Comparative safety of tenecteplase vs alteplase for acute ischemic stroke.

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.

An Overview of Clinically Imperative and Pharmacodynamically Significant Drug Interactions of Renin-Angiotensin-Aldosterone System (RAAS) Blockers.

INTRODUCTION: Hypertension is a leading cause of cardiovascular disease and chronic kidney disease, resulting in premature death and disability. The Renin-Angiotensin-Aldosterone System (RAAS) blockers, including Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs), are used as first-line antihypertensive therapy to treat hypertensive patients with comorbidities, including diabetes, ischemic heart disease, heart failure, and chronic kidney disease. The use of RAS blockers is associated with the risks, such as hyperkalemia, angioedema, etc. The drugs potentiating them interact pharmacodynamically, resulting in adverse consequences. This review article focuses on the clinically important drug interactions of RAAS blockers. MATERIALS AND METHODS: The electronic databases, such as Medline/PubMed Central/PubMed, Google Scholar, ScienceDirect, Cochrane Library, Directory of Open Access Journals (DOAJ), Embase, and reference lists were searched to identify relevant articles. RESULTS: The risk of hyperkalemia may be enhanced potentially in patients receiving a RAS blocker and potassium-sparing diuretics, potassium supplements, trimethoprim, adrenergic betablockers, antifungal agents, calcineurin inhibitors, pentamidine, heparins or an NSAID, concomitantly. The patients taking ACE inhibitors and mTOR inhibitors, DPP4 inhibitors, alteplase, or sacubitril/valsartan concurrently may be at increased risk of developing angioedema. CONCLUSION: Clinicians, pharmacists, and other healthcare practitioners should be accountable for medication safety. To avoid adverse implications, prescribers and pharmacists must be aware of the drugs that interact with RAAS blockers.

Oscillococcinum leading to angioedema, a rare adverse event.

Oscillococcinum is an alternative medicine prepared by serial dilution of wild duck heart and liver extracts. This preparation has been labelled as a 'non drowsy, homoeopathic medicine' that 'reduces the duration and severity of flu and flu-like symptoms'. Clinical evidence exists to support this claim and the product has not previously been reported to cause any serious adverse drug reactions. We bring to light, however, a case of angioedema in our patient who was using oscillococcinum for flu-like symptoms. Consumers must therefore exercise caution at the outset of allergy symptoms.

Pollen count and presentation of angiotensin-converting enzyme inhibitor-associated angioedema.

BACKGROUND: The incidence of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema is increased in patients with seasonal allergies. OBJECTIVE: We tested the hypothesis that patients with ACE inhibitor-associated angioedema present during months when pollen counts are increased. METHODS: Cohort analysis examined the month of presentation of ACE inhibitor-associated angioedema and pollen counts in the ambulatory and hospital setting. Patients with ACE inhibitor-associated angioedema were ascertained through (1) an observational study of patients presenting to Vanderbilt University Medical Center, (2) patients presenting to the Marshfield Clinic and participating in the Marshfield Clinic Personalized Medicine Research Project, and (3) patients enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE inhibitor-associated angioedema, population exposure to ACE inhibitor by date, and local pollen counts by date. RESULTS: At Vanderbilt, the rate of angioedema was significantly associated with tree pollen months (P = .01 from χ(2) test). When separate analyses were conducted in patients with a history of seasonal allergies and patients without, the rate of ACE inhibitor-associated angioedema was increased during tree pollen months only in patients with a history of seasonal allergies (P = .002). In Marshfield, the rate of angioedema was significantly associated with ragweed pollen months (P = .025). In ONTARGET, a positive trend was observed between the ACE inhibitor-associated angioedema rate and grass season, although it was not statistically significant (P = .057). CONCLUSIONS: Patients with ACE inhibitor-associated angioedema are more likely to present with this adverse drug event during months when pollen counts are increased.

Oral drug challenges in non-steroidal anti-inflammatory drug-induced urticaria, angioedema and anaphylaxis.

BACKGROUND: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. METHODS: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. RESULTS: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. CONCLUSION: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs.

Tongue angioedema in vivo: antagonist response of anti-inflammatory drugs.

INTRODUCTION: The toxicity of Dieffenbachia picta, an ornamental plant, arises from its ability to cause painful edema of oral mucous membranes, buccal ulcerations, and tongue hypertrophy after chewing on the stem or contact with the sap. OBJECTIVES: We compared the anti-inflammatory effect of eugenol (2-methoxy-4-(2-propenyl)phenol) to different drugs, and investigated the role of oxalate crystals in the development of the inflammation reaction. METHODS: Tongue edema in live mice were measured with a digital tachymeter, 2 h after topical application (0.1 mL) or tissue injection (0.05 mL) of D. picta sap. The mice were treated by intraperitoneal or topical application of drugs, 15 min after edema induction. Vascular permeability was quantified based on abdominal skin plasma extravasation of Evans blue dye in response to intradermal administration of D. picta sap. The proteolytic assay was carried out as previously described (Kunitz M. Crystalline soybean trypsin inhibitor. General properties. J Gen Physiol 1947; 30:291-310.). RESULTS: Arachidonate cascade antagonists and eugenol showed anti-edematogenic effects. High doses of eugenol (50 µg/kg) and sodium cromoglycate (100 mg/kg), but not a combination of the two, inhibited plasma extravasations. The sap without crystals, its methanol extract, or the ethanol-washed crystals in saline-reconstituted solution did not reproduce the tongue edema seen with the original sap. Topical application of 10% sodium bicarbonate completely abolished the tongue edema. CONCLUSIONS: The inflammatory response induced by D. picta may be due to mechanical tissue damage resulting from the physical presence of calcium oxalate crystals. We were, however, unable to exclude the possibility of an insoluble toxicity present within the sap as an etiological agent. We realized that emergency treatment should also aim to inhibit antidromic vasodilation and axon reflex flare, reducing mastocyte degranulation and release of tachykinins from nerve endings. We speculate that eugenol showed better antiedematogenic results because it seems to function not only as a classic non-steroidal anti-inflammatory drug, but also as a local anesthetic, blocking neurotransmission in the damaged tissue.

Drug-induced urticaria and angioedema: pathomechanisms and frequencies in a developing country and in developed countries.

A careful drug history should be obtained from all patients with acute or chronic urticaria/angioedema, especially in the elderly. Although strictly comparable data are lacking, drug-induced urticaria appears to be more common in developed countries than in Malaysia, at least in a Hospital setting. Culprit drugs include antibiotics, analgesics and contrast media. Pseudoallergic drug-induced urticaria mimicks true allergic urticaria, but without an evident immunological basis, and is at least as common as the allergic type. In Malaysia, and in many other countries compulsory, ingredient labelling of 'traditional' medicines would do much to reduce the frequency of drug-induced urticaria.

[Herbal medicines and severe adverse effects: uvular angioedema caused by Echballium elaterium]. / Hierbas medicinales y graves efectos adversos: angioedema de úvula causado por uso de Ecballium elaterium.

Herbal medicine is a growing alternative for established medicine. Many plants and herbs are currently in use for a myriad of diseases and symptoms. However, there are many reports in the literature of life-threatening adverse effects of these drugs. We report a 39 years old male, that consulted for pain in the nostrils and severe nasal obstruction, that appeared two hours after instilling Ecballium elaterirum in the nostrils. On physical examination, uvular edema was observed. The patient was successfully managed with intravenous betametasone and chlorphenamine.

Life-threatening uvular angioedema caused by Ecbalium elaterium.

Ecbalium elaterium, known as the wild or squirting cucumber, is a hairy perennial herbaceous vine of the Cucurbitaceae family, endemic to the Mediterranean region. All parts of the plant are toxic, particularly the gherkin-like fruits. It is frequently used in the treatment of sinusitis by nasal aspiration in some parts of the Mediterranean. The studies regarding to Ecbalium elaterium, argue that it has an anti-inflammatory characteristic. Two cases of uvular oedema have been ascribed to the undiluted use of this substance. Since they can threaten life, similar cases arising with the improper use of herbals should not be ignored in the emergency department. In this paper we present a life-threatening uvular angioedema caused by nasal aspiration of undiluted juice of squirting cucumber.

Severe uvular angioedema caused by intranasal administration of Ecbalium elaterium.

A 54-y-o woman presented to the Emergency Department with shortness of breath and sore throat after intranasal administration of Ecbalium elaterium as a folk remedy for her sinusitis. The patient's history included nasal aspiration of the juice of the squirting cucumber (Ecbalium elaterium) for acute maxillary sinusitis. An airway obstruction due to severe uvular angioedema was detected and confirmed by airway X-ray. The patient was treated with 100% oxygen with mask, 0.3 mg epinephrine s.c., and 80 mg prednisolone i.v. Renal and hepatic function tests were normal. After a 24-h observation, the patient was discharged in her previous state of health.

Angiotensin-converting enzyme inhibitor-induced angioedema: late onset, irregular course, and potential role of triggers.

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.

Tolerability of enalapril in congestive heart failure.

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)