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Efficacy of mepyramine maleate treatment in dogs with angioedema
Abstract
Twenty-seven dogs with angioedema, were enrolled in this clinical study. The cases were randomly assigned to the treatment group (n=15) and untreated placebo control group (n=12). It was concluded that mepyramine maleate has the potential to be helpful for dogs with angioedema.
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The present article gives a summary of suspected adverse reactions reported by Swedish veterinarians during the period 1991-1995. The summary shows that severe adverse drug-reactions sometimes occur in Swedish veterinary practice. In horses, several cases of acute reactions in animals treated with procaine benzylpenicillin were reported and seven horses died within a few minutes after intramuscular injections of the drug. In cattle and swine most reports referred to the use of antimicrobial agents. In dogs reactions to vaccines were the most frequently reported adverse effects. The reactions were, however, usually rather mild. In dogs there were also several reports of severe reactions related to treatments with non-steroid anti-inflammatory drugs (NSAID) and alpha 2-receptor agonists. Amongst the reports six deaths were observed for each of these groups of drugs. In cats, as in dogs, adverse effects to vaccines were the most frequently reported reactions.
Urticaria and angioedema may be elicited by a considerable number of drugs, particularly nonsteroidal antiinflammatory drugs, angiotensin converting enzyme inhibitors, radiocontrast media and antibiotics. Pathogenic mechanisms involved include pseudoallergy, idiosyncrasy and IgE-mediated hypersensitivity, occasionally also IgG antibodies. In this survey the common problems which still lack established diagnostic in vitro tests such as pseudoallergic reactions to analgesic drugs and idiosyncratic side effects to angiotensin-converting-enzyme inhibitors are presented. In addition some examples of drugs are given where, due to progress in research, instead of a pseudoallergic mechanism an immunological pathogenesis could be demonstrated.
H1-antihistamines are the cornerstone of symptomatic treatment in acute and chronic urticaria, in which they not only relieve itching, but also reduce the number, size, and duration of urticarial lesions. Relief of whealing, flaring, and erythema may be incomplete as the vascular effects of histamine are mediated to its action at H2-receptors as well as at H1-receptors, and other vasoactive substances may also be involved. In randomized, prospective, placebo-controlled, double-blind studies, the new low-sedating H1-antihistamines have been found to be effective and safe in urticaria. Sedating antihistamines, although effective, place patients at risk for adverse effects, including decreased psychomotor performance. The response to H1-antihistamines in some types of urticaria, for example, in urticarial vasculitis, is unsatisfactory. An H2-antihistamine administered concurrently with an H1-antihistamine may modestly enhance relief of itching and wheal formation in some patients with urticaria refractory to treatment with an H1-antihistamine alone. The available evidence does not justify the routine addition of H2-antihistamine treatment to H1-antihistamine treatment.
Sudden occurrence of subcutaneous or submucosal swelling, the so-called angioedema, is an established and potentially life-threatening condition. Several forms of angioedema show a great variety of tissue localizations and different underlying mechanisms such as genetic mutations, allergic reactions and nonallergic reactions exist. Unfortunately, angioedema is often unrecognized and/or incorrectly treated. To change this situation, a better understanding of angioedema and possible therapeutic approaches appears necessary.
Recent investigations have shed new light on the pathomechanism of nonallergic drug-induced angioedema and new therapeutic options targeting the kallikrein-kinin system have become available for patients in clinical trials. Furthermore, extensive clinical evaluations of commonly used inhibitors of the renin-angiotensin system have provided reliable data on the incidence of angioedema induced by these drugs. Accordingly, several thousand patients worldwide experience severe fatal attacks although timely medical care would have saved their lives.
Current data suggest that the nonapetide bradykinin plays a crucial role in the pathogenesis of most forms of nonallergic angioedema, while histamine acts as the main biogenic mediator in allergic angioedema. Thus, correct diagnosis is crucial for effective treatment. Standard antiallergic drugs such as glucocorticoids and antihistamines are most probably ineffective in nonallergic angioedema forms.
Urticaria is a relatively common autoimmune/autoreactive skin disorder that may severely impair quality of life. Although rarely life-threatening, widespread urticaria and its associated angioedema can be an extremely disabling and difficult-to-treat condition. Patients may suffer symptoms such as pruritus and disfigurement due to wheals for years or decades. Urticaria is caused by cutaneous mast-cell degranulation attributed to immunological, non-immunological, and idiopathic causes. The last decade has seen some notable advances in the understanding of the etiology and pathogenesis of common forms of urticaria and their management. Furthermore, the wide diversity in urticaria subtypes has been identified and this reflects a partial understanding of the causes or factors that trigger it as well as the molecular and cellular mechanisms that are involved in its physiopathology. In addition, new instruments for diagnosing urticaria variants and for assessing quality of life in urticaria patients have been developed. Finally, several clinical trials have demonstrated the efficacy of novel treatment approaches for urticaria, while other therapeutic concepts are under development. The objective of this article was to review the literature to be able to offer the readers comprehensive and updated information on the basic etiological and physiopathological mechanisms and to make special emphasis on the current management of urticaria, thus promoting continuous medical education.