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Biomedical subjects

D W Harron

Publications and source records attributed to D W Harron.

87 records · Page 5Linked to original sources
PubMed1981

Comparison of the beta-adrenoceptor blocking activity of oxprenolol, slow release oxprenolol and a combined oxprenolol diuretic preparation.

1 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg slow release oxprenolol with 0.25 mg cyclopenthiazide and placebo. Blood samples were obtained before and at 1, 2, 3, 6, 8, 12 and 24 h after drug administration and assayed for oxprenolol concentration. 2 The three formulations produced maximum reductions of 29% in the exercise tachycardia 3 to 6 h after drug administration. At 24 h the effects of the three preparations were not significantly different from placebo. 3 There were no significant differences in the plasma concentrations produced by the three formulations during the 24 h period. 4 These observations suggest that the slow release formulations of oxprenolol should be given twice daily to maintain cardiac beta-adrenoceptor blockade throughout a period of 24 h.

Adrenergic beta-Antagonists↗
PubMed1980

Debendox and congenital malformations in Northern Ireland.

An investigation was carried out in Northern Ireland into the alleged association between fetal abnormalities and Debendox, an antiemetic drug used in pregnancy. During the period 1966-78 the total number of births each year and the overall incidence of congenital malformations per 10 000 births fell. The incidences of cleft lip, cleft palate, reduction deformities, and defects of the heart and great vessels fell from 1966 to 1976 but increased in 1977 and 1978. During the same period (1966-78) the number of prescriptions for Debendox issued by general practitioners increased more than fourfold. These observations suggest that there is no relation between congenital malformations and the use of Debendox. This conclusion, however, does not take into account other drug- or environmental-related factors that may have resulted in a reduction in the number of congenital malformations and would hence have masked an increase associated with greater usage of Debendox. In particular, the amount of Debendox sold direct to the public without a prescription and the use of the drug by patients who were not pregnant could not be established. The amount of drug used in these ways is probably small, and it is difficult to see how it might influence the conclusions reached.

Abnormalities, Drug-Induced↗
PubMed1979

The interaction of warfarin with antacid constituents in the gut.

A study was made of the effect of 4 constituents of antacid preparations on the absorption of the coumarin derivate warfarin sodium using an in vitro experimental model. The constituents tested were activated dimethiocone (a silicone) magnesium trisilicate, bismuth carbonate and the adsorbant, kaolin. Slight decreased intestinal absorption was shown by magnesium trisilicate (19%) and bismuth carbonate (7%), the other 2 components showing no effects.

Animals↗
PubMed1979

Interaction of digoxin with activated dimethicone and other antacid constituents.

A study was made of the effect of activated dimethicone on the absorption of digoxin in relation to other commonly used antacid constituents using an in vitro experimental model. Dimethicone was found not to affect the absorption of digoxin in relation to aluminium hydroxide, bismuth carbonate, light magnesium carbonate and magnesium trisilicate whose effects on the absorption of digoxin were in agreement with values reported in the literature.

Antacids↗
PubMedDate not supplied

H2-receptor antagonism is not pro-arrhythmic in a chronic canine model.

Seven to 28 days after coronary artery ligation, programmed electrical stimulation was performed in conscious dogs. Groups of 6 previously inducible dogs in which no arrhythmia could presently be achieved were randomly allocated to receive quinidine, cimetidine, ranitidine or placebo. Results were assessed for the drugs' ability to induce ventricular tachycardia or fibrillation, and compared with placebo using Fisher's Exact Test. In the placebo group 4/6 dogs remained unchanged, one developed an arrhythmia, and one died. With quinidine, 3/6 dogs developed an arrhythmia (0.5 mg/kg, 4.0 mg/kg, 4.0 mg/kg) and three died (4 mg/kg, 8 mg/kg, 16 mg/kg) (p less than 0.05 compared with placebo). With cimetidine, 4/6 dogs remained unchanged, one developed an arrhythmia after 4 mg/kg, and one died after 0.5 mg/kg. After ranitidine 3/6 dogs remained unchanged and three died (1.0 mg/kg, 4.0 mg/kg, 16.0 mg/kg). PR, QTc, QRS, refractory periods, and mean systolic pressure remained unchanged after placebo, cimetidine, and ranitidine, but QTc increased (p less than 0.05) and mean systolic pressure fell (p less than 0.01) after quinidine. Heart rate did not change following placebo, but increased (p less than 0.05) after each of the three drug treatments. These results fail to show a significant arrhythmogenic effect of cimetidine or ranitidine in a model validated by the significant pro-arrhythmic effects of quinidine. The cause of death in all cases was ventricular fibrillation.

Animals↗
PubMedDate not supplied

Pharmacokinetics of praziquantel in healthy volunteers and patients with schistosomiasis.

The pharmacokinetics of a novel praziquantel preparation (Distocide) were investigated in Sudanese patients with hepatosplenic schistosomiasis and in healthy volunteers, and compared with those of Biltricide. The results of the first study indicated greater (P less than 0.05) plasma concentrations of Biltricide at 1.5, 2, 3 and 5 h after administration than with Distocide; plasma elimination half-lives (t 1/2) were not significantly different. In patients with hepatosplenic schistosomiasis, higher plasma levels of Distocide were noted (P less than 0.05 at 8 h) compared to healthy controls; however, due to wide inter-individual variations, there were no significant differences in maximum plasma concentration, time to maximum plasma concentration, area under the plasma concentration curve (AUC), volume of distribution, or clearance; t 1/2 was greater (P less than 0.05) in patients (11.9 +/- 5.4 h) than controls (2.3 +/- 0.4 h). In the presence of food, higher plasma concentrations of Distocide occurred compared to the fasting state; AUCs were greater (P less than 0.01) in both food groups, although the values of t 1/2 were shorter. The lower plasma levels and longer duration of action of Distocide may be advantageous in reducing side effects and prolonging exposure of the schistosomes to the drug.

Adult↗
PubMedDate not supplied

Effects of alinidine, a novel bradycardic agent, on heart rate and blood pressure in man.

The effects of the oral administration of alinidine (ST567) were studied on heart rate and blood pressure in healthy subjects in the supine and standing positions and on an exercise tachycardia. Exercise tachycardia was reduced by the three doses (20, 40 and 80 mg) of alinidine, and supine and standing heart rate by 80 mg alinidine. The maximum reductions in heart rate occurred at 1 to 2 h but were still present at 6 h. Systolic and diastolic pressure in the supine and standing positions was significantly reduced by alinidine, 80 mg. A comparison of the effects of placebo, alinidine (80 mg), propranolol, (40 mg), and clonidine (0.1 mg) showed that the effects of alinidine on heart rate and blood pressure in the supine and standing positions and after exercise were similar to those of propranolol; clonidine had little effect on these parameters. Alinidine, 40 and 80 mg, had no effect on an isoprenaline tachycardia, which was competitively antagonised by propranolol, 40 mg. The oral administration of alinidine, 40 mg once daily and 40 mg twice daily, for 8 days reduced heart rate in supine and standing positions and on exercise tachycardia with small reductions in systolic and diastolic pressure. The effect of the twice-daily regimen was greater. Some subjects had a dry mouth after alinidine, and 8-9 h after 80 mg all subjects felt drowsy an sleepy. Tiredness was reported during the first 2 days of the chronic-dosing study. One subject had a visual disturbance after 40 mg. These studies show that alinidine reduces heart rate in man without blocking Beta-adrenoceptors. This is a novel pharmacological action warranting further investigation.U

Adult↗
PubMedDate not supplied

Effect of alinidine on experimental cardiac arrhythmias.

Alinidine (2.9 +/- 0.7 mg/kg) prevented an adrenaline-induced ventricular arrhythmia in dogs respired with halothane. In ouabain-induced ventricular tachycardia, a cumulative dose of alinidine (15.5 mg/kg) reduced the number of ventricular beats by 91.6 +/- 1.9%. The drug was much less effective in abolishing the ventricular tachycardia 24 h after ligation of a coronary artery, with only a 36 +/- 15% reduction in ventricular ectopic beats after 15.5 mg/kg. The administration of alinidine (0.5-1.0 mg/kg) to anaesthetized dogs with no cardiac arrhythmia reduced sinus node rate with little effect on the response of the node to vagal stimulation.

Animals↗
PubMedDate not supplied

Investigation into mechanism of lack of reflex tachycardia in response to hypotensive action of indoramin in dogs.

In animals and man, the selective alpha 1-adrenoceptor antagonist indoramin reduces arterial pressure without increasing heart rate. We studied this mechanism of absence of reflex tachycardia in anaesthetised dogs. Indoramin reduced (p less than 0.05) arterial pressure with no reflex increase in heart rate, whereas phenoxybenzamine reduced (p less than 0.05) pressure but increased (p less than 0.05) heart rate. Atropine and propranolol pretreatment, vagotomy and division of the cardio-accelerator nerve did not prevent the reduction (p less than 0.05) in arterial pressure and heart rate seen with indoramin. Mexiletine, a drug which has membrane-stabilising activity, had no effect on heart rate or arterial pressure. Mexiletine and indoramin did not affect the increases in heart rate produced by stimulation of the cardio-accelerator nerve. Indoramin reduced (p less than 0.05) the increases in heart rate and arterial pressure produced by bilateral carotid occlusion, and potentiated the arterial pressure reduction but attenuated the heart rate response to intravenous isoprenaline. It also reduced (nonsignificantly) the responses to intravenous noradrenaline and phenylethylamine but had no effect on the arterial pressure and heart rate responses to bilateral central vagal stimulation. We conclude that the absence of the reflex tachycardia with hypotensive doses of indoramin does not result from the myocardial membrane-stabilising action of indoramin or from alteration in sympathetic and parasympathetic activity, but may occur partly from a reduction in baroreceptor sensitivity.

Animals↗
PubMedDate not supplied

The effects of encainide and its major metabolites, O-demethyl encainide and 3-methoxy-O-demethyl encainide, on experimental cardiac arrhythmias in dogs.

Encainide (E) is a class I antiarrhythmic agent which is metabolised in humans, with the formation in the majority of patients of O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide (MODE). As it has been suggested that these metabolites may contribute to the antiarrhythmic effect of E in humans, we have investigated the effects of E, ODE, and MODE on ventricular arrhythmias produced by ouabain and by coronary artery ligation. In the ouabain model, E restored sinus rhythm (SR) in eight of 13 dogs after a mean dose of 0.81 +/- 0.19 mg/kg (mean +/- SEM). ODE returned SR in five of 10 dogs after 0.30 +/- 0.06 mg/kg, and MODE returned SR in two of nine dogs after doses of 0.40 and 0.68 mg/kg, respectively. For comparison, mexiletine returned SR in six of six dogs after 3.50 +/- 1.02 mg/kg. In conscious dogs with ventricular arrhythmias 24 h after two-stage coronary artery ligation E restored SR in four of four dogs after 2.38 +/- 0.50 mg/kg. ODE restored SR in four of four dogs after 0.63 +/- 0.14 mg/kg, and MODE restored SR in four of four dogs after 1.39 +/- 0.30 mg/kg. Thus, ODE and MODE have antiarrhythmic activity which may contribute to the effects of E in patients with cardiac arrhythmias.

Anilides↗
PubMedDate not supplied

Cardiovascular effects of pinacidil and propranolol alone and in combination in normal humans.

The effects of a long-acting formulation of pinacidil (P1134), a new arteriolar vasodilator, have been investigated in normal humans. We observed the effects of pinacidil 37.5 mg when given alone, and when given in combination with propranolol 40 mg. The reflex tachycardia observed in the supine and standing positions after pinacidil was reduced by concurrent administration of propranolol. Combined treatment reduced systolic arterial pressure in the standing position from 117.0 +/- 2.5 to 98.3 +/- 3.5 mm Hg at 4 h after drug administration (p less than 0.01), which was greater than the hypotensive effect produced by either drug alone. These results indicate that the combination of pinacidil and a beta-adrenoceptor antagonist may be of value in the treatment of arterial hypertension.

Adult↗