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At least 1,387 records · Page 77Linked to original sources
PubMed1981

[Ambulatory treatment of heart rhythm disorders].

Partial suppression of symptomatic arrhythmias is feasible in most instances. Suitability of drugs for long-term treatment depends on their side effects, costs and action duration. Discrepancies between elimination half life and duration of action are described. Perhaps the most important shortcoming in long-term suppression of potentially dangerous arrhythmias is the short-lived action of most available drugs. In a once-daily regimen with allowance for occasional omission, a drug action duration of more than 48 hours is desirable. This applies only to perhexiline, nadolol, amiodarone, digitoxin, and digoxin in elderly patients.

Ambulatory Care↗
PubMed1983

Serum protein binding of drugs is not altered in patients with severe chronic cardiac failure.

The aim of this study was to investigate whether serum protein binding of drugs is altered in patients with severe chronic cardiac failure. A total of 27 patients of the cardiac unit participated in the study. One group comprised 15 subjects with chronic cardiac failure (grade III-IV according to the New York Heart Association); 12 patients served as controls (grade I-II). The extent of binding was determined in the therapeutic concentration range by means of equilibrium dialysis at pH 7.4 and 37 degrees C. The binding of six marker drugs shows no difference between controls and patients with chronic cardiac failure. Furthermore, measured free fractions were in the range reported in the literature for healthy, untreated individuals. Our selection of drugs comprised substances that are representative of the three major drug-binding sites on human albumin (diazepam-digitoxin-warfarin/phenytoin). Furthermore, propranolol and imipramine represent examples of drugs binding mainly to lipo- and glycoproteins. The results suggest that the binding of most drugs encountered in clinical practice will be unchanged in patients with chronic cardiac failure.

Adult↗
PubMed1983

[Electrocardiographic changes in the rat induced by digitalis glucosides].

Electrocardiographic changes induced by desacetil-lanatoside C and digitoxin, administered intravenously, have been studied in 25 anesthetized rats. No differences were observed between the actions of the two glucosides. Their negative chronotropic action can be effected with two mechanisms: one indirect, through vagal reflex, therefore immediate and, in general, brief; one direct, for direct action on the heart, which is gradual and long lasting. Their action on the a-v conduction is recorded by a rise in the duration of the P-Q tract, or, for higher doses, by blocking fenomena, which are brief and completely reversible. Signs of subendocardial damage are often observed, these too brief. The appearance of extrasystoles is rare.

Animals↗
PubMed1983

[Electrocardiographic changes in the rat induced by high doses of the coenzymatic forms of several vitamins of the B group].

No modification, neither immediate nor late, was observed after the intravenous injection of high doses of the coenzymatic forms of thiamine and pyridoxine. On the contrary, after the injection of high doses of the coenzyme A, a sudden, conspicuous and brief (20-25") diminution of heart rate was observed. Such a phenomenon was much more marked and longer if, before the coenzyme A, a digitalic compound (desacetil-lanatoside C or digitoxin) was administered.

Animals↗
PubMedDate not supplied

[Cardiac insufficiency in the elderly with particular reference to kidney function].

Cardiac insufficiency in the elderly is not a typically age-induced phenomenon, but is rather due to pathological changes of the heart. Renal function, on the other hand, does show age-related deterioration without any apparent pathological changes occurring. For the treatment of cardiac insufficiency in the elderly three groups of drugs are used: diuretics, cardiac glycosides, and vasodilators. When sinusrhythm is still present diuretics should be primarily employed, and in uneffective glycosides, and finally vasodilators. If hypertension is the main cause of heart failure diuretics and vasodilators should be preferred, and glycosides only used in the last instance. Heart failure complicated by tachyarrhythmia should be treated primarily with glycosides, then diuretics and vasodilators. Powerfully as well as long acting diuretics may cause hypovolaemia, hyponatremia, and in particular hypokalaemia in the elderly. Digoxin accumulates with impaired renal function, Digitoxin is not affected by renal function but its half-life is extremely long. In the case of atherosclerotic changes of the vascular system, vasodilators should be employed with caution to prevent extreme drops in blood pressure.

Aged↗
PubMed1981

[Underdosing and overdosing with digitalis].

Incorrect dosage of digitalis occurs frequently and is due in most cases to relative over- or underdosage. The narrow therapeutic range of all cardiac glycosides and the lack of an ideal preparation form the basis, and noncompliance of the ill-informed patient as well as the changing digitalis requirement from patient to patient, and even in the same patient, are the most frequent causes of dosage errors. Important guidelines for the dosage of digoxin and digitoxin (renal failure, diseases of the liver and gastrointestinal tract, body weight, age, electrolyte disorders, hypoxia, thyroid dysfunction and drug interactions) are discussed. Symptoms, signs and treatment of underdigitalization and digitalis intoxication, a frequent and often lethal complication, are reviewed.

Angina Pectoris↗
PubMed1981

Tissue binding sites involved in quinidine-cardiac glycoside interactions.

Quinidine has been shown to alter pharmacokinetics of digoxin by displacing the glycoside from mutual binding sites which are stereospecific with respect to quinidine. Characteristics of the binding site involved in quinidine-digoxin interaction were studied further in guinea pigs and rats. In the anesthetized rat quinidine significantly increased digoxin, but not digitoxin or ouabain, concentration in plasma during an i.v. infusion of a radiolabeled glycoside. In the anesthetized guinea pig, quinidine markedly increased plasma digoxin, but not digoxigenin or dihydrodigoxin, concentrations as estimated from a competitive binding assay using [3H]ouabain and a partially purified Na+, K+-adenosine triphosphatase preparation. Plasma sodium and potassium concentrations were not altered by quinidine either in control or digoxin-treated guinea pigs. In anesthetized guinea pigs, the quinidine concentrations in plasma was 6.4 +/- 1.1 muM after a 260-min fusion of quinidine at a rate of 26 mumol/kg/hr in control animals and 7.9 +/- 1.6 muM in those which were simultaneously infused with digoxin at a rate of 0.2 mumol/kg/hr. Antiarrhythmic agents, lidocaine, DL-propranolol or verapamil, did not cause a significant change in plasma digoxin concentration in the anesthetized guinea pigs. These results indicate that the binding site involved in quinidine-digoxin interaction has a strict structural requirement with respect ot the glycoside. Additionally, of the four antiarrhythmic drugs, quinidine appears to be the only agent which interacts with digoxin.

Animals↗
PubMed1980

Biological evaluation of hemoperfusion in acute poisoning.

The efficiency of Hemoperfusion in acute poisoning cannot be clinically estimated, because: a) concomitant intestinal absorption, hepatic metabolism and urinary excretion must be taken into account. b) with supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of hemoperfusion can only be estimated biologically. Measuring the blood level at the beginning and the end of hemoperfusion as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (form hourly differences of arterio-venous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge. In a practical way, if the blood level of drug is readily available after the patient is hospitalized, the optimum efficiency of hemoperfusion can be estimated beforehand, so that the decision to carry out the hemoperfusion can be maintained, postponed or abandoned. For the most part, the experience of toxicologists has shown hemoperfusion to be ineffective for drugs with weak extra-cellular distribution (such as Digitoxin, Tricyclic drugs, Heavy Metals, Colchicine). Its effectiveness for certain drugs, with poor in vitro dialysance (such as Paracetamol) or with small percentage of intestinal absorption (such as Paraquat) is still debatable. In the case of intoxications by hypnotic drugs, one hemoperfusion allows an average of 4 - 12% of the ingested medium and short barbiturates, 7 - 17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life-saving or insignificant is largely a matter of personal standards.

Barbiturates↗
PubMed1980

Reverse phase thin layer chromatographic procedure for identification of digoxin and related fluorescing substances.

A one-step method was developed to replace the current USP monograph procedrues for identification of digoxin and determination of related fluorescing substances. The new method is much quicker than the previous tests, which required paper chromatography and fluorometric measurements, respectively. Using reverse phase silica gel plates (C18 bonded to silica gel), digoxin was separated from digitoxin, gitoxin, and digoxigenin mono-digitoxoside, and partially resolved from digoxigenin bis-digitoxoside. A digoxin reference standard is used to correlate Rf values for identification, and a dilute solution of gitoxin is also co-spotted to give a maximum intensity limit for related fluorescing substances.

Chromatography, Thin Layer↗
PubMed1980

[Digoxin therapy in the aged under serum level control with special reference to hypertension].

In 125 patients with hypertension in the clinical degree of severity II despite normal concentrations of creatinine and potassium in the serum at the age of more than 65 years significantly higher digoxin serum concentrations of 2.36 +/- 1.19 nmol/l (= 1.84 +/- 0.93 ng/ml) and intoxications than in younger patients with 1.45 +/- 0.55 nmol/l (= 1.13 +/- 0.43 ng/ml) were found. After discussion of the results of other investigators comes the recommendation in patients at an older age (beginning with about 65 years) and in renal insufficiency to apply digitoxin instead of digoxin, taking into consideration the mean maintenance dose of 0.1 mg/die.

Adult↗
PubMed1980

Comparison of adriamycin- and ouabain-induced cytotoxicity and inhibition of 86rubidium transport in wild-type and ouabain-resistant C3H/10T1/2 mouse fibroblasts.

Ouabain (OUA) inhibited 86Rb uptake (50% inhibitory concentration = 0.8 X 10(-4) M) over concentration ranges close to those at which it caused a reversible cytotoxicity (50% lethal dose = 2.5 X 10(-4) M) in growing wild-type C3H/10T1/2 cells. On the other hand, Adriamycin (ADM) inhibited 86Rb uptake (50% inhibitory concentration = 2 X 10(-3) M) but at concentrations 10(4)-fold higher than those causing irreversible cytotoxicity in growing wild-type cells (50% lethal dose = 3 X 10(-8) M). While OUA inhibited 86Rb uptake more in wild-type cells than in a OUA-resistant mutant, ADM inhibited 86Rb uptake to the same extent in confluent wild-type and OUA-resistant cells. Further, three OUA-resistant mutants were not cross-resistant to ADM- or daunomycin (DM)-induced cytotoxicity during log phase or to ADM-induced cytotoxicity at confluence. In addition, ADM, DM, or 5-iminodaunomycin did not displace the cardiac glycosides digoxin or digitoxin from their respective antibody complexes. The order of potency of anthracycline derivatives in inhibiting 86Rb uptake in confluent wild-type cells was the same as their order of inhibiting the growth of wild-type cells and in detaching confluent wild-type cells (DM > ADM > 5-iminodaunomycin) but did not correlate with their cardiotoxic potentials (ADM > DM > 5-iminodaunomycin). Therefore, in this model system, ADM cytotoxicity is mediated differently from OUA cytotoxicity. Further, we find no biological evidence consistent withADM binding to the OUA site on the cell surface (Na+-K+) adenosine triphosphatase and therefore no evidence in this model system that ADM cardiotoxicity could be a digitalis-type toxicity per se.

Animals↗
PubMed1980

Sodium dependence of the positive inotropic effect of cardiac glycosides.

We have investigated the inotropic effects of digoxin, digitoxin and ouabain in cat ventricular muscle under conditions of reduced Na influx in an effort to determine the role of Na in the positive inotropic effect of these cardiac glycosides. When the normal, Na-dependent action potential is inactivated by potassium depolarization, these glycosides retain a positive inotropic effect. In contrast, when muscles are bathed in Na-poor or Na-free solutions, these glycosides do not influence contraction. This suggests that the cardiac glycosides are dependent on Na for their positive inotropic effects.

Animals↗
PubMed1993

Heavy chain position 50 is a determinant of affinity and specificity for the anti-digoxin antibody 26-10.

Antibody produced by a variant of the murine antidigoxin hybridoma 26-10 has reduced affinity for digoxin but enhanced recognition of the digoxin 12-hydroxyl due to a Tyr to His substitution at heavy chain position 50 (Schildbach, J. F., Panka, D. J., Parks, D. R., Jager, G. C., Novotny, J., Herzenberg, L. A., Mudgett-Hunter, M., Bruccoleri, R. E., Haber, E., and Margolies, M. N. (1991) J. Biol. Chem. 266, 4640-4647). Consistent with these data, the 26-10 Fab-digoxin x-ray crystal structure (Jeffrey, P. D., Strong, R. K., Sieker, L. C., Chang, C. Y., Campbell, R. L., Petsko, G. A., Haber, E., Margolies, M. N., and Sheriff, S. (1993) Proc. Natl. Acad. Sci. U. S. A., in press) reveals that Tyr-50 contacts a region of digoxin that includes the hapten-12 carbon. To determine the effects of other heavy chain position 50 substitutions, mutant antibodies were engineered, and their affinities for digoxin and digoxin analogues were measured. The affinity of the mutant antibodies for digoxin roughly correlates with the size of the position 50 side chain. Substitutions of Trp or Phe have no effect on affinity, whereas substitutions of Asn, His, Leu, Ala, Gly, and Asp confer progressively lower affinities. Although Trp and Phe mutants exhibit wild-type specificity, Asn and Asp mutants have improved affinity for digoxin relative to digitoxin (12-deshydroxydigoxin). Leu, Ala, and Gly mutants have improved affinity for 12-acetyldigoxin relative to digoxin as compared with 26-10. These results indicate that position 50 is a determinant of both antibody affinity and fine specificity for antibody 26-10 and that single-amino acid substitutions can alter antibody fine specificity. Models of the mutants were computationally constructed, and haptens were docked into the modeled binding sites. The results suggest that 12-acetyldigoxigenin occupies different orientations in the 26-10 and in the Ala mutant binding sites, resulting in altered binding.

Amino Acids↗
PubMed1995

Accidental intravenous administration of 50 mg of racemic adrenaline in a 2-year-old boy.

A 2-year-old boy received, by mistake, 50 mg racemic adrenaline intravenously, equivalent to 1.8 mg kg-1 of L-adrenaline. The blood pressure increased to 160/105 mmHg, the heart rate to 160 beats min-1, and pulmonary oedema developed over the next 2 h. He was treated with nitroprusside, nitroglycerin and digitoxin, and was intubated and ventilated. After 3 h a hypotensive phase occurred which required infusions of very high concentrations of catecholamines for 72 h. Renal failure required renal transplantation after which the child made an uneventful recovery.

Acute Kidney Injury↗
PubMed1995

Self-treatment with herbal and other plant-derived remedies--rural Mississippi, 1993.

Herbal and other plant-derived remedies have been estimated by the World Health Organization (WHO) to be the most frequently used therapies worldwide. Therapeutic agents derived from plants include pure chemical entities available as prescription drugs (e.g., digitoxin, morphine, and taxol), standardized extracts, herbal teas, and food plants; plant-derived remedies can contain chemicals with potent pharmacologic and toxicologic properties. Although precise levels of use of these remedies in the United States are unknown, in 1991, herbal products accounted for sales of approximately $1 billion. Previous reports about herbal remedies in the rural South have described the use and biologic activities of locally gathered plant species and details of preparation and dosage, but have not determined the prevalence of use of plant-derived remedies in the study population and the prevalence of use of specific remedies. To assess the prevalence of use of plant-derived remedies (excluding prescription drugs) and the prevalence of use of specific remedies in rural central Mississippi, The University of Mississippi conducted a survey during March-June 1993. This report describes two case reports of use of these remedies and summarizes the findings of the survey.

Adult↗
PubMed1994

Functional characterization of the basolateral rat liver organic anion transporting polypeptide.

To characterize the transport functions of a recently cloned basolateral organic anion transporting polypeptide of rat hepatocytes we performed further kinetic transport and substrate cis-inhibition studies in organic anion-transporting polypeptide-cRNA injected Xenopus laevis oocytes. The studies demonstrate saturable Na(+)-independent sulfobromophthalein (Michaelis-Menten constant, 1.5 mumol/L) and taurocholate (Michaelis-Menten constant, 50 mumol/L) uptake by organic anion-transporting polypeptide. Sulfobromophthalein uptake was inhibited by the following organic anions: 0.01 mmol/L bilirubin (43%), 0.1 mmol/L indocyanine green (81%), 0.1 mmol/L 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 52%) and 1 mmol/L probenecid (74%). Competitive inhibition was shown for indocyanine green (inhibition constant about 1.3 mumol/L). Sulfobromophthalein and taurocholate uptakes were also inhibited by cholate, chenodeoxycholate, deoxycholate and ursodeoxycholate, as well as their glycine and taurine conjugates. Organic anion-transporting polypeptide also mediated uptake of glycocholate, tauroursodeoxycholate and taurochenodeoxycholate. No cis-inhibition of sulfobromophthalein uptake was seen in the presence of ATP, para-aminohippuric acid, bumetanide, digitoxin, reduced glutathione, leukotriene C4, nicotinic acid, ouabain, oxalate, rifampicin, succinate or sulfate. Furthermore, radioactively labeled para-aminohippuric acid, alpha-ketoglutarate and reduced glutathione were not taken up by organic anion-transporting polypeptide in cRNA-injected frog oocytes. These data confirm that organic anion-transporting polypeptide represents a novel hepatocellular organic anion uptake system that can mediate Na(+)-independent transport of monovalent (e.g., bile acids) and divalent (e.g., sulfobromophthalein and indocyanine green) cholephilic organic anions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Rehabilitation of patients with chronic cardiac insufficiency. Immediate and midterm effects].

OBJECTIVES: While physical training is known to improve cardiac performance in patients with chronic congestive heart failure, we conducted this study to evaluate the effect of such training programmes. METHODS: The study group included 48 untrained patients with stable chronic heart failure controlled with the same daily oral regimen including 0.25 mg digitoxin, 40 mg furosemide and 50 mg captopril. Halt of the patients (n = 24) entered a physical rehabilitation programme for a 3-week period. Each daily session included passive mobilization of the limbs (10 min), respiratory exercises (10 min) and endurance exercise on an ergometric cycle with a maximum work load of 50, 60 and 70% of the theoretical maximal load for weeks 1, 2 and 3 respectively. The other 24 patients did not change their physical activity level and served as controls. The immediate and medium term effects (3 months after the end of the training programme) were assessed using exercise tests, left ventricular isotopic ejection fraction and plethysmography of the lower limbs. The quality of life was compared using the NYHA functional classification and the Goldsman questionnaire. RESULTS: At the end of the 3-week training period, and compared with the control group, there was a moderate improvement of VO2max (p < 0.02) and a 10% improvement in the ejection fraction (p < 0.05) in the trained patients. There was a clearly significant improvement in the anaerobic threshold and arterial blood flow rate (p < 0.001) and lowered vascular resistance (p < 0.001) and venous tone (p < 0.001). The quality of life was also improved in the training group. However, 3 weeks after the end of the training period, these differences disappeared. CONCLUSION: Patients with chronic heart failure can benefit from physical training showing functional improvement and no deleterious effect on left ventricular function. This beneficial effect is nonetheless temporary and would appear to be due to improved skeletal muscle oxidative capacity and peripheral haemodynamics.

Aged↗