Factors influencing the spontaneous reporting of adverse drug reactions--the experience of the Slovak Republic.

The system of adverse drug reaction (ADR) monitoring in the Slovak Republic is greatly influenced by changes taking place in the current health care delivery system. Under-reporting and reporting biases due to selective ADR reporting provide very serious problems in pharmacovigilance. In the year 2001, the number of reported ADRs increased due to reports of angiotensin converting enzyme (ACE) inhibitor-induced cough; this coincided with limits being imposed on the use of angiotensin-II receptor antagonists. These factors provide an example of selective ADR reporting, deforming the quality of drug safety monitoring. They also indicate that administrative strategies can significantly affect spontaneous reporting activities.

Evaluation of ischemia-reperfusion injury by malondialdehyde, glutathione and gamma-glutamyl transpeptidase: lack of specific local effects in diverse parts of the dog heart following acute coronary occlusion.

Alterations in the levels of glutathione, glutathione disulfide, malondialdehyde, and the activity of gamma-glutamyl transpeptidase in nonischemic and ischemic parts of the left ventricle and in the right ventricle were studied in canine hearts after occlusion of the left anterior descending coronary artery for 60 minutes and subsequent reperfusion for 20 minutes. Ischemia caused no significant change in malondialdehyde concentration and gamma-glutamyl transpeptidase activity in ischemic or nonischemic parts of the left ventricle, but it increased the activity of gamma-glutamyl transpeptidase in the continuously perfused right ventricle. Reperfusion of the ischemic areas of the left ventricle was accompanied by accumulation of malondialdehyde and an increase in gamma-glutamyl transpeptidase activity, not only in the reperfused and adjacent areas of the left ventricle, but also in the continuously perfused right ventricle. An increase in the level of glutathione disulfide and decrease in glutathione occurred in all parts of the myocardium during coronary occlusion; these changes were maintained in reperfusion. The findings indicate that the effects of acute occlusion and reperfusion of the left anterior descending coronary artery on myocardial concentrations of glutathione, glutathione disulfide and malondialdehyde or gamma-glutamyl transpeptidase activity are not confined to the local area.

[The effect of diltiazem on atrioventricular conduction in dogs]. / Ucinky diltiazemu na átrioventrikulárny prevod u psa.

The effect of diltiazem on atrioventricular conduction was studied in pentobarbital anesthetized dogs, conscious dogs, and atropine pretreated conscious dogs. In anesthetized dogs diltiazem administration resulted in diminished heart rate and aortal pressure, as well as prolongation of the functional refractory period of the AV node and of AV conductance. The effective refractory period of the atria and intraatrial conductance were not affected. The function of the AV node was comparable in the three groups studied. An anticholinergic action of diltiazem affecting the AV node has thus to be excluded. The recorded slight increase in heart rate in conscious dogs may be accounted for by the activation of baroreceptors induced by decreased aortal pressure.

Differences in the responses of the canine basilar and dorsal pedal artery to phenylephrine, clonidine and serotonin.

The effects of phenylephrine, clonidine and serotonin were studied on isolated preparations of the canine basilar and dorsal pedal artery. Differences were mainly observed in the responses of the two types of arterial preparations to clonidine and phenylephrine. While in the dorsal pedal artery, alpha 1- and alpha 2-receptors were involved in the response to alpha-agonists, in the basilar artery contractions induced by alpha 2-receptor stimulation prevailed. Moreover, in the latter artery the contractile responses induced by each of the agonists used were more dependent on the presence of extracellular calcium than those in the dorsal pedal artery.

[Vasodilating effects of etimizol in vitro and its relation to purinergic receptors]. / Vazodilatacné úcinky etimizolu in vitro a ich vztah k purínergickým receptorom.

The paper is concerned with the effect of the breath analeptic agent etimizole on the smooth muscle of vessels under in vitro conditions from the viewpoint of its assumed interaction with purinergic receptors. Isolated preparations of the coronary artery and a. dorsalis pedis of the dog served as experimental material. Etimizole administered in a cumulative manner in dependence on concentration decreases the strength of contraction of the preparations contracted with K+ ions. This relaxant effect, similarly as the effect of adenosine, is not affected by a removal of the endothelium, can be inhibited with theophylline and potentiated with dipyridamole. Etimizole in higher concentrations inhibits the response of vascular preparations to electrical stimulation. In the concentration of 10(-4) mol.l-1 it potentiates the relaxant effect of adenosine, the experimental effects not differing from the theoretical curve for the addition of effects. The obtained results support the assumption that the vasodilating effect of etimizole is mediated prevalently by P1 purinergic receptors.

[Hemodynamic effects of etacizine and lidocaine after intravenous administration in dogs]. / Hemodynamické úcinky etacizínu a lidokaínu po intravenóznom podaní u psa.

In acute experiments on anaesthetized dogs, the haemodynamic effect of etacizine (0.5 and 1.0 mg.kg-1 i.v.) and lidocaine (2.5 and 10 mg.kg-1 i.v.) were compared. Etacizine produced a decrease in heart rate and a temporary decrease in myocardial contractility. After the dose of 1 mg.kg-1 there occurred a temporary increase in peripheral vascular resistance. It did not affect aortal blood pressure, systolic and minute output volume of the heart. Lidocaine produced a decrease in heart rate, aortal blood pressure, systolic and minute output cardiac volume with a rapid return to the original values. Besides this negative effect it was possible to observe an increase in the minute output volume and peripheral vascular resistance with larger doses, which gives evidence of the central effect of the drug.

[Comparison of the effect of BL 343 Ac with beta-adrenolytics on heart muscle preparations]. / Porovnanie úcinkov látky BL 343 Ac s niektorými betaadrenolytikami na preparátoch srdcového svalu.

The paper evaluates the effect of the newly synthesized substance BL 343 Ac--propyl-4[(2-hydroxy-3-isopropylamino)-propoxy]carbanilate hydrochloride--on mechanical parameters of the myocardium of isolated guinea pig atria. At high concentrations of the substance a negative inotropic and chronotropic effect and prolongation of the functional refractory period of the preparations were recorded. These effects were comparable to those of propranolol and metipranolol. Furthermore, a mild increase in the rate of the reserpinized atria after application of 10(-7) mol.l-1 BL 343 Ac suggests a possible intrinsic sympathetic activity of the substance. BL 343 Ac has an antiisoprenaline effect with a pA2 value comparable to that of propranolol and metipranolol. However the slope of the Schild plot was different from 1, indicating that the substance possesses also other than competitively beta-adrenolytic properties.

Heterogeneity in the response to histamine of isolated dog arteries.

Arterial rings were used to evaluate the differences in the effect of histamine (HIS) on canine dorsal pedal (DPA) and coronary arteries. Moreover, the responses of intact coronary arteries (IA) to HIS were compared with those of arteries isolated from sham operated dogs (SA) and from dogs in the late postinfarction period (PA). DPA responded to HIS added cumulatively with contraction which was potentiated by cimetidine (CIM) and reversed by mepyramine (MEP). IA responded with relaxation potentiated by MEP and reversed by CIM. Under resting conditions, coronary arteries responded to a single concentration of HIS with contraction or relaxation (in IA, SA). In PA, only contractions were seen. Responses of PA were significantly higher than those of IA and SA. It appears that in PA the ratio of H1- and H2-receptors is changed.

Cardiac electrophysiologic actions of the hydrochloride of 1-methoxymethyl-2-(1-perhydroazepinyl)ethyl ester of 2-(n)-pentyloxycarbanilic acid in the anesthetized dog.

Cardiac electrophysiologic effects of the hydrochloride of 1-methoxymethyl-2-(1-perhydroazepinyl)ethyl ester of 2-(n)-pentyloxycarbanilic acid (BK 129) were studied in pentobarbital anesthetized dogs. Doses of 0.5, 1 and 2 mg kg-1 i.v. produced a dose dependent slowing down of S-A and idioventricular pacemakers, increase in atrioventricular (A-V), atrial and ventricular refractoriness, and decrease in intra-atrial, A-V and intra-ventricular conduction. Retrograde ventriculoatrial conduction was affected only slightly. In dogs with A-V blockade BK 129 suppressed norepinephrine-induced acceleration of S-A and idioventricular rhythm and intra-ventricular conductivity. These results suggest that BK 129 may be an effective agent for treating cardiac arrhythmias.

Antiarrhythmic activity of the hydrochloride of 1-methoxymethyl-2-(1-perhydroazepinyl)ethyl ester of 2-(n)-pentyloxycarbanilic acid.

Antiarrhythmic effects of the hydrochloride of 1-methoxymethyl-2-(1-perhydroazepinyl)ethyl ester of 2-(n)-pentyloxycarbanilic acid (BK 129) was studied in pentobarbital anesthetized dogs. The dose of 1 mg kg-1 i.v. suppressed ouabain-induced ventricular tachycardia for approx. 15 min. The minimal effective dosis was 0.72 +/- 0.09 mg kg-1 in comparison with 4.56 +/- 1.90 mg kg-1 of trimecaine and 6.80 +/- 0.86 mg kg-1 of quinidine. The doses of 1 and 2 mg kg-1 decreased ectopic activity 24-48 h after coronary artery ligation without complete suppression of extrasystoles. Epinephrine-induced arrhythmias were not prevented with the dose of 1 mg kg-1. The results demonstrate effectiveness of BK 129 in suppression of some types of arrhythmias.