Pharmacolocy: Pharmacogenetics Flashcards
One of your patients experiences marked decrease in blood pressure after taking anti-hypertensive debrisoquin. What genetic mutation might your patient have?
Debrisoquin-sparteine polymorphism. This is a genetic mutation in the CYP2D6, making your patient a slow metabolizer of the drug, enhancing its effect.
You have two patients. One responds to codeine with excessive analgesia. The other responds with inadequate analgesia. What genetic variation might exist between the two?
CYP2D6 activity. High enzyme activity = excessive analgesia. Low enzyme activity = inadequate analgesia
Why do you have to treat H. Pyolori infection with a combination of omeprazole, antibiotics and antacid?
Omeprazole eliminates H. Pyolori infection 100% in people with zero CYP2C19 enzyme activity. However, there is a mix of people who do have CYP2C19 activity and thus omeprazole can’t do the job alone.
One of your patients had a pulmonary embolism and you consider putting him on the anticoagulant Clopidogrel. What must you consider before you know this therapy will be effective?
If the patient has a functional CYP2C19. If not, it cannot even get into the liver to be metabolized. You must also make sure the patients CYP3A4 enzyme is not being inhibited by other drugs, otherwise Clopidogrel cannot get out of the liver in its active form.
What is the difference between Phenytoin and Clopidogrel when both are metabolized by CYP2C19?
Clopidogrel has a critical pathway. Phenytoin has alternatives modes of metabolism.
One of your patients had a pulmonary embolism and you consider putting him on the anticoagulant S-warfarin. What must you consider before you know this therapy will be effective?
If the patient has a functional CYP2C9. If they metabolize it slowly they may bleed to death.
Your patient is taking 5-flurouracil for cancer treatment. What should you look for in their first dose?
Neurotoxicity. This happens when they have inactivating polymorphisms of dihydropyrimidine dehydrogenase.
Your patient is given succinylcholine during anesthesia. What could be the cause of complete muscular paralysis during their procedure?
Inactivating polymorphisms in pseudocholinesterase.
A Tb patient was given Isoniazid. She starts developing hepato and neurotoxic effects. What enzyme may be deficient?
Phase II enzyme NAT2. It does not acetylate the drug.
One of your patients is being treated for cardiac arrhythmia with procainamide. He later develops arthralgia, arthritis, pericarditis, pleuritis and rash. What enzyme may be deficient and what enzyme may be metabolizing the drug?
Deficient in phase II NAT2. Metabolized by FMO and creates lupus-like symptoms.
How does the N-oxide metabolite made in procainamide metabolism elicit a lupus-like reaction?
It binds to proteins and anti-nuclear antibodies are generated
How do cancer risk factors vary between fast acetylators and slow acetylators?
Fast = colon cancer due to fast metabolism of pro-carcinogens. Slow = bladder, lung, and breast cancer if you smoke because you don’t metabolize the smoke as quickly.
A child in the ward is being treated with 6-MP (mercaptopurine) for acute lymphoblastic leukemia. What enzyme mutation would require you to decrease the dose 15 fold?
TPMT (Thiopurine Methyl Transferase). If this is defective 6-thioguanine nucleotides accumulate and become toxic.
One of your patients requires extremely high levels of warfarin. What enzyme mutation could be present in this patient?
VKORC1 (vitamin K epoxide reductase). This is warfarin’s target site and can be desensitized to warfarin, requiring higher doses.
