Is lisinopril ace inhibitor
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Lisinopril as an ACE Inhibitor: A Comprehensive Overview
Introduction to Lisinopril and ACE Inhibition
Lisinopril is a widely used medication that belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors are primarily prescribed for managing conditions such as hypertension, heart failure, and certain types of kidney disease. They work by inhibiting the enzyme ACE, which plays a crucial role in the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure and fluid balance 124.
Mechanism of Action: ACE Inhibition
Lisinopril functions by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby reducing blood pressure and decreasing the workload on the heart. This inhibition also leads to decreased degradation of bradykinin, a peptide that promotes vasodilation, further contributing to the antihypertensive effects of lisinopril 79.
Clinical Efficacy in Heart Failure and Myocardial Infarction
Heart Failure
Studies have demonstrated that lisinopril is effective in reducing morbidity and mortality in patients with chronic heart failure. The ATLAS study, for instance, compared low and high doses of lisinopril and found that higher doses significantly reduced the risk of death or hospitalization for heart failure 1. This suggests that maintaining adequate dosing of lisinopril is crucial for optimal therapeutic outcomes in heart failure management.
Myocardial Infarction
Lisinopril has also shown benefits in patients with acute myocardial infarction (MI). The GISSI-3 study highlighted that early administration of lisinopril in diabetic patients with acute MI significantly reduced 6-week mortality rates compared to those who did not receive the drug 4. This underscores the importance of early intervention with ACE inhibitors in improving survival rates post-MI.
Impact on Renal Function and Diabetic Nephropathy
Lisinopril is beneficial in slowing the progression of renal disease, particularly in patients with diabetes. The EURODIAB Controlled Trial of Lisinopril in IDDM demonstrated that lisinopril significantly reduced albumin excretion rates, a marker of kidney damage, especially in patients with certain ACE gene polymorphisms 2. This indicates that lisinopril not only helps in managing blood pressure but also offers renal protection in diabetic patients.
Pharmacokinetics and Bioavailability
Lisinopril is characterized by its long-acting nature, allowing for once-daily dosing, which improves patient compliance compared to other ACE inhibitors like captopril that require multiple daily doses 6. Pharmacokinetic studies have shown that lisinopril has a bioavailability of approximately 5.4% when administered orally, with a terminal elimination half-life of around 3.1 hours 5.
Structural Insights and Domain Selectivity
The crystal structure of the human ACE-lisinopril complex has provided valuable insights into the binding specificity of lisinopril. This structural information has facilitated the design of domain-selective ACE inhibitors, which may offer improved therapeutic profiles and reduced side effects 789.
Conclusion
Lisinopril is a potent ACE inhibitor with proven efficacy in managing hypertension, heart failure, and renal complications in diabetic patients. Its ability to reduce mortality in acute myocardial infarction and its favorable pharmacokinetic profile make it a cornerstone in cardiovascular and renal therapy. Understanding its mechanism of action and structural interactions further enhances its clinical application and potential for future drug development.
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Most relevant research papers on this topic
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.
High doses of ACE inhibitors are generally recommended for patients with heart failure, as they reduce morbidity and mortality, while very low doses may be tolerated but have limited benefits.
RCT
Large Human Trial
Highly CitedEffect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.
ACE inhibitor treatment can slow renal disease progression in type II diabetes mellitus patients, with lisinopril showing the most significant benefit for this group.
RCTLarge Human TrialHighly CitedOral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice
Oral lisinopril increases ACE2 in tissues relevant to COVID-19 transmission and pathogenesis, but the addition of losartan prevents these increases in ACE2 levels.
RCT
Animal StudyEffect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study.
Early treatment with lisinopril in diabetic patients with acute MI is associated with a decreased 6-week mortality.
RCTLarge Human TrialHighly CitedPharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE inhibitor.
Lisinopril-tryptophan, a novel C-domain ACE inhibitor, shows high selectivity and a 5.4% oral bioavailability, with potential clinical applications in treating hypertension.
Non-RCTAnimal StudyLong-acting angiotensin-converting enzyme inhibition: once-daily lisinopril versus twice-daily captopril in mild-to-moderate heart failure.
Both once-daily lisinopril and twice-daily captopril significantly increase exercise duration in patients with mild-to-moderate heart failure, without significantly impacting ventricular ectopic activity.
RCTCrystal structure of the human angiotensin-converting enzyme–lisinopril complex
The crystal structure of human ACE reveals its little similarity to carboxypeptidase A, offering potential for designing domain-selective ACE inhibitors with new pharmacological profiles.
Highly CitedCharacterization of domain-selective inhibitor binding in angiotensin-converting enzyme using a novel derivative of lisinopril.
LisW-S, a C-domain-selective derivative of lisinopril, shows high affinity and selectivity for human ACE, making it a promising lead candidate for cardiovascular drug development.
In Vitro StudyStructural basis of the lisinopril-binding specificity in N- and C-domains of human somatic ACE.
The molecular model reveals differences in lisinopril-binding residues in the N- and C-domains of human somatic ACE, potentially aiding in the development of new inhibitors based on natural BPP peptides.
Lisinopril, an angiotensin I-converting enzyme inhibitor, prevents entry of murine hematopoietic stem cells into the cell cycle after irradiation in vivo.
Lisinopril, an ACE inhibitor, effectively prevents murine hematopoietic stem cells from entering the cell cycle after irradiation, potentially playing a role in regulating stem cell proliferation through control of AcSDKP concentration.
In Vitro Study