Asunto(s)
Aminobutiratos , Angioedema , Compuestos de Bifenilo , Combinación de Medicamentos , Tetrazoles , Valsartán , Humanos , Valsartán/efectos adversos , Aminobutiratos/efectos adversos , Angioedema/inducido químicamente , Compuestos de Bifenilo/efectos adversos , Tetrazoles/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Masculino , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Anciano , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND Angioedema is characterized by localized self-limiting edema of the deep dermis, subcutaneous, and submucosal tissues. Acute episodes often involve the skin of the face, lips, tongue, limbs, and genitals, as well as internal areas of the body and respiratory and gastrointestinal mucosa, which could be life-threatening. Histamine and bradykinin are the most recognized vasoactive mediators in the pathophysiology of angioedema. Tissue plasminogen activator (tPA) is a fibrinolytic that is commonly used for the treatment of cerebrovascular accidents. Angioedema is a rare adverse effect of tPA, with an estimated incidence of 0.02% in patients with myocardial infarction or pulmonary embolism and 0.2% to 5.1% in patients with stroke. We report a unique case of tPA-associated angioedema with 24-h management. CASE REPORT A 79-year-old male patient presented to the Emergency Department with acute onset right-sided weakness, right-sided facial droop, and speech difficulties. Following the initial evaluation, it was determined that he was a candidate for receiving tPA therapy. On arrival at the Intensive Care Unit, he was noted to have right upper and then lower lip swelling. The patient was asymptomatic and did not show any signs concerning airway compromise. Treatment included systemic corticosteroids and antihistamines. The progression of the angioedema was further described with sequential images. The angioedema was completely resolved with treatment. CONCLUSIONS Angioedema is a rare but potentially life-threatening adverse effect of tPA. Although it generally has a mild self-limiting course, it can cause life-threatening airway compromise.
Asunto(s)
Angioedema , Fibrinolíticos , Activador de Tejido Plasminógeno , Humanos , Masculino , Angioedema/inducido químicamente , Anciano , Activador de Tejido Plasminógeno/efectos adversos , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéuticoRESUMEN
Angioedema is a rare but potentially fatal complication of angiotensin-converting enzyme inhibitor (ACEi) treatment. This class of drugs is widely used in the treatment of hypertension, cardiac failure and other common conditions.This case report discusses a male patient in his 60s who presented with acute swelling of the right side of his tongue, an unusual manifestation of angioedema, which typically involves bilateral swelling of orofacial structures.Accurate and early identification of this complication affords the opportunity for early, potentially life-saving intervention during the acute episode and also cessation of the treatment, reducing the risk of recurrence in the future.This case is one of only a few reported in English language medical literature and the first from Africa, suggesting either rarity or under-reporting. The case contributes to the understanding of ACEi-induced angioedema, particularly in Africa where hypertension is prevalent and ACEi is commonly used.
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Angioedema , Inhibidores de la Enzima Convertidora de Angiotensina , Humanos , Angioedema/inducido químicamente , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Masculino , Persona de Mediana Edad , Hipertensión/tratamiento farmacológico , Enfermedades de la Lengua/inducido químicamente , Lengua/patologíaRESUMEN
Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its genetically modified variant tenecteplase. It is potentially lethal when causing airway obstruction and can require intubation. The latest guideline for the early management of patients with acute ischemic stroke from the American Heart Association/American Stroke Association advises to treat this complication initially by interfering with the histamine pathway. This article aims to clarify the pathophysiological mechanism of r-tPA-induced angioedema and provides several arguments that this condition is primarily bradykinin-mediated and hence should be treated initially by intervening with the bradykinin pathway. Second, other-less frequently reported-adverse symptoms after r-tPA therapy and their proposed pathophysiological mechanisms leading to specific treatment are described. This manuscript describes the need for an update of the section "3.5 IV alteplase" from the American Heart Association/American Stroke Association guideline to treat this r-tPA-induced angioedema adequately and prevent potentially fatal outcomes.
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Angioedema , Fibrinolíticos , Accidente Cerebrovascular , Activador de Tejido Plasminógeno , Humanos , Angioedema/inducido químicamente , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Bradiquinina/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológicoAsunto(s)
Angioedema , Accidente Cerebrovascular , Activador de Tejido Plasminógeno , Humanos , Angioedema/inducido químicamente , Corteza Cerebral/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéuticoAsunto(s)
Angioedema , Fibrinolíticos , Accidente Cerebrovascular Isquémico , Tenecteplasa , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Tenecteplasa/uso terapéutico , Angioedema/tratamiento farmacológico , Angioedema/inducido químicamente , Fibrinolíticos/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Masculino , Femenino , Anciano , Accidente Cerebrovascular/tratamiento farmacológico , Persona de Mediana EdadRESUMEN
BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-Is) prevent the breakdown of bradykinin and can lead to life threatening angioedema. Tranexamic acid is an antifibrinolytic that inhibits formation of precursors involved in bradykinin synthesis and, in case reports, has been described as a potential treatment for ACE-I angioedema. METHODS: This retrospective study included patients who presented to the emergency department (ED) from January 2018 to August 2021 with angioedema while taking an ACE-I. Patients who received tranexamic acid (treatment group) were compared with patients who did not receive tranexamic acid (control group). Primary outcome was length of stay (LOS). Secondary outcomes evaluated included ICU admissions, intubations, and safety events. RESULTS: A total of 262 patients were included in this study (73 treatment; 189 control). Overall, the median ED LOS was longer in the treatment group than controls (20.9 h vs 4.8 h, p < 0.001). ICU admission rates were higher in the treatment group (45% vs 16%, p < 0.001). More patients were intubated in the treatment group (12% vs 3%, p = 0.018). No difference was seen between the treatment group and the controls for return within 7 days, complications related to thrombosis, and death. In patients presenting with severe angioedema symptoms who were admitted to the hospital, median LOS was not different between the two groups (58.7 h vs 55.7 h, p = 0.61). CONCLUSIONS: Patients who received tranexamic acid had increased ED LOS, rates of ICU admission, and need for intubation. This finding may be related to the severity of presentation. Administration of tranexamic acid appears safe to use in ACE-I angioedema. Prospective randomized controlled studies should be considered to determine whether tranexamic acid is an effective treatment for ACE-I angioedema.
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Angioedema , Ácido Tranexámico , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Ácido Tranexámico/uso terapéutico , Estudios Retrospectivos , Bradiquinina/uso terapéutico , Estudios Prospectivos , Angioedema/inducido químicamente , Angioedema/tratamiento farmacológicoRESUMEN
BACKGROUND: Angioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited. OBJECTIVE: We sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology. METHODS: By combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE. RESULTS: Three genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort. CONCLUSIONS: The present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.
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Angioedema , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Estudio de Asociación del Genoma Completo , Angioedema/inducido químicamente , Angioedema/genética , BradiquininaRESUMEN
BACKGROUND Angioedema is non-pitting edema that occurs in the deep layers of the skin and subcutaneous tissue due to vascular leakage of plasma resulting from 1 of 2 major pathophysiological processes: mast cell-mediated angioedema and bradykinin-mediated angioedema. While it is a well-recognized adverse reaction of angiotensin-converting enzyme inhibitors, the association of angioedema with angiotensin receptor blockers is relatively less studied. Direct local trauma, although rarely, has been suggested to induce angioedema under certain conditions. We present a unique case of direct, local, trauma-related angioedema in a patient on an angiotensin receptor blocker. CASE REPORT The patient, an 83-year-old woman on telmisartan for hypertension, hit her neck against the edge of a chair during a fall. Shortly thereafter, she developed progressive airway compromise due to airway angioedema, as noted on direct laryngoscopy. A contrast CT scan of the neck also noted edema of the periglottic and supraglottic regions. She required intravenous corticosteroid administration and intubation in the emergency room and was successfully extubated 3 days after admission. She had no prior history of angioedema or allergy. We hypothesize that increased levels of circulatory bradykinin in the setting of telmisartan, combined with a local release of bradykinin from trauma, was the main pathophysiologic cause of the angioedema. CONCLUSIONS This case report highlights the rare and often forgotten adverse reaction of angioedema with use of angiotensin receptor blockers and confirms the finding of local trauma as a possible trigger.
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Angioedema , Antagonistas de Receptores de Angiotensina , Femenino , Humanos , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/efectos adversos , Telmisartán/efectos adversos , Bradiquinina , Angioedema/inducido químicamente , Intubación , EdemaRESUMEN
Recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA), a genetically modified variant of conventional alteplase with longer half-life and higher fibrin specificity, has now emerged as a reasonable choice for thrombolytic treatment of acute ischemic stroke (AIS) in China. Orolingual angioedema is a rare but potentially life-threatening complication of intravenous thrombolysis. Currently, there is no documented evidence of orolingual angioedema occurring after thrombolysis with rhTNK-tPA. In this report, we present a unique case of a 75-year-old Chinese man who developed ipsilateral orolingual angioedema following the administration of rhTNK-tPA for AIS. Our case emphasizes the need for caution when using rhTNK-tPA due to its potential to induce ipsilateral orolingual angioedema.
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Angioedema , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Masculino , Humanos , Anciano , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Activador de Tejido Plasminógeno/efectos adversos , Fibrinolíticos/efectos adversos , Administración Intravenosa , Angioedema/inducido químicamente , Angioedema/tratamiento farmacológico , Isquemia Encefálica/complicacionesRESUMEN
PURPOSE: Orolingual angioedema (OA) secondary to administration of thrombolytic therapy is a rare, but serious, known adverse effect. Despite the lack of robust evidence for their use, C1 esterase inhibitors are recommended by guidelines for the treatment of refractory thrombolytic-associated OA. This report highlights the use of a C1 esterase inhibitor in a patient with tenecteplase-associated OA unresolved by antihistamine and corticosteroid therapy. SUMMARY: A 67-year-old white male with a history of hypertension managed with lisinopril presented to the emergency department with acute onset of slurred speech and left-sided hemiparesis. Following workup, an outside hospital's neurology stroke team suspected an acute infarct and determined the patient to be a candidate for tenecteplase. Approximately 1 hour after tenecteplase administration, the patient began complaining of dyspnea and mild oral angioedema. Immediate interventions for OA management included intravenous therapy with dexamethasone 10 mg, diphenhydramine 25 mg, and famotidine 20 mg. After an additional 30 minutes, the patient's OA symptoms continued to progress and a C1 esterase inhibitor (Berinert) was administered. Shortly after administration of the C1 esterase inhibitor, the patient's symptoms continued to worsen, ultimately leading to endotracheal intubation. Following intubation, symptom improvement was noted, and the patient was safely extubated after 30 hours. CONCLUSION: Although rare, OA is a potentially life-threatening complication of tenecteplase therapy and requires prompt pharmacological intervention to optimize patient outcomes. Currently, no single agent or treatment algorithm exists that has shown significant efficacy or safety in the setting of thrombolytic-associated OA. Until data are available for C1 esterase inhibitors in this application, these inhibitors should only be considered if there is continued symptom progression after intravenous administration of corticosteroids and antihistamines.
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Angioedema , Proteína Inhibidora del Complemento C1 , Humanos , Masculino , Anciano , Tenecteplasa/uso terapéutico , Proteína Inhibidora del Complemento C1/uso terapéutico , Complemento C1s , Angioedema/inducido químicamente , Angioedema/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
BACKGROUND: Angioneurotic edema is the most dangerous complication in angiotensin-converting enzyme inhibitors (ACEIs) therapy. Based on the current data, the clinical and genetic predictors of angioedema development are still understudied, which demonstrates the relevance of this study. OBJECTIVE: To reveal the pharmacogenetic predictors of the angioedema as a secondary side effect to enalapril in patients with essential arterial hypertension. METHODS: The study enrolled 111 subjects randomized into two groups: study group, patients with the angioedema as a secondary side effect to enalapril; and control group, patients without adverse drug reaction. All patients underwent pharmacogenetic testing. RESULTS: An association between the development of the angioneurotic edema and the genotypes AA rs2306283 of gene SLCO1B1, TT rs4459610 of gene ACE, and CC rs1799722 of gene BDKRB2 in patients was revealed. CONCLUSION: The findings justify further investigations of the revealed genetic predictors of angioedema with larger-size patient populations.
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Angioedema , Enalapril , Humanos , Enalapril/efectos adversos , Farmacogenética , Angioedema/inducido químicamente , Angioedema/genética , Hipertensión Esencial , Genotipo , Transportador 1 de Anión Orgánico Específico del HígadoRESUMEN
OBJECTIVES: Characterize the presentation of patients with non-angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema and determine risk factors associated with patient disposition and possible need for airway intervention. METHODS: The medical records of adult patients in the Emergency Department (ED) and diagnosed with non-ACEI-induced angioedema over 4.5 years were included. Demographics, vital signs, etiology, timeline, presenting symptoms, physical exam including flexible laryngoscopy, medical management, and disposition were examined. Statistical analyses were conducted using SPSS V 23.0 software calculating and comparing means, standard deviations, medians, and correlation of categorical and ordinate variables. RESULTS: A total of 181 patients with non-ACEI-induced angioedema were evaluated with flexible laryngoscopy by otolaryngology. Notably, 11 patients (6.1%) required airway intervention and were successfully intubated. Statistically significant factors (p ≤ 0.05) associated with airway intervention included the diastolic blood pressure (DBP) and mean arterial pressure (MAP) (p = 0.006 and 0.01 respectively), symptoms of dysphonia (p = 0.018), the presence of oropharyngeal, supraglottic, and hypopharyngeal edema (p ≤ 0.001 for each site), and the number of edematous anatomic subsites documented on physical exam (p < 0.001). Other patient demographics, prior history of angioedema, heart rate, systolic blood pressure, symptom onset, number of symptoms at presentation, and medication administered in the ED did not correlate with airway intervention. CONCLUSION: Dysphonia, DBP, MAP, anatomic location of edema and edema in multiple sites are associated with airway intervention and a higher level of care in non-ACEI-induced angioedema and can be useful in risk assessment in patient management. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2282-2287, 2024.
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Angioedema , Disfonía , Adulto , Humanos , Disfonía/complicaciones , Sistema Respiratorio , Laringoscopía , Angioedema/inducido químicamente , Angioedema/terapia , EdemaRESUMEN
BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.
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Lesión Renal Aguda , Angioedema , Insuficiencia Cardíaca , Hiperpotasemia , Hipotensión , Humanos , Anciano , Estudios Retrospectivos , Tetrazoles/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Farmacovigilancia , Hiperpotasemia/inducido químicamente , Hiperpotasemia/diagnóstico , Hiperpotasemia/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina , Valsartán/efectos adversos , Aminobutiratos/efectos adversos , Compuestos de Bifenilo/efectos adversos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/inducido químicamente , Combinación de Medicamentos , Hipotensión/inducido químicamente , Hipotensión/diagnóstico , Hipotensión/epidemiología , Angioedema/inducido químicamente , Angioedema/diagnóstico , Angioedema/epidemiología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Volumen SistólicoRESUMEN
INTRODUCTION: Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. METHODS: We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. RESULTS: Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). CONCLUSION: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.