Inotropic Action of Tolbutamide on Human Myocardium

Hildner, Frank J.; Yeh, Billy K.; Javier, Roger P.; Fester, Arieh; Samet, Philip

doi:10.1002/ccd.1810010108

Cited by 7 publications

(1 citation statement)

References 19 publications

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“…Moreover, several studies (Lasseter et al 1972 ;Hildner et al 1975) have reported that a concentration of tolbutamide of 0.1-1.0mM produces a positive inotropic effect. The authers had previously observed prostacyclin synthesis by cultured endothelial cells, using thin-layer radiochromatography (Kawaguchi et al 1982).…”

Section: Discussionmentioning

confidence: 99%

Tolbutamide effect on cultured human endothelial cells with special reference to platelet aggregation.

Kawaguchi

Oribe

Uzawa

1983

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 99%

Tolbutamide effect on cultured human endothelial cells with special reference to platelet aggregation.

Kawaguchi

Oribe

Uzawa

1983

Tohoku J. Exp. Med.

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Adverse Cardiovascular Effects of Sulphonylurea Drugs

Huupponen

1987

Medical Toxicology

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Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.

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Sulfonylurea derivatives in cardiovascular research and in cardiovascular patients

Schotborgh

Wilde

1997

Cardiovascular Research

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Sulfonylurea derivatives are hypoglycemic drugs frequently used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). In the beta-cell sulfonylureas act by blocking ATP-sensitive potassium channels (K.ATP channels). In several organ systems, including the cardiovascular system, sulfonylurea receptors and functional K.ATP channels have been identified. In the heart their role is not clear: an endogenous cardioprotective effect has been suggested. There is no doubt that K.ATP channels are effectively blocked by sulfonylureas. In the last decade sulfonylureas have been widely used as a pharmacological tool in experimental (cardiac) research. Blockade of K.ATP channels is the proposed cellular mechanism of action for all sulfonylurea-related effects. However, other membrane currents are affected as well. In addition, myocardial metabolism is modified by sulfonylurea pretreatment. Hence, it should seriously be questioned whether these drugs are suitable in assessing involvement of cardiac K.ATP channels in, for example, ischemia-related events. The detrimental effects of sulfonylureas in experimental studies on myocardial ischemia have led to speculation whether the widespread use of these drugs in patients with NIDDM, most often suffering from accompanying ischemic heart disease, should be reconsidered. However, a review of the clinical literature reveals that the most consistent finding is a lower incidence of ventricular arrhythmias associated with the use of glibenclamide, while no excess mortality has been shown for this agent in NIDDM with ischemic heart disease. Despite some direct effects on systemic and coronary vasculature, there are, at present, no firm clinical data on the basis of which sulfonylurea derivatives should be withheld from the cardiac patient.

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Inotropic Action of Tolbutamide on Human Myocardium

Cited by 7 publications

References 19 publications

Tolbutamide effect on cultured human endothelial cells with special reference to platelet aggregation.

Tolbutamide effect on cultured human endothelial cells with special reference to platelet aggregation.

Adverse Cardiovascular Effects of Sulphonylurea Drugs

Sulfonylurea derivatives in cardiovascular research and in cardiovascular patients

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