Question

A 47-year-old man was admitted to the hospital because of exertionally-related angina with coronary definition revealing a totally occluded right coronary artery and 80 % obtruse marginal stenosis. He was an avid hockey player and had attributed the chest pains to the sport. 1 month later, the chest pains persisted and he was admitted to the hospital for further observation.

Patient Referral:

Patient was sent to the Cardiovascular department for surgery. Percutaneous coronary intervention with deployment of a drug eluting stent and commencement of clopidrogel was administered.

Post-surgical observations:

After 1 month, the patient’s right coronary was totally occluded and the stents were replaced. 9 months after the replacement, the patient still experienced chest pains, but coronary angiography revealed no instent stenosis.

Further information from patient:

Patient no longer felt the chest pains, and presumably went about his usual routine. However, 2 years later, the patient presented with post prolonged ischemic chest pain with myocardial infarction.

Patient referral:

Patient sent for coronary angiography.

Angiography results:

A thrombus in the circumflex stent which was re-dilated and a further drug eluting stent was deployed.

Patient reaction to treatment:

2 years later, while playing a vigorous game of hockey, further chest pain and presentation revealing thrombus in stent to circumflex artery which was ballooned and the side branch protected using a stent. Patient referred for molecular testing.

Molecular testing results:

CYP2C19 genotype performed.

Results: *2/*2 homozygote representing a poor clopidrogrel metabolizer.

Treatment regimen:

Patient subsequently ceased clopidogrel and commenced prasugrel. After 3 months of new treatment, patient no longer showed ischemia.

Question：

1. To which group of pharmacokinetic genes did the biomarker belong that the physicians chose to help them properly treat the patient? What function do the genes in this group perform in the body?

2. List the 3 metabolism states for the gene utilized and the associated genotypes. What was the patient’s genotype and metabolism status?

3. What changes would you have made in this patient’s treatment if you could go back to the initial presentation in the hospital?

Answer 1

Ans-

1)The CYP2C19 gene is a member of the cytochrome P450 gene family. Where the CYP450 Gene is important for metabloism of drugs.The CYP2C19 enzyme plays a role in the processing or metabolizing of at least 10% of commonly prescribed drugs, including a drug called clopidogrel,proton pump inhibitor like Omeprazole.

2)The major metabolic pathway of for CYP2C19 is conversion to carboxylic acid by an esterase (CES1), forming clopidogrelic acid (SR26334) that is inactive. From a subsequent in vitro study of the metabolism of clopidogrel using recombinant DNA CYPs, it was concluded that CYP2C19 was the major oxidative pathway.this is Metabolic states for CYP2C19.

Patient having with Genotype of CYP2C19 and having the problem with the Metabolism of 10%drugs.include the clopidogrel medicine.patient having slow metabloism for these drug.

3)Clopidogrel is an antiplatelet medicine or blood thinner. It makes your blood flow through your veins more easily.this drugs used in case of heart attack of angina and stroke.due to CYP2C19 Gene defect clopidogrel doesn't not metablise and produce toxicity.in this case used the alternative antiplatlet prasugrel, ticagrelor for CYP2C19 poor or intermediate metabolizers.