Genomics Exam 2

Mr Bill Davies, a patient with the CYP1A2*1F/1F genotype is titrated to a 600 mg daily Clozapine regimen as an out-patient. He smokes a pack of cigarettes each day. He has no history of seizures. He is involuntarily hospitalized for three weeks, during which fluvoxamine is introduced and the clozapine regimen is maintained. During this hospitalization, he suffers two seizures.

QUESTION 1OF 2: What effect does cigarette smoke have on Clozapine disposition in this patient?

A. Cigarette smoke retards the rate of Clozapine elimination

B. Cigarette smoke increases the rate of Clozapine elimination

C. Cigarette smoke has no effect on the rate of clozapine elimination

B. Cigarette smoke increases the rate of Clozapine elimination

Mr Bill Davies, a patient with the CYP1A2*1F/1F genotype is titrated to a 600 mg daily Clozapine regimen as an out-patient. He smokes a pack of cigarettes each day. He has no history of seizures. He is involuntarily hospitalized for three weeks, during which fluvoxamine is introduced and the clozapine regimen is maintained. During this hospitalization, he suffers two seizures.

QUESTION 1OF 2: Which of the following could likely account for the seizures he experienced?

a. he has unrealistically high levels of clozapine in his blood

b. he is suffering clozapine insufficency

c. he has unrealistically high levels of fluvoxamine in his blood

d. he is suffering fluvoxamine insufficiency

a. he has unrealistically high levels of clozapine in his blood

Patients with long form of the serotonin transporter (SLC6A4) 5- HTTLPR, treated with citalopram respond..... than those with the short form

a. better

b. worse

a. better

The 5- HTR2A T102C SNP is associated with

a. less tardive dyskinesia upon treatment with neuroleptic drugs

b. less weight gain upon treatment with neuroleptic drugs

c. poorer outcomes upon treatment with neuroleptic drugs

c. poorer outcomes upon treatment with neuroleptic drugs

Jan bears the BDNF Val66Met allele (i.e. the 66 Met variant). This suggests she

A. has higher BDNF pathway activity

B. has better outcomes on clozapine therapy.

C . has poorer outcomes on clozapine therapy

C . has poorer outcomes on clozapine therapy

The ABCB1 SNP C1236T is associated with responses to risperidone and olanzapine.

A. better

B. worse

A. better

The primary role of the pharmacist in managing patients with asthma is to recommend pharmacogenomics testing.

a. true

b. false

b. false

Pharmacists can help patients manage their asthma therapy by:

A. Providing patient education for self-management

B. Educating patients on medication use

C. Determining the frequency of follow-up visits

D . All of the above

D . All of the above

Before stepping up the long-term asthma therapy, pharmacists should recommend pharmacogenomics testing for their patients.

True

False

False

Pharmacogenomics findings allow personalization of asthma therapy and will likely lead to:

a. more side effects

b. more dosage adjustments to achieve asthma control with inhaled corticosteroids

c. more effective outcomes

d. more trial and error for inhaled corticosteroids

c. more effective outcomes

Before stepping up the long term asthma therapy, pharmacists should check for:

A.Correct inhaler technique

B. Comorbidities

C. Environmental control

D .Al l of the above

D .Al l of the above

Informatics support can help with the successful implementation of asthma genetics testing.

True

False

True

5-lipoxygenase (ALOX5) has a variable nucleotide tandem repeat in its promoter region. Caucasians and Blacks exhibiting 5 repeats of -GGGCGG-:

A. Exhibit increased transcription of ALOX5

B Exhibit decreased transcription of ALOX5

C. Exhibit no ALOX5 transcription

A. Exhibit increased transcription of ALOX5

Caucasians and Blacks exhibiting 5 repeats of -GGGCGG- in the ALOX5 promoter:

A. Exhibit decreased clinical response to ABT-761

B Exhibit increased clinical response to AB7-61

C. are not treated with ABT-761

B Exhibit increased clinical response to AB7-61

The LTC4 synthase promoter SNP, A-444C, is associated with improved responses to:

a. ipratropium

b. albuterol

c. theophylline

d. salmeterol

e. montelukast

e. montelukast

The SNP at the 17q21 locus, rs7216839, has a strong association with:

A. adult-onset asthma

B. poor response to albuterol in asthma therapy

C. very good response to inhaled corticosteroid in asthma therapy

D. risk of asthma exacerbations in children

D. risk of asthma exacerbations in children

The CRHR1 SNP (present in the GAT haplotype), rs242941, yields....responsiveness to inhaled corticosteroids in asthma management

A . increased

B. decreased

A . increased

Concerning the B2-adrenergic receptor, individuals with Arg/Arg at position 16 are very likely to have Glu/Glu at position 27; individuals with a Gly/Gly at position 16 are likely to have GIn/GIn at position 27. This suggests:

A.There is a random association between variants at the two positions

B.There is a linkage disequilibrium between variants at the two positions

C. none of the above

B.There is a linkage disequilibrium between variants at the two positions

donepezil is an

a. NMDA antagonist

b. acetylcholine precursor

c. acetylcholinesterase inhibitors

d. acetylcholine receptor blocker

c. acetylcholinesterase inhibitors

selegilline is a

a. dopamine d3 receptor agonist

b. MOA-A inhibitor

c. MOA-B inhibitor

d. acetylcholinesterase inhibitor

e. anticholinergic

c. MOA-B inhibitor

The presenilin 2 N1411 variant is associated with:

A. decreased COX-2 expression

B. increased COX expression

C. unchanged COX-2 expression

B. increased COX expression

which of the following is/ are a hallmark of huntingtons disease

A. Acetylcholine deficits

B. Dopamine receptor hypersensitivity

C. Expanded polyglutamine repeats in htt

C. Expanded polyglutamine repeats in htt

Patients being treated with pramipexole who are homozygotes for Ser/Ser [the DRD3 Ser9Gly polymorphism]

A. have higher response rates than Gly/Gly patients

B. have lower response rates than Gly/Gly patients

A. have higher response rates than Gly/Gly patients

A patient with a high COMT activity phenotype will respond very well to

A . entacapone

B selegiline

C. levodopa

D. trihexyphenidyl HCl

E Benztropine

A . entacapone

Jane Doe is Alzheimer patient with the C allele at the choline acetyl transferase gene -5293 position (rs733722 -5293 C> T.) Unlike patients with a T at that position:

A. She is expected to have improved outcomes on donepezil therapy

B .She is expected to have poor outcomes on donepezil therapy

C. This allele provides no insights regarding donepezil treatment outcomes

B .She is expected to have poor outcomes on donepezil therapy

Alzheimer patients who are APOE4-negative:

A. respond very well to cholinomimetic therapy B.respond poorly to PPAR-gamma agonists

C. respond poorly to cholinomimetic therapy

A. respond very well to cholinomimetic therapy

A patient in your clinic has undergone genomic testing and has been identified as a CYP2D6 poor metabolizer. his provider has asked for your recommendation for an atypical antipsychotic to initiate in this patient. Which of the following drug choices would carry the highest risk of adverse effects for the patient.

a. clozapine

b. risperidone

c. quetiapine

d. ziprasidone

b. risperidone

CM is a 37-year-old female with schizophrenia who has been well-controlled on clozapine 200 mg in the morning and 400 mg at bedtime. Today, CM presents to the clinic and states that she is experiencing visual hallucinations and paranoid

thoughts. She has been adherent to her clozapine regimen. Which one of the following is the BEST explanation for the recent onset of psychotic symptoms in CM?

A. CM was started on fluvoxamine for obsessive-compulsive symptoms

B.MC stopped taking her omeprazole for mild GERD about a week ago

C. CM resumed her 1 ppd cigarette smoking habit a week ago

D. MC was started on paroxetine for depressive symptoms

E. CM quit smoking cigarettes 2 weeks ago and is using nicotine patches

C. CM resumed her 1 ppd cigarette smoking habit a week ago

Which one of the following would be the most appropriate recommendation regarding the use of paroxetine in a CYP2D6 ultra-rapid metabolizer?

A. Initiate paroxetine therapy at the recommended starting dose

b. Initiate paroxetine therapy at a 50% reduction of the recommended start dose

C. Initiate therapy with an alternative SSRI not predominantly metabolized by CYP2D6

D. Initiate paroxetine therapy at double the recommended starting dose

C. Initiate therapy with an alternative SSRI not predominantly metabolized by CYP2D6

Which one of the following patients taking citalopram 30 mg once daily would be MOST likely to be at increased risk for cardiac arrhythmias secondary to QTc prolongation?

A. A patient who is aCYP2C19 poor metabolizer

B. A patient who is a CYP2C19 ultra rapid metabolizer

C. A patient who is a CYP2D6 poor metabolizer

D. A patient who is a CYP2D6 ultra rapid metabolizer

E A patient who abruptly stops smoking cigarettes

A. A patient who is aCYP2C19 poor metabolizer

A Manhattan plot

a. is a pharmacokinetics plot

B. is a pharmacodynamics plot

C. summarizes results of a GWAS

D. directly captures all genomic SNPs

C. summarizes results of a GWAS

In conducting a GWAS, there is typically a predetermined candidate gene.

True

False

False

A patient's FEV1 continues to consistently improve after each acute bronchdilator use (albuterol MDI). A genetic testing for β2AR gene at codon 16 will likely reveal the following SNP:

a. Gly/Gly

b. Arg/Arg

a. Gly/Gly

A patient's mom and sister have osteoporosis, you are mostly concerned about the use of ICS with which of the following genetic polymorphism?

a. CRHR1

b. TBX21

c. NRC31

c. NRC31