Glycine/lysine acetylsalicylate inhalation(Vectura)

A 66-year-old man who had end-stage renal disease and was undergoing maintenance hemodialysis presented with facial edema together with a strip of blisters and crust over the right side of his reddened forehead. Initially, the symptoms seemed indicative of herpes zoster ophthalmicus. However, his left periorbital area was more swollen than the infected right periorbital area (Figure 1A). The intense swelling of the eyelids prevented him from opening his eyes and compromised the visual field. The patient’s dermatologicalhistoryshowedthathehadhadlocaltenderness and some tiny red papules over the right side of the forehead for several days. To control the zoster-related intractable neuralgia, he was administered a 3-day course of acetylsalicylate lysine (lysine aspirin, 500 mg, intravenously) at a local clinic during a 2-day interval between hemodialysis sessions right before his admission for the facial and periorbital edema. After acetylsalicylate lysine therapy was withdrawn, the patient was administered a 2-day course of methylprednisolone (10 mg, intravenously, every 8 h) together with celecoxib, and the swelling subsided 2 days later (Figure 1B). Therefore, acetylsalicylate lysine-induced facial and periorbital angioedema were diagnosed. The etiological factors of periorbital edema range from infectious/autoimmune disorders to malignancy/metabolic diseases [1]. However, aspirin-induced periorbital edema is rare. In the general population, the prevalence of aspirin sensitivity is 0.6‐2.5%, and it classically manifests as respiratory reactions or urticaria/angioedema [2]. The main mechanism underlying aspirin-induced periorbital edema is believed to be related to increased microvascular permeability, which causes increasing interstitial fluid pressure in the periorbital dermis that may be even worse in patients without urine output. The management of patients with aspirin-induced periorbital angioedema mainly involves discontinuing the offending drug and avoiding excessive ultrafiltration in hemodialysis. Cyclooxygenase-2-selective non-steroidal anti-inflammatory drugs could be a reasonable alternative choice of therapy in such cases [3].

It has recently been shown that antinociceptive tolerance develops by repeated systemic administration of non-steroidal anti-inflammatory drugs (NSAIDs) metamizol and lysine-acetylsalicylate. This is similar to the tolerance observed with opioid-induced analgesia [Vanegas and Tortorici, 2002, Cell and Mol. Neurobiol. 22, 655-661]. In the present study, we investigated the development of tolerance to the analgesic effects of the additional NSAIDs analgine, ketorolac and xefocam in juvenile and adult rats. After injection of each drug, tail-flick latencies were significantly elevated on the first day followed by a progressive decrease in tail-flick latency (i.e., tolerance) over the 5-day period, as well as cross-tolerance to morphine-induced analgesia. Tolerance to the analgesic effect of all three NSAIDs developed more rapidly in juvenile compared to adult rats. Pretreatment with naloxone completely prevented the analgesic effects of these drugs in tail-flick and hot plate tests for both juvenile and adult rats. Moreover, each NSAID exhibited cross-tolerance when tolerance to morphine had been induced by systemic morphine delivered repeatedly over 5-day period in both age groups. Our data confirm other recent findings that tolerance to the analgesic action of NSAIDs may depend on an opiate-mediated mechanism.