Examkin

Soru

Zorluk: ZorPharmacokinetic and Pharmacodynamic Principles

A 7171-year-old retired teacher presents to the cardiology clinic for a routine 11-month follow-up. He recently underwent percutaneous coronary intervention with the placement of a drug-eluting stent in the left anterior descending artery following a non-ST-elevation myocardial infarction. His current daily medication regimen includes aspirin, clopidogrel, bisoprolol, and rosuvastatin. During the evaluation, the patient reports persistent retrosternal burning and epigastric discomfort that worsens after meals and is only partially relieved by over-the-counter antacids. To address these symptoms, the physician initiates therapy with omeprazole. Which of the following pharmacokinetic alterations represents the most significant clinical concern regarding the addition of this new medication?

  1. Diminished enzymatic generation of an active thiol metaboliteCevap
  2. B
    Augmented systemic absorption of a weak acid medication due to elevated gastric pH
  3. C
    Prolonged elimination half-life of the HMG-CoA reductase inhibitor
  4. D
    Shift from concentration-dependent to capacity-limited elimination kinetics for the thienopyridine
  5. E
    Alteration in the unbound fraction of the beta-adrenergic antagonist in systemic circulation

Cevap

Diminished enzymatic generation of an active thiol metabolite
Clopidogrel is a thienopyridine antiplatelet agent that functions as a prodrug. It requires a two-step oxidative process in the liver, primarily mediated by the cytochrome P450 enzyme CYP2C19, to be converted into its active thiol metabolite. This active metabolite then irreversibly inhibits the P2Y12 ADP receptor on platelets. Omeprazole is a proton pump inhibitor and a potent inhibitor of CYP2C19. When omeprazole is co-administered with clopidogrel, it significantly reduces the biotransformation of clopidogrel to its active form. This pharmacokinetic interaction leads to decreased platelet inhibition and places the patient at an increased risk of adverse cardiovascular events, such as stent thrombosis.

Adım Adım Çözüm

1
Identify the mechanism of action of the newly prescribed drug (omeprazole).
Omeprazole is a proton pump inhibitor and a potent inhibitor of the hepatic enzyme CYP2C19.
Understanding the pharmacokinetic properties of new medications is essential to predict drug-drug interactions.
2
Analyze the patient's existing medication regimen for potential interactions with a CYP2C19 inhibitor.
The patient is taking clopidogrel, which is known to be a prodrug that relies on CYP2C19 for its metabolism.
Identifying susceptible drugs in the regimen highlights the potential clinical consequences.
3
Determine the pharmacokinetic consequence of inhibiting CYP2C19 in a patient on clopidogrel.
Inhibition of CYP2C19 prevents the conversion of clopidogrel into its active thiol metabolite, thereby reducing its antiplatelet efficacy.
Clopidogrel must be activated to irreversibly bind the P2Y12 receptor; preventing this step increases the risk of stent thrombosis.

Anahtar Kavram

Omeprazole is a strong CYP2C19 inhibitor that decreases the enzymatic conversion of the prodrug clopidogrel into its active thiol metabolite, significantly reducing its antiplatelet efficacy.
Bu soruyu puanla

Konular

Pharmacokinetic and Pharmacodynamic Principles

Bu konudan daha fazla soru