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At least 1,171 records · Page 65Linked to original sources
PubMed1989

[Dosage adjustment of drugs during continuous hemofiltration. Results and practical consequences of a prospective clinical study].

In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments. Under conditions of CVHF, maximum doses were defined for cefotaxime, ceftazidime, digoxin, digitoxin, imipenem, metronidazole++, netilmicin, phenobarbital, phenytoin, theophylline, tobramycin, and vancomycin. For the estimation of sufficient doses without blood level measurements, sieving coefficients (S) were calculated by a new method. In addition, S was integrated as a CVHF-specific factor into a common equation for drug dose adjustment in patients with renal insufficiency. The regression of dosage received from kinetics on blood-level-independent equation adjustment was r = 0.9923. Since the volumes of distribution in ICU patients are variable, it is suggested that further drug monitoring is necessary for toxic drugs.

Adult↗
PubMed1989

Plasma protein binding of ethinyloestradiol: effect of disease and interaction with drugs.

The protein binding of ethinyloestradiol (EE2) was investigated in the plasma from 14 healthy volunteers, 10 patients with hyperbilirubinemia, 10 patients with liver cirrhosis and 10 patients with renal failure. Binding assay was performed by equilibrium dialysis at 37 degrees C. The unbound fraction (mean +/- SD) of EE2 was 1.17 +/- 0.12 (volunteers), 2.74 +/- 0.77 (hyperbilirubinemics; p less than 0.001) 1.51 +/- 0.31 (cirrhotics; p less than 0.01) and 1.44 +/- 0.11 (renal failure; p less than 0.001). Studies with isolated albumin and alpha-1-acid glycoprotein showed that albumin is the major plasma protein to bind EE2. Warfarin (75 microM) and diazepam (75 microM) increased by 5.0% and 3.0%, respectively, the unbound fraction of EE2 when albumin concentration was 15 microM. Under similar conditions, digitoxin did not modify the binding of EE2. At therapeutic concentrations, warfarin and diazepam did not affect the binding of EE2 in plasma.

Adult↗
PubMed1988

Differences in color discrimination between three cardioactive glycosides.

Color discrimination ability of 100 in-patients suffering from congestive heart failure and treated with digitoxin (D), pengitoxin (P), or digoxin (Dg) was determined with the Farnsworth-Munsell 100 Hue test (FM 100) and compared with the color discrimination of 72 in-patients who were not treated with digitalis glycosides (control group C). Parallel to the performance of the FM 100, the glycoside plasma level was measured by radioimmunoassay. The total error score (TES) of the FM 100 was correlated with the glycoside plasma level and the patient's age. In the C as well as in the D or P groups up to 172 errors and in the Dg group up to 586 errors were observed. With the exception of Dg, no differences were observed between the regression lines indicating an age-dependent increase in TES even under D or P treatment. In contrast to the two glycosides, Dg enhances the TES in therapeutically relevant plasma concentrations. The differences between the glycosides are due to differences in their volume of distribution and their plasma protein binding.

Acetyldigoxins↗
PubMedDate not supplied

Binding of organic compounds to rat liver and lung.

The binding of various radioisotopically labeled organic compounds to rat liver and lung was investigated in vitro. Pieces of rat lung and slices of rat liver were incubated at 37 degrees C under a nitrogen atmosphere in a modified Krebs-Ringer phosphate solution (pH 7.4) CONTAININg the compound to be studied. Of the neutral compounds investigated, digitoxin, digoxin and dexamethasone were highly bound to both liver and lung tissue, whereas the degree of binding of amitrole, erythritol, and ouabain was 20% or less. The weak acids which were bound to the greatest extent in both liver and lung were phenobarbital, pentobarbital, and diphenylhydantoin. Barbital was poorly bound, and there was no evidence for the binding of 5,5-dimethyloxazolidine-2,4-dione or p-aminohippuric acid in either tissue. Binding of the cardiac glycosides and the barbiturates directly paralleled their lipid solubilities. The degree of binding of neutral compounds and weak acids to lung and liver tissue did not vary greatly with concentration, even though broad concentration ranges were studied. This was also true of the weak base morphine. On the other hand, the binding to liver and lung of the organic bases nicotine, pilocarpine, d-amphetamine, lidocaine, erythromycin, and chloroquine, did vary with concentration. The quaternary ammonium compound decamethonium was bound only to liver, and this binding also varied with concentration. Two additional quaternary ammonium compounds, tetraethylammonium and N1-methylnicotinamide, were not significantly bound to either tissue. Comparisons on the basis of equal content of solids revealed that the binding of diverse organic compounds in liver is greater than or equal to that in lung.

Amitrole↗
PubMed1986

[The antitoxic action of triamterene in cardiac glycoside poisoning].

The antagonistic effect of triamterene on the toxicity of cardiac glycosides was investigated in conscious rabbits using the infusion method. Pretreatment with triamterene (5 mg/kg and 10 mg/kg) significantly reduces the ouabain toxicity indicated by an increase of the dose producing arrhythmia (from 61 +/- 14 to 121 +/- 17 and 178 +/- 22 micrograms/kg, resp.) and lethality (from 114 +/- 18 to 236 +/- 5 and 329 +/- 11 micrograms/kg, resp.). The triamterene induced increase of plasma potassium concentration may contribute to the antitoxic effect, however, the effect persisted after the decrease of plasma potassium concentration (by addition of NaHCO3) to pretreatment values. Under the influence of digitoxin the antitoxic effect of triamterene (10 mg/kg) is also demonstrated by the delayed appearance of arrhythmias (113 +/- 3 min compared to 78 +/- 5 min) and of lethality (125 +/- 4 min compared to 92 +/- 6 min). Triamterene is not only a prophylactic but also a curative antitoxic agent in the digitalis intoxicated rabbit.

Animals↗
PubMed1985

A simple approach to estimate the variability of individual plasma drug concentrations in patients at a standardized multiple dosing regimen.

Equations were derived to simulate the course of plasma drug concentration versus time curves for a multiple dosing regimen of drugs with a long biological half-life in those cases when Vrel and t1/2 or k in a particular subject do not correspond to the average values underlying the calculation of a standard dose. Extreme course can be expected only when Vrel and t1/2 show deviation from the average values in the opposite direction. Thus, smaller Vrel and longer t1/2 result in an increase, greater Vrel and shorter t1/2 in a decrease in plasma drug concentration after giving the standard dose. An analysis of the course of plasma drug concentration curves at the loading phase permits the estimation of the actual t1/2 in the particular subject. As an application example, the loading phase of digitoxin is presented. The procedure allows an individual dosage adjustment on the condition that plasma drug concentration in the particular subject can be monitored regularly.

Digitoxin↗
PubMed1985

Lack of specificity of current anti-digoxin antibodies, and preparation of a new, specific polyclonal antibody that recognizes the carbohydrate moiety of digoxin.

Current immunoassays for digoxin do not distinguish digoxin from its glycosidic metabolites. We have synthesized a novel digoxin/bovine serum albumin conjugate via reductive ozonolysis of the lactone ring such that the carbohydrate moiety of digoxin remains intact. Antibodies raised against this conjugate show minimal cross reactivity to digoxigenin, bisdigitoxide, monodigitoxide, digoxigenin, and digitoxin. With this antibody, digoxin can be measured in the presence of these metabolites.

Animals↗
PubMed1985

[Use of anti-digoxin antibodies in digitalis poisoning in an infant].

Digitalis poisoning is rare, always iatrogenic and potentially lethal in infants. We report one case of severe poisoning in which treatment with digoxin Fab antibody fragments was successful. Evolution of plasma digitoxin levels showed an initial rapid decrease (T 1/2:1 hour), then a slower decline (T 1/2:5.5 days). No undesirable side-effects were observed.

Antibodies↗
PubMed1972

Ultrastructural changes in hepatocytes induced by pregnenolone-16a-carbonitrile (PCN).

Pretreatment with pregnenolone-16a-carbonitrile (PCN) protects the rat against the toxic effects of indomethacin, digitoxin, cyclophosphamide and many other injurious agents. In experiments in vivo Selye has recently shown that conditioning by higher PCN doses gives broader "protection spectra". In the present experiments, we studied the effect of different doses of PCN on the ultrastructure of the hepatocytes. PCN was administered to the groups of female rats at doses of 1.0, 0.1 and 0.03 mg, twice daily for three days respectively. Sixteen hours after the last dose, the specimens of liver tissue were fixed, dehydrated and embedded in Epon resin; the ultrathin sections selected from midzonal areas were negatively stained and studied under the electron microscope. We found that PCN produces morphological changes in rat hepatocytes mainly by smooth-surfaced endoplasmic reticulum (SER) proliferation and that the degree of ultrastructural alteration is dose dependent.

Animals↗
PubMed1979

[Haemoperfusion on coated activited charcoal. Experience in French anti-poison centres based upon 60 cases (author's transl)].

Sixty three sessions of haemoperfusion on coated activated charcoal were carried out in 60 cases of poisoning. The indications concerned 2 clinical situations: - massive poisoning with coma (by hypnotics or chlorine-containing solvents) with high extracellular concentrations of the toxic agent, with the aim of reducing the duration of the coma; - intoxications with a high mortality rate, such as those due to paraquat, colchicine, digitoxine, tricyclic antidepressants, and heavy metals, even when plasma levels were low in relation to the dose ingested. Such discordance may be related not only to predominantly intracellular fixation, but also to low intestinal absorption. The effectiveness of haemoperfusion was estimated in terms of the amount of toxic substance extracted, measured either indirectly by repeated calculation of the arteriovenous difference multiplied by the flow rate through the column, or directly by elution of the column. This method for the removal of toxic substances would not appear to be life-saving, is too costly for the extraction obtained and is not free from specific complications. Thrombocytopaenia remains an epiphenomenon, but the frequency of infection is significantly higher than with haemodialysis. An effective and safe method for the vascular extraction of poisons, particularly one favourising removal of toxic substances from intracellular localisation, remains to be found.

Antidepressive Agents, Tricyclic↗
PubMed1979

[Antiaccelerative and antiarrhythmic effect of veratramin on myocardial cells in culture].

It is shown that veratramin (2.5 X 10(-5)M) inhibits, partially or completely, the accelerative effect of adrenalin (5.5 X 10(-7) M), isoproterenol (10(-7) M), prostaglandin E2 (5 X 10(-5) M), and glucagon (10(-5) M) in experiments on cultures of newborn rat cardiac cells and the effect of histamine on 3--4-week embryo cultures. Veratramin (1.25--25 X 10(-5) M) arrests digitoxin-induced (1.25 X10(-5) M--5 X 10(-5) M) fibrillation of individual cells and of cell groups. Veratramin alone and in combination with adrenalin does not change the inotropic parameters of individual cells. Bearing in mind that veratramin (2.5 X 10(-5) M) inhibits the accelerative effect of substances which activate and those which do not activate adenylatecyclse, as well as the fact that it has no effect on the content of cAMP in cultures and does not correct the increase in the cAMP content induced by adrenalin (5.5 X 10(-7) M), the authors conclude that the chronotropic effect of veratramin is not associated with the cell receptor mechanisms but is due to its effect on the transport of ions through the cell membrane, which is a responsible process in the generation of impulses.

Animals↗
PubMed1982

[Digitalis therapy in the aged].

Cardiac glycosides still belong to the most frequently prescribed drugs, although the usefulness of digitalization in patients with sinus rhythm has been repeatedly challenged. In elderly patients, especially, the objective hemodynamic improvement remains minimal and treatment can often be interrupted without subsequent deterioration. On the other hand, signs of digitalis toxicity, such as nausea, vomiting, AV-block, ventricular extrasystoles or CNS-symptoms, occur in 15-30% of patients. Adverse effects are mainly due to toxic accumulation of digoxin in cases with age related reduction of kidney function. In view of its non-renal elimination digitoxin would seem to have a certain advantage in geriatric patients, however, its long t 1/2 (6-7 days) makes dose adjustments more difficult, as peak effects will only be attained after 4-5 weeks. For these reasons digitalis treatment in elderly patients should not be given without clinically manifest congestive heart failure and/or atrial fibrillation. Even in such cases a periodic reassessment of the therapeutic indication is recommended. Suspected "latent" cardiac failure or cerebrovascular insufficiency are no reasons for utilizing such potentially toxic drugs.

Aged↗
PubMed1983

Use of photolabels to probe the Na,K-ATPase and the beta-adrenergic receptor.

Radioactive photoaffinity labels have been used to probe the cardiac glycoside-binding site of Na,K-ATPase and the catecholamine-binding site of the beta-adrenergic receptor. For the Na,K-ATPase, a systematic positioning of the photoactive group on the first, second, and third digitoxoses of digitoxin showed that the specific radioactivity in the alpha subunit decreased 5- to 20-fold as the photoactive group was extended further away from the steroid nucleus, whereas the beta subunit is positioned very close to the alpha subunit in the region of the cardiac glycoside-binding site. For the beta-adrenergic receptor, a new class of orthoiodophenylazide derivatives of pindolol was prepared with carrier-free 125I. Photolysis of the beta-adrenergic receptor of duck, turkey, pigeon, and frog erythrocyte membrane with one of these compounds (iodoazidobenzylpindolol) allowed identification of the receptor polypeptides. It was found that the size of the polypeptides and the number of polypeptides varied.

Affinity Labels↗
PubMed1980

ATP-energized Ca2+ pump in isolated transverse tubules of skeletal muscle.

A modified protocol for isolation of transverse tubules incorporated an extra stage of purification. The existence of an ATP-energized Ca2+ pump in transverse tubules isolated from rabbit skeletal muscle has been demonstrated. Isolated transverse tubules had a Ca-ATPase activity of 0.78 mu mol/min . mg; this was 300% in excess of that activity attributable to sarcoplasmic reticulum contamination. The distribution of part of the CaATPase activity and ATP-energized Ca2+ uptake coincided with the distribution of transverse tubules in isopycnic sucrose gradients loaded with mechanically disrupted triad junctions. Transverse tubules accumulated over 70 nmol of Ca2+/mg of protein; this uptake was abolished by the Ca2+ ionophore A23187. Neither digitoxin nor monensin inhibited Ca2+ uptake, indicating that Ca2+ accumulation did not occur through a sodium/calcium exchange. Conditions for half-maximal Ca2+ uptake were 5 micro M free Ca2+ and 10 micro M ATP. The Ca2+ pump of isolated transverse tubules was distinguished from the Ca2+ pump of sarcoplasmic reticulum and sarcolemma in that the transverse tubule Ca2+ pump: 1) was not enhanced by oxalate; 2) was not energized by acetyl phosphate, p-nitrophenyl phosphate, or 3-O-methylfluorescein phosphate; and 3) did not hydrolyze p-nitrophenyl phosphate or 3-O-methyl-fluorescein phosphate. Using Ca2+-dependent 3-O-methylfluorescein phosphatase as a marker for sarcoplasmic reticulum, the contamination of the transverse tubule preparation was calculated to be 6%. This agreed with a contamination level of 5% estimated by freeze-fracture electron microscopy.

Adenosine Triphosphate↗
PubMed1983

[Alternatives to glycoside therapy?].

The narrow therapeutic range of digitalis glycosides and the danger of intoxication has prompted a search for alternative medication in recent years. Substances reducing the pre- and afterload of the heart are suitable therapeutic agents and vasodilators are, therefore, used as adjuvant or alternative therapy. Of all positive inotropic substances only the catecholamines play an established part in the treatment of acute myocardial failure. Pilot studies testing orally administrable positive inotropic substances are being conducted, but for the moment no such drugs are available for routine use. Digitalis still remains the drug of choice for all forms of primary impairment of contractility and/or supraventricular tachyarrhythmias. The appropriate dosage has to be adapted to the estimated lean body mass and, if necessary, reduced in a thin person, Digitoxin is preferentially used in cases with suspected renal insufficiency (especially in elderly patients).

Arrhythmias, Cardiac↗
PubMed1981

Residence time and accumulation of drugs in the body.

This investigation presents a simple and clinically useful theory of drug accumulation based on the mean residence time of drug molecules in the plasma compartment. The parameters decay fraction and accumulation factor, defined in terms of average steady-state amount in the body, are used to characterize the pharmacokinetics of multiple dosing. These parameters are calculated for digoxin and digitoxin.

Digitoxin↗
PubMed1978

Pharmacokinetic aspects of digoxin in patients with terminal renal failure. IV. Clinical implications of own observations with a recent review of literature.

Digoxin dosage regimens for patients on chronic intermittent hemodialysis (CIH) were calculated from pharmacokinetic data of digoxin in these patients between the during hemodialyses. Especially when a maximal digitalisation is not necessary an administration of 0.125 mg digoxin only on days without hemodialysis will be adequate. The regimens should be considered as a suitable starting-point in therapy as individual differences in bioavailability, apparent volume of distribution. clearance and sensitivity may necessitate an individual correction. The place of hemodialysis in the management of severe intoxications will also be discussed. Besides, it is advised to use digoxin instead of digitoxin in patients on CIH.

Digitoxin↗