In this case study, the patient is a 65-year-old Hispanic male who had a percutaneous coronary intervention (PCI) four months ago. His medical history includes CAD, HTN, HLD, and diabetes type 2. He was prescribed aspirin 81mg daily and Plavix (clopidogrel) 75mg daily after his procedure. Other medications include pravastatin, losartan, and metformin. The patient states that he ran out of clopidogrel about a month ago. In patients with drug-eluting stents (DES), dual antiplatelet therapy (DAPT) has shown effectiveness in preventing stent thrombosis (Almaddah & Khouzam, 2017). DAPT with aspirin and a P2Y12 inhibitor is crucial for patients post PCI to prevent future thrombotic events (Zhang, Li, Tang, & Chen, 2017). Such medications include clopidogrel, ticagrelor, or prasugrel. Aspirin 81mg is to be taken lifelong and Plavix for 12 months or sometimes longer depending on the patient. The physician was made aware and immediately ordered a 600mg loading dose of Plavix and a refill of 75mg tabs daily.

 

Pharmacokinetics of clopidogrel:

Pharmacokinetics is the study of drug movement within the body and includes absorption, distribution, metabolism, and excretion (Rosenthal & Burchum, 2021, p. 13). Clopidogrel is rapidly absorbed in the gastrointestinal tract and can be administered with or without food. Bioavailability is about 50%. It is a prodrug that undergoes metabolism to its active form, formed primarily by hepatic CYP2C19 (Rosenthal & Burchum, 2021, p. 387). A loading dose of clopidogrel (300-600mg) increases antiplatelet response. Clopidogrel is excreted by the urine and feces (UpToDate, 2021).

 

Pharmacodynamics of clopidogrel:

Pharmacodynamics is the study of the biochemical and physiological effects on the body (Rosenthal & Burchum, 2021, p. 22). The dose-response relationship is the minimal amount of medication needed to elicit a response. CYP450 enzymes must metabolize clopidogrel to produce the active metabolite that inhibits platelet aggregation. The active metabolite inhibits ADP’s binding to its platelet P2Y12 receptor, an irreversible action (RxList, 2020). Effects begin two hours after the initial dose, and the inhibition reaches a steady-state between 3-7 days. At the recommended dose of 75mg, platelet aggregation is inhibited by 40% and 60% (Rosenthal & Burchum, 2021, p. 387).

 

Pharmacogenetics:

Some individuals are homozygous for nonfunctional alleles of the CYP2C19 gene. These are termed poor metabolizers of clopidogrel. They may not benefit adequately from the medication as they cannot convert it to its active form (Rosenthal & Burchum, 2021, p. 387). However, testing is not recommended to start the medication.

 

Plan of care:

The patient does not take any medications that may interact with Plavix, such as CYP2C19 inhibitors (omeprazole), opioids, or NSAIDs. The risks of taking dual antiplatelets are bleeding and bruising. Therefore, the patient needs to notify their provider if undergoing any surgical or dental procedures. The patient should also be educated on adverse effects, such as bleeding and thrombotic thrombocytopenic purpura (TTP). Patients should notify the doctor of any uncontrolled bleeding when taking DAPT and when to seek care. The patient needs to continue DAPT to prevent stent thrombosis and myocardial infarction. Patients should also or minimize grapefruit juice consumption when taking Plavix (UpToDate, 2021). He should continue DAPT for at least a year and contact the medical office if refills of medications are needed before they run out. DAPT is an essential regimen in preventing any thrombotic events.

 

 

Resources

Almaddah, N., & Khouzam, R. N. (2017). Is there a safe time to stop clopidogrel in patients on dual antiplatelet therapy after a percutaneous coronary intervention and placement of drug-eluting stents? Journal of Thoracic Disease, 9(12), 4806-4807. doi:10.21037/jtd.2017.11.69

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.). St. Louis, MO: Elsevier.

RxList. 2020. Plavix. Retrieved from https://www.rxlist.com/plavix-drug.htm#description

UpToDate. (2021). Clopidogrel: Drug information. Retrieved from https://www.uptodate.com/contents/clopidogrel-drug-information

Zhang, Y.J., Li, M. P., Tang, J., & Chen, X. P. (2017). Pharmokinetic and pharmodynamic responses to clopidogrel: Evidences and perspectives. International Journal of Environmental Research and Public Health, 14(3), 301. Retrieved from https://doi.org/10.3390/ijerph14030301

 

Discussion: Pharmacokinetics and Pharmacodynamics

As an advanced practice nurse assisting physicians in the diagnosis and treatment of disorders, it is important to not only understand the impact of disorders on the body, but also the impact of drug treatments on the body. The relationships between drugs and the body can be described by pharmacokinetics and pharmacodynamics.

Pharmacokinetics describes what the body does to the drug through absorption, distribution, metabolism, and excretion, whereas pharmacodynamics describes what the drug does to the body.

Photo Credit: Getty Images/Ingram Publishing

When selecting drugs and determining dosages for patients, it is essential to consider individual patient factors that might impact the patient’s pharmacokinetic and pharmacodynamic processes. These patient factors include genetics, gender, ethnicity, age, behavior (i.e., diet, nutrition, smoking, alcohol, illicit drug abuse), and/or pathophysiological changes due to disease.

For this Discussion, you reflect on a case from your past clinical experiences and consider how a patient’s pharmacokinetic and pharmacodynamic processes may alter his or her response to a drug.

To Prepare
  • Review the Resources for this module and consider the principles of pharmacokinetics and pharmacodynamics.
  • Reflect on your experiences, observations, and/or clinical practices from the last 5 years and think about how pharmacokinetic and pharmacodynamic factors altered his or her anticipated response to a drug.
  • Consider factors that might have influenced the patient’s pharmacokinetic and pharmacodynamic processes, such as genetics (including pharmacogenetics), gender, ethnicity, age, behavior, and/or possible pathophysiological changes due to disease.
  • Think about a personalized plan of care based on these influencing factors and patient history in your case study.
By Day 3 of Week 1

Post a description of the patient case from your experiences, observations, and/or clinical practice from the last 5 years. Then, describe factors that might have influenced pharmacokinetic and pharmacodynamic processes of the patient you identified. Finally, explain details of the personalized plan of care that you would develop based on influencing factors and patient history in your case. Be specific and provide examples.

By Day 6 of Week 1

Read a selection of your colleagues’ responses and respond to at least two of your colleagues on two different days by suggesting additional patient factors that might have interfered with the pharmacokinetic and pharmacodynamic processes of the patients they described. In addition, suggest how the personalized plan of care might change if the age of the patient were different and/or if the patient had a comorbid condition, such as renal failure, heart failure, or liver failure.