Potential side effects of renin inhibitors – mechanisms based on comparison with other renin–angiotensin blockers

Cheng, Hao; Harris, Raymond C.

doi:10.1517/14740338.5.5.631

Cited by 29 publications

(10 citation statements)

References 91 publications

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“…3,17,22,[24][25][26][27][28][29] The rate of diarrhea with aliskiren at a 300-mg dose was 2.3%, and it increased with higher doses. 5,17,26,29 The occurrence of angioedema with respiratory symptoms was rare (0.06%); other types of edema were reported as 0.4% and 0.5% in the aliskiren and placebo groups, respectively. Increases in serum potassium level of >5.5 meq/L were reported at a rate of 0.9% in patients receiving aliskiren versus 0.6% in those receiving placebo during clinical trials.…”

Section: Adverse Effects and Toxicitiesmentioning

confidence: 99%

Aliskiren

Daugherty

2008

American Journal of Health-System Pharmacy

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Section: Adverse Effects and Toxicitiesmentioning

confidence: 99%

Aliskiren

Daugherty

2008

American Journal of Health-System Pharmacy

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“…In normal human physiology, bradykinin is metabolized by ACE to inactive peptides. Some animal and human studies found that ARBs may increase bradykinin levels by reducing its metabolism and as consequence may cause cough and angioedema . Most studies concluded that the incidence of cough and angioedema is higher in users of ACE inhibitors compared to users of ARBs, DRI, and placebo .…”

Section: Introductionmentioning

confidence: 99%

The impact of age and sex on the reporting of cough and angioedema with renin–angiotensin system inhibitors: a case/noncase study in VigiBase

Alharbi

Kholod

Souverein

et al. 2017

Fundamemntal Clinical Pharma

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The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20,) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting.

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“…[114][115][116][117] Other adverse effects (,5%) include angioneurotic edema, abdominal pain, anemia, angina, gastroesophageal reflux, gout, myositis, renal stone formation, rhabdomyolysis, seizure, and hyperuricemia. 118 Hypotension may also occur in patients with an activated RAAS, such as in volume or salt-depleted patients, such as or patients on diuretics.…”

Section: Adverse Effects Of Renin Inhibitorsmentioning

confidence: 99%

Direct Renin Inhibitors as Antihypertensive Agents

Israili

Velasco²,

Bermúdez³

2010

American Journal of Therapeutics

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Hypertension, a serious disease affecting almost a billion people (25% of adults) worldwide, is a major modifiable risk factor for cardiovascular (CV) and renal disease. Despite numerous advances in the pharmacologic treatment of high blood pressure (BP) and availability of several antihypertensive drugs to treat hypertension, a significant proportion of treated hypertensive patients still have uncontrolled high BP, and thus, face serious morbidity and mortality. Furthermore, it is not sufficient to aim for optimum BP control, but to treat all CV risk factors, protect end-organ damage, prevent progression of disease, and prevent long-range adverse effects of the drugs. Therefore, new therapeutic modalities have to be developed to achieve the above objectives. Some years ago, investigators identified renin inhibition as the preferred pharmacologic approach to blockade of the renin-angiotensin system. Renin is a monospecific enzyme that catalyzes the rate-limiting step in the synthesis of angiotensin II. Amplified enzymatic activity and additional physiologic effects occur when renin and prorenin bind to the (pro)renin receptor. Until very recently, development of clinically effective renin inhibitors remained elusive but molecular modeling was used to develop aliskiren and other renin inhibitors that produce sustained suppression of plasma renin activity after oral administration with a dose-dependent BP. Additional studies will ultimately determine the place of renin inhibition in the treatment of hypertension and related CV disorders.

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Potential side effects of renin inhibitors – mechanisms based on comparison with other renin–angiotensin blockers

Cited by 29 publications

References 91 publications

Aliskiren

Aliskiren

The impact of age and sex on the reporting of cough and angioedema with renin–angiotensin system inhibitors: a case/noncase study in VigiBase

Direct Renin Inhibitors as Antihypertensive Agents

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