Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digitoxin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,351 records · Page 75Linked to original sources
PubMed1991

Blood binding of selezen (imidazole salicylate) in man.

The interactions of selezen (imidazole salicylate) with human blood components were studied by equilibrium dialysis. These interactions were limited to the binding of salicylate to human serum albumin (HSA). The binding was saturable and involved several classes of binding sites with different association constants. A competition study indicated that salicylic acid at high concentration was able to displace warfarin and digitoxin but not glibenclamide from their HSA sites. On the other hand, selezen serum binding was decreased in renal impaired patients and this result was probably linked to the decreases in HSA concentration. So the use of small dosage regimens of selezen to these patients can be proposed. The same recommendation may be done for cirrhotic patients, where the decrease of selezen binding percentage was observed and due to both hypoalbuminemia and hyperbilirubinemia.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

[Pseudotumor cerebri].

Pseudotumor was diagnosed in six patients aged three to 38 years during an eight year period. The diagnosis was based on headache, choked disks and normal cerebrospinal fluid and CT scans. Other symptoms were visual impairment, VIth nerve palsy and ataxia. Sagital sinus trombosis was excluded by angiography or magnetic resonance imaging. Pharmacological treatment with digitoxin, acetazolamide, furosemide or corticisteroids reversed clinical symptoms and signs in two patients. In the other four, shunt surgery with cerebrospinal fluid diversion to the right atrium or the peritoneal cavity rapidly reversed clinical symptoms and signs.

Adolescent↗
PubMed1990

[Heparin-induced thrombocytopenia and thrombosis--a case report].

The course of the disease of a 48-year-old female patient is described who in pre-existing chronic myocarditis (and absolute atrial arrhythmia) during an attempt of rhythmisation with digitoxin and quinidine under protection of heparin developed a fatally ending thrombocytopenia and thrombosis and attention is paid to the necessity of the control of the coagulation status and the numbers of thrombocytes before and after every heparin therapy. The criteria according to Makhoul and Greenberg have a diagnostic value and they shall help in the early recognition of the heparin-induced thrombocytopenia and thrombosis and in the prevention of their full development.

Cerebral Hemorrhage↗
PubMed1990

Interaction between nifedipine and cardioactive drugs.

Nifedipine (N) and dehydronifedipine (DHN) plasma levels were measured by gas chromatography in 37 patients before and 2 h after the intake of 20 mg N. They suffered from cardiovascular diseases and were treated with N in daily doses of 30 or 60 mg in combination with nitrates, beta-receptor blocking agents, digitoxin, saluretics and/or vasodilators for several weeks or months. Simultaneously, blood pressure and heart rate were measured. For comparison, six healthy volunteers between the ages of 25 and 46 years took 20 mg N on an empty stomach. Their mean plasma N level amounted to 47.7 (SD: 13.6) ng.ml-1, the DHN level reached a mean value of 46.7 (SD: 22.8) ng.ml-1 2 h after administration. The mean plasma N level of the patients rose from 14.1 to 34.1 ng.ml-1 and that of DHN, from 5.4 to 16.0 ng.ml-1. In 26 of 37 patients the heart rate increased without correlating with the altitude of the N level. The ratio DHN/N was 0.83 (SD 0.24) in the volunteers, while in the patients it amounted to 0.59 (SD 0.30). If the criterion DHN/N plasma level reached values greater than 1.0 the N degradation was enhanced (n = 4), and if it reached values less than 0.2, N degradation was depressed (n = 9). The results did not indicate inhibition of N degradation under long-term treatment with simultaneously administered cardioactive drugs.

Adult↗
PubMedDate not supplied

The use of zonal ultracentrifugation in the investigation of the binding of delta9-tetrahydrocannabinol by plasma lipoproteins.

The major classes of lipoprotein, very low density, low density, and high density, as well as the lipoprotein-free protein were isolated from plasma by rate-zonal centrifugation. Fractionation of plasma after the addition of delta9-tetrahydrocannabinol (THC) showed that over 60% of the drug is associated with the lipoprotein; the remainder of the drug appears to be bound by albumin. In human plasma the low density lipoprotein is the major lipoprotein; in rat plasma the very low density and high density lipoproteins predominate. The distribution of THC in the lipoprotein reflected this species difference. In both species the distribution of THC among the lipoproteins appears to be related to their content of neutral lipid or total lipid rather than that of phospholipid or protein. Fractionation of plasma after the addition of estradiol, imipramine, prostaglandin E2, digitoxin, or dicumarol demonstrated that the lipoproteins contribute little to their binding. Thus, even among lipid-soluble compounds, the binding of THC in plasma is unusual.

Animals↗
PubMed1987

[Binding of drugs to artificial plasma substitutes].

The binding of different drugs to plasma proteins as well as the binding to other structures (e.g. dialysis membranes, i.v. delivery sets) is well documented and of therapeutic importance. Colloid solutions of macromolecules are widely used as plasma substitutes and plasma expanders. A possible binding of drugs to these macromolecules was investigated by means of equilibrium dialysis. Benzodiazepines, beta-blockers, cardiac glycosides, local anesthetics, non steroidal antiinflammatory drugs, glibenclamide, phenobarbitone and phenprocoumon (10(-7) in 50 mM tris buffer, pH 7.4) were dialyzed against tris buffer diluted (1:5) commercially available plasma substitutes consisting of hydroxyethyl starch (HES), dextran, gelatine and polyvinylpyrrolidone (PVP). Binding to plasma substitutes was observed with the highest values for penbutolol and oxypolygelatine (41%), digitoxin and HES 200 (35%), phenprocoumon and PVP (43%). It is concluded that the binding of drugs to plasma substitutes is in most cases negligible and not of clinical relevance. Since some drugs seem to bind to some extent to different macromolecules this should be borne in mind and could be of some influence e.g. in perfusion experiments with isolated organs.

Chemical Phenomena↗
PubMed1989

[Animal experiment studies of the ocular toxicity of cardiac glycosides].

The addition of different types of cardiac glycosides (strophanthin, digoxin, digitoxin) to the perfusion medium of isolated cat eyes, kept alive by extracorporeal perfusion, leads to changes in ERG. There is a dose-dependent reduction of the b-wave amplitude in scotopic and photopic electroretinogram (ERG). At the same time the implicit time of the potentials increases. In the scotopic-isolated P III component, both amplitude and implicit time increase. The concentrations inducing ERG changes that are fully reversible after cessation of drug application correlate well with the known toxic drug blood levels in humans. The disappearance rate of the drug induced effects was almost equal under these conditions (extracorporeal perfusion) for the different glycosides. In conclusion, our results indicate that at least part of the visual symptoms of glycoside intoxication are already evident at the retinal level.

Animals↗
PubMed1989

[The past and present of cardiac glycosides. II. Structure, physical and chemical properties. Pharmacodynamics].

An outline is presented on the physical and chemical properties and structure of the most important cardiac glycosides, i.e. digoxin, digitoxin and g-strophanthin. The overall effects of cardiac glycosides on the cardiovascular system not only are a composite of changes in the force of ventricular contraction and heart rate but also result from effects on the autonomic nervous system and on vascular smooth muscle. Furthermore reflex adjustments to the initial hemodynamic changes caused by the drug are also important. In the normal heart and circulation cardiac glycosides increase inotropy and decrease the chronotropy and dromotropy of the heart. They increase the peripheral vascular resistance and venous tone. Cardiac output remains unchanged or decreases slightly owing to increased peripheral vascular resistance and slowed heart rate. In patients with compromised cardiac inotropy the effects of the glycosides on the heart is essentially the same as in normal subjects, however by suppressing the enhanced sympathetic activity the negative chronotropic and dromotropic effects are more prominent. Peripheral vascular resistance is lowered, cardiac output and venous capacity are increased.

Cardiac Glycosides↗
PubMed1987

Characterization of the alpha +-like Na+,K+-ATPase which mediates ouabain inhibition of adrenergic induction of N-acetyltransferase (EC 2.3.1.87) activity: studies with isolated pinealocytes.

Ouabain inhibits (IC50 congruent to 200 nM) the congruent to 100-fold adrenergic cyclic AMP stimulation of rat pineal arylalkylamine N-acetyltransferase (EC 2.3.1.87, serotonin N-acetyltransferase, NAT) activity in intact pineal glands. In the present study, ouabain binding sites in pineal membranes were characterized in detail and compared to sites in isolated pinealocytes, which mediate the inhibition of Na+,K+-ATPase, as indicated by 86Rb uptake and norepinephrine (NE) stimulation of NAT activity. High affinity ouabain-binding sites were identified in crude preparations of pineal membranes (Kd congruent to 14 nM; Bmax congruent to 4 pmol/mg of protein) and similar sites were also found in ovine and bovine pineal tissue. The ouabain Kd value for the rat pineal binding sites was similar to the estimated ouabain IC50 values for 86Rb uptake and the NE stimulation of NAT activity in intact rat pinealocytes. In addition, the relative orders of potency of four cardiac glycosides in displacing [3H]ouabain from high affinity binding sites and inhibiting both 86Rb uptake and NE stimulation of NAT activity were the same (acetyldigitoxin greater than ouabain greater than digitoxin greater than strophanthidin). The similarities in the characteristics of the high affinity [3H]ouabain-binding sites and the sites involved in the inhibition of 86Rb uptake and stimulation of NAT activity indicate that an alpha +-like Na+,K+-ATPase mediates the inhibitory effects of ouabain on the adrenergic induction of pineal NAT activity.

Acetyltransferases↗
PubMedDate not supplied

Separation, purification, and characterization of digitoxigenin-monodigitoxoside UDP-glucuronosyltransferase activity.

Glucuronidation of digitoxigenin-monodigitoxoside was investigated in liver microsomes from spironolactone-induced male Wistar rats. Isolation of a specific digitoxigenin-monodigitoxoside UDP-glucuronosyltransferase was possible utilizing chromatofocusing chromatography with a gradient from pH 10.1 to 8.0 after solubilizing the microsomal protein with the nonionic detergent Emulgen 911. The digitoxigenin-monodigitoxoside UDP-glucuronosyltransferase was further purified using UDP-hexanolamine Sepharose 4B affinity chromatography. The highly purified (75-fold) enzyme showed activity toward digitoxigenin-monodigitoxoside and slight activity toward digitoxigenin-bisdigitoxoside, whereas digitoxin and substrates for p-nitrophenol, 17 beta-OH steroid, and 3 alpha-OH steroid UDP-glucuronosyltransferases were not glucuronidated. In addition, bilirubin, morphine, estrone, 4-hydroxybiphenyl, and aromatic amines were not glucuronidated by this protein. These results strongly confirm the presence of a form of UDP-glucuronosyltransferase, which is highly specific for the glucuronidation of digitoxigenin-monodigitoxoside.

Animals↗
PubMed1987

Update on rifampin drug interactions.

Rifampin, a potent inducer of the hepatic microsomal system, has been shown to cause clinically important interactions when combined with other drugs, including oral anticoagulants, oral contraceptives, digitoxin, methadone hydrochloride, sulfonylureas, and barbiturates. Additional literature on previously described interactions has been published recently on quinidine, glucocorticoids, digoxin, and theophylline. New rifampin interactions have been described for cyclosporine, ketoconazole, chloramphenicol, beta-blockers, verapamil, and phenytoin. These interactions seem to be of clinical significance.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside. Differences in activation and induction properties in rat and mouse liver.

Glucuronidation of digitoxigenin-monodigitoxoside (DT1), a metabolite of the cardiac glycoside digitoxin, is mediated by the microsomal isozymes, UDP-glucuronosyltransferase(s) (UDP-GT). The present studies examined the activation and induction properties of UDP-GT activity toward DT1 in hepatic microsomes of rats and mice. When compared to enzyme activity present in native (latent) microsomes of the rat (0.104 +/- 0.010 nmol/min/mg of protein), the activity toward digitoxigenin-monodigitoxoside in mouse native microsomes was 3.5-fold higher (0.379 + 0.44 mumol/min/mg of protein). After treatment with ionic (sodium cholate), zwitterionic [3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS)], or nonionic (Emulgen 911, Triton X-100) detergents, or with UDP-N-acetylglucosamine, enzyme activity in rat microsomes remained unchanged. In contrast, UDP-GT activity (DT1) in mouse liver microsomes treated with detergents or with the nucleotide was increased 2-3-fold above native enzyme activity. Pretreatment of rats with the microsomal enzyme inducers, 3-methylcholanthrene and phenobarbital, had no effect on this enzyme activity, whereas pretreatment with pregnenolone-16 alpha-carbonitrile (PCN) and dexamethasone (DEX) increased enzyme activity toward DT1 800 and 380%, respectively. These findings support the hypothesis that PCN and DEX induce a unique form of UDP-GT in the rat that selectively glucuronidates DT1. In marked contrast, the activity of this enzyme in mouse liver was not affected by pretreatment with any of the microsomal inducers, including PCN and DEX. In both rat and mouse, the P-450p-dependent N-ethylmorphine demethylase activity was increased 10-15-fold in PCN-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Demonstration of a Na+/H+ exchange activity in purified canine cardiac sarcolemmal vesicles.

Purified canine cardiac sarcolemmal membrane vesicles exhibit a sodium ion for proton exchange activity (Na+/H+ exchange). Na+/H+ exchange was demonstrated both by measuring rapid 22Na uptake into sarcolemmal vesicles in response to a transmembrane H+ gradient and by following H+ transport in response to a transmembrane Na+ gradient with use of the probe acridine orange. Maximal 22Na uptake into the sarcolemmal vesicles (with starting intravesicular pH = 6 and extravesicular pH = 8) was approximately 20 nmol/mg protein. The extravesicular Km of the Na+/H+ exchange activity for Na+ was determined to be between 2 and 4 mM (intravesicular pH = 5.9, extravesicular pH = 7.9), as assessed by measuring the concentration dependence of the 22Na uptake rate and the ability of extravesicular Na+ to collapse an imposed H+ gradient. All results suggested that Na+/H+ exchange was reversible and tightly coupled. The Na+/H+ exchange activity was assayed in membrane subfractions and found most concentrated in highly purified cardiac sarcolemmal vesicles and was absent from free and junctional sarcoplasmic reticulum vesicles. 22Na uptake into sarcolemmal vesicles mediated by Na+/H+ exchange was dependent on extravesicular pH, having an optimum around pH 9 (initial internal pH = 6). Although the Na+/H+ exchange activity was not inhibited by tetrodotoxin or digitoxin, it was inhibited by quinidine, quinacrine, amiloride, and several amiloride derivatives. The relative potencies of the various inhibitors tested were found to be: quinacrine greater than quinidine = ethylisopropylamiloride greater than methylisopropylamiloride greater than dimethylamiloride greater than amiloride. The Na+/H+ exchange activity identified in purified cardiac sarcolemmal vesicles appears to be qualitatively similar to Na+/H+ exchange activities recently described in intact cell systems. Isolated cardiac sarcolemmal vesicles should prove a useful model system for the study of Na+/H+ exchange regulation in myocardial tissue.

Alamethicin↗
PubMed1985

Cross-resistance and biochemical studies with two classes of HeLa cell mutants resistant to cardiac glycosides. The unusual behavior of cardenolide SC4453.

In HeLa cells two different types of mutants resistant to the cardiac glycoside ouabain (OuaR mutants) or erythrophleum alkaloid cassaine (CasR mutants) have been obtained. One type of mutants resistant to these compounds (designated as group A) are highly resistant (between 50 and 2000-fold) to various cardiac glycosides and their genins such as ouabain, oleandrin, digitoxin, digitoxigenin, strophanthidin, convallatoxin, gitoxin, gitoxigenin, gitaloxin, bufalin, and digoxigenin, but exhibit no cross-resistance to SC4453, a digoxin analog which contains a pyridazine ring in place of the lactone ring in the C-17 position. The second type of mutants (group B) exhibit cross-resistance to all of the cardiac glycosides including SC4453, but their level of resistance is at least 5-10-fold less than that of group A mutants. Interestingly, both groups of mutants exhibited similar degree of cross-resistance towards digoxin and actodigin (AY22241), indicating some differences in their behavior from other cardiac glycosides. Both classes of mutants exhibit no cross-resistance to a wide variety of other structurally and functionally related compounds, e.g. sanguinarine nitrate, ethacrynic acid, penicillic acid, veratridine, harmaline hydrochloride, 5,5'-diphenylhydantoin, quindonium bromide, methyl quinolizinum bromide, estradiol 17 beta-acetate, 21-acetoxy-pregnenolone, vanadium pentoxide, digitonin, and adriamycin, indicating that the genetic lesions in both groups of mutants are specific for cardiac glycosides. This inference is supported by the observation that both group A and B mutants show reduced binding of [3H]ouabain. In group A mutants, a part of the Na+/K+-ATPase activity is highly resistant to inhibition by ouabain, indicating that the genetic lesion in these mutants directly affects Na+/K+-ATPase. In contrast, the Na+/K+-ATPase from the group B mutants showed similar resistance towards ouabain and SC4453 as observed for the parental HeLa cells, indicating that these mutants are affected in a cellular component, other than Na+/K+-ATPase, which is involved in the interaction of cardiac glycosides with the cells. The lack of cross-resistance of the group A mutants to SC4453 and normal sensitivity of their Na+/K+-ATPase to this compound provides strong evidence that the mechanism of interaction of SC4453 with Na+/K+-ATPase differs from that of other cardiac glycosides.

Abietanes↗
PubMed1985

Characterization of digitalis-like factors in human plasma. Interactions with NaK-ATPase and cross-reactivity with cardiac glycoside-specific antibodies.

Much of the evidence for a physiologically important endogenous inhibitor of the sodium pump has been either contradictory or indirect. We have identified three discrete fractions in desalted deproteinized plasma from normal humans that resemble the digitalis glycosides in that they: are of low molecular weight; are resistant to acid and enzymatic proteolysis; inhibit NaK-ATPase activity; inhibit Na+ pump activity in human erythrocytes; displace [3H]ouabain bound to the enzyme; and cross-react with high-affinity polyclonal and monoclonal digoxin-specific antibodies but not with anti-ouabain or anti-digitoxin antibodies. An additional fraction cross-reacted with digoxin-specific antibodies but had no detectable activity against NaK-ATPase. The three inhibitory fractions differed from cardiac glycosides in that their concentration-effect curves in a NaK-ATPase inhibition and [3H]ouabain radioreceptor assays were steeper than unlabeled ouabain. This suggests that these inhibitors are not simple competitive ligands for binding to NaK-ATPase. In the presence of sodium, no fraction required ATP for binding to NaK-ATPase, and in the presence of potassium, only one fraction had the reduced affinity for the enzyme that is characteristic of cardiac glycosides. Unlike digitalis, all three NaK-ATPase inhibitory fractions stimulated the activity of skeletal muscle sarcoplasmic reticulum Ca-ATPase. The presence of at least three fractions in human plasma that inhibit NaK-ATPase and cross-react to a variable degree with different digoxin-specific antibody populations could explain much of the conflicting evidence for the existence of endogenous digitalis-like compounds in plasma.

Adenosine Triphosphate↗
PubMed1986

Biochemical and cross-resistance studies with HeLa cell mutants resistant to cardiac glycoside SC4453. Regulation of the resistant form of Na+/K+-ATPase in the mutant cells.

In HeLa cells, stable mutants which are between 25-to about 200-fold resistant to the cardiac glycoside derivative SC4453 (a digoxin analog which contains a pyridazine ring in place of a lactone ring in the C-17 position) have been isolated after a single step selection in the presence of the drug. Based on their cross-resistance pattern towards various cardiac glycosides, the mutants resistant to SC4453 (SCR mutants) appear to be of two different kinds and they differ from the two classes of ouabain-resistant mutants described previously (Gupta, R. S., and Chopra, A. (1985) J. Biol. Chem. 260, 6843-6850). One type of SCR mutants (designated as group C) exhibit a high degree of cross-resistance to all cardiac glycosides and their genins (viz. ouabain, digitoxin, digoxin, digoxigenin, convallatoxin, gitoxin, strophanthidin, and bufalin). In contrast, the second type of SCR mutant (group D) exhibit considerable resistance to only SC4453, digoxin, and digoxigenin, but showed very little or no cross-resistance to the other cardiac glycosides examined. The cross-resistance of the mutants towards cardiac glycosides was highly specific as they exhibited no cross-resistance towards a large number of other structurally and functionally related compounds (viz. ethacrynic acid, sanguinarine nitrate, penicillic acid, methyl quinolizinum bromide, 5,5'-diphenylhydantoin, deoxycorticosterone, vanadium pentoxide, and adriamycin). The cellular uptake of 86Rb in the mutant cells was found to be resistant to specific cardiac glycosides. Studies on the sensitivity of plasma membrane Na+/K+-ATPase to cardiac glycosides show that about 10-15% of the enzymic activity in the mutant cells was highly resistant to inhibition by the specific drugs to which the mutants exhibit increased resistance. Very interestingly, when the mutant cells are grown in cardiac glycoside-containing medium, the resistant form of the enzyme accounts for about 50-60% of the total enzyme. These results show that both classes of SCR mutants are affected in Na+/K+-ATPase and that the amount of the resistant enzyme in the mutant cells is regulated in response to cardiac glycosides.

Cardiac Glycosides↗
PubMed1986

[Active principles of plant origin: a tool for studying membrane receptors].

Ever since ancient times, considerable interest has been shown in plants for therapeutic use. Nowadays, however, studies of plant extracts are no longer based on empiricism; they provide great support to fundamental research, especially for a better understanding of the mediator/receptor couples. This applies to the study of cholinergic (atropine, muscarine, etc.), adrenergic (yohimbine, rauwolscine, etc.), dopaminergic (apomorphine, bromocriptine, etc.), purinergic (caffeine, theophylline, etc.), opiate (morphine), GABA (strychnine, muscimol, bicuculline, etc.), cardiac glycosides (gitaloxin, digitoxin) and PAF-acether receptors (ginkgolides from Ginkgo biloba).

Cell Membrane↗
PubMed1987

Monovalent cation dependence of tissue plasminogen activator synthesis by HeLa cells.

HeLa cells synthesize and secrete increased levels of tissue plasminogen activator (tPA) when incubated for 18 h with 10-20 nM phorbol myristate acetate. This response was inhibited by a number of conditions which affect intracellular Na+ and K+ concentrations. Removing extracellular Na+, while maintaining isotonicity with choline+, reduced the secretion of both functional and antigenic tPA in a linear fashion. A series of cardiac glycosides and related compounds strongly inhibited tPA secretion with the following rank order of potency: digitoxin = ouabain greater than digoxin greater than digitoxigenin greater than digoxigenin greater than digitoxose greater than digitonin. These compounds also inhibited cellular Na+/K+-ATPase activity over an identical concentration range. Two compounds which selectively increase cellular permeability to K+, valinomycin, and nigericin, strongly inhibited tPA secretion, with IC50 values of approximately 50 nM. In contrast, monensin, which selectively increases cellular permeability to Na+, was much less active. Valinomycin, but not nigericin, also inhibited cellular Na+/K+-ATPase activity. Phorbol myristate acetate, 5-20 nM, increased Na+/K+-ATPase activity up to 2-fold and tPA secretion up to 15-fold. We conclude that the secretion of tPA by HeLa cells treated with phorbol myristate acetate proceeds via a mechanism which requires extracellular Na+ and a functional Na+/K+-ATPase ("sodium pump") enzyme.

Cations, Monovalent↗