Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart

Hirsh, Paul D.; Weiner, Howard J.; North, Robert L.

doi:10.1016/0002-9149(80)90441-5

Cited by 32 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent observations of decreased tissue glycoside concentrations in animals receiving both drugs as compared to those receiving digoxin alone provide a pos sible explanation for the observation of de creased volume of distribution for digoxin [13]. Decreased tissue glycoside concentra tions further support the observations of de creased cardiac inotropism in spite of the higher serum glycoside levels [14,15].…”

Section: Introductionmentioning

confidence: 83%

“…These observations are in agreement with those reported earlier in hu man subjects [3], The decreased cardiac con centration of digoxin in quinidine-treated an imals as confirmed in our studies using un anesthetized and unrestrained guinea pigs may pose highly significant clinical implica tions. The decreased cardiac stores of digoxin following quinidine provide explanation for decreased cardiac contractile performance observed in subjects receiving both drugs [14,15]. Higher serum glycoside levels secondary to digoxin-quinidine interaction may, there fore, lead to an altered relationship between the serum and cardiac tissue digoxin levels and the cardiac effects.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Digoxin-Quinidine Interaction in Unanesthetized Guinea Pigs

Geiger¹,

Das²,

Parmar³

1982

Pharmacology

View full text Add to dashboard Cite

The clinically relevant interaction between quinidine (3 mg/kg) and digoxin (0.6 mg/kg plus 20 μCi ³H-digoxin) was investigated using unanesthetized and unrestrained guinea pigs for in vivo pharmacokinetic and tissue disposition studies. Quinidine caused a significant elevation of plasma levels of digoxin as early as 5 min after injection, and the increase persisted for at least 8 h. A significant decrease in the volume of distribution for digoxin from 3.6 to 2.7 liters/kg (20%) was observed in quinidine-treated animals. No change was noted in the dominant elimination half-life of digoxin in quinidine-treated animals. The decreased volume of distribution appeared to be due to displacement of digoxin from tissue stores by quinidine as evidenced by decreased tissue to plasma ratios for kidney (41 %), intestine (41%), fat (33%), lung (31%), left ventricle (27%), liver (24%), left atrium (22%), right ventricle (21%), right atrium (18%), pancreas (12%), and bladder (-4%) samples.

show abstract

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Digoxin-Quinidine Interaction in Unanesthetized Guinea Pigs

Geiger¹,

Das²,

Parmar³

1982

Pharmacology

View full text Add to dashboard Cite

show abstract

“…Myocardial performance, as reflected by systolic time intervals, has been reported to worsen despite the increased serum digoxin concentration caused by quinidine (Das et al 1984;Hirsh et al 1980;Steiness et al 1980). However, the evaluation of the combined effects of these 2 drugs on myocardial contractility is complicated by the negative inotropy produced by quinidine.…”

Section: Significance Of the Quinidine-digoxin Interactionmentioning

confidence: 99%

Pharmacokinetic Interactions with Digoxin

Rodin

Johnson

1988

Clinical Pharmacokinetics

100

View full text Add to dashboard Cite

Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin. Drugs which reduce digoxin absorption include the antacids aluminium hydroxide, magnesium hydroxide and magnesium trisilicate, the antidiarrhoeals kaolin and pectin, the hypocholesterolaemic agent cholestyramine and the chemotoxins cyclophosphamide, vincristine and bleomycin. Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients. Capsule preparations of digoxin in solution are less subject to several of the interactions which affect the absorption and bioavailability of digoxin tablets. Various drugs induce alterations in the volume of distribution and clearance of digoxin. Cardiac patients receiving digoxin therapy are particularly prone to interactions with commonly co-administered medications such as the antiarrhythmics quinidine and amiodarone, the calcium channel blockers verapamil and nifedipine, and possibly some vasodilating agents. Studies of digoxin interactions have yielded discrepant results, indicating the need for careful analysis of investigational design before arriving at clinical conclusions.

show abstract

“…Some case reports have implied increased inotropy' I whereas assessment of left ventricular (LV) performance with systolic time intervals has suggested a decrease in inotropy. 6 7 The goal of this investigation was to define the inotropic result of the digitalis-quinidine interaction in conscious dogs. The LV and left atrium (LA) were both examined because of the known differences in anatomic, biochemical, electrical and mechanical properties between atrium and ventricle.…”

mentioning

confidence: 99%

Effect of the ouabain-quinidine interaction on left ventricular and left atrial function in conscious dogs.

Goldman¹,

Hager²,

Olajos³

et al. 1983

Circulation

View full text Add to dashboard Cite

SUMMARY The effect of the ouabain-quinidine interaction was examined in 10 conscious dogs. Left ventricular (LV) pressure, LV dP/dt, LV diameter and left atrial (LA) diameter were measured with highfidelity micromanometers and sonomicrometer crystals. Ouabain, 0.025 mg/kg, significantly (p < 0.05) increased LV dP/dt, LV and LA fractional shortening and LV and LA velocity of circumferential fiber shortening (Vcf). In a separate experiment, quinidine was administered as a bolus dose, 3.85 mg/kg, followed by an infusion, 0.28 mg/kg/min. This resulted in steady-state quinidine concentrations that produced no change in wall motion or hemodynamics. When ouabain was given 1 hour into the quinidine infusion, only LV dP/dt increased significantly (p < 0.05). Ouabain alone increased LV dP/dt 26.4 + 3.5 %, whereas ouabain during the quinidine infusion increased it by 9.5 ± 2.3%. Similar differences were seen in the responses to ouabain in the absence and presence of quinidine: LV Vcf, 22.4 ± 4.9% vs 6.0 ± 2.1%, LV fractional shortening, 23.1 ± 4.6% vs 5.8 ± 2.1%, LAVcf, 22.7 ± 5.9 vs 4.6 ± 2.0% and LA fractional shortening, 21.8 7% vs 7.8 + 3.3%. Thus, in the presence of quinidine the increase in intropy usually seen with ouabain was markedly attenuated. These data suggest that the quinidine-induced increase in digoxin serum concentrations is accompanied by a decrease in the contractile response of the heart to digoxin.DIGITALIS and quinidine have been used together for many years. However, only recently has a pharmacokinetic interaction between digoxin and quinidine been described. 1-3 Serum digoxin levels have been noted to increase two-or threefold in the presence of steadystate quinidine concentrations.' The basis of this interaction appears to be a quinidine-induced decrease in the digoxin volume of distribution and in the total body clearance of digoxin, the latter a result of a diminution in both digoxin renal and nonrenal clearance. Available data suggest that there is an increased vagal or chronotropic effect of digoxin in the presence of quinidine. The impact of this interaction on the inotropic effect of digoxin is unclear. Some case reports have implied increased inotropy' I whereas assessment of left ventricular (LV) performance with systolic time intervals has suggested a decrease in inotropy.6 7 The goal of this investigation was to define the inotropic result of the digitalis-quinidine interaction in conscious dogs. The LV and left atrium (LA) were both examined because of the known differences in anatomic, biochemical, electrical and mechanical properties between atrium and ventricle. In addition, it has been shown that the LA and LV have similar wall velocities at rest, but the velocity of LV shortening was more sensitive to increases in afterload.i Also, cholinergic control is different in the LA than in the LV.9 10 In this study, to ensure that the changes measured were Received July 30, 1982; revision accepted January 28, 1983. Circulation 67, No. 5, 1983 1054 changes in inotropy, the drug doses were ...

show abstract

Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart

Cited by 32 publications

References 21 publications

Digoxin-Quinidine Interaction in Unanesthetized Guinea Pigs

Digoxin-Quinidine Interaction in Unanesthetized Guinea Pigs

Pharmacokinetic Interactions with Digoxin

Effect of the ouabain-quinidine interaction on left ventricular and left atrial function in conscious dogs.

Contact Info

Product

Resources

About