enalapril and Angioedema

Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Chronic Disease; Drug Combinations; Enalapril; Heart Failure; Humans; Risk Factors; Tetrazoles; Valsartan

Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.

Topics: Abnormalities, Drug-Induced; Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Biphenyl Compounds; Bradykinin; Contraindications; Drug Combinations; Drug Costs; Drug Synergism; Enalapril; Enzyme Inhibitors; Female; Follow-Up Studies; Heart Failure; Humans; Hyperkalemia; Hypertension; Kidney; Multicenter Studies as Topic; Natriuretic Peptides; Neprilysin; Pregnancy; Prodrugs; Prospective Studies; Pyridines; Randomized Controlled Trials as Topic; Stroke Volume; Tetrazoles; Thiazepines; Valsartan

Topics: Algorithms; Anaphylaxis; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Enalapril; Humans; Hypertension; Lip Diseases; Male; Middle Aged; Recurrence; Tongue Diseases

Topics: Anaphylaxis; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertension; Male; Middle Aged; South Africa

A case of angioedema caused by enalapril, undiagnosed for 5 years was presented. Enhanced blood and tissue eosinophilia shown in nasal smear was observed. In addition increased activity of coagulation system was shown manifested by enhance of concentration of Hageman factor and cardiolipin antibodies IgM and IgA isotype. The role of coagulation, complement and fibrinolysis systems in pathogenesis of ACE-inhibitors induced angioedema was discussed. The influence of bradykinin on activity of eosinophils was analyzed.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Eosinophilia; Humans; Male

The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning.

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Australia; Enalapril; Europe; Humans; Lisinopril; Sweden

We report the case of a patient with an angioedema during therapy with enalapril and tramadol. The most likely cause of the adverse effect if the ACE-inhibitor enalapril. A rechallenge with the ACE-inhibitor is dangerous and should not be performed. Because of its potential risks, further treatment with ACE-inhibitors should be avoided in all patients with ACE-inhibitor-induced angioedema. Possible therapeutic alternatives include diuretics, beta-blocking agents, calcium antagonists and also angiotensin II receptor antagonists.

Topics: Analgesics, Opioid; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Humans; Male; Tramadol

To review reports of angiooedema and urticaria associated with angiotensin converting enzyme inhibitors (ACEI) in the New Zealand Centre for Adverse Reactions Monitoring and Intensive Medicines Monitoring Programme (IMMP) database.. Adverse reaction reports describing angiooedema and/or urticaria between April 1981 and December 1994 were examined. Captopril, enalapril and lisinopril were intensively monitored on the IMMP during this period.. Of a total of 116 reports there were 68 reports of angiooedema and 37 of urticaria alone and 11 where angiooedema and urticaria occurred in the same patient. The total number of patients is unknown, but cohorts of patients on captopril, enalapril and lisinopril in the IMMP were 16342, 25686 and 11235, totalling 53263 patients. There were 63 reports of angiooedema/urticaria in patients monitored on the IMMP, giving a reported rate of 1.2/1000 (0.9-1.5). Forty seven reactions occurred between 3 weeks and 4 years after commencement of therapy. Severe angiooedema occurred in 9 patients with early-onset angiooedema and 6 with late-onset angiooedema. There were no deaths. Seventeen patients had up to 12 episodes before diagnosis. Angiooedema/ urticaria occurred without gender preference. Although a dose relationship was not apparent, 3 patients developed angiooedema or urticaria after an increase in dose.. Although reactions are more common shortly after initiation of ACEI therapy, late onset reactions may be less well recognised. Clinicians should be reminded, and ACEI data sheets should emphasise, that onset may be delayed for weeks or months, that patients may have multiple episodes with long symptom free intervals, and that angiooedema may occur with or without urticaria.

Topics: Adverse Drug Reaction Reporting Systems; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Drug Monitoring; Enalapril; Humans; Lisinopril; Urticaria

We report the case of a patient who, 9 months after initiation of enalapril and hydrochlorothiazide combination treatment for hypertension, developed angio-oedema with near fatal outcome. Our patient was successfully intubated using a flexible bronchofiberoscope. This case demonstrates that patients given an angiotensin-converting enzyme (ACE) inhibitor may develop serious facial and laryngeal swelling even several months after the initiation of treatment. The occurrence of even mild swelling should lead to prompt cessation of the drug. Patients with incipient ACE inhibitor-related angio-oedema should, without any delay, be referred to hospital for emergency treatment.

Topics: Angioedema; Enalapril; Humans; Intubation, Intratracheal; Male; Middle Aged

The authors reports an unrecognised secondary effect, but perhaps not as rare as has been thought, of enalapril: the acute abdomen. Three similar cases have previously been reported. The underlying mechanism is probably the inhibition of degradation of tissue kinins to inactive peptides as in subcutaneous and/or submucous angioneurotic oedema. Todate, this secondary effect has not been reported with other angiotensin converting enzyme inhibitors. The relationship between the acute abdomen and angioneurotic oedema with primary hyperaldosteronism is discussed.

Topics: Abdomen, Acute; Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Contraindications; Enalapril; Female; Humans

Angioedema of the face and neck is a rare but potentially fatal complication of angiotensin-converting enzyme inhibitor (ACEI) use. We retrospectively reviewed five cases of ACEI angioedema seen at our institution over the past 2 1/2 years. Four of the cases occurred with enalapril and one with lisinopril. Onset of symptoms varied from two days to ten months. Importantly, three of the five patients had been receiving medication three months or longer, suggesting clinicians must consider this complication during long-term administration of these agents. Three of the five patients were markedly obese, had a history of previous face and neck surgery, or had been intubated in the past. Thus, we propose that previous manipulation or trauma of the upper airway, perhaps resulting in airway narrowing, may represent a risk factor for upper airway obstruction secondary to ACEI-induced angioedema.

Topics: Adult; Aged; Aged, 80 and over; Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Causality; Dipeptides; Enalapril; Female; Humans; Lisinopril; Male; Middle Aged; Obesity; Retrospective Studies; Time Factors

Angiotensin-converting enzyme inhibitors are a widely used antihypertensive modality. While they have a favorable side effect profile, there is a .1% to .2% incidence of potentially life threatening angioedema. The edema usually presents in the head and neck, especially the face, lips, tongue, and glottis. Patients may initially be treated with standard anti-allergic therapy; however, the situation may dictate a more aggressive therapeutic approach. The authors present the case of a patient who presented with angioedema 18 times over a 3-year period to qualified emergency physicians before the correct diagnosis of angiotensin-converting enzyme inhibitor-induced angioedema was made. Despite recent literature on the subject, there appears to be a lack of familiarization among emergency department physicians regarding this relatively common adverse effect.

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Emergency Service, Hospital; Enalapril; Humans; Male

We present the cases of two patients with angiotensin-converting enzyme (ACE) inhibitor-induced angioedema that required intubation for life-threatening airway compromise. This side effect has been previously reported with all ACE inhibitors, but its incidence and potential for a fatal outcome may not be fully appreciated. A review of the literature reveals 227 reports of this reaction with an overall incidence of approximately 0.1% to 0.2%. The etiology is nonimmunogenic and thought to be related to accentuated bradykinin activity. There is no clinical profile that identifies patients at increased risk for this side effect. There are unique clinical characteristics to this idiosyncratic reaction: angioedema may suddenly occur even though the drug has been well tolerated for months or years; symptoms may regress spontaneously while the patient continues the medication, erroneously prompting an alternative diagnosis; the pathology has a special predilection for the tongue, a circumstance that renders orotracheal and nasotracheal intubation difficult; symptoms may progress rapidly despite aggressive medical therapy, necessitating emergency airway procedures; and a rebound phenomenon following successful medical therapy has been described. We recommend intensive medical treatment before angioedema is severe enough to thwart standard methods to ensure a protected airway. Once even minor angioedema is attributed to an ACE inhibitor, an alternative class of antihypertensive medication should be chosen. Individuals with a history of idiopathic angioedema probably should not be given ACE inhibitors.

Topics: Angioedema; Captopril; Enalapril; Female; Humans; Male; Middle Aged

This report reviews the tolerability profile of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, in the treatment of patients with congestive heart failure. Data have been collected from 546 patients treated with enalapril for up to 9 months in clinical trials other than the Cooperative North Scandinavian Enalapril Survival Study. Results in patients treated with enalapril (n = 193) or placebo (n = 195) in double-blind, controlled clinical trials show that the incidences of death, serious adverse experiences, and adverse experiences requiring discontinuation of double-blind therapy, as well as the overall incidence of such experiences, were similar in the 2 groups. However, certain adverse experiences that are related to the mechanism of action of ACE inhibitors were seen more often after enalapril than after placebo treatment. Dizziness and hypotension were the most frequent adverse experiences reported in patients with heart failure treated with enalapril. The most frequent laboratory adverse experiences were increases in blood urea nitrogen and serum creatinine levels. hyperkalemia was also seen in patients receiving enalapril. It is possible to identify patients at risk of these experiences before initiating treatment with enalapril and to take certain measures (such as withholding or reducing the dose of diuretic drugs and discontinuing potassium supplements or potassium-sparing diuretic drugs) to reduce the likelihood that hypotension, increases in blood urea nitrogen and serum creatinine levels, or hyperkalemia will occur. Angioedema, a recognized adverse effect of ACE inhibitors, was not seen in the clinical trials reviewed here. Cough , another recognized adverse effect of these agents, was seen infrequently and rarely resulted in the discontinuation of enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angioedema; Blood Urea Nitrogen; Cough; Creatinine; Drug Tolerance; Enalapril; Heart Failure; Humans; Hyperkalemia; Hypotension

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Heart Failure; Humans; Hypertension

PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest.. Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg. The study design incorporated two wash-out periods (~36 h each) to minimize any potential risk of angioedema due to overlapping ACE and neprilysin inhibition. Suspected cases of angioedema were reported to, and blindly adjudicated by, an independent angioedema adjudication committee (AAC).. Of the 10,513 patients entering the enalapril run-in, 9419 entered the sacubitril/valsartan run-in and 8432 received double-blind treatment. Overall, 148 suspected angioedema events occurring in 144 patients were reported to AAC, with one event reported during screening period. Of the remaining 147 events, 54 were confirmed as angioedema by AAC. A confirmed event was experienced by 15 (0.14%) and 10 (0.11%) patients, during the enalapril and sacubitril/valsartan run-ins, respectively, and by 10 (0.24%) and 19 (0.45%) patients in the corresponding randomized arms during the double-blind phase. The frequency of confirmed angioedema was higher in black patients. Most events were mild. Only five patients required hospitalization and none required mechanical airway support.. The number of confirmed angioedema events in PARADIGM-HF was low and there was no-marked excess risk of angioedema with sacubitril/valsartan versus enalapril.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Allergic Agents; Biphenyl Compounds; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Risk Assessment; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Enalapril; Female; Humans; Kininogen, High-Molecular-Weight; Lisinopril; Male; Middle Aged; Peptide Fragments; Quinapril

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiovascular Diseases; Cough; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure, Systolic; Hospitalization; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Neprilysin; Renal Insufficiency; Tetrazoles; Valsartan

Angioedema is a rare but potentially serious adverse event of angiotensin-converting enzyme inhibitor therapy. However, no prospective, controlled studies have reported on its incidence and clinical characteristics.. We studied the occurrence of angioedema in a randomized, double-blind, controlled trial of 12 557 persons with hypertension treated with enalapril maleate, 5 to 40 mg/d, using a prospective ascertainment and adjudication of angioedema by an expert committee.. Angioedema occurred in 86 (0.68%) of the subjects. Stepwise logistic regression identified black race (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.72-4.82), history of drug rash (OR, 3.78; 95% CI, 1.80-7.92), age greater than 65 years (OR, 1.60; 95% CI, 1.02-2.53), and seasonal allergies (OR, 1.79; 95% CI, 1.06-3.00) as independent risk factors for angioedema. The incidence of angioedema was higher after initiation of therapy (3.6/1000 patients per month) and declined to 0.4/1000 patients per month. Treatment was not given in 44 (51%) of the cases; antihistamines were administered in 35 (41%); corticosteroids, in 20 (23%); and epinephrine, in 1 (1%). Two patients were hospitalized but none had airway compromise.. Enalapril-related angioedema is uncommon. Although it is most likely to occur early after initiation of therapy, it may occur at any time. It is more likely to occur in black patients, those older than 65 years, and those with a history of drug rash or seasonal allergies. Fatal angioedema or angioedema requiring airway protection did not occur in this study.

Topics: Adult; Aged; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Incidence; Logistic Models; Male; Middle Aged; Risk Factors

Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril.. The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP.. Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P < 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated.. Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angioedema; Antihypertensive Agents; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Male; Metalloendopeptidases; Middle Aged; Pyridines; Thiazepines; Treatment Outcome

In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a double-blind fashion to 6797 participants with ejection fraction < or = 0.35. During 40 months' average follow-up, 28.1% of participants randomized to enalapril reported side effects compared with 16.0% in the placebo group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms related to hypotension (14.8% vs 7.1%, p < 0.0001), azotemia (3.8% vs 1.6%, p < 0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001), hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p < 0.05). Side effects resulted in discontinuation of blinded therapy in 15.2% of the enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus enalapril is well tolerated by patients with LVD; however, hypotension, azotemia, cough, fatigue, and other side effects result in discontinuation of therapy in a significant minority of patients.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Enalapril; Fatigue; Female; Follow-Up Studies; Heart Failure; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Sex Factors; Time Factors; Uremia; Ventricular Dysfunction, Left

Inhibitors of angiotensin converting enzyme may cause angio-oedema. To see if this might be due to potentiation of the tissue effects of bradykinin the thickness of weals raised by intradermal injection of saline or 1, 3, or 10 micrograms bradykinin was measured before and three times after single doses of captopril, enalapril, or placebo. The mean thickness increased with increasing doses of bradykinin. It did not change with time after the administration of placebo or captopril but increased from 0.61 mm before enalapril to 1.12 mm two and a half hours and 1.06 mm five hours after enalapril was given. Five subjects flushed when given bradykinin after captopril and four after enalapril, but none flushed when given bradykinin after placebo. It is concluded that angiotensin converting enzyme inhibitors potentiate the effects of intradermal bradykinin in vivo and that this may partially explain why they cause angio-oedema in susceptible patients.

Topics: Adult; Angioedema; Bradykinin; Captopril; Dose-Response Relationship, Drug; Enalapril; Humans; Middle Aged; Skin; Time Factors

Topics: Angioedema; Antihypertensive Agents; Enalapril; Humans; Respiratory System

Angiotensin converting enzyme inhibitors (ACEi) are widely used for the treatment of multiple conditions such as hypertension, heart failure and chronic kidney disease. Angioedema is a rare but potentially fatal complication of ACEi use and unilateral tongue edema is a very rare presentation. We report a case of a 55-year-old man, with a history of hypertension, on enalapril for three years, who presented to the hospital with unilateral tongue swelling, without airway compromise. Other causes were excluded and the diagnosis of angioedema due to enalapril was established. The patient was discharged with discontinuation of ACEi with total resolution of symptoms and without relapse after several months. Although very rare, unilateral tongue swelling should be considered in the presentation of angioedema associated with ACEi. Tight surveillance is important to prevent fatal complications such as airway obstruction. ACEi discontinuation is crucial to avoid clinical relapse.. Os inibidores da enzima de conversão da angiotensina (iECAs) são amplamente usados no tratamento de várias patologias como a hipertensão arterial, insuficiência cardíaca e doença renal crónica. O angioedema é uma complicação rara mas potencialmente fatal desta medicação e o edema unilateral da língua é uma apresentação rara desta condição. Reportamos o caso de um homem de 55 anos com hipertensão, medicado há três anos com enalapril, que à admissão hospitalar apresentava edema unilateral da língua sem compromisso da via aérea. Outras etiologias foram excluídas, tendo-se assumido o diagnóstico de angioedema associado ao enalapril. Após suspensão do iECA os sintomas diminuíram progressivamente, sem recorrência do quadro após vários meses. Ainda que raro, o edema unilateral da língua deve ser considerado na apresentação do angioedema associado a iECA. É importante uma vigilância apertada para prevenir complicações fatais, tais como a obstrução da via aérea. A descontinuação do iECA é fundamental para evitar recidiva.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Edema; Enalapril; Humans; Hypertension; Male; Middle Aged; Mouth Diseases; Recurrence; Tongue; Tongue Diseases

Topics: Abdominal Pain; Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Glomerulosclerosis, Focal Segmental; Humans; Hypertension; Jejunal Diseases; Jejunum; Tomography, X-Ray Computed

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Factor XII; Humans; Male; Mutation

Cough and upper airway angioedema are well-recognized adverse reactions of angiotensin-converting enzyme inhibitor (ACEI) therapy. Visceral angioedema is an infrequent and often unrecognized complication of ACEI therapy. We describe a patient in whom the diagnosis was delayed for > 2 years. A 60-year-old woman with hypertension on treatment with enalapril presented with complaints of abdominal pain and diarrhea for 2 days. Physical examination was significant for diffuse abdominal tenderness and hypotension. Laboratory data were normal except for leukocytosis and elevated creatinine. Computed tomography (CT) of the abdomen showed diffuse small bowel wall thickening. ACEI-induced visceral angioedema was considered, enalapril was discontinued and supportive care was provided. Patient's symptoms and CT appearance improved 48 and 72 hours, respectively, after stopping enalapril. She remained symptom-free 1 year after discharge.

Topics: Abdominal Pain; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Middle Aged; Radiography, Abdominal; Tomography, X-Ray Computed; Viscera

Angioedema orolingual tras trombolisis intravenosa.

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bradykinin; Capillary Permeability; Cerebral Cortex; Drug Synergism; Drug Therapy, Combination; Enalapril; Female; Fibrinolytic Agents; Histamine Antagonists; Humans; Hypertension; Infarction, Middle Cerebral Artery; Infusions, Intravenous; Thrombolytic Therapy; Tissue Plasminogen Activator

The patient, a hypertensive man, 77 years of age, presented at a local rural hospital after noticing increasing swelling of his tongue, leading to difficulty talking and then difficulty breathing. These symptoms developed over about 2 hours and he had not noted any rash. He had been on enalapril 10–20 mg for 23 years. He had also been on hydrochlorothiazide and atorvastatin for some years. He had not taken any non-steroidal anti-inflammatory drugs (NSAIDs) before the swelling developed.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Male; Tongue Diseases

Angiotensin-converting enzyme inhibitors are leading cause of drug-induced angioedema, with incidence of 0.1 to 0.2%. The angioedema is not of immune nature; in predisposed individuals it is caused by accumulation of vasoactive mediators due to reduced activity of angiotensin-converting enzyme.. We presented a 63-year old male patient suffering from hypertension and chronic obstructive pulmonary disease, who had developed two episodes of angioedema during a 5-year long therapy with enalapril. The first episode happened after three, and the second after five years of the therapy. On both occasions, the patient was admitted to the hospital and tracheotomy was avoided in the last moment.. Long-term therapy with angiotensin-converting enzyme inhibitors could be associated with delayed angioedema, especially in patients with inflammation of airways caused by infection or chronic irritation.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertension; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Male; Tongue Diseases

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Child, Preschool; Diuretics; Drug Therapy, Combination; Enalapril; Furosemide; Humans; Nicardipine; Tongue; Treatment Outcome; Withholding Treatment

A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema.

Topics: Adrenergic beta-Antagonists; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Enalapril; Female; Humans

Angioedema remains a rare but potentially life-threatening complication of angiotensin-converting enzyme (ACE) inhibitor use. Most presentations involve edema of the tongue or oral pharynx. However, in recent years, a visceral form involving the gastrointestinal tract also has been described. We present the case of a rare presentation of esophageal and retropharyngeal edema related to ACE inhibitor use. A review of ACE inhibitor-related angioedema is also presented.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Deglutition Disorders; Enalapril; Esophageal Diseases; Female; Humans; Middle Aged; Somatosensory Disorders; Tomography, X-Ray Computed

A 59-year-old woman treated chronically with enalapril, an angiotensin-converting enzyme inhibitor (ACE-I) presented with difficult swallowing and speaking. Although her symptoms were clinically consistent with an adverse angioedema reaction to the ACE-I, initial imaging was not entirely consistent with our conceptual understanding of angioedema. This case report will discuss the myriad possible imaging presentations of this disease, as well as the differential diagnosis for this atypical manifestation of ACE-I-induced angioedema.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diagnosis, Differential; Enalapril; Female; Humans; Middle Aged; Pharyngeal Diseases; Radiography

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans

Two cases of penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angio-tensin II receptor blockers are reported.. The first case of penile angioe-dema involved a 68-year-old man who arrived at the emergency department (ED) with a 2-12-hour history of penile swelling occurring three days after initiation of irbesartan in addition to longstanding lisinopril therapy. All parts of the physical examination were normal, except for the genital examination. The patient's penis was edematous at midshaft only and was nontender with normal skin coloring. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking both lisinopril and irbesartan, and symptoms resolved within 48 hours with supportive care alone. In the second case, a 48-year-old man arrived at the ED complaining of penile swelling over the previous two days. Enalapril had been initiated one month before his arrival at the ED. The patient's penis was nontender and edematous at midshaft. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking enalapril, given oral prednisone 60 mg, and asked to continue his prednisone for five days after discharge. The swelling resolved within two days of stopping enalapril, and he had no further episodes of penile swelling. Neither patient was rechallenged with the offending medications.. Penile angioedema was reported in two patients. The first case involved a patient receiving both lisinopril and irbesartan. The second patient was receiving enalapril only.

Topics: Aged; Angioedema; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Enalapril; Glucocorticoids; Humans; Irbesartan; Lisinopril; Male; Middle Aged; Penis; Prednisone; Tetrazoles

A 40-year-old woman presented with 3 episodes of abdominal pain. Abdominal ultrasound demonstrated edema of the small bowel. Double-balloon enteroscopy (DBE) showed diffuse swelling of the small intestine, petechial bleeding in the jejunum, and focal inflammation of the ileum. Pain and small bowel edema resolved spontaneously within 48 h during each episode. Review of the patient's history revealed that she had been started on enalapril for arterial hypertension two weeks before her first episode. Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the small bowel was suspected and enalapril was discontinued. The patient remained symptom-free after discontinuing the ACE inhibitor. Review of the literature reveals only 11 similar cases with this case being the first to apply DBE to visualize macroscopic alterations to the small intestine. Angioedema of the intestine is a diagnostic pitfall frequently leading to prolonged diagnostic procedures and is a potential cause for abdominal pain in patients taking ACE inhibitors.

Topics: Abdominal Pain; Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Diagnosis, Differential; Enalapril; Endoscopy, Gastrointestinal; Female; Humans; Hypertension; Intestine, Small; Ultrasonography

Angioedema is a rare but potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. A patient who presented with facial angioedema four months after initiating antihypertensive treatment with enalapril is described. Angioedema due to angiotensin-converting enzyme inhibitors usually appears during the first weeks of treatment. Late-onset angioedema is often unrecognized.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Humans; Hypertension; Male; Time Factors

Topics: Angioedema; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Aspirin; Drug Hypersensitivity; Enalapril; Female; Humans; Hypertension; Middle Aged; Propafenone; Urticaria

Topics: Aged; Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diagnosis, Differential; Drug Combinations; Drug Hypersensitivity; Dyspnea; Enalapril; Heart Arrest; Humans; Hydrochlorothiazide; Male; Tongue Diseases

The following case reports describe the clinical presentation, diagnosis and management of two patients who attended Liverpool University Dental Hospital with rapidly increasing swelling of the lips and tongue. Both patients were suffering from angioedema and were taking an angiotension-converting enzyme (ACE) inhibitor (ACEI). A provisional diagnosis of ACEI-induced angioedema was made. An intramuscular injection of chlorpheniramine maleate was given to both patients and they were immediately transferred to the local accident and emergency department. These cases illustrate the potential role of the general dental practitioner in the early recognition and management of this potentially life-threatening condition.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Chlorpheniramine; Enalapril; Histamine H1 Antagonists; Humans; Lip Diseases; Male; Perindopril; Tongue Diseases

To describe a case of intermittent visceral angioedema associated with long-term enalapril use.. A 72-year-old white woman developed severe abdominal pain as a result of visceral angioedema associated with long-term enalapril therapy. She had been taking enalapril 20 mg/day for 9 years prior to the first reported episodes of abdominal pain.. Visceral angioedema associated with angiotensin-converting enzyme (ACE) inhibitors is a documented adverse effect. However, onset of symptoms has never been reported after 9 years of use. Not until 2 years after initial presentation were the symptoms correlated to enalapril administration. Since discontinuation of enalapril, the patient has not reported any symptoms for >2 years. An objective causality assessment categorized this adverse drug event as a result of enalapril as possible.. Development of angioedema from ACE inhibitors occurs in <1% of the population. Limited case reports have identified intermittent visceral angioedema from ACE inhibitors. However, it is important to recognize that this adverse effect can also occur in patients who have been treated with ACE inhibitor therapy for several years.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Viscera

We describe a patient who had recurrent life-threatening episodes of isolated macroglossia due to the use of an angiotensin-converting enzyme (ACE) inhibitor. No associated facial, labial, pharyngeal, or laryngeal edema was noted. Aggressive treatment with epinephrine, steroids, and antihistamines resulted in rapid resolution of the tongue swelling and respiratory distress. Recurrent isolated angioedema of the tongue is an extremely rare variant of ACE inhibitor-related angioneurotic edema. The widespread use of ACE inhibitors mandates a special awareness by physicians of this potentially life-threatening yet treatable side effect.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hypertension; Macroglossia; Male

Angiotensin-converting enzyme (ACE) inhibitors are associated with angioedema episodes that are potentially life-threatening. Few data are available on the outcome of patients reporting this adverse effect when they are switched to another drug. Scattered reports of angioedema associated with angiotensin II receptor blocker (ARB) use question the safety of using these drugs in patients with ACE inhibitor-related angioedema. We describe 64 consecutive patients with ACE inhibitor-related angioedema, the outcome after discontinuing this treatment, and the safety of using ARBs.. Retrospective analysis of 64 consecutive patients (January 1993 to June 2002) presenting with angioedema onset while receiving treatment with an ACE inhibitor.. Patients were recommended to stop ACE inhibitor use, substituting it upon advice of the physician. Fifty-four patients were available for follow-up (median follow-up, 11 months; range, 1-80 months): 26 had switched to an ARB, 14 to a calcium antagonist, and 14 to other antihypertensive drugs. Angioedema disappeared or drastically reduced upon withdrawal of the ACE inhibitor in 46 patients (85%). For the remaining 8 patients, angioedema was due to a cause other than ACE inhibitor use in 2; angioedema persisted independent of the treatment and without apparent cause (idiopathic angioedema) in 4; angioedema persisted after switching to an ARB and disappeared upon its withdrawal in 2.. Stopping ACE inhibitor use without further assessments is a successful measure in the large majority of patients developing angioedema while taking this drug. Only a small percentage of patients with ACE inhibitor-related angioedema continue with this symptom when switched to an ARB.

Topics: Aged; Aged, 80 and over; Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Middle Aged; Retrospective Studies

While ACE-inhibitors have proven their prognostic benefit in many hypertension studies, a new approach has been proposed by inhibiting neutral endopeptidase, which degrades natriuretic peptides. The combined inhibition of ACE and endopeptidase was named "vasopeptidase-inhibition" and tested in several trial. Though effective in lowering blood pressure, a superiority to ACE-inhibitors alone could not be shown. A potentially serious side effect was the increased incidence of angioneurotic edema, which led to a complete stop in the development of this pharmaceutical strategy.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Drug Combinations; Enalapril; Endopeptidases; Humans; Hypertension; Pyridines; Thiazepines; Treatment Outcome

Isolated visceral angioedema is an extremely rare complication of angiotensin-converting enzyme inhibitors (ACEIs). We report the first known case of ACEI-associated visceral angioedema occurring in a liver transplant recipient who presented with acute-onset abdominal pain, nausea, vomiting, diarrhea, radiologic findings of small bowel edema, and ascites. Heightened awareness of the phenomenon of isolated ACEI-associated visceral angioedema is necessary given the increasing use of these medications for treating hypertension related to calcineurin inhibitors and the need to avoid unnecessary surgical or diagnostic interventions in solid-organ transplant recipients.

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Hypertension; Liver Transplantation; Tomography, X-Ray Computed; Viscera

A case of severe late-onset angioedema with life-threatening upper airway obstruction, related to ACE inhibitor treatment is presented. The patient was a middle-aged man treated for hypertension, presenting with stridor requiring intubation, which was difficult. The patient developed cardiac arrest but was successfully resuscitated, after intubation. Etiology, risk factors, and treatment, with special attention to air way management, are discussed.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Humans; Male; Middle Aged; Tomography, X-Ray Computed

Topics: Aged; Angioedema; Angiogenesis Inducing Agents; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Immunoglobulin E; Serine Endopeptidases; Tryptases

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Hypertension; Tomography, X-Ray Computed; Tongue Diseases

Angiotensin converting enzyme inhibitors like captopril, enalapril, lisinopril, trandopril and ramipril may rarely induce a life threatening angioedema. We present two cases of severe angioedema induced by enalapril and ramipril along with possible precipitating factors observed in these patients. The importance of prompt recognition and early management of such cases is emphasized.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Epinephrine; Female; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Precipitating Factors; Ramipril; Sympathomimetics

Reporting a case of adverse pharmacological reaction to Enalapril ingestion with severe respiratory obstruction, as outcome of lingual edema owing to tongue edema. The incidence of this condition among the population consumers of this drug accounts more or less to 1 per thousand. The cases appear at the fifth life's decade in the black population, even at the first month of treatment is when the adverse course appears and can produce a severe respiratory obstruction.

Topics: Aged; Aged, 80 and over; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Enalapril; Female; Humans; Hypertension; Injections, Intravenous; Steroids; Tongue Diseases

Angioedema and cough are known side effects of angiotensin-converting enzyme (ACE) inhibitors. Angiotensin-converting enzyme is a potent inhibitor of kinase II, which facilitates the breakdown of bradykinin. An increase in bradykinin levels results in continued prostaglandin E2 synthesis, vasodilation, increased vascular permeability, and increased interstitial fluid. In contrast, the angiotensin II receptor blockers (ARBs) do not increase bradykinin levels. Angioedema as a complication of ACE inhibitor therapy is not widely recognized; this complication is even less recognized with second-line ARBs. We report angioedema associated with losartan (an ARB) in a patient who had experienced angioedema secondary to enalapril (an ACE inhibitor). Almost half of patients with ARB-associated angioedema also had developed angioedema while receiving ACE inhibitor therapy. Clinicians should exercise caution when using ARBs in patients with a history of angioedema secondary to ACE inhibitors.

Topics: Adult; Angioedema; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cough; Diabetes Mellitus, Type 1; Enalapril; Female; Humans; Losartan; Pharyngitis

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Arthralgia; Cough; Drug Tolerance; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Polycystic Kidney Diseases

Angio-oedema are often massive but temporary swellings of the soft tissue of the face or the throat, which can also affect other regions of the human body (e.g. the skin or internal organs). An oedema of the face and throat represents a life-threatening situation. Apart from the clinical condition of the patient and detailed knowledge of the medical history (incl. medical applications), the treatment should depend on the different pathogenesis. In this reported case, we describe the severe clinical development of an angio-oedema under a long-term treatment with an ACE-inhibitor, which in the end was only successfully treated with the application of a C1 inhibitor concentrate.

Topics: Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Complement C1 Inactivator Proteins; Critical Care; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Middle Aged; Risk Factors; Tongue Diseases

Topics: Adolescent; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Emergencies; Enalapril; Humans; Male

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Hypertension; Middle Aged; Tomography, X-Ray Computed

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Epiglottis; Female; Humans; Laryngeal Diseases

Angioedema is a rare but potentially fatal side effect of angiotensin converting enzyme (ACE) inhibitors. We report for the first time, two children with systemic lupus erythematosus who developed acute angioedema after the long-term use of enalapril. Prompt recognition and appropriate management of ACE-induced angioedema prevented life-threatening complications. This report highlights the potential risks of angioedema associated with the use of ACE inhibitors in children. Patients should be advised to seek medical treatment immediately if they experience swelling of the face, neck, or tongue, and especially if they have trouble breathing, speaking, or swallowing.

Topics: Adolescent; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Child; Enalapril; Female; Humans; Lupus Erythematosus, Systemic; Male

Topics: Abdominal Pain; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Middle Aged; Recurrence; Time Factors

Topics: Angioedema; Antihypertensive Agents; Emergency Nursing; Enalapril; Eye; Female; Humans; Middle Aged; Triage

Inhibitors of angiotensin converting enzyme may rarely cause an angioneurotic oedema of the upper aerodigestive tract. The pathomechanism of this side effect depends on an interaction of the drug with hormones regulating the vascular resistance such as the kallikrein kinin system and the prostaglandin system. Anglo-oedema is characterised by subcutaneous or submucosal swelling, which preferably affects the lips, the soft palate, the tongue and the larynx. Pathomechanisms, differential diagnosis and treatment of ACE-inhibitor induced oedema of the upper aerodigestive tract are described by means of 3 case reports.

Topics: Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Deglutition Disorders; Enalapril; Humans; Hypertension; Lisinopril; Male; Middle Aged

Angioedema is a rare but potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors (ACEI) which usually occurs within the first weeks of therapy. We report three patients in whom ACEI-induced angioedema began with a late onset of 12-33 months, and who had an irregular, unpredictable course under ACEI therapy. In two patients, other drugs or trauma appeared to trigger some of the episodes. After withdrawal of the ACEI, the trigger drugs were well tolerated in provocation tests and upon re-exposure. To avoid putting some patients unnecessarily at risk for long periods, one should consider this irregular pattern of ACEI-induced angioedema and regularly monitor patients for this adverse effect.

Topics: Aged; Anesthesia, Local; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bronchial Provocation Tests; Cilazapril; Enalapril; Female; Humans; Male; Middle Aged; Risk Factors; Skin Tests; Time Factors

We describe a rare case of ACE inhibitor-induced angioedema during long-term therapy in a 51-year-old male patient with essential hypertension; and this is the third case reported of this adverse reaction in Japan. The patient received enalapril for 66 months, and complained of a dry cough which was mild and tolerable. Recently, he noted tenderness of his mouth, face, swelling of lips and tongue for 3 to 4 h after taking his morning dose of enalapril. These symptoms abated spontaneously, so he continued taking the drugs. He again noted similar episodes of angioedema 29 days after the first experience. He had no further episodes of angioedema or dry cough after cessation of enalapril. This case of angioedema developed during long-term therapy with enalapril administered as 19,930 mg of enalapril maleate. We emphasize that angioedema may occur at any time during the use of enalapril.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Humans; Hypertension; Male; Middle Aged; Time Factors

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Drug Eruptions; Drug Therapy, Combination; Enalapril; Facial Dermatoses; Humans; Male; Middle Aged; Mouth Diseases

For more than five years, a patient suffered recurrent episodes of abdominal pain accompanied by diarrhoea, nausea and vomiting. An angiotensin converting enzyme (ACE) inhibitor causing visceral oedema was eventually implicated.

Topics: Abdominal Pain; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Hypertension; Intestinal Diseases; Middle Aged

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cough; Dose-Response Relationship, Drug; Enalapril; Humans; Hypertension; Isoquinolines; Kidney Diseases; Lisinopril; Otolaryngology; Quinapril; Tetrahydroisoquinolines

Topics: Aged; Angioedema; Enalapril; Female; Humans; Methylprednisolone

Adverse reactions to drugs are well recognized as a cause of acute or chronic urticaria, and angio-oedema. Angiotensin-converting enzyme (ACE) inhibitors, used to treat hypertension and congestive heart failure, were introduced in Europe in the middle of the eighties, and the use of these drugs has increased progressively. Soon after the introduction of ACE inhibitors, acute bouts of angio-oedema were reported in association with the use of these drugs. We wish to draw attention to the possibility of adverse reactions to ACE inhibitors after long-term use and in patients with pre-existing angio-oedema.

Topics: Acute Disease; Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Facial Dermatoses; Female; Humans; Male; Middle Aged

This case report describes an unrecognized adverse effect of an ACE inhibitor (enalapril): attack of acute abdominal pain. This symptom was observed 3 times over a period of 5 years in a 43 year old woman, occurring 24 h after she was taking the ACE inhibitor, and disappearing 3 to 5 days after the withdrawal of enalapril.

Topics: Abdomen, Acute; Adult; Angioedema; Enalapril; Female; Humans

Inhibitors of angiotensin converting enzyme (ACE) are suspected of inducing angioedemas in up to 0.2% of all patients. These angioedemas are mainly localized in the upper airways and therefore can cause severe airway obstruction and even death due to suffocation. We report the case of a 64-year-old man, who underwent emergency tracheotomy because of severe angioedema of the larynx, which was refractory to pharmacological treatment. We conclude that patients with ACE inhibitor-induced angioedemas should be observed by monitoring in an intensive care unit to ensure the possibility of early intubation, because conventional antiallergic-antiedematous therapy by histamine-receptor antagonists and corticosteroids is an insufficient, unreliable form of therapy in severe cases. Especially otolaryngologists should know about this uncommon potentially life-threatening side-effect of ACE inhibitors.

Topics: Angioedema; Clemastine; Clonidine; Combined Modality Therapy; Drug Hypersensitivity; Emergencies; Enalapril; Humans; Hypertension, Renal; Laryngeal Edema; Male; Middle Aged; Prednisolone; Ranitidine; Tracheotomy

Topics: Adult; Angioedema; Cardiomyopathy, Dilated; Enalapril; Humans; Hypertension; Male; Tongue Diseases

Angio-oedema as an adverse effect of angiotensin converting enzyme-inhibitors (ACE-inhibitors) is reported to occur in one to two of 1,000 treated patients per year. This estimate may be too low, since the swelling of face, lips, tongue and throat is very often attributed to food allergy. Furthermore, attacks of oedema may occur after months or even years of ACE-inhibitor treatment, thereby obscuring the link to the medication. This adverse effect is non-immunogenic. The oedema is explained by local enhancement of bradykinin, which under normal circumstances is broken down by angiotensin converting enzyme. The question of what makes some people vulnerable is still unsolved. The oedema can develop quickly and may lead to suffocation. In many cases, conventional antiallergic treatment in the form of steroids, antihistamines and epinephrine has inadequate effect. Intubation of the larynx may be necessary, but can be extremely difficult in the case of massive glassy oedema. Involvement of the neck can sometimes hinder tracheotomy, making early intervention essential. The authors describe two patients with moderate swellings, and discuss a potential, yet experimental, use of C1-inhibitor concentrate in the treatment of ACE-inhibitor provoked angioedema.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Face; Female; Humans; Middle Aged; Pharynx

Topics: Abdominal Pain; Adult; Angioedema; Enalapril; Female; Humans; Intestinal Diseases

Topics: Airway Obstruction; Angioedema; Emergencies; Enalapril; Female; Humans; Hypertension; Middle Aged; Osteoarthritis; Time Factors; Tongue Diseases

Topics: Adult; Aged; Angioedema; Cheilitis; Dairy Products; Drug Hypersensitivity; Enalapril; Female; Food Hypersensitivity; Gingival Hyperplasia; Gingivitis; Granuloma; Humans; Hypersensitivity; Melkersson-Rosenthal Syndrome; Mouth Diseases; Pesticides; Spices

A 37-year-old female with a history of hypertension for 5 years was brought to the emergency room with swelling of the tongue and neck after the second dose of enalapril. After administration of hydrocortisone by her physician, she went to the emergency room. Her dyspnea and dysarthria were relieved. However, she experienced recurrence of the symptoms followed by respiratory arrest. She suffered severe anoxic brain damage and died three days later. Although angioedema is a rare occurrence with the use of enalapril, it is potentially life threatening.

Topics: Adult; Angioedema; Enalapril; Female; Humans; Respiratory Insufficiency

Few drug reactions are more life threatening than the sudden development of edema involving the mucosal and submucosal layers of the upper aerodigestive tract. Drug-induced angioedema is a recognized entity of angiotensin-converting enzyme (ACE) inhibitors, and despite reports in medical journals and drug insert warnings, captopril and enalapril continue to be widely prescribed. As these drugs are efficacious and usually well-tolerated in the treatment of mild forms of hypertension, their popularity is rising. From June 1, 1984 to August 1, 1991, 36 patients with angioedema secondary to ACE inhibitors presented at the Medical College of Virginia Hospitals. Thirty were successfully managed with medical therapy. Two were intubated, 1 had placement of a nasal trumpet, and 3 required tracheostomies. Of extreme importance is the recognition that angioedema resulting from ACE inhibitors is probably not immunoglobulin E (IgE) mediated and that antihistaminics and steroids may not alleviate the airway obstruction. The otolaryngologist must be prepared for the need of possible early surgical intervention.

Topics: Adult; Aged; Aged, 80 and over; Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Dexamethasone; Dipeptides; Diphenhydramine; Enalapril; Epinephrine; Female; Humans; Injections, Intravenous; Laryngeal Edema; Lisinopril; Male; Middle Aged; Mouth Diseases; Pharyngeal Diseases; Prognosis

Topics: Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Drug Hypersensitivity; Enalapril; Humans; Lisinopril; Male

Inhibition of angiotensin converting enzyme (ACE) may cause angioneurotic oedema. In order to define the clinical spectrum of this important adverse effect, we analysed data on 60 patients with angioneurotic oedema notified to the Drug Commission of the German Medical Association, after taking captopril (n = 24), enalapril (n = 25) or lisinopril (n = 11). In 48 cases the oedema affected the face, tongue and pharynx, while swelling of the extremities (n = 4), the trunk (n = 2) or the genitalia (n = 1) was observed less frequently. While oedema appeared most often after 1 to 21 days, it started within an hour in one patient, and only after 6 months of therapy in five patients. After discontinuation of the ACE inhibitor, the angioneurotic oedema resolved within 72 hours; additional therapeutic measures (glucocorticoids, antihistamines, adrenaline, C1 inhibitors) did not shorten the recovery time. In view of the increasing use of ACE inhibitors, the features of this unusual adverse reaction need to be widely recognized, since angioneurotic oedema of the larynx is potentially life-threatening.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Complement C1 Inactivator Proteins; Enalapril; Epinephrine; Glucocorticoids; Histamine Antagonists; Humans; Lisinopril; Time Factors

Angioedema has been reported to occur in association with all angiotensin-converting enzyme inhibitors used in the United States. We reviewed nine cases of angioedema associated with lisinopril use seen in the emergency department at our hospital among 1,970 patients that had been prescribed lisinopril from March 1989 to May 1990. Cases were considered as probably (six cases) or possibly (three cases) drug related, depending on the temporal relationship of the initiation of therapy and the onset of angioedema. All of the cases had edema of the lips, buccal mucosa, and or face. None presented with laryngeal edema or stridor. The angioedema resolved within 1 to 2 days with diphenhydramine treatment and discontinuation of lisinopril. Our data suggest that the incidence of angioedema associated with lisinopril is greater than that associated with captopril or enalapril.

Topics: Adult; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Emergencies; Enalapril; Humans; Hypertension; Lisinopril; Male; Middle Aged

Acute angioneurotic edema due to angiotensin converting enzyme (ACE) inhibitors usually develops shortly after therapy has been started. In this case, hypopharyngeal edema occurred with a delay of nine days. It required endotracheal intubation and could only be differentiated from an inflammatory process by examination under general anesthesia. The mechanism of action of ACE inhibitors, the pathogenesis of angioneurotic edema, its therapy outside as well as in the hospital, and the case described are being discussed. It is concluded that severe reactions induced by ACE inhibitors must be expected even after considerable time of therapy.

Topics: Acute Disease; Adult; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Humans; Male

To evaluate and describe the clinical course of angio-oedema reactions induced by angiotensin converting enzyme inhibitors.. All reports of angio-oedema reactions associated with angiotensin converting enzyme inhibitors submitted to Swedish Adverse Reactions Advisory Committee were reviewed and the clinical courses summarised. Numbers of cases judged to be induced by angiotensin converting enzyme inhibitors were related to their annual usage, estimated from total sales of defined daily doses, as well as to the estimated number of new patients. All cases of angio-oedema associated with angiotensin converting enzyme inhibitors reported to the World Health Organisation's international drug information system were also summarised.. 36 of the 38 reported cases in Sweden between 1981 and 1990 were judged to be related to angiotensin converting enzyme inhibitors. During 1981 through 1990, altogether 1309 cases of angio-oedema associated with angiotensin converting enzyme inhibitors were registered with the international drug information system. The incidence of reported cases of angio-oedema increased largely in parallel with the increased sales (usage) of angiotensin converting enzyme inhibitors. Of the 36 Swedish patients, 77% experienced the reaction within the first three weeks after starting treatment. 10 patients needed hospitalisation, two of whom had life threatening laryngeal obstruction. With one exception all 36 patients were free of symptoms within one week after discontinuing the drug.. Angio-oedema induced by angiotensin converting enzyme inhibitors is a rare but potentially life threatening reaction, which in most instances occurs shortly after the start of treatment. Any patient in whom the reaction is suspected should have the treatment interrupted and, if necessary, be admitted for observation.

Topics: Adult; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Female; Humans; Male; Middle Aged; Prognosis; Time Factors

Topics: Aged; Ampicillin; Angioedema; Drug Hypersensitivity; Enalapril; Female; Humans; Nitrofurantoin

A case of life-threatening angioedema occurring after 13 months of enalapril therapy is reported. Clinicians should be aware that such severe reactions can occur, even after long-term therapy. Patients who take angiotensin-converting enzyme inhibitors should be carefully questioned during each follow-up examination concerning angioedema symptoms.

Topics: Aged; Angioedema; Enalapril; Female; Humans; Hypertension; Time Factors

Topics: Angioedema; Enalapril; Female; Humans; Middle Aged

A review of two cases of angioedema associated with therapeutic doses of the angiotensin-converting enzyme inhibitor enalapril are presented along with a review of the relevant literature. Although angioedema of the facial and oral pharyngeal regions is a relatively rare occurrence with the use of ACE inhibitors, recognition of these agents as the cause of such a condition, when subacute, can lead to a rapid cure. Knowledge of these effects may also be helpful in the management of an acute clinical manifestation and, as importantly, may help prevent a recurrent episode due to the ill-guided continuation of the drug.

Topics: Adult; Angioedema; Enalapril; Humans; Lip Diseases; Male; Middle Aged

Since 1984 25 cases of enalapril induced angioedema have been reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs. Two patients with enalapril induced angioedema are described. The pathophysiological mechanism of this potentially life-threatening adverse effect is probably not a direct allergic response to the drug itself. Enalapril inhibits angiotensin converting enzyme, which not only metabolizes angiotensin I but also bradykinin and 'substance P'. Bradykinin and 'substance PH may then accumulate and cause angioedema in a direct or indirect way. It is of great importance that instances of oropharyngeal swelling are considered a possible result of an adverse reaction to ACE-inhibitors.

Topics: Adult; Aged; Angioedema; Drug Therapy, Combination; Enalapril; Female; Humans; Male

Angiotensin-converting enzyme (ACE) inhibitors are now in widespread use for the treatment of essential and renovascular hypertension. Consequently, angioedema, an uncommon complication of ACE inhibitor therapy is being encountered with increasing frequency. Since ACE inhibitor angioedema predominantly involves the face, lips, oral cavity, and occasionally the larynx the otolaryngologist is often consulted to evaluate affected patients. Treatment ranges from simple cessation of the drug to emergent airway intervention. The pertinent pharmacologic properties of ACE inhibitors and the pathophysiology of angioedema are discussed. The authors' experience with the evaluation and treatment of ACE inhibitor induced angioedema is presented.

Topics: Adrenal Cortex Hormones; Aged; Angioedema; Captopril; Diphenhydramine; Enalapril; Female; Humans; Laryngeal Diseases; Male; Middle Aged; Mouth Diseases

Angioedema is a disorder characterized by well-demarcated nonpitting edema involving the tongue, floor of the mouth, larynx, lips, and face. This condition can progress to upper airway obstruction and death. Angiotensin-converting enzyme inhibitors (ACEIs), relatively new antihypertensive agents, act by blocking the formation of angiotensin II, a potent vasoconstrictor and stimulator of aldosterone formation. ACEIs also retard the breakdown of bradykinin, a potent vasodilator, which may lead to the edema seen in nonhereditary angioedema. These ACEIs include enalapril, captopril, lisinopril, saralasin acetate, and a combination of ACEI with diuretics (for example, Capozide). From August 1987 to January 1989, we treated six patients with a nonhereditary form of angioedema related to ingestion of angiotensin-converting enzyme inhibitors. Symptoms developed in all patients within 12 hours after their initial dose of an ACEI. They presented with shortness of breath and dysphagia associated with tongue and floor of the mouth edema. Two of the six required intubation and monitoring in the surgical intensive care unit for 36 to 48 hours. Three required supportive treatment and observation in an intermediate care unit, and one received supportive care in the clinic and was discharged the same day. Specifically, treatment consisted of cessation of inciting agent, steroids, antihistamines, and epinephrine, if not otherwise contraindicated. Assays of C1 esterase inhibitor levels and C4 were normal in all six patients; this was important in order to rule out hereditary forms of angioedema. These cases will be discussed, including a review of the literature, methods of diagnosis, pathophysiology, and treatment of angioedema.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Female; Humans; Male; Middle Aged

Angiotensin converting enzyme (ACE) inhibitors have been associated with the onset of angioedema in a small subset of treated patients. The angioedema commonly involves the face and oropharyngeal tissues and may result in life-threatening airway compromise. The mechanism by which ACE inhibitors precipitate angioedema has not been well-defined, and retrospective analysis of reported cases has failed to identify a group of patients at high risk. We report four cases of ACE inhibitor-related angioedema that required immediate medical intervention. All four cases occurred in patients with a prior history of idiopathic angioedema, an otherwise uncommon clinical entity. These observations suggest that patients with a history of idiopathic angioedema are at increased risk for the development of ACE inhibitor-related angioedema and should be treated cautiously with this class of drugs.

Topics: Adult; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Lisinopril; Male

Inhibitors of angiotensin converting enzyme can rarely cause an angioneurotic edema of the upper airways. This complication depends on the interaction with hormones regulating the vascular resistance such as the kallikrein kinin and the prostaglandin systems. We present two cases of angioneurotic edema of the tongue induced by inhibitors of angiotensin converting enzyme. We describe the symptoms of this side effect and discuss possible therapeutic approaches.

Topics: Angioedema; Captopril; Enalapril; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Risk Factors; Tongue Diseases

Angiotensin-converting enzyme (ACE) inhibitors have several side effects of concern to the otolaryngologist. Angioedema is a rare, but potentially lethal adverse effect when associated with upper airway obstruction. Four cases of ACE-inhibitor-induced angioedema, three with significant upper airway obstruction, are reported. Angioedema secondary to ACE inhibition appears to be mechanism based. The probable link is the potentiation of bradykinin, which results in vasodilation, increased vascular permeability, and angioedema. Since angioedema can progress to upper airway obstruction, otolaryngologists must be aware of this association. The differential diagnosis and treatment of this adverse effect is discussed, as well as a review of ACE inhibitors and other causes of angioedema.

Topics: Adult; Airway Obstruction; Angioedema; Captopril; Enalapril; Female; Humans; Male; Middle Aged; Tongue Diseases

Topics: Adult; Angioedema; Enalapril; Humans; Hypertension; Male; Orbital Diseases; Visual Acuity

Topics: Aged; Angioedema; Drug Administration Schedule; Enalapril; Female; Humans; Time Factors

A report of three patients who developed angiodema while receiving enalapril. Patient 1 came in with an 8-hour history of facial swelling after enalapril had been started 2 days earlier. The second patient came in with severe angiodema of the tongue, larynx, and glottis requiring emergency tracheostomy, hydroxyzine, and steroids. He had been treated with enalapril for 1 year. The third patient developed facial swelling within a few hours of the first dose of enalapril. Angiodema with enalapril can occur early or late in the course of therapy. A possible mechanism for this drug reaction is the potentiation of bradykinin with resultant kinin system activation.

Topics: Aged; Airway Obstruction; Angioedema; Diphenhydramine; Enalapril; Humans; Hypertension; Male; Middle Aged; Tracheostomy

Topics: Airway Obstruction; Angioedema; Captopril; Enalapril; Humans; Tracheotomy

Topics: Angioedema; Enalapril; Face; Humans; Male; Middle Aged

Angioedema that occurs in the head and neck may be a serious and possibly life-threatening condition. We present two cases of oropharyngeal angioedema associated with the use of angiotensin-converting enzyme inhibitors in patients with no underlying renal failure. Angiotensin-converting enzyme-inhibiting agents are now commonly used to control hypertension. Treatment of acquired angioedema is directed first at protecting the airway by careful observation, intubation, or if necessary, tracheostomy. The causative agent is withdrawn, and the patient is treated with antihistamines and steroids until the acute episode resolves. Although not used in our patients, the treatment of angioedema with subcutaneous epinephrine has been described. As more patients are treated with angiotensin-converting enzyme inhibitors, it becomes essential for the otolaryngologist to become aware of this potentially life-threatening complication.

Topics: Airway Obstruction; Angioedema; Captopril; Enalapril; Female; Humans; Middle Aged; Mouth Diseases; Pharyngeal Diseases

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.

Topics: Adult; Age Factors; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Heart Failure; Hematologic Tests; Humans; Hypertension; Hypotension; Kidney Diseases; Lisinopril; Male; Middle Aged

Two cases of enalapril(Reniten)-induced angioedema are described. In both patients the time lag between the first manifestation of angio-edema and diagnosis was more than one year, during which several bouts of edema occurred. One patient developed life-threatening swelling of the tongue and the larynx followed by asystole and apnea. The second patient had recurrent edema of the tongue and dyspnea. In general, enalapril-induced edema is not thought to be based on immunological mechanisms. However, in both patients we found elevated titres of antinuclear antibodies, which were reversible upon cessation of enalapril medication. The possible pathomechanisms are discussed.

Topics: Angioedema; Antibodies, Antinuclear; Drug Hypersensitivity; Enalapril; Female; Humans; Middle Aged; Time Factors

A 65-year-old male with a long history of congestive heart failure presented to the emergency room with facial swelling 7 h after the first dose of enalapril. He was treated with diphenhydramine and hydrocortisone which improved his angioedema. However, there was a profound relapse of the angioedema followed by respiratory arrest. He suffered severe anoxic brain damage and died five days later. It is likely that the long half-life of enalapril lead to this rebound phenomenon. Enalapril induced angioedema is reviewed with suggestions for management.

Topics: Aged; Angioedema; Coronary Disease; Enalapril; Heart Failure; Humans; Hypoxia, Brain; Male; Respiratory Insufficiency

Based on data from three studies with complete recording of adverse events in about 12,000 patients each, we determined that angioedema in association with the angiotensin converting-enzyme inhibitor enalapril maleate occurred during the first week of therapy at the rate of one case per 3000 patients per week. Thereafter, the incidence was 14-fold lower, without evidence of a temporal trend in incidence beyond the first week of therapy. The cumulative incidence was one case per 1000 patients treated (0.1%). An additional 138 case reports consistent with the diagnosis of angioedema were obtained from our overall controlled and marketed experience using enalapril in more than 1.2 million patients. These reports were examined to further characterize the reaction. The cases generally were mild, and they resolved on discontinuation of drug therapy. Seven patients experienced angioedema or urticaria in association with both enalapril and captopril, a structurally different angiotensin converting-enzyme inhibitor. This further suggested that the side effect is mechanism based. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be interrupted promptly, respiratory distress should be treated appropriately, and subsequent therapy should be initiated with an agent from an alternative class of medication.

Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Data Collection; Enalapril; Humans; Hypertension; Time Factors

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).

Topics: Adolescent; Adult; Aged; Angioedema; Cough; Enalapril; Evaluation Studies as Topic; Family Practice; Female; Humans; Hypertension; Hypotension; Male; Middle Aged; Product Surveillance, Postmarketing; United Kingdom

Topics: Agranulocytosis; Angioedema; Captopril; Enalapril; Humans; Sepsis

Topics: Aged; Aged, 80 and over; Angioedema; Captopril; Enalapril; Female; Humans; Male; Middle Aged; Time Factors; United Kingdom; Urticaria