Phenylbutazone and sulfinpyrazone interaction with oral anticoagulant phenprocoumon.

To compare the marked hypoprothrombinemic augmentation in man of racemic warfarin sodium by the pyrazolons phenylbutazone and sulfinpyrazone with that of the coumarin anticoagulant phenprocoumon, these interactions were studied prospectively in six normal subjects. Large single doses of racemic phenprocoumon, 0.6 mg/kg orally, were administered with and without daily phenylbutazone, 300 mg, or sulfinpyrazone, 400 mg, beginning three days before phenprocoumon and continuing for 14 days. Daily blood samples were drawn for phenprocoumon content and one-stage prothrombin time. Phenylbutazone markedly increased both the phenprocoumon concentrations and prothrombin times, whereas sulfinpyrazone did not.

Abnormalities of urinary sediment and renal failure following sulfinpyrazone therapy.

A patient with recurrent thrompophlebitis had sterile pyuria with white blood cell casts and transient, mild renal failure during therapy with sulfinpyrazone. These abnormalities resolved on cessation of therapy, but similar changes in the urinary sediment recurred during therapy with sulfinpyrazone. These abnormalities resolved on cessation of therapy, but similar changes in the urinary sediment recurred during a second course of sulfinpyrazone therapy.

The consent form as a possible cause of side effects.

In a multicenter trial of aspirin or sulfinpyrazone in the treatment of unstable angina, we examined the possible importance to the outcome of mentioning potential side effects in the consent form. Inclusion, in two of the three centers, of a statement outlining possible gastrointestinal side effects resulted in a sixfold increase (P less than 0.001) in the number of subjects in these centers withdrawing from the study because of subjective, minor gastrointestinal symptoms. Major gastrointestinal complications such as peptic ulcer or bleeding as diagnosed by study physicians were similar in the three centers. Furthermore, no patient discontinued therapy because of subjective, nongastrointestinal side effects. Post hoc analysis suggests that the inclusion of gastrointestinal side effects in the consent form may have increased the likelihood of patients attributing gastrointestinal symptoms to drug therapy, leading to subsequent withdrawal from the study.

Role of blood platelets in coronary artery disease.

Over the past decade, research in blood platelet physiology has led to the suggestion that platelets play an important part in the pathogenesis and complications of coronary artery disease. Occlusive intravascular platelet aggregates have been shown to cause ischemic myocardial damage in the experimental animal and to be present in some patients who die suddenly. The interplay between endothelial damage and platelet aggregation has been implicated in the etiology of atherosclerosis. Products released from platelets during aggregation may cause arterial spasm. Patients with overt ischemic heart disease and with the risk factors associated with coronary artery disease have been found to have abnormally reactive platelets. Clinical studies of drugs that inhibit platelet aggregation have been reported to show a beneficial effect in preventing cardiac deaths or myocardial infarction; other studies have been negative or shown only a trend toward benefit. This report reviews the theoretical and experimental basis for the platelet hypothesis and the current data on the use of antiplatelet drugs in patients with coronary disease.

10. Antithrombotic therapy: role of platelet-inhibitor drugs. II. Pharmacologic effects of platelet-inhibitor drugs (second of three parts).

In this three-part series, the first part described the role of platelets in thrombogenesis, this second part considers the pharmacologic effects of platelet-inhibitor drugs, and the third part will discuss their clinical application. This second article comprises (1) the physiologic contribution of the vessel wall to the prevention of thrombosis, particularly the role of prostacyclin, (2) the mechanisms of action of platelet-inhibitor drugs in the prevention of thrombosis, (3) the ideal dose and ideal therapeutic combinations of conventional platelet-inhibitor drugs, (4) other agents and new agents that inhibit platelet function, and (5) drug side effects.

Gastrointestinal blood loss in patients undergoing maintenance dialysis.

Gastrointestinal blood loss was measured for 14 days in 19 patients treated by hemodialysis and in 2 patients treated by chronic ambulatory peritoneal dialysis. 51Cr was used as a marker for erythrocytes. Fecal blood loss was 5.0 +/- 3.3 ml/day in hemodialysis patients who were not taking drugs affecting thrombocyte aggregation and 4.6 +/- 4.3 ml/day in those receiving sulfinpyrazone. There was no relationship between the severity of anemia, duration of dialysis, dose of heparin, grade of uremic intoxication, or dose of aluminum hydroxide and amount of fecal blood loss. It is concluded that gastrointestinal blood loss is not a major determinant of anemia in chronic renal failure. However, sulfinpyrazone is preferable to acetylsalicylic acid for prevention of shunt thrombosis in uremic patients because of their propensity for gastrointestinal bleeding.

Risks and benefits of drugs used in the management and prevention of gout.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are now commonly used for the treatment of acute gout, but caution is required in view of their adverse effects, especially in the elderly. Colchicine is still an effective acute agent, but care must be taken to monitor toxicity. Intra-articular glucocorticosteroid therapy is useful and very safe; oral steroids and corticotrophin (adrenocorticotrophic hormone) may have a small role in acute therapy and seem safe when used over short time spans. Low dose colchicine may have a cost and toxicity advantage over NSAIDs in the prophylaxis of gout when commencing therapy aimed at reducing elevated plasma urate concentrations. Allopurinol is more frequently used than uricosuric agents such as probenecid, and toxicity may be largely avoided by tailoring dosage schedules according to renal function.

Combined aspirin and sulfinpyrazone in the prevention of recurrent hemodialysis vascular access thrombosis.

We carried out a pilot study in 15 hemodialysis patients with recurrent vascular access thrombosis to examine whether the combination of low dose aspirin (85 mg once daily) and sulfinpyrazone (200 mg three times daily) is safe and effective in the prevention of vascular access thrombosis. Hemostatic measurements were performed prior to and after four weeks of starting the drug combination. Baseline values for fibrinopeptide A were elevated in all patients while those for platelet factor 4, fibrinogen, antithrombin III and protein C were generally within normal limits. A major reduction in the frequency of vascular access thrombosis from 0.114 per month to 0.04 per month was noted during combined drug treatment (p less than 0.001). Although in vitro platelet aggregation to various stimuli was markedly suppressed and platelet thromboxane B2 formation was almost completely inhibited in patients on aspirin/sulfinpyrazone, this was not associated with a significant further prolongation of the bleeding time. A relatively high rate of complications, particularly mild gastrointestinal bleeding, was noted in patients on aspirin/sulfinpyrazone that could not be predicted on the basis of pre-treatment hemostatic test results.

A study of the effect of sulphinpyrazone ('Anturan') on blood viscosity.

A double-blind, placebo-controlled crossover study of the effect of sulphinpyrazone on blood viscosity and its determinants (haematocrit, plasma fibrinogen and plasma viscosity) was carried out in 7 healthy male volunteers. Apart from a transient rise in fibrinogen (p less than 0.05) after 3 days of sulphinpyrazone treatment, no significant change in viscosity factors was seen over a 14-day period.

Non oliguric acute renal failure after treatment with sulfinpyrazone.

Two cases with acute reversible renal failure while receiving sulfinpyrazone after acute myocardial infarction are presented. Sulfinpyrazone 200 mg q.i.d. was started a few days after the myocardial infarction. In both patients BUN and creatinine rose significantly, and returned to previous values when the drug was discontinued. No other known causes of renal failure were present in either of the patients.

Decrease in renal function due to sulphinpyrazone treatment early after myocardial infarction.

Twenty-nine patients with recent myocardial infarction were randomly allocated to a placebo group (n = 14) and to a group (n = 15) who received sulphinpyrazone, 4 x 200 mg daily for 7 days. Renal function significantly and transiently deteriorated in the sulphinpyrazone group compared to the placebo group. In the sulphinpyrazone group the 24 hour-urinary prostaglandin E2 and kallikrein excretion were suppressed. These data suggest that the decrease in renal function caused by sulphinpyrazone early after myocardial infarction could be mediated by an inhibition of renal prostaglandin and/or kallikrein-kinin synthesis.

Acute renal failure due to sulfinpyrazone.

A case of sulfinpyrazone-associated acute renal failure is reported. Sulfinpyrazone can cause reversible acute renal failure from acute tubular necrosis in patients with volume depletion. Brown tubular casts on urine microscopy and a fractional excretion of sodium greater than 1 are helpful in the diagnosis. Uric acid nephropathy and allergic interstitial nephritis should be included in the differential diagnosis of sulfinpyrazone-associated acute renal failure. Acute reduction of renal blood flow due to inhibition of renal prostaglandin synthesis and kallikrein activity by the drug is a possible mechanism. Treatment of sulfinpyrazone-induced acute tubular necrosis consists of intravascular hydration, supportive care, and withholding sulfinpyrazone. The patients at risk for acute renal failure due to sulfinpyrazone are those who have intravascular volume depletion as sensed by the kidneys.