ACE-I induced angioedema: a case report and review of literature

Although rare, angioedema has been documented to occur following the administration of angiotensin-Converting Enzyme Inhibitors. Angiotensin-converting enzyme inhibitors are the leading cause of drug induced angioedema. Angiotensin-converting enzyme inhibitors induced angioedema is a class effect that can affect between 0.1% and 0.5% of patients taking the drug. It is rarely documented in Nigeria. Lisinopril is a commonly prescribed angiotensin-converting enzyme inhibitors-I which is considered to be generally safe and well tolerated. We report a case of angioedema following the use of lisinopril

Enzyme Inhibitors and Activators

Enzymes are very effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Enzyme inhibitors and activators that modulate the velocity of enzymatic reactions play an important role in the regulation of metabolism. Enzyme inhibitors are also useful tool for study of enzymatic reaction as well as for design of new medicine drugs. In this chapter, we focused on the properties of enzyme inhibitors and activators. Here we present canonical inhibitor classification based on their kinetic behavior and mechanism of action. We also considered enzyme inhibitors that were used for design of various types of pharmacological drugs and natural inhibitors as a plausible source for design of future drugs. Mechanisms of action of enzyme activators and some features of allosteric modulators are considered

Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study

Background: Angiotensin converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. Methods and results: 4,723 out-patients with stable HFrEF prescribed either enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21,939 patient-years, 360 (49.5%), 337 (52.4%), and 1,119 (33.4%) patients died amongst those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality as compared with ramipril treatment (HR 1.46, 95% CI 1.30-1.65, p < 0.001, and HR 1.38, CI 1.22-1.56, p < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, p = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, p = 0.40; HR 1.12, 95% CI 0.96-1.32, p = 0.16; and HR 1.08, HR 1.10, 95% CI 0.93-1.31, p = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HFrEF, rhythm, and systolic blood pressure. Conclusion: Our results suggest that enalapril, lisinopril and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses

Use of Antihypertensive Agents and Association With Risk of Adverse Outcomes in Chronic Kidney Disease: Focus on Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers.

Background Our objective was to determine patterns of antihypertensive agent use by stage of chronic kidney disease (CKD) and to evaluate the association between different classes of antihypertensive agents with nonrenal outcomes, especially in advanced CKD . Methods and Results We studied 3939 participants of the CRIC (Chronic Renal Insufficiency Cohort) study. Predictors were time-dependent angiotensin-converting enzyme inhibitor or angiotensin receptor blocker , β-blocker, and calcium channel blocker use (versus nonuse of agents in each class). Outcomes were adjudicated heart failure events or death. Adjusted Cox models were used to determine the association between predictors and outcomes. We also examined whether the associations differed based on the severity of CKD (early [stage 2-3 CKD ] versus advanced disease [stage 4-5 CKD ]). During median follow-up of 7.5 years, renin-angiotensin-aldosterone system inhibitor use plateaued during CKD stage 3 (75%) and declined to 37% by stage 5, while β-blocker, calcium channel blocker, and diuretic use increased steadily with advancing CKD . Renin-angiotensin-aldosterone system inhibitor use was associated with lower risk of heart failure (hazard ratio, 0.79; 95% confidence interval, 0.67-0.97) and death (hazard ratio, 0.78; 95% confidence interval, 0.67-0.90), regardless of severity of CKD . Calcium channel blocker use was not associated with risk of heart failure or death, regardless of the severity of CKD . β-Blocker use was associated with higher risk of heart failure (hazard ratio, 1.62; 95% confidence interval, 1.29-2.04) and death (hazard ratio, 1.22; 95% confidence interval, 1.03-1.43), especially during early CKD ( P<0.05 for interaction). Conclusions Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use decreased, while use of other agents increased with advancing CKD . Use of agents besides angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be associated with suboptimal outcomes in patients with CKD

Comparison of First-Line Dual Combination Treatments in Hypertension: Real-World Evidence from Multinational Heterogeneous Cohorts.

Background and objectives: 2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D).Methods: Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure.Results: A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97-1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87-1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95-1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01-1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01-1.17; p=0.040) than A+D.Conclusions: There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice

Minimal Information About Sample Preparation for Phosphoproteomics

This guideline describes parameters and conditions involved in phosphopeptide sample preparation. It covers from the description and preparation of the cells and tissues to the fractionation and specific enrichment of phosphopeptides for MS analysis. The guideline is prepared in order to easily cope with many of the experimental designs used in phosphoproteomic studies. 
 
The document is subdivided as follows:
1. General features
2. Sample processing
3. Protein Purification/Fractionation
4. Peptide Purification/Fractionation
5. Phosphopeptide enrichment
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Neural networks and support vector machines based bio-activity classification

Classification of various compounds into their respective biological activity classes is important in drug discovery applications from an early phase virtual compound filtering and screening point of view. In this work two types of neural networks, multi layer perceptron (MLP) and radial basis functions (RBF), and support vector machines (SVM) were employed for the classification of three types of biologically active enzyme inhibitors. Both of the networks were trained with back propagation learning method with chemical compounds whose active inhibition properties were previously known. A group of topological indices, selected with the help of principle component analysis (PCA) were used as descriptors. The results of all the three classification methods show that the performance of both the neural networks is better than the SVM

Effectiveness of Angiotensin-Converting Enzyme Inhibitors in Pediatric Patients with Mid to Severe Aortic Valve Regurgitation

The long-term benefit of angiotensin-converting enzyme inhibitors in pediatric patients with aortic valve regurgitation is under consideration. Eighteen patients with mid to severe aortic valve regurgitation were retrospectively evaluated. Echocardiographic parameters (left ventricular end-diastolic diameter, shortening fraction, left ventricular posterior wall thickness, and grade of aortic valve regurgitation) were analyzed before and during therapy with angiotensin-converting enzyme inhibitors. Data are given as standard deviation scores (Z-scores) derived from body surface-adjusted normal values. Median (interquartile range) age at start of therapy was 8.4 (5.4 to 10.0) years, and total follow-up 2.3 (0.9 to 5.4) years. Left ventricular end-diastolic diameter increased from 3.6 (2.3 to 4.5) to 3.7 (2.4 to 4.8), and left ventricular posterior wall diameter decreased from 1.9 (1.1 to 3.0) to 1.1 (0.5 to 2.3). Grade of aortic valve regurgitation increased from 3.5 (2.3 to 4.0) to 4.0 (2.0 to 4.0), and shortening fraction decreased from 39% (34% to 43%) to 37% (34% to 42%). No significant effect of angiotensin-converting enzyme inhibitors on left ventricular dimensions or function was found in our population of patients with mid to severe aortic valve regurgitation. Angiotensin-converting enzyme inhibitors may not alter left ventricular overload in pediatric patients with aortic valve regurgitatio