Drugs and Therapeutics
James Sherifi in General Practice Under the NHS, 2023
Angiotensin receptor blockers (ARBs) work further down the angiotensin-rennin pathway and have the advantage of not causing cough, although, unlike ACE inhibitors, they have not been shown to reduce cardiac mortality. Nifedipine—1967, AmlodipineAngina, Hypertension, Chilblains Nifedipine was developed by Bayer and introduced to the UK market in the mid-1970s for the treatment of angina and hypertension. The drug had a cumbersome thrice-daily dosing regimen, leaving it wide open for replacement. This took a surprisingly long time to happen, until 1989, when once-daily amlodipine (Pfizer) came to market, with others including lacidipine, lercanidipine, and felodipine. Amlodipine came off patent in 2007, after which it pretty much had the market to itself.
Therapy of acute myocardial infarction
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Angiotensin receptor blockers (ARBs) are associated with less cough than ACEIs, but the rates of hyperkalemia and the potential for worsening renal function are similar with both drug classes. Two large trials have evaluated ARBs in the post-MI setting. In the Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan (OPTIMAAL), patients 50 years of age or older with acute MI accompanied by HF, anterior Q waves on ECG, or a left ventricular ejection fraction <35% were randomized to losartan or captopril and followed for an average of 2.7 years (108). Mortality was nonsignificantly higher in the losartan group (18.2% vs. 16.4%, p = 0.069), with similar outcomes in older and younger subjects. In the Valsartan in Acute Myocardial Infarction Trial (VALIANT), 14,703 patients with acute MI were randomly assigned to receive captopril, valsartan, or both drugs and followed for a median of 25 months (109). Mortality was similar in all three arms, but side effects and withdrawals were more common in patients randomized to combination therapy. More than half of the patients in VALIANT were 65 years of age or older, 3160 patients were aged 75 years or older, and outcomes with respect to the three treatment groups were similar across age categories, including patients over age 85 (110).
Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
In established diabetic nephropathy, the urinary albumin excretion can be >300 mg/24 hour (the normal range is <3 mg/24 hour). Patients with intermediate albumin excretions of above 3 mg/24 hour (microalbuminuria) have an elevated risk of developing established diabetic nephropathy. Microalbuminuria suggests early-stage glomerular damage, although not all will progress to established diabetic nephropathy. Screening with urine albumin : creatinine ratio (UACR) in a single urine sample is simpler than a 24-hour urine collection to estimate urinary albumin excretion. Microalbuminuria in diabetes is associated with slightly higher blood pressure and higher rates of cardiovascular disease compared to normoalbuminuric diabetics. Better glucose and blood pressure control reduce progression of microalbuminuria to diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers have been shown to be beneficial.
New drugs in preclinical and early stage clinical development in the treatment of heart failure
Published in Expert Opinion on Investigational Drugs, 2019
Juan Tamargo, Ricardo Caballero, Eva Delpón
HFrEF is the underlying diagnosis for less than 50% of the patients with symptomatic HF [1–4]. Treatment of HFrEF is based on the combination of neurohormonal antagonists that reduce morbidity and mortality, while other drugs (diuretics, digoxin, calcium channel blockers, inotropic agents, vasopressin antagonists) improve HF signs/symptoms and can potentially reduce hospitalizations but not mortality [2–4]. Very recently, two new drugs were found to improve survival. The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan reduces by 20% the risk of cardiovascular death and HFH compared with enalapril [16]. This drug is recommended for use as a replacement for an ACEI/ARB to further reduce the risk of HFH and death in patients with HFrEF. The antianginal drug ivabradine, an inhibitor of the pacemaker cardiac current If, reduces HFH (26%) as compared with placebo in patients in sinus rhythm and a heart rate (HR) >70 bpm on maximally tolerated doses of β-blockers [17]. Several other drugs, however, fail to meet the primary outcomes in phase 2–3 RCTs)(Table 2) [18–32]. However, despite the use of guideline-directed medical and device therapies have improved survival and reduced the hospitalization rate, patients with HFrEF present frequent disease exacerbations and poor quality of life (QoL) and the 12-month all-cause mortality rates for hospitalized and stable/ambulatory HF patients were 17% and 7%, respectively, and the 12-month hospitalization rates were 44% and 32%, respectively [3,4].
Local renin-angiotensin system molecular mechanisms in intrauterine adhesions formation following gynecological operations, new strategy for novel treatment
Published in Journal of Obstetrics and Gynaecology, 2022
Sheida Shabanian, Majid Khazaie, Gordon A. Ferns, Mohammad-Hassan Arjmand
Renin-Angiotensin System (RAS) as an endocrine system plays a critical role in regular electrolytes, vascular resistance, and blood volume. RAS contains several peptides. Renin, an aspartic protease produced by the kidney, cleavage angiotensinogen to generate angiotensin I (Ang I), a 10 amino acids molecules, and then angiotensin convert enzyme (ACE) convert Ang I to angiotensin II (AngII), the main active peptide in the RAS, that exerts its actions by binding to angiotensin receptors (Kurdi et al. 2005). Angiotensin receptor types 1 and 2 (ATR1 and 2) mediate the actions of AngII and belong to trans-membrane G-protein (Aplin et al. 2009). Interactions between AngII and AT1R lead to increase cell proliferation, vasodilation, and activation signalling to stimulates organ fibrosis (Filippatos et al. 2001). Also, besides AngII and angiotensin receptors type 1 and 2, other components including Ang1-7, ACE2, and Mas receptors have been identified in the RAS system (Kibel et al. 2015).
Evaluation of pathophysiological relationships between renin-angiotensin and ACE-ACE2 systems in cardiovascular disorders: from theory to routine clinical practice in patients with heart failure
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Alberto Aimo, Giuseppe Vergaro, Claudio Passino, Aldo Clerico
An integrated approach that includes the biochemical pathways and physiological activities related to the RAS, NP, ACE/ACE2, and NEP systems is summarized in Figure 2. The pathophysiological effects of the RAS are mainly mediated by three different receptors (i.e. AT-1, AT-2, and Mas), which share different affinity and specificity for binding the active peptides, Angio-II and Angio-(1-7) [24,25,86,126,127]. Angiotensin receptor type I (AT-1) and II (AT-2) are seven-transmembrane G protein-coupled receptors that have a similar affinity for Angio-II, even though these two receptor proteins have a sequence homology of only 34% [128–132]. However, activation of both receptors is likely to stimulate different signaling mechanisms/pathways and produce distinct and often antagonistic biological responses (Figure 2).
Related Knowledge Centers
- Angiotensin II Receptor Type 1
- Angiotensin II Receptor Type 2
- Circumventricular Organs
- Ligand
- Signal Transduction
- Basal Ganglia
- Angiotensin
- G Protein-Coupled Receptor
- Renin–Angiotensin System
- Vasoconstriction
- Angiotensin II Receptor Type 1
- Angiotensin II Receptor Type 2