Angiotensin converting enzyme inhibitors

Soudijn, W.

doi:10.1007/bf01959035

Cited by 7 publications

(3 citation statements)

References 6 publications

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“…25 The relative risk of influenza pneumonia associated with various conditions was calculated by logistic regression analysis, adjusting for all associated variables selected according to their univariate analysis P value (P < 0.20). 26 Estimates of relative risk (RR) and corresponding two-sided 95% confidence intervals (CI) demonstrating statistical significance were derived from the regression model. Since the mode of inheritance of the D allele has not been clarified, we examined its effect separately as follows: recessive (DD vs ID + II), additive (DD vs ID vs II) or dominant (DD + ID vs II).…”

Section: Discussionmentioning

confidence: 99%

Association of angiotensin‐I converting enzyme DD genotype with influenza pneumonia in the elderly

Onishi

Morimoto

Yang

et al. 2002

Geriatrics Gerontology Int

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Background: Although angiotensin‐I converting enzyme (ACE) is known to associate with cough reflex and inflammatory conditions, and both may participate in influenza pneumonia in the elderly, no study has been carried out on the association between influenza pneumonia and the insertion/deletion (I/D) polymorphism of the ACE gene (ACE). Methods: The subjects were 934 elderly inpatients (mean ± SD age of 82 ± 8 years) in a long‐term care hospital. The association between ACE I/D and the incidence of influenza‐pneumonia events was assessed over a winter season. Data were analyzed by multiple logistic regression analysis, with adjustment for age, gender, already known clinical risk factors, and ACE‐inhibitor use. Results: During the follow‐up period, 330 patients developed influenza (Directigen FLU‐A) and 89 developed influenza pneumonia (Center for Disease Control and Prevention (CDC) criteria with chest X‐ray required), 16 fatal and 73 non‐fatal. Compared to non‐influenza subjects (n = 604) and influenza patients without pneumonia (n = 241), ACE DD genotype (vs ID + II) resulted in a significant risk for all pneumonia (relative risk 2.32 [95% CI: 1.30–4.14] and 2.76 [1.39–4.04]), non‐fatal pneumonia (1.91 [1.01–3.63] and 2.57 [1.23–5.39]) and fatal pneumonia (6.27 [1.68–23.3] and 5.15 [1.29–20.5]). Conclusion: ACE I/D polymorphism is a strong and independent risk indicator of influenza pneumonia events in elderly inpatients.

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Section: Discussionmentioning

confidence: 99%

Association of angiotensin‐I converting enzyme DD genotype with influenza pneumonia in the elderly

Onishi

Morimoto

Yang

et al. 2002

Geriatrics Gerontology Int

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“…Optimization of the lead resulted in the development of captopril, the first orally active ACE inhibitor in therapeutic use (Fig. 10) (for a short overview see Soudijn [11]). …”

Section: Rational Drug Designmentioning

confidence: 99%

The role of medicinal chemistry in drug research

Soudijn

1991

Pharmaceutisch Weekblad Scientific Edition

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Classical medicinal chemistry, that is molecular modifications of existing bioactive compounds, leading to me-too drugs with value added and often to me-too drugs which will never reach the market or to drugs in another pharmacological field than that originally intended, will be with us for a long time to come. The ultimate goal, however, is of course rational or at least semi-rational drug design. In some instances this goal seems to have already been reached as in the case of angiotensin-converting enzyme inhibitors and H2 antagonists. In the (near) future results from the steady progress in molecular biology in combination with computer-assisted drug modelling--possibly coupled with artificial intelligence techniques--will help the medicinal chemist in his efforts to attain this goal.

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“…This idea had to be reconciled with the molecular model of ACE of Ondetti and Cushman [22], in which the sulfhydryl group was supposed to play a role in the binding of the drug to the enzyme. This is illustrated by the following quotation from Soudijn [33]: "... The first was the search for a compound lacking a sulfhydryl group and the second concerned the data on structureactivity relationships that were available for captopril and some of its derivatives [31].…”

Section: Pathway Ii1: Pathophysiologicalmentioning

confidence: 99%

How adverse drug reactions can play a role in innovative drug research

Rikken¹,

Vos²

1995

Pharm World Sci

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We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.

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Angiotensin converting enzyme inhibitors

Cited by 7 publications

References 6 publications

Association of angiotensin‐I converting enzyme DD genotype with influenza pneumonia in the elderly

Association of angiotensin‐I converting enzyme DD genotype with influenza pneumonia in the elderly

The role of medicinal chemistry in drug research

How adverse drug reactions can play a role in innovative drug research

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