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Not only has the use of tyrosine kinase inhibitors (TKI) for the treatment of metastatic renal cell carcinomas (mRCC) changed the therapeutic options for this disease significantly, but with the occurrence of typical side effects this therapy also poses a challenge for the treating physician. Fatigue und hypothyroidism are two common side effects of TKI therapy that can often appear simultaneously. By reducing the patients' quality of life these side effects often lead to a discontinuation of therapy. With this review we want to give the treating physician an overview of the classification and the specific treatment of TKI-induced fatigue and hypothyroidism in order to maximize patients' compliance and the therapeutic efficacy of TKI therapy.

Fentanyl was replaced by R 30730/Janssen (Fentatienyl) for neurolept analgesia (with intubation) of 34 persons who had ophthalmic surgery on account of detachment of the retina. The effects of the drug on the size of the pupils, blood pressure, heart rate and respiration were observed; also the duration of analgesia and the incidence of nausea and vomiting. There was a very slight negative effect on the size of the pupil, similar to that seen with halothane; systolic blood pressure fell by an average of 20%; the duration of analgesia and the degree of respiratory depression varied considerably. 12 of the 35 patients suffered from marked nausea and vomiting after the operation.

The antiarrhythmic effect of tocainide, an amine analogue of lidocaine, was tested in the course of a double-blind trial on 12 patients with ventricular arrhythmias. Daily dose was 400 or 600 mg every eight hours. In all tested patients the frequency of ventricular extrasystoles, analysed by means of ambulatory 24-hour ECG monitoring, decreased by an average of 70%. In four of nine patients the severity of the ventricular extrasystoles (Lown's classification) was improved by at least one functional class. There was no correlation between the anti-arrhythmic effect and the plasma level of tocainide, which was between 4.1 and 9.7 micrograms/ml. Four patients had side effects in the form of CNS symptoms, but the drug did not have to be discontinued. Tocainide is an orally effective antiarrhythmic drug, an alternative in the treatment of ventricular arrhythmias.

The antiarrhythmic effects of Encainide in acute intravenous and long-term oral therapy were investigated in 10 patients suffering from chronic atrial ectopic beats previously non-responsive to conventional therapy. The efficacy of Encainide was assessed by 24-hour ECG monitoring during the acute i.v. application and in 4 week intervals over a period of 4 to 6 months. Plasma concentrations of Encainide and the O-demethyl- (ODE) and 3-methoxy-O-demethyl metabolites (3-MODE) were determined after i.v. administration and during oral therapy. A significant reduction of arrhythmias by 76% was found after 1.0 mg/kg Encainide given intravenously. Atrial ectopic beats with bundle branch block QRS-morphology were reduced by more than 90% after only 0.5 mg/kg. During long-term oral therapy 6 of the 9 patients were treated successfully. Following i.v. administration Encainide-plasma concentrations rapidly decreased with a half life of approximately 75 min in the final distribution phase. During oral therapy Encainide levels were not detectable under steady state conditions 4 to 6 hours after the last dose, or they were only minimal, but the average concentrations of ODE and 3-MODE were 71.3 +/- 21.3 and 75.6 +/- 13.5 ng/ml. Encainide increased PR interval and QRS duration significantly. QT-interval changed as a result of the QRS-prolongation. Encainide was well tolerated during acute and chronic therapy. No severe side effects were seen, except in one case, in which dose reduction by 50% was necessary because of blurred vision.(ABSTRACT TRUNCATED AT 250 WORDS)