pharmacogenomics 1-Dr P
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Questions and Answers

What is the significance of variation in response to medication?

  • It only affects clinical outcomes
  • It leads to improved individual and societal outcomes
  • It has no impact on individual and societal outcomes
  • It has a significant personal, clinical, and economic impact (correct)

    • What percentage of UK hospital admissions are attributed to adverse drug reactions (ADRs)?

  • 15%
  • 3.5%
  • 6.5% (correct)
  • 10%

    • What is the cost to the taxpayer due to adverse drug reactions (ADRs) in the UK?

  • £500 million
  • £1 billion (correct)
  • £750 million
  • £1.5 billion

    • What percentage of ADRs are considered avoidable?

    <p>70%</p> Signup and view all the answers

    What is the cornerstone of medical ethics related to adverse drug reactions (ADRs)?

    <p>&quot;primum non nocere&quot; first, do no harm</p> Signup and view all the answers

    What do adverse drug reactions (ADRs) include?

    <p>Undesirable side effects</p> Signup and view all the answers

    Which factor is considered in the NHS strategy when deciding which gene-drug associations to incorporate into clinical practice?

    <p>Clinical benefit</p> Signup and view all the answers

    What are the different metaboliser phenotypes that can result from differential metabolism by CYPs?

    <p>Ultrarapid, intermediate, poor, and extensive metabolisers</p> Signup and view all the answers

    Which drugs are broken down by the liver enzyme CYP2D6?

    <p>Antidepressants, antiarrhythmics, and antipsychotics</p> Signup and view all the answers

    How many variant alleles of CYP2D6 have been described?

    <p>Over 70</p> Signup and view all the answers

    What effect does genetic variation in CYP2D6 have on codeine metabolism for poor metabolizers?

    <p>Failure to effectively convert codeine into morphine</p> Signup and view all the answers

    Which drug interacts with CYP2C9 and VKORC1, necessitating correct dosing based on individual genetic makeup?

    <p>Warfarin</p> Signup and view all the answers

    What is the purpose of genetic testing before prescribing azathioprine?

    <p>To determine the patient's response to the drug based on their genetic makeup</p> Signup and view all the answers

    Which protein plays a crucial role in influencing the response to certain medications like antidepressants and statins?

    <p>ABCB1</p> Signup and view all the answers

    What role do cytochrome P450 genes (CYP2D6, CYP2C19, CYP3A4) play in pharmacogenetic testing for psychiatric medications?

    <p>Evaluating the patient's metabolic capacity for drug activation and inactivation</p> Signup and view all the answers

    In the context of pharmacogenomics, what is the significance of variants in ABCB1?

    <p>They impact the patient's response to various medications</p> Signup and view all the answers

    What is the primary focus of point of care testing (POCT) in community pharmacies as highlighted by the NHS Long Term Plan?

    <p>Diagnosis and monitoring of chronic diseases</p> Signup and view all the answers

    How does pharmacogenomic testing contribute to cost saving and increased drug adherence?

    <p>By personalizing treatment regimens based on genetic profiles</p> Signup and view all the answers

    Which genes are primarily involved in immune-mediated adverse drug reactions (ADRs)?

    <p>HLA-B, HLA-A, HLA-C</p> Signup and view all the answers

    What impact do genetic variants across different ethnic groups have on drug metabolism?

    <p>They may affect drug efficacy and safety differently across ethnicities</p> Signup and view all the answers

    What is the primary goal of pharmacogenomics in personalized prescribing according to the NHS Long Term Plan?

    <p>To optimize treatment outcomes through tailored medication approaches</p> Signup and view all the answers

    What is the role of cytochrome P450 genes in drug metabolism across different therapeutic areas?

    <p>They play a crucial role in activating and breaking down medications in the body</p> Signup and view all the answers

    What percentage of UK hospital inpatients experience adverse drug reactions (ADRs) during their stay in hospital?

    <p>15%</p> Signup and view all the answers

    Why is the integration of pharmacogenomics into routine NHS practice considered a goal?

    <p>To provide safer and more appropriate therapies for patients</p> Signup and view all the answers

    What does pharmacogenomics aim to achieve in terms of drug dosing?

    <p>Tailored prescriptions and dosages to individual's genes</p> Signup and view all the answers

    What is the difference between pharmacogenetics and pharmacogenomics?

    <p>Pharmacogenomics examines how single gene variations affect drug responses, while pharmacogenetics explores how an individual's entire genome regulates drug responses.</p> Signup and view all the answers

    What aspect of drug response does pharmacokinetics describe?

    <p>Absorption and distribution of drugs in the body</p> Signup and view all the answers

    How does DNA variation influence an individual's ability to respond effectively to a particular drug?

    <p>By influencing the body's ability to break down or respond effectively to the drug</p> Signup and view all the answers

    What is the primary focus of pharmacodynamics?

    <p>Molecular effect of drugs on their targets</p> Signup and view all the answers

    Why is prioritizing gene-drug pairs for implementation an important step for the NHS?

    <p>To reduce ineffective or harmful treatments</p> Signup and view all the answers

    What percentage of adverse drug reactions (ADRs) are considered avoidable?

    <p>70%</p> Signup and view all the answers

    What is the goal of integrating pharmacogenomics into routine NHS practice?

    <p>To provide safer and more appropriate therapies for patients</p> Signup and view all the answers

    What does pharmacogenomics enable in terms of medicines optimisation?

    <p>Informing medicine selection</p> Signup and view all the answers

    Which gene variant is associated with an increased risk of hypersensitivity reactions to Abacavir?

    <p>HLA-B*1502</p> Signup and view all the answers

    What type of reactions can HLA-B gene variants play a role in, particularly in relation to carbamazepine?

    <p>Hypersensitivity reactions</p> Signup and view all the answers

    Which gene variant is more prevalent in Northern European populations and is associated with a broader range of carbamazepine-induced hypersensitivity reactions?

    Signup and view all the answers

    Which gene variant is implicated in causing irreversible hearing loss in response to gentamicin use?

    <p>MT-RNR1</p> Signup and view all the answers

    What type of testing has reduced the incidence of hypersensitivity reactions to Abacavir in real-world clinical practice?

    <p>Pharmacogenomics testing for HLA-B*5701</p> Signup and view all the answers

    Which gene variant is highly prevalent in Southeast Asia and predisposes patients to TEN after carbamazepine use?

    <p>HLA-B*1502</p> Signup and view all the answers

    Which gene variant is more prevalent in Northern European populations and associated with a broader range of carbamazepine-induced hypersensitivity reactions?

    <p>HLA-A*3101</p> Signup and view all the answers

    What type of reactions are thiopurines, such as azathioprine, used to treat?

    <p>Autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease, and organ transplant recipients</p> Signup and view all the answers

    Which enzyme influences the metabolism of thiopurines, such as azathioprine?

    <p>Thiopurine S-methyltransferase (TPMT)</p> Signup and view all the answers

    Which gene variant is common in Asians and increases the risk of myelosuppression when treated with standard drug doses?

    <p>TPMT*3A</p> Signup and view all the answers

    Which enzyme is responsible for the metabolism of clopidogrel, and has variants that affect its efficacy and risks?

    <p>CYP2C19</p> Signup and view all the answers

    What percentage of the variance in warfarin dose requirements is due to CYP2C9 variations?

    <p>Approximately 10%</p> Signup and view all the answers

    Which gene has two variants (CYP2C92 and CYP2C93) that reduce enzyme activity and require lower warfarin dosages?

    <p>CYP2C9</p> Signup and view all the answers

    Which major histocompatibility complex (MHC) region on chromosome 6 in the human genome is associated with severe drug-induced hypersensitivity reactions and liver injuries?

    <p>HLA-A gene</p> Signup and view all the answers

    Which allele increases the risk of bleeding when metabolizing clopidogrel?

    <p>CYP2C19*17</p> Signup and view all the answers

    Which antiviral medicine for HIV has a hypersensitivity reaction in around 5% of patients, which can be severe and fatal?

    <p>Abacavir</p> Signup and view all the answers

    Which enzyme's loss-of-function variants (CYP2C19*2, *3, *5) make clopidogrel ineffective and have been associated with adverse clinical outcomes?

    <p>CYP2C19</p> Signup and view all the answers

    What percentage of the variance in warfarin dose requirements is due to VKORC1 variations?

    <p>Approximately 25%</p> Signup and view all the answers

    What is responsible for causing severe systemic symptoms, liver damage (potentially fatal), and blistering skin rashes like Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)?

    <p>(MHC) region on chromosome 6</p> Signup and view all the answers

    Which enzyme is responsible for the metabolism of Warfarin?

    <p>CYP2C9</p> Signup and view all the answers

    Which enzyme's gain-of-function allele increases the risk of bleeding?

    <p>CYP2C9</p> Signup and view all the answers

    Study Notes

    • The NHS strategy considers factors like allele frequency, clinical benefit, drug usage, and body of evidence when deciding which gene-drug associations to incorporate into clinical practice.

    • Cytochrome P450 enzymes (CYPs), which impact drug metabolism, are coded by genes that vary in the population.

    • Differential metabolism by CYPs can lead to various metaboliser phenotypes, such as ultrarapid, intermediate, poor, and extensive metabolisers.

    • CYP2D6 is a liver enzyme that breaks down certain antidepressant, antiarrhythmic, and antipsychotic drugs.

    • Over 70 variant alleles of CYP2D6 have been described, with some causing increased and others decreased enzyme activity.

    • CYP2D6 is associated with several therapeutic areas, including antidepressants, antipsychotics, beta blockers, and antiarrhythmics.

    • Poor metabolizers require lower doses of some drugs, while ultrarapid metabolizers require higher doses to achieve the same effect.

    • Genetic variation in CYP2D6 affects codeine metabolism, with poor metabolizers failing to effectively convert codeine into morphine and ultrarapid metabolizers producing high levels of morphine.

    • Warfarin, a common anticoagulant, interacts with CYP2C9 and VKORC1, leading to the importance of correct dosing based on individual genetic makeup to prevent life-threatening side-effects.

    • Warfarin is commonly prescribed for people with blood clot conditions, such as DVT and PE, and those at risk of developing blood clots, like those with artificial heart valves.

    • Warfarin metabolism is influenced by variations in the CYP2C9 and VKORC1 genes.

    • European populations have two variants (CYP2C92 and CYP2C93) of the CYP2C9 gene, which reduce enzyme activity and require lower warfarin dosages.

    • Approximately 10% of the variance in warfarin dose requirements is due to CYP2C9 variations.

    • Approximately 25% of the variance in warfarin dose requirements is due to VKORC1 variations.

    • Genetic testing for these variants helps healthcare professionals prescribe safe and effective warfarin dosages.

    • Clopidogrel, an anti-clotting medication, requires metabolism by the CYP2C19 enzyme and has variants that affect its efficacy and risks.

    • Loss-of-function variants in CYP2C19 (CYP2C19*2, *3, *5) make the drug ineffective and have been associated with adverse clinical outcomes.

    • The gain-of-function allele CYP2C19*17 increases the risk of bleeding.

    • Severe drug-induced hypersensitivity and drug-induced liver injuries are a heterogeneous group of rare, potentially lethal reactions that can be caused by more than 200 unrelated compounds.

    • These reactions can result in mild skin rashes or severe systemic symptoms, liver damage (potentially fatal), and blistering skin rashes like Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

    • The strongest genetic associations with these reactions have been with HLA alleles, which reside in the polymorphic major histocompatibility complex (MHC) region on chromosome 6 in the human genome.

    • A rare variant of the HLA-A gene (HLA-A*33:01) causes excessive immune reactions to common medications that result in liver damage.

    • Abacavir, an antiviral medicine for HIV, has a hypersensitivity reaction in around 5% of patients, which can be severe and fatal.

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    Description

    Test your knowledge about the usage and metabolism of warfarin, a medication commonly prescribed for conditions related to blood clots and for people at risk of developing blood clots, such as those with artificial heart valves. Learn about CYP2C9, VKORC1, and the genetic changes involved in warfarin metabolism.

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