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2.
Dtsch Med Wochenschr ; 117(9): 337-40, 1992 Feb 28.
Article in German | MEDLINE | ID: mdl-1544354

ABSTRACT

Because she felt unwell, an 80-year-old woman who was receiving treatment with digitoxin (0.07 mg daily) raised the dose on her own initiative to twice or three times the previous level. She then experienced faintness, visual abnormalities and bradyarrhythmia (rate about 40/min). The ECG showed 2 degrees AV block. The digitoxin level was 70.8 ng/ml--far above the upper limit of the therapeutic range (7.5-25 ng/ml). One striking abnormality was thrombocytopenia (33,000/microliters), though the white and red cell counts were normal. Petechiae were not present and there was no evidence of internal bleeding. As the AV block had not produced any critical fall in ventricular rate, there was no need to start treatment with digitalis-binding antibody fragments (Fab fragments). Instead, the patient was given cholestyramine 4 g three times daily with the aim of interrupting the enterohepatic circulation of digitoxin. From then on the rise in platelet count paralleled the fall in digitoxin level. Seven days after discontinuing digitoxin the platelet count reentered the normal range (147,000/microliters). However, the digitoxin level (39.5 mg/ml) was still well above the therapeutic range.


Subject(s)
Digitoxin/poisoning , Thrombocytopenia/chemically induced , Aged , Aged, 80 and over , Cholestyramine Resin/therapeutic use , Diagnosis, Differential , Digitoxin/blood , Electrocardiography , Female , Humans , Poisoning/diagnosis , Poisoning/drug therapy , Thrombocytopenia/diagnosis
3.
Z Kardiol ; 80 Suppl 4: 93-7, 1991.
Article in German | MEDLINE | ID: mdl-1833904

ABSTRACT

Enoximone, a new phosphodiesterase-inhibitor with positive inotropic and vasodilating activities is available for intravenous use in patients with severe heart failure. A review of the current knowledge regarding the adverse effects of this substance reveals that they are characterized by cardiovascular, central nervous, and gastrointestinal side effects. Adverse effects occurred in 20% of patients and were mostly due to the pharmacological properties of enoximone. Cardiovascular side effects (10%) were the most frequent; ventricular and supraventricular arrhythmias were most common. Two to three percent of the patients experienced hypotension due to the vasodilator activity of enoximone. Headache, insomnia, and anxiety were the most frequent adverse effects on the central nervous system. Three percent of the patients treated experienced vomiting, nausea, abdominal pain, and diarrhea. An increase of liver enzymes and serum glucose could be observed, mostly in patients with previous liver disease or diabetes. Pharmacokinetic drug interactions are not known; possible pharmacodynamic interactions result from the pharmacological properties of the drugs. Intravenous therapy with enoximone causes a few serious side effects that can only be controlled by careful observation of the patients treated.


Subject(s)
Cardiotonic Agents , Heart Failure/drug therapy , Imidazoles/adverse effects , Phosphodiesterase Inhibitors , Drug Interactions , Enoximone , Heart Failure/physiopathology , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Imidazoles/therapeutic use
4.
J Cardiovasc Pharmacol ; 14 Suppl 1: S75-7, 1989.
Article in English | MEDLINE | ID: mdl-2480490

ABSTRACT

Clinical trials in patients with congestive heart failure have shown a wide disparity in the hemodynamic responses to chronic therapy with newer positive inotropic drugs. Therefore, the long-term efficacy of enoximone was studied in 10 patients with severe congestive heart failure. Patients were evaluated clinically, left ventricular dimensions and contractile state were assessed by echocardiography, and exercise testing was performed at basic conditions and after 1 and 8 weeks of enoximone treatment with a daily dose between 150-300 mg. Previous therapy of heart failure was continued during the study period. Clinical symptoms of eight patients were improved after 1 week and six patients showed sustained improvement after 8 weeks of enoximone treatment. The administration of enoximone increased ejection fraction by about 25% after 1 week with a similar response after 8 weeks. Five of six patients who were able to perform exercise testing initially experienced an increased exercise capacity over the study period. The enoximone regimen was continued in the responders; after 1 year, data on three patients are available and show sustained efficacy of enoximone treatment in two patients. The administration of the drug was well tolerated without any deterioration of arrhythmias. There is evidence that oral enoximone treatment may be useful as additional therapy in patients with severe heart failure.


Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/drug therapy , Imidazoles/therapeutic use , Aged , Cardiotonic Agents/adverse effects , Chronic Disease , Dobutamine/therapeutic use , Enoximone , Female , Heart Failure/physiopathology , Humans , Imidazoles/adverse effects , Male , Middle Aged
5.
Eur Heart J ; 8 Suppl L: 147-51, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3330526

ABSTRACT

In a randomized, controlled study 10 male patients with angiographically confirmed ischaemic heart disease received AQ-A 39 (falipamil), a heart rate reducing agent in a single intravenous dose (2 mg kg-1) in comparison to propranolol (0.1 mg kg-1). Both drugs reduced heart rate in supine position slightly. The rise of heart rate induced by orthostasis was diminished by AQ-A 39 to 4 +/- 2 beats min-1 and by propranolol 9 +/- 2 beats min-1. After submaximal exercise heart rate during placebo was 129 +/- 3, during AQ-A 39 113 +/- 3 and during propranolol 103 +/- beats min-1. Systolic arterial pressure decreased by propranolol only. The double product obtained by placebo was 231 +/- 10 while it was for 194 +/- 9 after AQ-A 39 and 158 +/- 6 mmHg min-1 after propranolol, respectively. Both substances increased exercise time as compared to placebo. Furthermore, AQ-A 39 increased noradrenaline plasma levels in the upright position and after submaximal exercise compared to the values obtained following placebo. The dose of isoproterenol necessary to induce an increase of heart rate by 20 beats min-1 was after AQ-A 39 4.2 times greater and following propranolol 9.2 times greater than during placebo. The results suggest that AQ-A 39 will be useful in the short term management of patients with ischaemic heart disease.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Coronary Disease/drug therapy , Heart Rate/drug effects , Phthalimides/therapeutic use , Propranolol/therapeutic use , Blood Pressure/drug effects , Clinical Trials as Topic , Humans , Isoindoles , Male , Middle Aged , Physical Exertion , Posture , Random Allocation
8.
Z Rheumatol ; 43(4): 182-4, 1984.
Article in German | MEDLINE | ID: mdl-6495892

ABSTRACT

The influence of maintenance therapy with Isoxicam, 200 mg daily, on digoxin steady-state plasma levels was studied on 12 healthy volunteers. One person dropped out from the investigation program on account of cardiac sensations following the invasion phase with digoxin. No statistically significant differences could be shown during concomitant therapy or after withdrawal of Isoxicam. Neither were toxic glycoside plasma concentrations observed. There were no pathological clinicochemical parameters, in particular no changes in renal function values.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Digoxin/blood , Piroxicam/analogs & derivatives , Thiazines/therapeutic use , Acetyldigoxins/administration & dosage , Anti-Inflammatory Agents/blood , Drug Interactions , Drug Therapy, Combination , Humans , Thiazines/blood
9.
Klin Wochenschr ; 61(18): 883-91, 1983 Sep 15.
Article in German | MEDLINE | ID: mdl-6632729

ABSTRACT

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured concomitantly by a specific and sensitive tlc-method. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro-tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced proportional to the reduction of endogenous creatinine clearance. In older patients the elimination of TA was impaired.


Subject(s)
Kidney Diseases/drug therapy , Liver Diseases/drug therapy , Triamterene/metabolism , Adult , Age Factors , Aged , Biological Availability , Chemical Phenomena , Chemistry , Female , Half-Life , Hepatitis/drug therapy , Humans , Kinetics , Liver Cirrhosis/drug therapy , Male , Middle Aged , Triamterene/blood
10.
Klin Wochenschr ; 61(10): 523-7, 1983 May 16.
Article in English | MEDLINE | ID: mdl-6876685

ABSTRACT

The effect of iv digoxin on normal sinus node function was studied after pharmacologic autonomic blockade (AB) in ten patients. Sinus cycle length (SCL), sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined before and after AB with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg body weight) iv, and 15 min, 30 min, and 45 min after 1 mg iv digoxin. AB resulted in a significant decrease (P less than 0.01) in SCL (916 +/- 158 to 716 +/- 120 ms), in SNRT (1,229 +/- 221 to 871 +/- 190 ms), and in SACT (79 +/- 34 to 44 +/- 10 ms). Fifteen minutes after iv digoxin there was no significant change observed in SCL (716 +/- 120 to 708 +/- 92 ms), in SNRT (871 +/- 190 to 864 +/- 148 ms), or in SACT (44 +/- 10 to 46 +/- 15 ms). Similar results were obtained 30 min after digoxin administration. It is concluded that a single therapeutic dose of digoxin has no direct effect on electrophysiologic parameters of normal intrinsic sinus node function.


Subject(s)
Atropine/pharmacology , Digoxin/pharmacology , Propranolol/pharmacology , Sinoatrial Node/drug effects , Adult , Aged , Female , Humans , Male , Middle Aged , Propranolol/administration & dosage
11.
Eur J Clin Pharmacol ; 25(2): 237-41, 1983.
Article in English | MEDLINE | ID: mdl-6628507

ABSTRACT

With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.


Subject(s)
Triamterene/metabolism , Adult , Biological Availability , Female , Humans , Infusions, Parenteral , Kinetics , Male , Triamterene/administration & dosage
12.
Clin Exp Hypertens A ; 5(2): 249-69, 1983.
Article in English | MEDLINE | ID: mdl-6831748

ABSTRACT

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured by a specific and sensitive tlc-method concomitantly. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced according to endogenous creatinine clearance. In older patients the elimination of TA was impaired.


Subject(s)
Kidney Diseases/metabolism , Liver Diseases/metabolism , Triamterene/metabolism , Age Factors , Aged , Biological Availability , Female , Humans , In Vitro Techniques , Kinetics , Time Factors , Triamterene/analogs & derivatives , Triamterene/blood , Triamterene/urine
13.
Fortschr Med ; 100(43): 1993-6, 1982 Nov 18.
Article in German | MEDLINE | ID: mdl-7152435

ABSTRACT

During the last years as a result of improved diagnostic methods and new developed drugs with different mechanism of action the therapy of congestive heart failure has become more differentiated. Digitalis and diuretics constitute conventional therapy, but systemic vasodilators offer an innovative approach in acute and chronic heart failure. The vasodilators produce disparate modifications of cardiac function depending upon their differing alterations of preload and afterload. Nitrates principally cause vasodilation, nitroprusside, phentolamine and prazosin produce balanced arterial and venous dilation, whereas hydralazine predominantly causes arteriolar dilation. New positive inotropic agents like dopamine and dobutamine are still restricted to parenteral use.


Subject(s)
Heart Failure/drug therapy , Chronic Disease , Digitalis , Dihydralazine/therapeutic use , Humans , Nitrates/therapeutic use , Plants, Medicinal , Plants, Toxic , Pulmonary Edema/drug therapy , Pulmonary Heart Disease/drug therapy , Vasodilator Agents/therapeutic use
15.
Eur J Rheumatol Inflamm ; 5(2): 82-6, 1982.
Article in English | MEDLINE | ID: mdl-7084286

ABSTRACT

The influence of maintenance therapy with benoxaprofen, 600 mg daily, on digoxin steady-state plasma levels was studied in 12 patients with rheumatic disease. No difference could be shown during concomitant therapy or after withdrawal of benoxaprofen (p greater than 0.10 and p greater than 0.90, respectively). Toxic concentrations were not observed. There were no changes in renal function values.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Digoxin/blood , Propionates/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Drug Interactions , Humans , Propionates/therapeutic use , Time Factors
20.
Klin Wochenschr ; 59(12): 617-21, 1981 Jun 15.
Article in English | MEDLINE | ID: mdl-7253536

ABSTRACT

In a prospective study salivary magnesium was measured by atomic absorption spectrophotometry in 168 patients on chronic digoxin therapy. Magnesium concentration in saliva was correlated with clinical data and plasma digoxin levels. A significant elevation in salivary magnesium concentration was caused by digoxin therapy (0.58 +/- 0.39 mmol/l, n = 93) in comparison to patients with no digitalis treatment (0.17 +/- 0.07 mmol/l, n = 35). Magnesium concentrations in saliva were significantly higher in toxic patients (1.1 +/- 0.68 mmol/l, n = 32) than in nontoxic patients. Possibly toxic patients showed a magnesium level of saliva of 0.63 +/- 0.39 mmol/l (n = 40). In 89% of the intoxicated patients salivary magnesium concentrations were higher than 1.0 mmol/l. The overlap of magnesium between toxic and nontoxic patients was less as compared to calcium and potassium concentrations in saliva. No changes were noted in serum magnesium levels. Magnesium concentration in saliva was influenced by chronic digoxin therapy only. No significant increase of magnesium in saliva was observed within 24 h after i.v. injection of 1.0 mg digoxin in four healthy volunteers. It is concluded that salivary magnesium concentration is a valid method for monitoring digoxin therapy in addition to plasma digoxin levels.


Subject(s)
Digoxin/poisoning , Magnesium/metabolism , Saliva/metabolism , Digoxin/blood , Electrolytes/blood , Heart Failure/drug therapy , Humans , Prospective Studies
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