agonist. A. Second generation antipsychotics such as aripiprazole exhibit antagonist activity at 5-HT2A receptors. In fact, 5-HT 2A serotonin receptor blockade is a key factor in the mechanism of action of second generation antipsychotics. Blocking serotonin receptors modulates the release of all kinds of neurotransmitters in the CNS including dopamine, norepinephrine, glutamate, GABA, and acetylcholine. C. Aripiprazole is indicated for treatment of Tourette syndrome. Aripiprazole can also be used to treat major depressive disorder, schizophrenia and bipolar disorder. D. Aripiprazole is known to cause extrapyramidal symptoms (EPS). All antipsychotic agents are associated with EPS but there is a greater risk of EPS with first generation antipsychotics than with second generation antipsychotics.

Which of the following second generation antipsychotic agents is most likely to cause anticholinergic adverse effects? A. Aripiprazole B. Clozapine C. Risperidone D. Ziprasidone

B. As a group, second generation antipsychotics are less likely than first generation drugs to cause anticholinergic side effects. Amongst the second generation antipsychotics, aripiprazole, risperidone, aripiprazole, and ziprasidone have low affinity for antimuscarinic receptors, whereas clozapine, olanzapine, and quetiapine have higher affinity for these receptors. Clozapine has the highest affinity for muscarinic receptors and is therefore the most likely to cause antimuscarinic adverse effects including tachycardia, blurred vision, urinary retention, and constipation. Amongst second generation antipsychotics, clozapine also confers the highest risk of seizures.

Which of the following Parkinson's disease medications is correctly paired with its mechanism of action? A. Amantadine - Catechol-O-methyltransferase inhibitor B. Pramipexole - D3 dopamine receptor agonist C. Ropinirole - D2 dopamine receptor antagonist D. Selegiline - Monoamine oxidase-A inhibitor

B. Pramipexole is a D3 dopamine receptor agonist. Pramipexole can be used as initial monotherapy for Parkinson's disease or in combination with other dopaminergic agents. Pramipexole can also be used to treat restless leg syndrome. A. Amantadine is a drug originally developed to treat the influenza virus, but also has utility in treating motor symptoms associated with Parkinson's disease. Amantadine enhances the effect of endogenous dopamine by increasing dopamine synthesis and release while also inhibiting its reuptake. Amantadine therapy can alleviate some of the motor symptoms of parkinson's disease, although it is less efficacious than levodopa and its effects may be short lived. C. Ropinirole is a D2 dopamine receptor agonist, not antagonist. Pramipexole is also a dopamine receptor agonists used as initial treatment of Parkinson's disease. Ropinirole can be used to treat both Parkinson's disease and restless leg syndrome. D. Selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor. MAO-B selectively metabolizes dopamine in the central nervous system. MAO-B inhibitors such as selegiline increase the amount of dopamine available in the neuronal synapses.

A patient with schizophrenia is prescribed olanzapine. For this patient, which of the following parameters does NOT require routine monitoring? A. Body mass index B. Cardiac ejection fraction C. Fasting serum glucose D. Low density lipoprotein

B. Cardiac ejection fraction assesses the contractility of cardiac ventricles and is usually measured with an echocardiogram. Although second generation antipsychotic (e.g. clozapine) medications are known to have cardiotoxic effects, routine monitoring of ejection fraction in asymptomatic patients is not common practice. Compared to clozapine, olanzapine had been rarely associated with cardiomyopathy. However, physicians should have a low threshold for investigating symptoms concerning for cardiomyopathy or cardiotoxicity in patients taking antipsychotic medications. Patients taking olanzapine, quetiapine and clozapine (Second generation antipsychotics) are associated with risk of adverse metabolic effects including weight gain, dyslipidemia, and diabetes

Extrapyramidal symptoms are mediated by which of the following dopaminergic pathways? A. Mesocortical B. Mesolimbic tract C. Nigrostriatal tract D. Tuberoinfundibular

C. The nigrostriatal tract is one of four major dopaminergic pathways and is responsible for movement. Extrapyramidal symptoms are movement disorders thought to occur as a result of interactions between antipsychotic agents and the nigrostriatal dopaminergic pathway. Antipsychotic agents, especially first generation antipsychotics, decrease dopaminergic activity within the nigrostriatal pathway to cause extrapyramidal symptoms including acute dystonia, akathisia, tardive dyskinesia, and drug-induced parkinsonism.

Your patient suffering from schizophrenia has not achieved adequate control of his symptoms after more than two years of monotherapy with three different antipsychotics. After three weeks of switching treatment to a 4th agent, your patient returns to your clinic complaining of being fatigued, and having episodes of fever that come and go. His lab results reveal the presence of a leukopenia and thrombocytopenia. What drug was this patient most likely taking that produced these side effects? A) aripiprazole B) chlorpromazine C) clozapine D) olanzapine E) risperidone

C) Clozapine has the potential to cause agranulocytosis. Hence it is not considered a drug of first or 2nd choice, and the need for regular blood tests for patients taking this drug B) Chlorpromazine. 1st generation antipsychotics are not known for producing agranulocytosis D and E) Olanzapine and Risperidone. 2nd generation antipsychotics is not known for producing agranulocytosis.

Which of the following statements regarding entacapone and tolcapone is most accurate? A. Entacapone decreases the bioavailability of levodopa B. Only entacapone carries a risk of fatal hepatotoxicity C. Only tolcapone inhibits central COMT D. Only tolcapone should be administered in combination with levodopa

C. Both entacapone and tolcapone inhibit catechol-O-methyltransferase (COMT) peripherally. However, only tolcapone is able to cross the blood-brain barrier and act as a central COMT inhibitor as well. A. Entacapone and tolcapone both increase the bioavailability of levodopa by inhibiting peripheral catechol-O-methyltransferase (COMT). However, only tolcapone acts as both a peripheral and central COMT inhibitor. COMT converts levodopa to 3-O-methyldopa (3-OMD) in the periphery and converts dopamine to 3-methoxytyramine (3-MT) in the CNS. B. Tolcapone is associated with severe hepatitis and fatal acute hepatic failure. Entacapone may rarely cause clinically apparent liver injury, but it has not been associated with acute liver failure. Patients taking tolcapone should be routinely monitored with liver function tests. D. Both entacapone and tolcapone are catechol-O-methyltransferase (COMT) inhibitors which should only be used in combination with levodopa. COMT inhibitors increase the bioavailability and extend the duration of levodopa by preventing the degradation of levodopa.

When treating Parkinson's disease patients, it is standard clinical practice to prescribe levodopa in combination with carbidopa. How does carbidopa increase the effectiveness of levodopa therapy? A. Central inhibition of catechol-O-methyltransferase B. Direct agonism of D2 dopaminergic receptors C. Peripheral inhibition of DOPA decarboxylase D. Peripheral inhibition of catechol-O-methyltransferase

C. Carbidopa is a DOPA decarboxylase inhibitor that leads to increased bioavailability of levodopa in the central nervous system. Additionally, by blocking peripheral conversion to dopamine, carbidopa decreases peripheral side effects of levodopa therapy. Adding a DOPA decarboxylase inhibitor to levodopa significantly reduces the nausea, vomiting, arrhythmias, and postural hypotension associated with peripheral dopamine activity. Adding carbidopa to levodopa does not decrease symptoms of anxiety and agitation, however, because these are due to the central effects of dopamine. Anxiety and agitation can even be increased because more dopamine is available to the brain. A. Tolcapone inhibits central catechol-O-methyltransferase (COMT) in order to prevent degradation of dopamine. Carbidopa does not inhibit the activity of COMT. B. Carbidopa does not act via direct agonism of D2 dopaminergic receptors. Instead, carbidopa inhibits peripheral conversion of levodopa to dopamine in order to increase the bioavailability of levodopa in the central nervous system. D. Entacapone and tolcapone both inhibit peripheral catechol-O-methyltransferase (COMT). Carbidopa does not inhibit the activity of COMT.

Which of the following statements about second generation antipsychotics (SGAs) is most accurate? A. SGAs are first-line agents for obsessive compulsive disorder B. SGAs are appropriate as monotherapy for major depressive disorder C. SGAs are effective in treating positive symptoms of schizophrenia D. SGAs should not be used to treat patients with Tourette syndrome

C. First generation antipsychotic agents primarily target the positive symptoms of schizophrenia, but are not effective in treating negative symptoms of schizophrenia. SGAs are effective in treating both the positive and the negative symptoms of schizophrenia. A. Selective serotonin reuptake inhibitors (SSRIs) are first-line agents for treatment of obsessive compulsive disorder (OCD). SGAs can be used as adjunctive agents in OCD patients who fail a trial of SSRI monotherapy. Cognitive behavioral therapy alone or in combination with medication is also used to treat OCD. B. SSRIs are first-line agents for treating major depressive disorder. SGAs are used as adjunctive agents for depressed patients with severe or refractory symptoms that do respond to initial trials of antidepressant monotherapy. D. SGAs can be used to treat Tourette syndrome. Pharmacotherapy with alpha-2 agonists such as clonidine and guanfacine may also be used. Behavioral and supportive therapies are also used to treat and manage Tourette syndrome.

Patients prescribed thioridazine at high doses should be counseled on which possible ophthalmologic adverse effect? A. Central retinal artery occlusion B. Corneal deposits C. Retinal deposits D. Retinitis pigmentosa

C. High dose thioridazine administration is associated with development pigmentary retinopathy from retinal deposits. Patients may experience decreased visual acuity, constriction of visual field, visual discoloration, and loss of night vision. A. Central retinal artery occlusion (CRAO) is caused by embolic occlusion resulting in sudden, severe, unilateral, and painless loss of vision. CRAO is not associated with thioridazine. B. Chlorpromazine is associated with the formation of corneal deposits as well as lenticular deposits, which may result in cataracts. Thioridazine is more often associated with retinal deposits leading to pigmentary retinopathy. D. Retinitis pigmentosa is an inherited condition which causes progressive vision loss. Retinitis pigmentosa is not caused by thioridazine. However, advanced cases of thorazine induced pigmentary retinopathy can mimic retinitis pigmentosa.

Which of the following patients' symptoms is least likely to be caused by haloperidol based on the temporal relationship between initiation of the drug and onset of symptoms. A. 17-year-old boy with Tourette syndrome who starts to fidget and shift in place after 4 days of staring oral haloperidol. B. 24-year-old man with schizophrenia who was given one dose of haloperidol to manage agitation 6 hours ago. His family now notices that his eyes appear to be forced upward with his neck forced backwards. C. 40-year-old man with schizophrenia who has been taking oral haloperidol for one month. Over the past week, he has begun to develop uncontrollable lip smacking and facial grimacing. D. 45-year-old woman with schizophrenia who begins to move and walk around extremely slowly 4 weeks after starting oral haloperidol.

C. High potency antipsychotic agents including haloperidol, trifluoperazine and fluphenazine are associated with an increased risk of developing tardive dyskinesia. Tardive dyskinesia, which may present as lip smacking, facial tics and grimacing typically develops insidiously after long-term (greater than 3 months) use of antipsychotic agents. It is unlikely to develop rapidly and after only one month of neuroleptic drug exposure. Tardive dyskinesia is potentially irreversible so physicians should monitor patients closely for these symptoms and consider discontinuation of the medication and/or switching to an alternative drug (such as a second generation antipsychotic or clozapine).

A 40-year-old man was recently diagnosed with Parkinson's disease, but he has not yet started pharmacotherapy. In addition to resting tremor in his left hand and often unsteady and slow movement, he also complains of an irresistible urge to move his legs because of an uncomfortable tingling sensation as he rests in bed at night. Which of the following medications would be most appropriate initial therapy for this patient? A. Carbidopa B. Entacapone C. Pramipexole D. Selegiline

C. In this vignette, a man with newly diagnosed Parkinson's disease is complaining about symptoms of restless leg syndrome. Pramipexole is often used as initial treatment for Parkinson's disease especially in patients younger than 60 years old in order to delay the use of levodopa. Pramipexole would also be appropriate for this patient suffering from restless leg syndrome, which is characterized by an irresistible urge to move the legs during times of rest, usually because of an uncomfortable sensation. A. Carbidopa is a DOPA decarboxylase inhibitor. Carbidopa is used in combination with levodopa to prevent peripheral conversion to dopamine and increase bioavailability of levodopa centrally. Carbidopa is not used as monotherapy for Parkinson's disease. Carbidopa is also not used to treat with restless leg syndrome. B. Entacapone is a peripheral catechol-O-methyltransferase inhibitor (COMT). COMT is the enzyme responsible for converting levodopa to its inactive metabolite, 3-methyldopa. COMT inhibitors should only be used in combination with levodopa; they are otherwise ineffective. Entacapone is usually used as an adjunct to minimize the "wearing off symptoms" associated with levodopa. Entacapone is not used to treat restless leg syndrome. D. Selegiline is a monoamine oxidase-B (MAO-B) inhibitor. Selegiline is usually used as adjunctive treatment to levodopa. Selegiline is not generally used as monotherapy for Parkinson's disease nor does it alleviate symptoms of restless leg syndrome.

Levodopa is known to precipitate all of the following side effects EXCEPT: A. Cardiac arrhythmias B. Gastrointestinal distress C. Hyperphagia D. Visual hallucinations

C. Levodopa is not associated with hyperphagia or weight gain. In fact, levodopa is known to cause gastrointestinal distress and may be responsible for weight loss in a small number of patients. A. Peripheral conversion of levodopa to dopamine can lead to postural hypotension as well as a variety of cardiac arrhythmias including tachycardia, premature ventricular contractions, and atrial fibrillation. B. Gastrointestinal distress, including nausea and vomiting, is the most common side effect associated with levodopa. These symptoms result from peripheral conversion of levodopa to dopamine with resulting stimulation of the chemoreceptor trigger zone chemoreceptor trigger zone by dopamine outside of the blood-brain barrier. Fortunately, most patients develop tolerance the emetic effects. D. Levodopa can lead to visual hallucinations. Excess dopamine in the central nervous system can cause psychotic features including hallucinations, agitation, disordered thoughts, and delusions. As a result, levodopa is contraindicated in patients with psychotic disorders.

Compared to high potency agents, low potency antipsychotic medications have a _______. A. Greater affinity for D2 dopaminergic receptors B. Higher incidence of extrapyramidal side effects C. Higher risk of precipitating anticholinergic symptoms D. Lower risk of sedation

C. Low potency antipsychotic medications are more likely than high-potency agents to cause anticholinergic side effects including xerostomia, constipation, and urinary retention. The low-potency medications are also more likely to cause alpha-1 blockade and orthostatic hypotension. A. Low potency antipsychotic medications have less affinity for D2 dopaminergic receptors when compared to high-potency agents. B. Low potency antipsychotics are associated with a lower incidence of extrapyramidal side effects when compared to high potency agents like haloperidol. Low potency antipsychotics are less likely to precipitate symptoms such as dystonia, akathisia, and tardive dyskinesia. D. Low potency agents are associated with a higher risk of sedation than high potency drugs because low potency agents exhibit increased H1 histamine receptor antagonism.

Which of the following antipsychotic agents is most likely to cause orthostatic hypotension as an adverse effect? A. Fluphenazine B. Haloperidol C. Thioridazine D. Trifluoperazine

C. Orthostatic hypotension can result from alpha-1 blockade, which leads to vasodilation and a subsequent drop in blood pressure. Low-potency antipsychotics such as thioridazine and chlorpromazine have increased affinity for the alpha-1 receptors and thus an increased risk of orthostatic hypotension. A. Fluphenazine is a high potency antipsychotic medication. Fluphenazine and other high potency antipsychotics are less likely than low potency antipsychotics to cause orthostatic hypotension. B. Haloperidol is a typical, high potency antipsychotic. High potency antipsychotic medications are associated with decreased risk of orthostatic hypotension. D. Like haloperidol and fluphenazine, trifluoperazine is a high-potency antipsychotic. Trifluoperazine is associated with a lower risk of orthostatic hypotension when compared to a low-potency agent.

A patient with schizophrenia is prescribed fluphenazine. Fluphenazine would be expected to improve ALL BUT which of the following symptoms? A. Belief that the United States government is specifically trying to control this patient through radio waves despite no evidence to support this belief. B. Hearing music and speech which cannot be heard by other people in the same room C. Inability to express emotion due to monotone voice and lack of facial expression D. Speaking sentences which cannot be understood by most other people; for example, "Block lock the clock sock."

C. Patients with schizophrenia may display a blunted, or flat affect which is characterized by lack of facial expression and lack of vocal inflection. Flat affect, social withdrawal, anhedonia, apathy, and avolition are all considered negative symptoms of schizophrenia. Typical antipsychotics, such as fluphenazine, are not effective against negative symptoms mediated by the mesocortical dopaminergic pathway. Typical antipsychotic medications are used to treat the positive symptoms of schizophrenia mediated by the mesolimbic dopaminergic pathway.

Second generation antipsychotic medications induce sedation via which of the following mechanisms? A. Alpha-1 adrenergic receptor antagonism B. D2 dopaminergic receptor antagonism C. H1 histamine receptor antagonism D. Muscarinic receptor antagonism

C. Second generation antipsychotics (SGA) block H1 histamine receptors. As a result, SGA's cause sedation and drowsiness. Sedation is most prominent with clozapine and quetiapine and patients should be warned about drowsiness with the first few doses of treatment. The other choices do not induce sedation A. Alpha-1 adrenergic receptors mediate smooth muscle vasoconstriction. Second generation antipsychotics block alpha-1 receptors and can cause orthostatic hypotension. B. Most second generation antipsychotics antagonize D2 dopamine receptors. D2 dopaminergic blockade in the nigrostriatal tract is known to cause extrapyramidal side effects. D. Muscarinic receptor antagonism can cause xerostomia, constipation, and urinary retention. Sedation is not a typical effect of muscarinic antagonism.

Second generation antipsychotics (SGAs) are more likely than first generation antipsychotics (FGAs) to cause which adverse effect? A. Antimuscarinic symptoms B. Extrapyramidal symptoms C. Hypercholesterolemia D. Neuroleptic malignant syndrome

C. Second generation antipsychotics, especially olanzapine, clozapine and quetiapine, are associated with increased risk of metabolic effects and metabolic syndrome. Ziprasidone carries the lowest risk of these metabolic effects. As a class, SGAs are more likely to cause weight gain, hypercholesterolemia, and hyperglycemia when compared to FGAs. However, all patients started on antipsychotic medications should be regularly monitored for metabolic side effects. A. Second generation antipsychotics have a lower affinity for muscarinic receptors than first generation antipsychotics. As a result, FGAs are more likely to cause antimuscarinic symptoms including dry mouth, constipation, blurred vision and urinary retention. B. First generation antipsychotics are more likely than second generation antipsychotics to cause extrapyramidal symptoms such as acute dystonia, akathisia, and parkinsonism. D. First generation antipsychotics are more likely than second generation antipsychotics to cause neuroleptic malignant syndrome (NMS). NMS is characterized by mental status changes, "lead pipe" rigidity, autonomic instability, fever and rhabdomyolysis.

A patient suffering from schizophrenia was recently initiated on treatment with a different 2nd generation antipsychotic after having failed to respond to several other agents over the past two years. While taking this drug, the patient is required to have weekly blood counts during the 1st 6 months of therapy, and biweekly blood tests thereafter to screen for evidence of developing neutropenia. What other "unusual" side effect is also uniquely associated with this drug, in contrast to other 2nd generation antipsychotics? A) dry mouth B) insomnia C) prolonged QTc D) seizures E) weight loss

D) Amongst the 2nd generation antipsychotics, clozapine is unique for having a dose-dependent risk for producing seizures A) Clozapine produces hypersalivation, not dry mouth B) Clozapine produces sedation, not insomnia. C) All antipscyhotics will prolong the QT in a dose-dependent manner E) Clozapine produces weight gain, not loss

A 28-year-old woman who is diagnosed with paranoid schizophrenia is initiated on onalzapine (10 mg at bedtime) to try and stabilize her condition. Two days after initiating drug therapy she is brought to the emergency room complaining of muscle rigidity, fever, and increased mental confusion. Upon evaluation her temperture is 40 oC, BP 160/100 mm Hg, heart rate 110/min. What is the most likely diagnosis for her current condition? A) drug-induced autonomic side effects B) extrapyramidal symptoms C) malignant hyperthermia D) neuroleptic malignant syndrome E) tardive dyskinesia

D) NMS is a rare, but potentially life-threatening syndrome associated with the use of medications that block dopamine transmission. It usually evolves ofer 1-3 days after onset of therapy. Its incidence is lower with atypicals (2nd generation) antipsychotics compared to 1st generation drugs, but cases have been reported (Treat NMS with bromocriptine/dantrolene) B) EPS is are not the most likely explanation for elevated body temperature, tachycardia, or mental confusion. E) TD is a syndrome consisting of characteristic involuntary movements that occur after chronic use of antipsychotic medications, typically after 6 months or more of therapy. The symptoms include smacking of lips, choreoathetoid movements, lateral jaw movements and facial grimacing.

A 19 -year-old man is brought to the University Emergency Department by the New Orleans police after they found him running down the middle ground of Canal boulevard in his boxer shorts and combat boots on a freezing winter day. Besides his relative lack of clothing, his appearance indicates poor hygeine, and he seems to be suffering auditory hallucinations. Upon arrival he seems extremely suspicious of the medical staff, and claims that Richard Nixon will save us all once he becomes re-elected president of the United States. An emergency room physician gives him a single dose of i.m. diazepam to reduce his anxiety, before seeking a psychiatric consult. His physical exam, blood glucose and electrolytes are normal, and a panel of blood tests for drugs of abuse are negative. An on-duty psychiatric resident makes a tentative diagnosis of schizophrenia and recommends a first generation (typical) antipsychotic be given i.m. to reduce his agitation, and stabalize his behavior. Which of the following drugs would be an appropriate choice? A) Aripiprazole B) Chlordiazepoxide C) Clozapine D) Haloperidol E) Olanzapine

D) This is a 1st generation antipsychotic commonly used in this clinical situation (to treat acute agitation). Droperidol is a haloperidol analog with a shorter half-life, and proven track record, that is also commonly used. While 2nd generation drugs might also be effective, the clinical evidence supporting their efficacy in this situation is not strong A) Aripiprazole is an atypical (2nd generation) antipsychotic. While a 2nd generation drug might be effective, there are few clinical studies documenting their efficacy compared to older 1st generation drugs in this setting. B) Chlordiazepoxide is a benzodiazepine (Librium), and he has already been given diazepam. C) Clozapine is an atypical (2nd generation) antipsychotic that is typically reserved for treating patients resistant to other antipsychotics E) Olanzapine is an atypical (2nd generation) antipsychotic. While a 2nd generation drug might be effective, there are few clinical studies documenting their efficacy compared to older 1st generation drugs in this setting.

Antipsychotics are notorious for producing side effects, and the side effect profiles differ between 1st generation and 2nd (atypical) generation antipsychotics. Second generation drugs have a lower incidence of Extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Which of the following drugs is a representative of this drug class? A) buspirone B) chlorpromazine C) haloperidol D) quetiapine E) temazepam

D) quetiapine is the non-proprietary name for Seroquel, a commonly prescribed 2nd generation antipsychotic A) Buspirone is a 5-HT1A serotonin partial agonist that is indicated for treating generalized anxiety disorder. It has no significant effect on D2 receptors, and is not an antipscyhotic. B and C) Chlorpromazine and haloperidol are 1st generation antipsychotics E) temazepam is a benzodiazepine sometimes used for short term management of insomnia

A 60-year-old man is diagnosed with Parkinson's disease and started on ropinirole monotherapy. Over the next year, his family states that his personality has changed significantly and he has been gambling more frequently and making large, impulsive purchases such as a boats and luxury watches. T2*/SWI weighted MRI of the brain reveals loss of hyperintensity within the posterior third of the substantia nigra as well as age-related volumetric changes in the gray and white matter. What is the most likely explanation for this patient's behavioral changes? A. Bilateral amygdala brain lesions B. Degeneration of the frontotemporal lobe C. Depressive disorder due to Parkinson's disease D. Medication side effect

D. Dopamine receptor agonists such as ropinirole are known to enhance impulse control disorders. Patients taking high dose dopamine receptor agonists are at risk of developing pathological gambling, shopping and hypersexuality. MRI of this patient's brain shows typical changes associated with Parkinson's disease (absent swallow tail sign). This patient's behavioral changes are most likely secondary to initiation of the dopamine receptor agonist, ropinirole. A. Kluver-Bucy syndrome is characterized by hypersexuality, hyperorality and hyperphagia. Kluver-Bucy syndrome often occurs after HSV-1 encephalitis with resulting damage to the bilateral amygdala in the temporal lobes. There is no indication from the clinical story or the radiographic findings that this patient suffered any damage to the temporal lobes. B. Frontotemporal dementia is a neurodegenerative condition marked by significant atrophy of the bilateral frontal and temporal lobes. Frontotemporal dementia often presents with significant personality changes and/or aphasia. Based on radiographic imaging, this patient does not appear to have frontotemporal dementia. C. It is well recognized that Parkinson's disease can induce a state of depression. Although this patient is exhibiting major personality changes, his presentation is not consistent with depressive disorder. Rather, his impulsive behaviors are secondary to initiation of the dopamine receptor agonist, ropinirole.

Which of the following adverse effects of first generation antipsychotics is not directly caused by dopamine receptor antagonism? A. Amenorrhea B. Galactorrhea C. Gynecomastia D. Priapism

D. Dopamine secretion from the hypothalamus normally inhibits prolactin release from the anterior pituitary gland. Blockade of dopaminergic receptors in the central nervous system removes this inhibitory effect and results in hyperprolactinemia which causes impotence in men and amenorrhea in women. Antipsychotic medications may cause priapism in rare cases; usually priapism is caused by alpha-1 receptor antagonism and not dopamine receptor antagonism. (Priapism is a prolonged erection) A. Hyperprolactinemia resulting from dopaminergic blockade in the central nervous system leads to amenorrhea in women. Amenorrhea, impotence and galactorrhea are more likely to be caused by high potency antipsychotics than low potency antipsychotics. B. Galactorrhea is an adverse effect of antipsychotic medications caused by hyperprolactinemia resulting from dopaminergic blockade. Galactorrhea can also be a sign of excess prolactin secretion from a prolactinoma or other pituitary tumors. C. Gynecomastia, excess development of breast tissue, can be caused by excess prolactin in men taking antipsychotic medications

If entacapone were used as monotherapy for a Parkinson's disease patient, which of the following results would be most likely to occur? A. Gradual improvement of bradykinesia B. Gradual improvement of cogwheel rigidity C. Immediate relief of resting tremor D. No appreciable change in Parkinsonian features

D. Entacapone is a peripheral catechol-O-methyltransferase (COMT) inhibitor which inhibits the peripheral methylation of levodopa to the inactive metabolite 3-O-methyldopa. Entacapone is only effective when used in combination with levodopa. Entacapone prolongs the half life of levodopa and thus prevents the "wearing-off" symptoms and motor fluctuations often seen shortly before the next dose of levodopa is due.

Which of the following second generation antipsychotics (SGA) is most likely to cause extrapyramidal symptoms? A. Clozapine B. Olanzapine C. Quetiapine D. Risperidone

D. Extrapyramidal symptoms such as akathisia and bradykinesia are caused by dopamine-2 receptor antagonism in the nigrostriatal tract, which is normally involved in the control of muscle movement. The defining difference between second generation antipsychotics and their first generation predecessors is a reduced incidence of extrapyramidal symptoms. Amongst the second generation antipsychotics, risperidone is the most likely to cause extrapyramidal symptoms. A. Clozapine is less likely than risperidone to cause extrapyramidal symptoms (EPS). Patients who need an antipsychotic agents but are at high risk of developing EPS should be prescribed clozapine or quetiapine. B. Olanzapine is less likely than risperidone to cause extrapyramidal side effects. C. Quetiapine is less likely than risperidone to cause extrapyramidal side effects. In fact, quetiapine and clozapine are the two second generation antipsychotic medications which are least likely to cause extrapyramidal side effects.

A young man with Tourette syndrome still has uncontrollable tics despite taking clonidine. He is prescribed an antipsychotic medication as adjunctive therapy. Two months later he calls his physician complaining of enlarged breasts and inability to maintain an erection. Which of the following drugs is most likely responsible? A. Clonidine B. Aripiprazole C. Clozapine D. Risperidone

D. The patient in the vignette above was most likely started on risperidone in order to manage his treatment refractory Tourette syndrome. Amongst the atypical antipsychotics, risperidone exhibits the strongest blockade of D2 dopaminergic receptors in the central nervous system. Therefore, risperidone is most likely to cause hyperprolactinemia and its downstream effects including gynecomastia, impotence, amenorrhea, and decreased libido. (Notably, risperidone also has the highest risk of causing extrapyramidal symptoms among the second generation) A. Clonidine is an alpha-2 adrenergic agonist used to treat hypertension and Tourette's syndrome. But it is not associated with gynecomastia or impotence. B. Aripiprazole is less likely than risperidone to cause gynecomastia and impotence. C. Most second generation antipsychotics (SGAs)are known to block D2 dopaminergic receptors in the central nervous system and precipitate hyperprolactinemia. However, within the class of SGAs, risperidone is the most likely to cause hyperprolactinemia resulting in gynecomastia and impotence in men and galactorrhea and menstrual disturbances in women. Additionally, unlike risperidone and aripiprazole, clozapine has not been well studied in the treatment of Tourette syndrome and is not typically used for this indication.

A patient with Parkinson's disease has been taking carbidopa/levodopa for 7 years. Over the past year, he has begun to experience worsening tremors. He does not complain of significant bradykinesia or gait disturbance. Based on recommendations from another friend with Parkinson's disease, the patient inquires about taking trihexyphenidyl. Should this patient be prescribed trihexyphenidyl? A. No, because benztropine is the preferred antimuscarinic agent for Parkinson's disease B. No, trihexyphenidyl may precipitate or worsen bradykinesia C. Yes, but carbidopa/levodopa therapy should be discontinued if the patient is taking trihexyphenidyl D. Yes, trihexyphenidyl can improve symptoms of tremor

D. Trihexyphenidyl and benztropine are anticholinergic agents which are used to treat parkinsonism. These anticholinergic agents can improve the tremor and rigidity associated with Parkinson's disease. However, neither trihexyphenidyl nor benztropine are effective at treating bradykinesia. In this patient with worsening tremor, trihexyphenidyl would be a good adjunctive agent in addition to carbidopa/levodopa. A. Both benztropine and trihexyphenidyl are anticholinergic agents which can be used to target symptoms of tremor and rigidity in patients with Parkinson's disease. Both drugs have similar efficacy but trihexyphenidyl is more commonly used to treat patients with Parkinson's disease while benztropine is commonly used to treat psychotropic drug-induced parkinsonism. B. Trihexyphenidyl will not precipitate or worsen bradykinesia. However trihexyphenidyl is an anticholinergic agent which is associated with adverse effects including confusion, constipation, urinary retention and tachycardia. C. Trihexyphenidyl is often used as an adjunctive agent to carbidopa/levodopa in patients with Parkinson's disease whose primary complaint is tremor. There is no need to discontinue carbidopa/levodopa therapy. Trihexyphenidyl is sometimes used as monotherapy in younger patients with predominant tremor problems as a way of delaying the need for initiating carbidopa/levodopa.

One of the challenges of treating patients with antipsychotics is patient tolerance for drug-related side effects. While not all antipsychotics exhibit the same side effect profile, there is one dose-dependent effect that represents a significant health risk that is unrelated to their antagonistic effect on D2 or 5-HT2A receptors. Which side effect fits this description? A) diabetes B) increased risk for infections C) malignant hyperthermia D) osteoporosis E) QTc prolongation

E) Both typical and of atypical antipsychotic drugs share a qualitatively similar, dose-related increased risk of QTc prolongation and sudden cardiac death. This side effect has been attributed to drug-induced block of cardiac repolarization currents (mainly IK1) A) Diabetes is associated with several atypical antipsychotics, but not with aripiprazole or ziprasidone B) increased risk for infections is not a common side effect C) Antipsychotics are not associated with malignant hyperthermia, although it does share many clinical symptoms with neuroleptic maliganant syndrome D) Those antipsychotics that produce hyperprolactemia (1st generation antipsychotics & risperidone) can produce osteoporosis. However this is not a side effect common to all antipsychotics

Two years later, after being well controlled on monthly injections of haloperidol deconate, a patient appears for a followup appointment displaying a mask-like facial expression, abnormal postering, lip smacking and tongue protrusions. What is the most likely diagnosis for these new symptoms? A) Acute dyskinesia B) extrapyramidal symptoms C) Neuroleptic malignant syndrome D) Parkinsonism E) Tardive dyskinesia

E) Tardive dyskinesia. A late occurring (tardive) hyperkinetic movement disorder (dyskinesia) that is differentiated from acute dyskinesia & parkinsonism by the very late occurance after initiating drug therapy A) Acute dyskinesia would occur relatively soon after initiating drug therapy, and not after several years of otherwise stable treatment B) Extrapyramidal symptoms are usually seen within a few weeks, not years. D) Parkinson-like symptoms caused by block of dopaminergic pathways would occur relatively soon after initiating drug therapy with a dopamine antagonist, and not after several years of otherwise stable treatment.

Your patient is switched from haloperidol to quetiapine (Seroquel) because of its lower incidence of endocrine side effects. Other than having a weaker inhibitory effect on D2 receptors, blockade of which additional receptor subtype also contributes to the lower incidence of endocrine side effects seen with this new treatment? A) alpha 1 B) dopamine (D1) C) histamine (H2) D) muscarinic (M2) E) serotonin (5-HT2A)

E) The 5-HT2A subtype of serotonergic receptors stimulate the release of prolactin from the pituitary, while D2 receptor stimulation inhibits prolactin release. The relative balance between D2 & 5-HT2A antagonism seen with most atypical antipsychotics (with the exception of risperidone) results in little effect on prolactin release. Risperidone can produce a rise in prolactin release similar to 1st generation antipsychotics