Related Experiment Videos
Influence of digitalis and diuretics on ouabain binding sites on human erythrocytes
Insights
Chronic digitalis treatment may increase digitalis binding sites on red blood cells. Diuretic use, especially with hypokalemia, significantly elevates these binding sites, impacting cardiac glycoside therapy.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Cell Biology
Background:
- Digitalis glycosides are crucial for treating heart failure.
- Previous studies suggested increased digitalis binding sites with chronic digitalis use.
- The impact of concomitant diuretic therapy on these binding sites was unclear.
Purpose of the Study:
- To investigate the effect of chronic digitalis and diuretic treatment on the number of digitalis binding sites in human erythrocytes.
- To determine if diuretic-induced hypokalemia influences digitalis binding site expression.
Main Methods:
- Quantification of 3H-ouabain binding sites and dissociation constant (KD) in erythrocytes from different patient groups.
- Groups included controls, digitalis-only patients, and patients on digitalis with various diuretic regimens (K+-sparing, K+-losing).
- Analysis included patients with chronic hypokalemia.
Main Results:
- Patients on digitalis alone showed a slight increase in ouabain binding sites compared to controls.
- Concomitant diuretic use significantly increased binding sites (p < 0.001).
- Chronic hypokalemia, particularly with K+-losing diuretics like furosemide, led to the most substantial increase in ouabain binding sites.
Conclusions:
- Diuretic treatment, especially when causing chronic hypokalemia, significantly increases digitalis (ouabain) binding sites in human red blood cells.
- This finding has implications for understanding tachyphylaxis and optimizing cardiac glycoside therapy in patients on diuretics.
- The study highlights the importance of electrolyte balance in digitalis pharmacodynamics.
Abstract:
It has been reported that during chronic treatment with digitalis, the number of digitalis binding sites is increased in human erythrocytes [22]. From this finding a tachyphylaxis for cardiac glycosides has been postulated. We reinvestigated this problem in several groups of patients. The number of 3H-ouabain binding sites per erythrocyte in control persons (group I) was 214 +/- 60, n = 43 (means +/- SD). The dissociation constant (KD) was 1.8 +/- 0.5 nM. Thirteen patients (group II) taking cardiac glycosides only, for at least 6 months, had 281 +/- 99 (p less than 0.05) ouabain binding sites per single red cell, KD = 1.8 +/- 0.7 nM. Group III (34 patients) took digitalis for more than 6 months and diuretics for at least 3 months (352 +/- 126 (p less than 0.001), KD = 1.6 +/- 0.6). Twenty-three of these (group IV) were taking a combination with "K+-saving" diuretics (336 +/- 194 (p less than 0.01), KD = 1.6 +/- 0.5) and (group V, 11 patients) a combination with "K+-losing" diuretics (462 +/- 133 (p less than 0.001), KD = 1.4 +/- 0.4). Nine patients (group VI) had a chronic hypokalemia, mainly due to taking furosemide (437 +/- 98 (p less than 0.001), KD = 1.5 +/- 0.4). Four control persons took 50 mg hydrochlorothiazide daily for more than 4 months without measurable K+-losses and without changes in ouabain binding sites. It is concluded from these findings that diuretic treatment with chronic hypokalemia in addition to digitalis is accompanied by a significant increase in ouabain binding sites in human red cells.(ABSTRACT TRUNCATED AT 250 WORDS)