C.S. was a 49 year old female with severe peripheral arterial disease (PAD) who had underwent numerous operations to reestablish circulation in her legs. I was taking care of her every few months or so when her stent would clot off or she would need another bypass in her legs. She took her Plavix and aspirin daily and could not understand why she was continuing to have problems.
Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics
Clopidogrel (Plavix) is a prodrug, meaning is must be converted by the liver into its active form using the cytochrome P-450 enzyme system (Arcangelo, Peterson, Wilbur & Reinhold, 2017). The most active enzyme in the metabolism of this drug is the CYP2C19 enzyme (Polasek, 2011). After conversion, it works to decrease platelet activation and subsequent aggregation and is commonly used in stroke, cardiac, and PAD patients. The binding of the active metabolite is not reversible and continues for the lifespan of the platelet (7-10 days), therefore it is important to stop the drug 7-10 days before procedures like surgery (Drugs.com, 2012).
Pharmacogenetics is the study of how an individual’s genotype effects how they respond to the drug (Arcangelo, Peterson, Wilbur & Reinhold, 2017). As a drug that relies on the body to produce the active metabolite, Clopridogrel depends upon a “healthy” or un-mutated CYP2C19 enzyme. Some populations carry an allele that decreases or even stops the activity of the CYP2C19 enzyme and subsequently makes drugs like Clopidogrel much less effective (Han et al., 2015). This can account for up to a 70% variability in the response to Clopidogrel and may be the reason C. S. is experiencing repeated stent thrombosis (Polasek, 2011). The availability of genetic testing can help practitioners individualize drug regimens to optimize care for patients like C.S. (Scott, 2012).
Plan of Care
For C.S., genetic testing might benefit her if it is available and affordable on her insurance plan. I would see if her family history includes PAD and if her family had issues with stent thrombosis as well. If genetic testing is not an option, changing her medication regime to something that does not rely on the CYP2C19 enzyme, such as ticagrelor (Brilinta), would be recommended. With any platelet inhibitor, she must be educated on the risk of bleeding and bleeding precautions for home. To reduce the risk of drug-herb interactions on bleeding time, I would screen her home med list for over the counter supplements such as Omega-3, garlic, ginger, etc. that may interact with the medication and increase bleeding risk (Arcangelo, Peterson, Wilbur & Reinhold, 2017).