Tisk Factors of Clopidogrel: How is Clopidogrel Metabolized? (Research Paper Sample)

Clopidogrel
Name
Institution Affiliation
Clopidogrel
Explain mechanism of action, general indications, contraindications, and risk factors/side effects of clopidogrel
Clopidogrel is an agent administered to prevent the occurrence of blood clotting the veins and arteries (Aschenbrenner & Venable, 2009).The oral agent is used to prevent risks of myocardial infarction (heart attack), stroke and other heart and blood-related disorders such as coronary artery disease. The agent is also essential in allowing blood flow in the body and especially to the legs. Doctors also recommend clopidogrel to patients who have had a heart attack or any other circulatory complications at one point in their lives (Aschenbrenner & Venable, 2009). Clopidogrel, whose activation requires CYP2C19, inhibits the ADP receptor located in the cell membranes of the platelets. Specifically, the agent acts to inhibit the receptor’s P2Y12, which is vital in platelet activation. Once the patient takes the clopidogrel pills, it takes almost two hours to notice the inhibition effect on the platelets. However, if a rapid effect of response is needed, the doctor or nurse may administer a dose of 600 or 300 mg.
Research shows that taking clopidogrel tablets reduces the risks death to cardiovascular complications, stroke or myocardial infarction. Taking the tablets has also proven to reduce the death rate for patients with ST-elevation myocardial infarction (STEMI). In addition, clopidogrel has proven to reduce the likelihood of a new stroke, new myocardial infarction for patients who have had such complications recently or at one time in their lives (Aschenbrenner & Venable, 2009).
A patient can take Clopidogrel in with food or not but preferably with sufficient water to minimize its side effects. Patients with ACS should start taking the tablets by first loading 300mg followed by 75mg dosage only once in a day in combination with 75-325mg of aspirin. Patient with STEMI should also take 75mg of clopidogrel only once in a daily basis. Medics say that the loading phase of clopidogrel is not crucial or very necessary.
Doctors have contraindicated clopidogrel for patients suffering from active pathological bleeding like intracranial hemorrhage or peptic ulcer. The tablets are also contraindicated in clopidogrel-hypersensitive patients. This also includes the patients who are hypersensitive to all components of clopidogrel. A patient awaiting a surgical procedure or dental work should shun from taking the medicine at least for five days before the scheduled day for the procedure. However, the patient should seek medical advice from a qualified health practitioner before shunning from the medicine.
All medicines have side effects, and clopidogrel is not an exception. Common side effects associated with the medicine include nausea, stomach pain, skin rash, diarrhea and itching. Others include mouth swelling, difficulty in breathing, chest pains, fever, sore throat, appetite loss and increased bleeding during menstruation among others (Aschenbrenner & Venable, 2009). Any patient should seek medical assistance instantly in case of any of the above side effects.
How is clopidogrel metabolized? What enzymes are necessary? Explain why a patient taking clopidogrel should avoid CYP2C19 inhibitors. What happens if a patient taking clopidogrel also takes a CYP2C19 inhibitor? Give some examples of strong, moderate, and weak CYP2C19 inhibitors.
The metabolization or activation of clopidogrel occurs in the liver by the action of cytochrome P450 enzymes including the CYP2C19. The metabolizing enzyme (CYP2C19) is effective in speeding up the process of biotransformation on in various drugs such as antidepressants, antimalarial drugs and proton pump drugs among others. The three sites of the active metabolite include original stereo Centre at C7, another stereo Centre at C4, and a double bond at C3-C16.
As earlier mentioned, CYP2C19 is the enzyme responsible for the activation or transformation of the clopidogrel to its active form. We know that patients take the clopidogrel to reduce blood clotting in their arteries and veins. A patient taking the tablets should avoid CYP2C19 inhibitors as they impair the Plavix’s antiplatelet activity. One common example of such inhibitors is the moderate inhibitor, omeprazole (McQueen, 2010). The intended goal of taking the clopidogrel will not be achieved if the patient takes the tablets in combination with the inhibitors. Instead, the patient should consider taking other weak inhibitors of CYP2C19 such as Pantoprazole and Dexlansoprazole. An example of a strong CYP2C19 is Fluconazole (McQueen, 2010).
Discuss the use of CYP2C19 testing related to clopidogrel dosage/response. What are the possible different genotypes (alleles) and how do they affect response?
There are tests available for the determining the genotype of the patients CYP2C19. The genotypic characteristics of the activation enzyme are important because they influence the formation of the active metabolite of clopidogrel. Therefore, the genetic testing is essential for examining the patient’s blood to check whether or not, there is a genotype related to the reduced ability for Plavix metabolism. Another use of the testing is to examine the blood of the patient
It clear that, the response of the platelets depends on the nature of the Plavix, that is, either active or inactive. The genotype of the CYP2C19 has a significant influence on the active metabolite of the Clopidogrel and the antiplatelet effects. The formation of the active metabolite is also influenced by the genetic variation of...