Pharmacodynamics of Perindopril
Question:
Discuss about the Pharmacokinetics Pharmacology for Perindopril and Aspirin.
The clinical management of cardiovascular conditions requires the administration of a range of prescription drugs as well as over-the-counter medicine in accordance with the clinical condition of the treated patients. Perindopril is listed in top-10 Australian prescription drugs and prescribed for effectively treating cardiovascular conditions including coronary artery disease, heart failure and hypertension (NPS_Medicinewise_Australian_Prescriber, 2017). Contrarily, aspirin is an over-the-counter (OTC) drug administered with the objective of minimizing the predisposition of high-risk patients in terms of acquiring cardiovascular accident or heart attack (Victoria_State_Government, 2017). Indeed, the OTC administration of aspirin is undertaken in the context of treating pain pattern in the selected patients (Health_Direct, 2017). This paper effectively compares, evaluates, and critically analyses the pharmacodynamics, pharmacokinetics and nursing practice implications of perindopril and aspirin through evidence-based literature exploration. The paper also undertakes a well-structured comparison of key issues associated with the administration of both drugs in nursing practice.
Perindopril is clinically prescribed in the form of Perindopril arginine in Australia. Perindopril arginine leads to ACE (angiotensin-converting enzyme) inhibition and reduction in blood pressure in the high-risk patients. Perindopril arginine tablets are available in 2.5mg-10mg composition and require oral administration for effectively controlling the elevation in systolic and diastolic blood pressure in adults. This drug also contains the inactive ingredients including isomalt, Silica colloidal anhydrous, magnesium stearate, Hypromellose, hydroxypropyl cellulose, macrogol-8000 and titanium dioxide (NPS-Medicinewise, 2017). Arginine component of perindopril exhibits water soluble property. Perindopril is indeed an active prodrug that transforms itself to perindoprilat (diacid product) in the human liver. Most of the components of perindopril are released through urine following its administration to the intended patient (Australian_Government, 2009). Perindopril exhibits rapid absorption and acquires peak plasma concentration within an hour of its administration. The bioavailability of perindopril is 75% and 30%-50% of its active components assimilate in the systemic circulation and undergo hydrolysis that resultantly produces perindoprilat with 25% mean bioavailability. The dietary administration before or after the utilization of perindopril does not directly impact the pharmacokinetics of perindopril. However, it might decrease the absorption rate of perindopril between 14% – 18% (NIH, 2017). The single oral administration of perindopril linearly elevates its plasma concentration curve in a dose-dependent fashion. Perindopril exhibits a mean half-life of 0.8h-1h after its major elimination from the recipient body. Indeed, 4%-12% dosage of perindopril is excreted through urine in unmodified form. Perindopril undergoes glucuronidation/hydrolysis across the circulatory system and transforms into active metabolites including perindoprilat glucuronides, hydrolyzed perindopril, dehydrated perindopril and its diastereoisomers. Perindoprilat concentration elevates gradually with the rise in peak plasma concentration after 3-7 hours of its administration. Perindoprilat disintegration from the ACE binding location occurs in a slow and gradual manner that leads to its extended half-life of nearly 120h.
Contrarily, aspirin is utilized as a first line treatment in effectively controlling pain pattern in a variety of clinical scenarios (Lecchi, D’Alonzo, Negro, & Martelletti, 2014). Th elevated peak plasma concentration of aspirin and short absorption time increase the bioavailability of aspirin in a dose dependent manner. Aspirin is not regarded as a first line therapy antiplatelet therapy. However, the antiplatelet property makes aspirin as a potential anti-thrombotic agent. Secondary prevention strategies substantiate the requirement of aspirin administration to reduce the risk of cerebrovascular accident (CVA) and myocardial infarction (MI) by (25-30) % (Espinosa, Murad, & Khasawneh, 2012). Aspirin follows rapid absorption mechanisms in the intestine and stomach, which match with the absorption pattern of Perindopril. This drug is converted to salicylate primarily in liver, stomach and intestine. Contrary to the pharmacokinetics of Perindopril, salicylate production from aspirin and its assimilation in the circulatory system reduces the aggregation of platelets. Enteric coating over aspirin tablets has been done with the objective of minimizing the risk of gastrointestinal intolerance. The half-life of aspirin is much shorter than Perindopril. Indeed, aspirin requires 15-20 minutes under the impact of rapid pre-systemic hydrolysis (induced by esterase) (Mekaj, Daci, & Mekaj, 2015). Like perindopril, salicylate metabolism in liver proceeds through hepatic conjugation with glucuronic acid or saturable glycin. Salicylate metabolism progresses at a slow pace that eventually leads to its 90% processing in the liver. Pronged elevated aspirin dosage reciprocally extends its half-life. Aspirin follows the same excretion pattern exhibited by perindopril through its metabolic pathways. Indeed, 10% components of the unmodified salicylate are apparently tracked in patient’s urine. However, urinary pH determines the extent of excretion of free ionized salicylate as well as salicylate metabolites (UNIL, 2018).
Pharmacokinetics of Perindopril
ACE inhibition occurs in a dose and concentration dependent fashion immediately after the single-dose administration of perindoprilat to the selected patient. However, the extent of ACE inhibition (after single-dose administration of perindopril) exhibits reduction in a time-dependent manner with a gradual elevation of ID50. Perindopril selectively minimizes the pressor response against angiotensin- I that fails to supersede the intensity of ACE inhibition pattern.
Aspirin substantially inhibits the production of COX-1 (cycloxygenase-1) in low dosage of 75mg-80mg while concomitantly inhibiting the generation of TXA2 (Espinosa, Murad, & Khasawneh, Aspirin: Pharmacology and Clinical Applications, 2012). The selectivity of acetyl salicylic acid (ASA) for COX-1 isoform enhances the antiplatelet aggregation action of aspirin to a considerable extent. ASA presumably inhibits PGI2 in a dosage of 250mg-500mg. The oral administration of ASA inhibits serum thromboxane B2. Aspiring administration rarely causes renal complications in the treated patients (Nagelschmitz, et al., 2014).
Nurse professionals must carefully monitor patient’s systolic and diastolic blood pressure while administering perindopril. The dosage adjustment of perindopril is necessarily warranted while treating the patients affected with diabetes and renal complications. This is because of the potential of perindopril in terms of impacting the hospital admission incidence rate for diabetic and hypertensive patients (Wong, et al., 2015). Contrarily, nurses require understanding the significance of aspirin utilization as a secondary prevention strategy in patients affected with MI, ischemic stroke, and cardiovascular diseases. The elevated risk of relapse of a cardiovascular event necessitates the requirement of aspirin administration to the high-risk patients. Therefore, nurses should thoroughly perform the risk-assessment of cardiac patients and administer second-line therapy for MI relapse. Low dose aspirin therapy is recommended for primarily reducing the predisposition of cardiovascular disease in high-risk patients. Nurses should also record the age of the treated patients while selecting them for aspirin intervention. Patients with greater than 50 years of ages should receive aspirin therapy for reducing their risk of MI or stroke. Low-dose aspirin therapy is also recommended for stroke and heart attack patients for an indefinite period with the objective of reducing the risk of disease relapse and resultant mortality (Ittaman, VanWormer, & Rezkalla, 2014).
Nurses require monitoring patient’s vitals (including pulse and BP) during perindopril therapy. Any abnormal vital finding needs to be reported to the concerned physician for immediate medical attention. The prescription refill frequency should be regularly monitored and evaluated in the context of determining the medication compliance. Nurses also need to record the pattern of angioedema while after administering perindopril to the intended patient. The regular monitoring of serum creatinine and blood urea nitrogen is necessarily required after perindopril administration. Nurses require monitoring complete blood count in patients affected with renovascular disease while administering perindopril to the target patients. This is due to their risk of acquiring eosinophilia, neutropenia and haemoglobin reduction under the sustained impact of perindopril. The regular monitoring of blood glucose, uric acid, and alkaline phosphatase is necessarily required while concomitantly evaluating the cardiac output pattern in the patients treated with perindopril. Nurses must administer education sessions for the treated patients with the objective of improving their knowledge and compliance in relation to the utilizing of perindopril for controlling their cardiovascular manifestations. Perindopril is associated with a reduced rate of liver injury. Indeed, less than two percent cases reportedly exhibit aminotransferase elevation after the regular administration of perindopril therapy. However, nurses might require evaluating ALT and AST levels in patients with pre-existing liver disease while administering perindopril in the clinical setting (NIH, Drug Record – Perindopril, 2018). Similarly, nurses must monitor ALT and AST levels in the treated patients while administering booster dosages of aspirin in the context of reducing the potential risk of hepatotoxicity (Laster & Satoskar, 2014). Nurses must not administer aspirin to patients with pre-existing asthma or allergic conditions in the context of their high-risk of hypersensitivity. Movement limitation and pain related to the injection site also require monitoring after aspiring administration. Evaluation of malaise, tachycardia and fever needs to be undertaken for evaluating the pattern of cardiometabolic complications after aspirin administration. Nurses also require monitoring the level of serum salicylate and bleeding time while concomitantly evaluating the appearance of aspiring overdose symptomatology including sweating, diarrhea, lethargy, mental confusion, agitation, tinnitus, and hyperventilation. This is because of high risk of salicylate toxicity in the treated patients (American_College_of_Medical_Toxicology, 2015).
Conclusion
The paper effectively discussed and comparatively analysed the pharmacokinetics, pharmacodynamics and nursing practice implications associated with the utilization of perindopril and aspirin. The similarities between the profiles of perindopril and aspirin include their rapid absorption, hepatic metabolism, and urinary excretion rate. However, the significant differences were recorded in the bioavailability, adverse reactions, half-life, and prescription status of both drugs. Systematic monitoring of patient symptomatology and laboratory evaluation are necessarily required with the objective of minimizing the risk of potential clinical complications following the administration of perindopril or aspirin to the selected patients.
References
American_College_of_Medical_Toxicology. (2015). Guidance Document: Management Priorities in Salicylate Toxicity. Journal of Medical Toxicology, 11(1), 149-152. doi:10.1007/s13181-013-0362-3
Australian_Government. (2009). Australian Public Assessment Report for Perindopril arginine/amlodipine (as besylate). Australia: TGA. Retrieved from https://www.tga.gov.au/sites/default/files/auspar-coveram.pdf
Espinosa, E. V., Murad, J. P., & Khasawneh , F. T. (2012). Aspirin: Pharmacology and Clinical Applications. Thrombosis. doi:10.1155/2012/173124
Health_Direct. (2017, December). Health_Direct. Retrieved from Over-the-counter medicines: https://www.healthdirect.gov.au/over-the-counter-medicines
Ittaman, S. V., VanWormer, J. J., & Rezkalla, S. H. (2014). The Role of Aspirin in the Prevention of Cardiovascular Disease. CMR, 12(3-4), 147-154. doi:10.3121/cmr.2013.1197
Laster, J., & Satoskar, R. (2014). Aspirin-Induced Acute Liver Injury. ACG Case Rep J, 48-49. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435341/
Lecchi, M., D’Alonzo , L., Negro, A., & Martelletti , P. (2014). Pharmacokinetics and safety of a new aspirin formulation for the acute treatment of primary headaches. Expert Opinion on Drug Metabolism and Toxicology, 10(10), 1381-1395. doi:10.1517/17425255.2014.952631
Mekaj, Y. H., Daci, F. T., & Mekaj, A. Y. (2015). New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism. Therapeutics and Clinical Risk Management, 1449-1456. doi:10.2147/TCRM.S92222
Nagelschmitz, J., Blunck, M., Kraetzschmar, J., Ludwig, M., Wensing, G., & Hohlfeld, T. (2014). Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clinical Pharmacology: Advances and Applications, 51-59. doi:10.2147/CPAA.S47895
NIH. (2017, October 16). PRESTALIA- perindopril arginine, amlodipine besylate tablet . Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98cc3e47-3463-4162-96ac-bf97d77eb041#section-11.3
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NPS-Medicinewise. (2017, February). APO-Perindopril Arginine Tablets. Retrieved from https://www.nps.org.au/medical-info/medicine-finder/apo-perindopril-arginine-tablets
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Wong, M. C., Tam, W. W., Wang, H. H., Zhang, D., Cheung , C. S., Yan, B. P., . . . Griffiths, S. M. (2015). The effectiveness of perindopril vs. lisinopril on reducing the incidence of diabetes and renal diseases: A cohort study of 20,252 patients. International Journal of Cardiology, 384-388. doi:10.1016/j.ijcard.2015.04.191
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