Digitalis tolerance and effect of acetyl-strophanthidin upon serum potassium of dogs with acidosis and uremia

Schäfer, Hans Hendrik; Witham, A.Calhoun; Burns, Julie H.

doi:10.1016/0002-8703(60)90198-8

Cited by 17 publications

(2 citation statements)

References 7 publications

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“…This behaviour could also be confirmed in experiments on intact animals (Baker, 1947;Lown et al, 1952;Schafer et al, 1960;Schaumann and Chatoor, 1966;Lown and Wittenberg, 1968) as well as on isolated cardiac muscle preparations (v. Konschegg, 1913;Friedman and Bine, 1947; Burstein et al, 1949; Garb and Venturi, 1954;Miiller, 1963;Baker and Willis, 1970;Prindle et al, 1971;Fricke and Klaus, 1971b). However, recent invitro studies by Fricke and Klaus (1971b) with strophanthidin-3-Fn'cke and Klaus, The influence of reduced serum potassium level 63 bromoacetate (SBA), and alkylating derivative of strophanthidin, first described by Hokin et al (1966), challenged this well-known potassiumdigitalis antagonism: Whereas the toxicity of strophanthidin and digitoxin was decreased -as expected -by an increase of the extracellular potassium concentration from 5 mmoles/1 up to 16 mmoles/1, the toxicity of strophanthidin-3-bromoacetate remained unchanged.…”

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confidence: 67%

The influence of reduced serum potassium level on the toxicity of some cardenolides in guinea pigs

Fricke

Klaus

1981

Basic Res Cardiol

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Recent experiments on the pharmacological properties of the semisynthetic cardiotonic steroid strophanthidin-3-bromoacetate (SBA) have challenged the well-known potassium digitalis antagonism in isolated heart muscle preparations. In order to establish these results in vivo, the minimum lethal doses (LDmin) of ouabain (OUA), digoxin (DO), digotoxin (DT), k-strophanthidin (STR) and SBA were determined by the infusion toxicity method in guinea pigs at normokalemia and hypokalemia. The experimentally induced decrease of the serum potassium concentration (5.0 mmoles/l vs. 3.3 mmoles/l) significantly reduced the LDmin of DO (1.42 vs. 1.05 mumoles/kg), DT (1.78 vs. 1.24 mumoles/kg) and STR (20.16 vs. 15.98 mumoles/kg), whereas the LDmin of OUA (0.37 vs. 0.34 mumoles/kg) was not altered. Contrary, the LDmin of SBA was even slightly, but not significantly increased during hypokalemia (16.77 vs. 19.04 mumoles/kg). In addition, from the experimental data an optimum time of infusion (Topt), corresponding to the LDmin, can be derived, which is equivalent to the time for optimum "utilization" of the drug. The obtained sequence: STR less than OUA less than DO less than DT less than SBA represents the well-known differences in the onset of the pharmacological action in man resp. animal. Hypokalemia in general resulted in a shortening of the Topt, thus indicating a more rapid "utilization" of the drug tested. The above differences of the cardenolide action at reduced serum potassium concentration may be dependent on the recently reported divergent influence of potassium on the association- resp. dissociation rate constants for the interaction of these drugs with their binding site at the Na+-K+-ATPase.

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confidence: 67%

The influence of reduced serum potassium level on the toxicity of some cardenolides in guinea pigs

Fricke

Klaus

1981

Basic Res Cardiol

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“…The method as used gives an estimate of CO2 content. Acidosis may counteract the toxic effect of digitalis as a result of cellular influx of hydrogen ion and sodium and efflux of potassium (Bliss, Fishman & Smith, 1963;Schafer, Witham & Burns, 1960), a phenomenon which could be associated with reduced tissue binding of digoxin. Coltart (1978) reported that hyperkalemia in dogs reduces the digoxin induced inhibition of Na + -K+ -ATPase activity and also reduces total and microsomal-bound myocardial digoxin concentrations.…”

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confidence: 99%

Loading dose of digoxin in renal failure.

Gault¹,

Churchill²,

Kalra³

1980

Brit J Clinical Pharma

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1 Twenty‐two dialysis dependent patients received an intravenous loading dose of digoxin of 10 microgram/kg and the mean +/‐ s.d. serum digoxin concentration 24 h later was 1.5 ng/ml +/‐ 0.4 (range 0.8–2.1 ng/ml). No evidence of toxicity was observed. 2 The average apparent volume of distribution of digoxin in dialysis dependent patients was found to be reduced by about one third compared with that reported for individuals with normal renal function, but there was great variation. 3 An appropriate intravenous loading dose of digoxin in most patients with advanced renal failure is 10 microgram/kg.

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