A non-fatal case of intoxication with foxglove, documented by means of liquid chromatography-electrospray-mass spectrometry.

The non-fatal self-poisoning of a 36-year-old female patient, who ingested a concoction of foxglove (Digitalis Purpurea), is presented. On the admission, initial symptoms were nausea and vomiting, abdominal pain, and cardiovascular shock with sinus bradycardia. Blood and urine were assayed for 17 cardiotonic hetorosides, using a highly specific LC-MS procedure. Serum and urine specimens were collected over five days and analyzed by liquid chromatography-electrospray-mass spectrometry (LC-ES-MS). This accurate procedure allowed the determination of the digitalis glycosides and their metabolites in serum and urine. The serum concentrations of digitalis glycosides were maximum on the first day (gitoxin 13.1 ng/mL, digitoxin 112.6 ng/mL, digitoxigenin 3.3 ng/mL, and digitoxigenin mono-digitoxoside 8.9 ng/mL) and decreased over five days. We observed a peak gitaloxin level (112.6 ng/mL) on the fifth day only. After administration of atropine as well as dimeticone, alginic acid, and metoclopramide, health status improved. The peak urine concentrations were reached at hour 30 and were respectively 91.3 and 69.9 ng/mL for gitaloxin and digitoxin, while those of digitoxigenin, digitoxigenin mono-digoxoside and gitoxin were lower (respectively 0.7, 1, and 5.6 ng/mL). The patient was discharged on the fifth day when there were no residual symptoms.

Sodium sensitivity in young adults with high resting end-tidal CO2.

BACKGROUND: Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO2 to high sodium intake was greater than normal. OBJECTIVE: To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO2. DESIGN: Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days (an additional 190 mmol/day sodium chloride). Resting end-tidal partial pressure of CO2 and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet. Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. RESULTS: Subjects with high end-tidal partial pressures of CO2 had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading. Sodium loading decreased mean partial pressure of CO2 (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group. However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P < 0.05) blood pressure after sodium loading were all positive functions of individual resting end-tidal partial pressures of CO2. Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO2. CONCLUSIONS: The results indicate that a high resting partial pressure of CO2 augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans.

Digitalis glycosides in serum, urine, and cerebrospinal fluid, determined with a commercial radioimmunoassay.

We evaluated a commercial (Clinical Assays, Inc.) 125I radioimmunoassay for digitoxin for use in measuring cardiac glycosides in serum, buffer, urine, and cerebrospinal-fluid samples. We also assessed interference of seven cardioactive metabolites of digitoxin, including digoxin, with the assay. The precision of the assay was adequate for all matrixes studied for glycoside concentrations less than 5 microgram/L. Reactivity in the assay was dependent on the nature of the matrix: buffer and serum samples containing digitoxin showed a stronger reactivity than did samples of urine and cerebrospinal fluid. Patients' samples must therefore be analyzed with a standard curve prepared by use of the same matrix. The digitoxosides of digitoxin showed a slightly higher reactivity in the assay than did digitoxin itself, but digitoxigenin showed a 50% lesser reactivity. Digoxin, its digitoxosides, and digoxigenin hardly react at all in the assay and so do not interfere with digitoxin determinations.

Pharmacokinetic investigations with 3H-penta-acetyl-gitoxin in volunteers and patients with respect to the occurrence of drug latentiation.

After oral administration of 3H-penta-acetyl-gitoxin (Pengitoxin W.H.O., Pentagit) 1.5 mg to four volunteers, serum radioactivity diclines with a half-life of 62 +/- 10 hours. After an oral maintenance dose of 0.4 mg pengitoxin in five digitalized patients, four of them with a cannulated bile duct, serum radioactivity declines with half-life of 56 +/- 8 hours. In volunteers within 4 days 50.7% of the administered radioactivity is excreted in urine; in the patients 52.3% in urine and 28.0% in bile. By thin-layer chromatographic studies, 16-acetyl-gitoxin was charactrized as the main metabolite in serum, bile and urine. Furthermore, in the first 8 hours after administration, two additional metabolites occur in urine.

Absorption and metabolism in man of 16-epi-gitoxin, a new semi-synthetic cardioactive glycoside.

The pharmacokinetics of 3H-16-epi-gitoxin have been investigated after oral administration: The peak serum level occurred after 30-60 min, and its subsequent decline was in two phases with half-lives of 3.5 and 19.5 h, respectively. Within 3 days 66-70% of the administered radioactivity were eliminated by renal excretion. In the first 16 h 15% of excreted activity was in metabolites, but thereafter the glycoside was excreted in unchanged form. The metabolites were characterized by thin-layer chromatography and radio-scanning; it is assumed that they correspond to the bis- and monodigitoxosides as well as to the genin of 16-epi-gitoxin. The unusual pharmacokinetics of the glycoside are discussed in relation to its special kinetics at the molecular level, i.e. the rapid dissociation rate of the glycoside-(Na+ + K+)-ATPase-complex.

[Determination of serum-digitalisglycoside concentrations by radioimmunoassay before, during and after operations with extracorporal circulation (author's transl)]. / Radioimmunologische Bestimmung der Serumglykosidkonzentration bei Eingriffen mit extrakorporaler Zirkulation

In 13 adult patients serum-glycoside concentrations, renal glycoside elimination and endogenic creatinine clearance were determined before, during and in the first 4 days following the operation. A postoperative digitalis cumulation has not been seen. But there was a diminished digitalis tolerance in the immediate postoperative phase. Two patients got ventricular bigeminus. The low potassium values at the same time may possibly affect the sensitivity of digitalis.