Genetic and Genomic Considerations in Pharmacotherapeutics Flashcards

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1
Q

Genetic variants alter drug metabolism by

A

either reducing benefits or increasing toxicity

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2
Q

Drugs with high therapeutic index, altered rates of metabolism may have ____ effect on the clinical outcome

A

little

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3
Q

Dugs with low or narrow therapeutic index, small increases in drug levels can lead to ______ and small decrease can lead to _____

A

toxicity/therapeutic failure

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4
Q

P450-2D6 (CYP2D6) variants

A

drug metabolism can reduce the benefits of therapy
women with inadequate CYP2D6 activity cannot convert tamoxifen to its active form therefore the drug cannot adequately protect from breast cancer

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5
Q

CYP2C19 variants

A

drug metabolism can reduce the benefits of therapy
reduces benefits of clopidogrel (Plavix), a drug that prevents platelet aggregation. Patients are at increased risk of stroke, MI
People with this genetic variation should use a different antiplatelet drug

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6
Q

N-acetyltransferase-2

A

drug metabolism can reduce the benefits of therapy
the enzyme that metabolizes isoniazid, Americans of European heritage metabolize isoniazid rapidly and produce 2 forms of N-acetyltransferase-2.
Dosage must be adjusted

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7
Q

CYP2D6 variants

A

drug metabolism can reduce the benefits of therapy

European heritage are unable to convert codeine to morphine. Pain is not relieved.

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8
Q

CYP2C9 variants

A

drug metabolism can increase drug toxicity

increased risk for toxicity from warfarin (coumadin), an anticoagulant with a narrow therapeutic index.

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9
Q

TMPT variants

A

drug metabolism can increase drug toxicity
standard doses of thiopurine or mercaptopurine can accumulate at high levels posing a risk for fatal bone marrow damage
FDA recommends testing before use

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10
Q

dihydropyrimidine dehydrogenase

A

drug metabolism can increase drug toxicity

poor job of metabolizing fluorouracil, a drug used to treat cancer

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11
Q

Genetic variants that alter the structure of drug receptors and other target molecules and can influence drug responses

A

Beta adrenergic receptor (ADRB1)

Vitamin K epoxide reductase complex 1 (VKORC1)

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12
Q

Beta adrenergic receptor (ADRB1)

A

beta receptors produced by ADRB1 variant genes respond more intensely to beta agonists, causing enhanced effects of blockade by beta antagonist. hypertension activation of these receptors may produce an exaggerated increase in blood pressure. Hypertension blockade of these receptors may produce an exaggerated decrease in blood pressure.
explains why beta blockers work better against hypertension in people with light skin

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13
Q

Vitamin K epoxide reductase complex 1 (VKORC1)

A

readily inhibited by warfarin, allowing anticoagulation with a reduced warfarin dosage. FDA recommends testing before warfarin is used

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14
Q

Genetic variants that affect drug targets on cancer cells and viruses

A

HER2 overexpression
EGFR expression
CCR5 tropism

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15
Q

HER2 overexpression

A

Increased therapeutic effect
trastuzumab only acts against breast cancers that overexpress HER2
FDA requires positive test for HER2 overexpression before trastuzumab is used

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16
Q

EGFR expression

A

Increased therapeutic effect
Cetuximab only works against colorectal cancers that express EGFR
FDA requires evidence of EGFR expression

17
Q

CCR5 tropism

A

Increased therapeutic effect
Maraviroc only acts against HIV strains that express CCR5
FDA requires evidence of CCR5 tropic strain

18
Q

Genetic variants that affect the immune system

A

HLA-B 1502

HLA-B 5

19
Q

HLA-B 1502

A

increases risk for life-threatening skin reaction in patients taking carbamazepine
Asian ancestry

20
Q

HLA-B 5

A

increases risk for fatal hypersensitivity reactions in patients taking abacavir

21
Q

Barriers to pharmacogenomics

A

lack of education

financial cost for testing

22
Q

What is needs to be done before testing?

A

obtain informed consent
educate patient on reason for testing, potential results, and options for treatment based on results
also inform that results may more received for weeks or more