Pharmacotherapy for Cardiovascular Disorders
Pharmacokinetics refers to the study of the process by which a drug is absorbed, distributed, metabolized, and eliminated. Pharmacokinetics determines the drug’s fate in the body. Pharmacodynamics refers to the study of the mechanism of drug action. Pharmacodynamics focuses on the pharmacological effect caused by the interaction of a drug and a receptor. Genetic variations greatly influence the pharmacokinetics and pharmacodynamics of a drug. Do you need help with your assignment ? Reach out to us at eminencepapers.com.
Genetic polymorphisms exist for enzymes responsible for metabolizing drugs. An example of such an enzyme is the Cytochrome P450. The isoforms that exhibit prominence in genetic polymorphisms are CYP2D6 and CYP2C9 (Danielak et al., 2017). Based on the polymorphisms, drugs are metabolized at different rates. Poor metabolizers have very low or no activity of the enzyme. Intermediate metabolizers’ enzyme activity is reduced. Extensive metabolizers’ enzyme activity is normal. Ultra-rapid metabolizer’s enzyme activity is high.
Genetic polymorphisms have various implications on the pharmacokinetics of a drug. Poor to intermediate metabolizers of a particular drug will have a reduced clearance of the drug (Man et al., 2018). The drug remains in circulation for prolonged durations. Ultra-rapid metabolizers of a particular drug have a higher clearance rate of the drug (Man et al., 2018). The drug remains in circulation for short durations. Extensive metabolizers exhibit a normal pharmacokinetic profile. The rate of drug clearance of these patients is neither rapid nor slow.
Genetic polymorphisms have various implications on the pharmacodynamics of a drug. Poor to intermediate metabolizers of prodrugs, such as Simvastatin, will transform only a small amount of the drug to the active form (Danielak et al., 2017). This will significantly reduce the efficacy of the drug. Ultra-rapid metabolizers of prodrugs will transform larger amounts of the drug into the active form. This leads to toxicity. For active drugs, poor enzyme metabolizers lead to toxicity (Bertholee & Maring, 2017). This is because only a small amount of the drug will be inactivated. For a drug in the active form, ultra-rapid metabolizers convert most of the drug into the inactive form, thus decreasing the efficacy of the drug.
Changes in pharmacokinetic and pharmacodynamic parameters due to genetic polymorphisms influence drug therapy. The pharmacokinetic change of decreased drug clearance leads to an increased risk of drug toxicity when a normal dose is given (Bertholee & Maring, 2017). A higher clearance rate caused by ultra-rapid metabolizers leads to decreased efficacy of the drugs. For an active drug, ultra-rapid metabolizers will have a decreased activity of the drug because it is deactivated within a short period. For prodrugs, ultra-rapid metabolizers will have an increased drug action and increased possibility of toxicity.
The prescribed drugs, Atenolol, Doxazosin, Hydralazine, and Sertraline, are all active except Simvastatin. If the patient is a poor to intermediate metabolizer, the dose of the active drugs will be reduced. This will help to prevent toxicity caused by the accumulation of these drugs. Simvastatin will be replaced with another lipid-lowering agent that is not a prodrug, such as Gemfibrozil. If the patient is an ultra-rapid metabolizer, the dose of the active drugs will be increased. This will prevent instances of decreased activity. The dose of Simvastatin will be reduced to prevent toxicity for this type of patient.
Variation in genetics plays an integral part in the pharmacodynamics and pharmacokinetic properties of drugs. The specific type of polymorphism should be identified because they have unique impacts on the activity of the drug. Furthermore, the impact of genetic polymorphisms depends on whether the drug is in the active form of the prodrug form. Based on the treatment plan, adjustments in the dose of the drug should be made. The adjustments can be dose reduction, increment, or drug substitution. This helps to improve therapeutic outcomes and increase the quality of life of patients.
References.
Bertholee, D., & Maring, J. G. (2017). Genotypes Affecting the Pharmacokinetics of Anticancer Drugs. 317–337. https://doi.org/10.1007/s40262-016-0450-z
Danielak, D., Kara, M., & Komosa, A. (2017). Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite. 1623–1632. https://doi.org/10.1007/s00228-017-2334-z
Man, F. M. De, Goey, A. K. L., & Schaik, R. H. N. Van. (2018). Individualization of Irinotecan Treatment : A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics. Clinical Pharmacokinetics, 57(10), 1229–1254. https://doi.org/10.1007/s40262-018-0644-7
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Question 
Patient AO has a history of obesity and has recently gained 9 pounds. The patient has been diagnosed with hypertension and hyperlipidemia. Drugs currently prescribed include the following:
Pharmacotherapy for Cardiovascular Disorders
Atenolol 12.5 mg daily
Doxazosin 8 mg daily
Hydralazine 10 mg qid
Sertraline 25 mg daily
Simvastatin 80 mg daily.
As an advanced practice nurse, it is your responsibility to recommend appropriate treatment options for patients with cardiovascular disorders. To ensure the safety and effectiveness of drug therapy, advanced practice nurses must consider aspects that might influence pharmacokinetic and pharmacodynamic processes, such as medical history, other drugs currently prescribed, and individual patient factors.
Reference: Murphy, S. L., Xu, J., Kochanek, K. D., & Arias, E. (2018). Mortality in the United States, 2017. Retrieved from https://www.cdc.gov/nchs/products/databriefs/db328.htm
To Prepare
Review the Resources for this module and consider the impact of potential pharmacotherapeutics for cardiovascular disorders introduced in the media piece.
Review the case study assigned by your Instructor for this Assignment.
Select one of the following factors: genetics, gender, ethnicity, age, or behavior factors.
Reflect on how the factor you selected might influence the patient’s pharmacokinetic and pharmacodynamic processes.
Consider how changes in the pharmacokinetic and pharmacodynamic processes might impact the patient’s recommended drug therapy.
Think about how you might improve the patient’s drug therapy plan based on the pharmacokinetic and pharmacodynamic changes. Reflect on whether you would modify the current drug treatment or provide an alternative treatment option for the patient.