Blockade of Chlorpropamide-Alcohol Flushing by Indomethacin Suggests an Association Between Prostaglandins and Diabetic Vascular Complications

Blood glucose and atherosclerosis.

“…CPAF can be blocked by prior administration of indomethacin; those whose CPAF can be blocked with indomethacin are free of both small vessel and large vessel disease. 50 It was suggested that, since indomethacin is a prostaglandin synthesis inhibitor, prostaglandins might be involved in the pathogenesis of the vascular complications of diabetes. Studies in twins suggest that indomethacin blocking of CPAF may, like CPAF itself, be an inherited phenomenon.…”

Chlorpropamide ? alcohol flush: the case in favour

“…Inhibitors of prostaglandin synthesis, such as indomethacin [27], aspirin [28] and naproxen [12], have also been shown to block the flush reaction, especially in those patients free of complications [27]. This raises the possibility that prostaglandins might be involved in the mediation of CPAF and the complications of diabetes.…”

Chlorpropamide-alcohol flush: a critical reappraisal

“…CPAF blockade by other prostaglandin inhibitors had previously been reported with either acetyl salicylate [20] or indomethacin [19]. In this later study, patients were selected as CPAF-positive on the basis of a substantial temperature rise (> 1.0 ~ in a CPAF test, presumably without reference to placebo testing.…”

“…Nonetheless, prostaglandins were implicated in both the mechanism by which the flush develops [10] and the aetiology of both small and large blood vessel disease in diabetic patients [19], by reasoning similar to that underlying the previous announcement of 'Sensitivity to enkephalin as a cause of Type 2 diabetes' [8], still promoted 3 years later [49]. The blockade of CPAF by naloxone [8] indicated the complexity of the underlying mechanism, as well as providing a lead to disclosing the combination of chlorpropamide and alcohol as the first known stimulus increasing plasma met-enkephalin [13], in both flushers and non-flushers.…”

“…Furthermore, Hillson et al [12], Krbberling et al [17] and Wilkin [21] have all demonstrated that cheek temperature rise after ethanol is determined by the initial cheek temperature among other factors. Early studies at King's College Hospital, London declared there was 'no correlation between the increase in skin temperature and the basal skin temperature' [8], but one was found subsequently [19]. There was no bimodality of basal cheek temperature in patients on long-term chlorpropamide therapy studied in Oxford [11] or in patients given single doses of chlorpropamide or placebo in Germany [17].…”