Assignment: Pharmacotherapy for Cardiovascular Disorders
NURS 6521 Assignment: Pharmacotherapy for Cardiovascular Disorders
Advanced Pharmacotherapy
How the factor I chose (Obesity) might influence the pharmacokinetic and pharmacodynamic processes in the patient
Numerous interrelated mechanisms play a role in the development of high blood pressure in obesity, often leading to end organ damage including chronic kidney disease and cardiovascular disease. The mechanism of hypertension in non-obese individuals is different from the mechanism of hypertension in obesity. According to Cataldi et al. (2019), the major determinants of hypertension in non-obese individuals in peripheral vasoconstriction, while obesity-related hypertension relies on hyperactivation of the sympathetic nervous system (SNS) along with the resulting rise in aldosterone and rennin release and cardiac output.
The mechanism responsible for hyperactivation of the SNS is connected to the release of substances such as free fatty acids, inflammatory cytokines, and adipokines from adipose tissue. These substances might indirectly or directly activate autonomic neurotransmission, by affecting insulin sensitivity. Moreover, the syn
Assignment Pharmacotherapy for Cardiovascular Disorders
thesis of both aldosterone and angiotensin II that causes a rise in blood pressure and promotes retention of sodium ions occurs in the adipose tissue. Nonalcoholic-fatty liver disease (NAFLD) that usually coexists with obesity additionally has a crucial role in causing insulin resistance and also activating the renin-angiotensin-aldosterone (RAA) system (Cataldi et al., 2016).
The psychologic complexity of obesity-related to hypertension presents numerous challenges in its pharmacological management. According to Cohen (2017), there is a strong correlation between obesity and treatment resistant hypertension, which requires the additive and synergistic effects of numerous antihypertensive drugs to adequately control blood pressure. As explained by Sharid and McKenzie (2020), treatment resistant hypertension is blood pressure that remains above goal despite being concurrently managed by three antihypertensive drugs of different classes, or blood pressure that is controlled with more than three medications.
The etiology of resistant hypertension in patients with obesity is a result of several factors, including dysfunctional neurohormonal pathways, especially increased secretion of aldosterone, and also the systemic effect of adipokines suck as adiponectin and leptin. Although obesity does not change the oral absorption of medications, the pharmacodynamics and pharmacokinetics of numerous drugs are affected by excess adiposity. These changes are mediated via a range of pathophysiologic mechanisms such as increased neurohormonal activity, altered renal and hepatic clearance, and expanded volume of distribution (Cohen, 2017).
How changes in the processes might impact the patient’s recommended drug therapy
Volume of distribution of a drug is the overall quantity of the drug in the body of an individual relative to the
Assignment Pharmacotherapy for Cardiovascular Disorders
concentration of the drug in a certain body compartment and offers an estimation of the level to which the drug is distributed/delivered into oft tissues. Cohen (2017) indicates that patients with obesity are likely to have expanded plasma volume, which may change the volume of distribution. This leads to considerable differences in plasma concentration of some drugs in patients with obesity compared to patients with normal weight, despite comparable soft tissue concentrations. Particularly, the volume of distribution of lipophilic drugs is impacted by excess adiposity. These medications tend to easily diffuse into adipose tissue, which makes it hard to attain therapeutic plasma levels (Cohen, 2017).
NAFLD plays a significant role in the dysfunctional clearance of medications in obesity. Cohen et al.(2017) indicate that Hepatic steatosis contributes to reduced hepatic microvascular blood flow, leading to an altered delivery of medications to the liver. Also, NAFDL causes abnormal function of hepatic enzymes, resulting in both decreased and increased rates of hepatic clearance of drugs. According to Cohen (2017), altered renal clearance is another crucial factor that makes the predictability of clearance of medication in obesity complex. Because obesity is connected with amplified glomerular hyperfiltration and amplified cardiac output, patients with obesity can experience faster medication clearance compared to patients with normal weight.
Obese patients respond differently to treatment with certain hypertensive drugs compared to non-weight patients, an indication that obese patients are vulnerable to atypical responses to drugs. Because there is upregulation of rennin-angiotensin aldosterone system activity and SNS activity, inhibition of these neurohormonal pathways contributes to amplified hemodynamic responses in obese individuals whose hypertension is not resistant to treatment. For example, an in vivo study involving a direct measure of renal hemodynamic revealed that patients with obesity had a higher renal vasodilatory response to angiotensin-converting enzyme inhibition with captopril compared to non-obese patients (Cohen, 2017).
How I might improve the patient’s drug therapy plan
I would improve the patient’s drug therapy plan by replacing atenolol and doxazosin with an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB). Atenolol and doxazosin is beta-blocker and alpha-blocker respectively. I would make this recommendation because ACES and ARBs that medications target the mechanism of obesity-related hypertension. According to Shariq and McKenzie, (2020), while the majority of hypertension guidelines fail to address patients with obesity as a unique population, some recommendations for optimal choice for agents for controlling blood pressure in obese patients have emerged. Due to the role that the RAA plays in the pathogenesis of hypertension in obese individuals, there is strong evidence for considering ARBs and ACEIs as first-line therapies. ARBs and ACEIs effectively lower blood pressure by inhibiting the renin-angiotensin system. These medications have the added benefit of improving insulin sensitivity which is a common comorbidity in individuals with obesity (Shariq and McKenzie, 2020). Cataldi et al.(2016), emphasize that medications targeting the RAA system could be a practical choice because of the release of aldosterone and angiotensin- II from the adipose tissue. Although beta-blockers counteract the overactivation of the SNS, these drugs are associated with insulin resistance and weight gain.
References
Cataldi, M., di Geronimo, O., Trio, R., Scotti, A., Memoli, A., Capone, D., & Guida, B. (2016). Utilization of antihypertensive drugs in obesity-related hypertension: a retrospective observational study in a cohort of patients from Southern Italy. BMC Pharmacology and Toxicology, 17, 9. https://doi.org/10.1186/s40360-016-0055-z
Cohen, J. B. (2017). Hypertension in Obesity and the Impact of Weight Loss. Current Cardiology Reports, 19(10), 98. doi: 10.1007/s11886-017-0912-4
Shariq, O. A, & McKenzie, T. J. (2020). Obesity-related hypertension: a review of pathophysiology management, and the role of metabolic surgery. Gland Surgery, 9(1), 80-93. doi: 10.21037/gs.2019.12.03
Cardiovascular disorders represent a spectrum of life-threatening medical disorders affecting the cardiovascular system. These include but are not limited to hypertension, heart failure, stroke, ischemic heart disease, and coronary artery diseases. These diversified arrays of conditions remain the second most leading cause of mortality in the United States of about 1 in every 4 deaths (Olvera Lopez et al., 2021). In this assignment, a factor influencing pharmacodynamic and pharmacokinetics will be selected and explored extensively in relation to a case study involving AO, a patient diagnosed with hypertension and hyperlipidemia with a history of obesity.
Effects of Age on the Pharmacodynamic and Pharmacokinetics Processes
A couple of factors influence pharmacodynamic and pharmacokinetic processes. For instance, age, genetics, behaviors, and ethnicity. Aging is designated by accelerated impairment of functional capabilities of entire organ systems, diminished homeostatic mechanisms, and altered reaction to receptor stimulation (Peeters et al., 2019). The aforementioned processes influence the pharmacodynamic and pharmacokinetic processes with the resultant need for dose adjustments or rather contraindication of some pharmacologic agents in the elderly. Additionally, aging is associated with a reduction in the first-pass metabolism attributed to a decrease in the liver bulk and blood flow. Similarly, impaired hepatic and renal functions correlated with aging significantly hinder the renal and hepatic clearance of a majority of drugs (Laurent, 2017). Consequently, in the case of AO, 86-year-old taking atenolol, simvastatin, sertraline, hydralazine, and doxazosin, the bioavailability of the mentioned drugs will increase.
According to Peeters et al. (2019), aging is further associated with a reduction in cumulative muscle mass and total body water but with an increase in the percentage of body fat. As a result, the volume distribution of lipid-soluble drugs increases while it decreases for non-lipid soluble drugs. Pharmacodynamically, on the other hand, aging is accompanied by altered sensitivity to drugs with a general increase in sensitivity to drugs in the elderly. Ultimately, adjustments of the doses AO’s drug regimen are critical to avoid adverse side effects or rather toxicity.
Impact of Changes in Process on the Patient’s Recommended Drug Therapy
Atenolol which is indicated for therapeutic management of hypertension is largely metabolized by the liver and excreted by the kidney. Subsequently, the dose will be adjusted depending on the renal and liver function. Similarly, geriatric patients have decreased sensitivity to beta-blockers due to increased total peripheral resistance, and reduced cardiac and pulmonary function (Khalil & Zeltser, 2021). Therefore, the beta-blocker should be substituted with another class of antihypertensive. On the other hand, doxazosin also metabolized by the liver is associated with hypotension when utilized in the geriatric population and thus will necessitate periodic monitoring of vital signs and dose adjustments (Khalil & Zeltser, 2021). Sertraline should be avoided in adolescents and children due to an increased risk of suicidal ideation. It is a good agent in the elderly as it reduces stress and depression which significantly perpetuate hypertension. It is a vital medication in the elderly as it reduces symptoms of BPH. Hydralazine dose should be adjusted depending on the individualized rate of acetylation. Lastly, the safety profile of simvastatin, atenolol, and doxazosin has not been established in children less than 10 years.
How I would Improve the Patient’s Drug Plan
Patient AO is a geriatric hypertensive hyperlipidemic patient and at risk of BPH, therefore being on doxazosin is crucial. This medication reduces the blood pressure and symptoms of BPH in addition to decreasing LDL and cholesterol (Redon & Redon, 2019). However, this therapeutic agent is associated with orthostatic hypotension and edema especially in the elderly. Consequently, I will periodically monitor the vital signs, weight, edema, and liver function tests of AO and reduce the dose accordingly. I will gradually taper down the dose while simultaneously monitoring the adverse effects. Atenolol is relatively contraindicated in the elderly and therefore I will consider substituting it with a first-line antihypertensive such as hydrochlorothiazide(Redon & Redon, 2019). AO has gained 9 pounds which might be due to edema associated with atenolol and doxazosin, therefore, a diuretic such as hydrochlorothiazide when deployed will control the blood pressure as well as edema (Redon & Redon, 2019).
The doses of sertraline, hydralazine, and simvastatin will remain unadjusted. However, the patient will be assessed periodically and educated on the importance of taking medications as advised by the healthcare provider. Similarly, I will educate the patient on the side effects associated with these medications such as sexual dysfunction, fatigue, diarrhea, and drowsiness, and the need to consult the care provider if the symptoms persist or become intolerable (Redon & Redon, 2019). Additionally, I will advise and educate the patient on lifestyle modification and behavior changes to help control hypertension such as diet modification, smoking, and alcohol cessation, and regular physical activity. Finally, I will follow up with the patient at the medical outpatient clinic.
Conclusion
Pharmacological treatment alongside supportive measures form the mainstay treatment in patients with cardiovascular disorders. The drug regimen is largely affected by a variety of factors such as age, gender, ethnicity, and genetics which affect the pharmacodynamic and pharmacokinetic process. It is crucial for individualization of the drug regimen based on a critical evaluation of the above processes.
References
Khalil, H., & Zeltser, R. (2021). Antihypertensive Medications. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK554579/
Laurent, S. (2017). Antihypertensive drugs. Pharmacological Research: The Official Journal of the Italian Pharmacological Society, 124, 116–125. https://doi.org/10.1016/j.phrs.2017.07.026
Olvera Lopez, E., Ballard, B. D., & Jan, A. (2021). Cardiovascular Disease. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK535419/
Peeters, L. E. J., Kester, M. P., Feyz, L., Van Den Bemt, P. M. L. A., Koch, B. C. P., Van Gelder, T., & Versmissen, J. (2019). Pharmacokinetic and pharmacodynamic considerations in the treatment of the elderly patient with hypertension. Expert Opinion on Drug Metabolism & Toxicology, 15(4), 287–297. https://doi.org/10.1080/17425255.2019.1588249
Redon, J., & Redon, P. (2019). Evidence from clinical trials and use of antihypertensive drugs in children and adolescents. In Updates in Hypertension and Cardiovascular Protection (pp. 263–277). Springer International Publishing. https://doi.org/10.1007/978-3-030-18167-3_17