Pharmacokinetic interaction between cefdinir and two angiotensin-converting enzyme inhibitors in rats.

1996 ◽  
Vol 40 (4) ◽  
pp. 979-982 ◽  
Author(s):  
A Jacolot ◽  
M Tod ◽  
O Petitjean

The pharmacokinetic interaction between cefdinir and an angiotensin-converting enzyme inhibitor (captopril or quinapril) was investigated in rats. The linearity of cefdinir pharmacokinetics was demonstrated in three groups of rats receiving 10, 20, or 40 mg of cefdinir per kg of body weight intravenously. Then, three other groups of rats were established as follows: group 1 (n = 5) received cefdinir (10 mg/kg) intravenously, and 12 blood samples per rat were drawn between 0 and 8 h after injection of the dose; group 2 (n = 5) was treated in the same way as group 1, but captopril (0.8 mg/kg) was coadministered by intraintestinal injection into all animals; group 3 (n = 6) was treated in the same way as group 2, but quinapril (0.8 mg/kg) replaced captopril. Plasma cefdinir concentrations were measured by liquid chromatography, and the data were analyzed by a noncompartmental method. Finally, three groups of four or five rats each were set up as described above, but the cefdinir dose was 20 mg/kg and the animals were sacrificed 1 h after drug injection to collect blood to determine the unbound cefdinir fraction (fu) by ultrafiltration. The angiotensin-converting enzyme inhibitors increased the mean cefdinir area under the concentration-time curve up to 8 h by a factor of 1.8 (captopril; P < 0.05) and a factor of 3.5 (quinapril; P < 0.05). With captopril, mean cefdinir clearance was decreased by a factor of 2, and the volume of distribution increased by the same factor, while the fu increased from 15.4% +/- 3.0% (cefdinir alone) to 22.8% +/- 10.9% (cefdinir plus captopril). Captopril increased the cefdinir half-life from 0.62 +/- 0.17 to 2.92 +/- 0.95 h. With quinapril, the interaction was so strong that no elimination phase was detectable in four of the six rats, and therefore, no pharmacokinetic parameter values other than the cefdinir fu could be calculated; the cefdinir fu increased to 25.1% +/- 11.1%. It is concluded that captopril and quinapril (and/or their metabolites) have a major impact on the disposition of cefdinir in rats, probably by competition at the plasma protein-binding level and at the tubular anionic carrier level. This latter mechanism should also be relevant in humans.

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244349
Author(s):  
Jean-Louis Georges ◽  
Floriane Gilles ◽  
Hélène Cochet ◽  
Alisson Bertrand ◽  
Marie De Tournemire ◽  
...  

Background Angiotensin-converting enzyme 2 is the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for entry into lung cells. Because ACE-2 may be modulated by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk of coronavirus disease 2019 (COVID-19) pneumonia. Aim This study sought to analyze the association of COVID-19 pneumonia with previous treatment with ACEIs and ARBs. Materials and methods We retrospectively reviewed 684 consecutive patients hospitalized for suspected COVID-19 pneumonia and tested by polymerase chain reaction assay. Patients were split into two groups, according to whether (group 1, n = 484) or not (group 2, n = 250) COVID-19 was confirmed. Multivariable adjusted comparisons included a propensity score analysis. Results The mean age was 63.6 ± 18.7 years, and 302 patients (44%) were female. Hypertension was present in 42.6% and 38.4% of patients in groups 1 and 2, respectively (P = 0.28). Treatment with ARBs was more frequent in group 1 than group 2 (20.7% vs. 12.0%, respectively; odds ratio [OR] 1.92, 95% confidence interval [CI] 1.23–2.98; P = 0.004). No difference was found for treatment with ACEIs (12.7% vs. 15.7%, respectively; OR 0.81, 95% CI 0.52–1.26; P = 0.35). Propensity score-matched multivariable logistic regression confirmed a significant association between COVID-19 and previous treatment with ARBs (adjusted OR 2.36, 95% CI 1.38–4.04; P = 0.002). Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged > 60 years, women, and hypertensive patients. Conclusions This study suggests that ACEIs and ARBs are not similarly associated with COVID-19. In this retrospective series, patients with COVID-19 pneumonia more frequently had previous treatment with ARBs compared with patients without COVID-19.


2014 ◽  
Vol 155 (43) ◽  
pp. 1695-1700
Author(s):  
Veronika Szentes ◽  
Gabriella Kovács ◽  
Csaba András Dézsi

Diabetes mellitus as comorbidity is present in 20–25% of patients suffering from high blood pressure. Because simultaneous presence of these two diseases results in a significant increase of cardiovascular risk, various guidelines focus greatly on the anti-hyperintensive treatment of patients with diabetes. Combined drug therapy is usually required to achieve the blood pressure target value of <140/85 mmHg defined for patients with diabetes, which must be based on angiotensin converting enzyme-inhibitors or angiotensin receptor blockers. These can be/must be combined with low dose, primarily thiazid-like diuretics, calcium channel blockers with neutral metabolic effect, and further options include the addition of beta blockers, imidazolin-l-receptor antagonists, or alpha-1-adrenoreceptor blockers. Evidence-based guidelines are obviously present in local practice. Although most of the patients receive angiotensin converting enzyme-inhibitor+indapamid or angiotensin converting enzyme-inhibitor+calcium channel blocker combined therapy with favorable metabolic effects, yet the use of angiotensin converting enzyme-inhibitors containing hidrochlorotiazide having diabetogenic potencial, and angiotensin receptor blocker fixed combinations is still widespread. Similarly, interesting therapeutic practice can be observed with the use of less differentiated beta blockers, where the 3rd generation carvediolol and nebivolol are still in minority. Orv. Hetil., 2014, 155(43), 1695–1700.


Author(s):  
Tatsiana М. Sabalenka ◽  
Volha V. Zakharava ◽  
Natallia R. Prakoshyna

Backgraund: The pathogenesis of angioedema induced by angiotensin-converting enzyme inhibitors is based on the accumulation of bradykinin as a result of angiotensin-converting enzyme blockade. The SARS-CoV-2 virus by binding to the angiotensin-converting enzyme 2 receptor, may inhibit its production, which in turn leads to an increase in bradykinin levels. Thus, infection with SARS-CoV-2 may be a likely trigger for the development of angioedema. Aims: to analyze the cases of hospitalizations of patients with angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers during the COVID-19 pandemic. Materials and methods: a retrospective analysis of the medical records of inpatient patients admitted to the Vitebsk Regional Clinical Hospital in May-December 2020 with isolated (without urticaria) angioedema while receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was performed. All patients received smears from the naso- and oropharynx for COVID-19 by polymerase chain reaction. Results: there were admitted 15 patients (9 men and 6 women) aged 44-72 years for emergency indications, which was 53.6% among all patients with isolated angioedema. In two cases, a concomitant diagnosis of mild COVID-19 infection was established with the predominance symptoms of angioedema in the clinical picture with localization in the face, tongue, sublingual area, soft palate. All patients had a favorable outcome of the disease. Conclusions: patients with аngiotensin-converting enzyme inhibitor-induced angioedema may need to be hospitalized to monitor upper respiratory tract patency. There were cases of a combination of аngiotensin-converting enzyme inhibitor-induced angioedema and mild COVID-19 infection. Issues requiring additional research: the effect of SARS-CoV-2 infection on the levels of bradykinin and its metabolites; the trigger role of COVID-19 infection in the development of angioedema in patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers; recommendations for the management of patients with аngiotensin-converting enzyme inhibitor-induced angioedema and a positive result for COVID-19.


Medicina ◽  
2007 ◽  
Vol 43 (2) ◽  
pp. 131
Author(s):  
Irena Milvidaitė ◽  
Dalia Lukšienė ◽  
Birutė Šlapikienė ◽  
Marija Babarskienė ◽  
Valdas Liukaitis ◽  
...  

The aim of this work was to assess the quality of pharmacological treatment in patients within one year after acute myocardial infarction. Material and methods. We performed a prospective survey of 985 consecutive patients with acute myocardial infarction who were treated in the Clinic of Cardiology of Kaunas University of Medicine Hospital in 2004. About half of patients were hospitalized from different regions of Lithuania. According to the follow-up protocol, an information on 514 patients and their used treatment within 13.8±3.2 months after myocardial infarction were collected by letter with questionnaire. Results. Beta-adrenoblockers, angiotensin-converting enzyme inhibitors, and antithrombotic drugs were the most drug used (76%, 74%, and 76%, respectively) in patients following myocardial infarction. Most of the patients used a three-drug combination (36.8%), more rarely – two-drug (24.1%) or four-drug complex (19.8%). One drug was used only in 12.1% of cases; 7.2% of patients did not use any cardiac drugs. Betaadrenoblocker with angiotensin-converting enzyme inhibitor was the most common (40.3%) used drug combination in patients on two drug complex. The combination of beta-adrenoblocker, angiotensin-converting enzyme inhibitor, and antithrombotics was more frequently used in patients on three drug complex. The combination of two or three cardiac drugs with statin was used in several cases (1.6–10.3%). Conclusions. These findings underscore that the use of beta-adrenoblockers, angiotensin-converting enzyme inhibitors, and antithrombotics was high (about 75%) in patients during the first year after myocardial infarction, and the combination of these three drugs was used more commonly. The discordance between existing guidelines for statin use after myocardial infarction and current practice was determined in patients following myocardial infarction.


2016 ◽  
Vol 84 (12) ◽  
Author(s):  
Erik Rupnik ◽  
Stojan Kariž ◽  
Črtomir Iglič ◽  
Mihaela Zidarn

Background. Angioedema is a rare but potentially very serious complication of treatment with angiotensin converting enzyme inhibitors (ACEI). Angioedema is due to the accumulation of bradykinin, because angiotensin converting enzyme is the key enzyme for its degradation.Case reports. We present two patients with life-threatening angioedema while taking ACEI. Both patients had already had episodes of angioedema. Angioedema didn't respond to adrenaline. In both patients intubation was difficult.Conclusion. In the acute phase of angioedema due to ACEI it is necessary to protect the airways. Bradykinin receptor inhibitors shorten the duration of episodes of angioedema. In the long term it is essential to permanently avoid ACEI.


Author(s):  
B. Raghuveer ◽  
Merugu Padma Latha

Background: Hyponatraemia is commonly associated with disease conditions or as an adverse effect of certain drugs. Angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blockers are drugs that have been commonly prescribed for the treatment of hypertension and cardiac diseases. It has become important to evaluate and investigate the incidence of hyponatremia on consumption of these drugs. The study aims to observe the incidence of the adverse drug reaction-hyponatraemia in hypertensive patients on ACEI therapy.Methods: The patient’s data was collected using proforma following which they were randomized into three groups receiving enalapril, ramipril and captipril. Serum sodium levels were assayed by direct ISE method. Statistical analysis of data was performed using SPSS version 21.0. Chi-square test was used to compare occurrence of hyponatremia in the patients on ACEI. P<0.5 was considered as statistically significant.Results: Among all, 26 (52%) of the study population administered with ACEI developed hyponatremia. Predisposition to develop hyponatremia was high in males compared to females. The study also revealed that Enalapril had a higher association with hyponatremia compared to other drugs.Conclusions: Hyponatremia was induced in 52% of patients taking ACEI. This study revealed that monitoring of serum sodium levels in the patients with ACEI administration will help to prevent unexpected adverse reactions like hyponatremia.


2009 ◽  
Vol 22 (5) ◽  
pp. 508-512
Author(s):  
Sheryl J. Herner ◽  
Shilpa A. Kinikar ◽  
Lori A. Miyashiro ◽  
Sarah J. Billups ◽  
Toyin S. Tofade

Angiotensin-converting enzyme inhibitors (ACE-Is) are a cornerstone of therapy with proven morbidity and mortality benefit in many disease states. The unpredictable, bothersome cough that occurs in 15% to 41% of patients oftentimes leads to noncompliance or discontinuation. Management of ACE-I-induced cough remains controversial. The authors’ objective was to determine whether patients experiencing an ACE-I-induced cough could be successfully switched to a different ACE-I without recurrent cough. A total of 10 participants deemed to have ACE-I-induced cough were enrolled in an interventional case series to assess whether they could tolerate rechallenge with an alternative ACE-I. During phase 1, ACE-I therapy was stopped for up to 4 weeks to allow the cough to resolve. During phase 2, participants were rechallenged with an alternative ACE-I and followed for 4 months. Of the 10 participants who consented to enroll, 6 were rechallenged with a second ACE-I. Cough recurred in 4 of these within 1 week (5-7 days), whereas 2 participants continued ACE-I therapy cough-free. Results suggest that a small percentage of patients with ACE-I-induced cough tolerate an alternative ACE-I. For patients with a true ACE-I-induced cough who are motivated to continue an ACE-I, a trial of a second ACE-I may be worthwhile.


2014 ◽  
Vol 13 (1) ◽  
pp. 64-68
Author(s):  
L. L. Kirichenko ◽  
S. V. Gatsura ◽  
A. N. Golosova ◽  
K. V. Ovsyannikov ◽  
O. V. Budik ◽  
...  

The paper focuses on the justification for preferential administration of antihypertensive combination therapy. Pharmacotherapeutic features of starting the treatment with a combination of angiotensin-converting enzyme inhibitors (ACEI) and calcium antagonists (AC) are reviewed. The authors also present the latest evidence on the ACEI/AC combination effects on such vascular parameters as microcirculation and endothelial dysfunction.


2018 ◽  
Vol 12 (3) ◽  
pp. 556-558 ◽  
Author(s):  
Marijana Rincic Antulov ◽  
Runar B. Båtevik

Angiotensin-converting enzyme inhibitors (ACEI) are widely used to treat hypertension and congestive heart failure. A rare side effect of ACEI therapy is angioedema, which in very rare cases may present as gastrointestinal angioedema (GA). A 45-year-old female presented with suddenly occurring diffuse abdominal pain. Imaging studies revealed small bowel wall edema. The patient had been on ACEI therapy for the last 6 months. The therapy was withdrawn, and the patient recovered quickly. There is no specific diagnostic test to confirm ACEI-induced GA, but symptoms usually regress completely after therapy discontinuation. An early diagnosis of ACEI-induced GA is important to avoid invasive diagnostic investigations and even laparotomy.


1996 ◽  
Vol 90 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Michael A. Bennett ◽  
Herbert Thurston

1. This study was designed to examine the effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in Goldblatt two-kidney, one-clip hypertensive rats. Four weeks after clipping, hypertensive and sham rats were treated with either perindopril (1 mg day−1 kg−1) or quinapril (3 or 30mg day−1 kg−1). After 6 weeks mesenteric resistance arteries were mounted in a myograph for measurements of vascular structure. The endothelium-dependent relaxation response to acetylcholine and bradykinin and the response to the nitric oxide donor sodium nitroprusside were recorded. 2. All treatment regimes lowered the blood pressure and reversed both cardiac and resistance artery hypertrophy. Two-kidney, one-clip rats treated with quinapril showed a dose-dependent reduction in media cross-sectional area and media to lumen ratio. 3. Hypertension of 10 weeks' duration was associated with an impaired endothelium-dependent relaxation response to acetylcholine and bradykinin. Treatment with perindopril and either dose of quinapril prevented the development of impaired endothelium-dependent relaxation but had no effect on the response to sodium nitroprusside. Treatment had no effect on endothelium-dependent relaxation in sham rats. 4. Angiotensin-converting enzyme inhibitor treatment is effective in normalizing blood pressure and cardiovascular structural changes. Angiotensin-converting enzyme inhibitor treatment prevented the development of impaired endothelium-dependent relaxation to both acetylcholine and bradykinin. The ability of angiotensin-converting enzyme inhibitors to reverse cardiovascular structural changes and prevent the development of abnormal endothelium-dependent relaxation may contribute to the overall effect of this type of antihypertensive drug.


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