A 67-year-old man with coronary heart disease developed chest pain again on the sixth day after a percutaneous cardiac intervention. Redo coronary angiogram revealed stent thrombosis. He had good medication compliance. Suboptimal response to clopidogrel was suspected. He had a past medical history of hypertension, diabetes mellitus, and gastroesophageal reflux disease.

His medications included: metoprolol 25 mg twice daily; metformin 1000 mg twice daily; omeprazole 20 mg once daily; rosuvastatin 20 mg once daily; clopidogrel 75 mg once daily; aspirin 80 mg once daily. 

(a) Describe the mechanism of action and metabolism of clopidogrel. (4 marks)

(b) From the medication list, identify a drug with potential drug-drug interaction that could lead to decreased metabolism of clopidogrel and explain why. (2 marks)

(c) Suggest TWO alternative medications to avoid the drug-drug interaction described in question (b) and explain why. (4 marks)

(d) Explain the impact of genetic variations on the metabolism of clopidogrel and the potential clinical consequences. What is the prevalence of poor metaboliser by genotype (subjects carry 2 no-function alleles in Han Chinese in Hong Kong? (4 marks)

(e) The genotyping testing result suggests that the patient carries 2 genes associated with decreased metabolism of clopidogrel. Name TWO other alternative medications to clopidogrel as dual antiplatelet therapy with aspirin. (2 marks)

(f) Discuss the difference in metabolism between clopidogrel and the other TWO alternative antiplatelet medications you suggested in question (e) and explain why they are more useful in patients with suboptimal responses to clopidogrel. (4 marks)