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Biomedical subjects

J D Fitzgerald

Publications and source records attributed to J D Fitzgerald.

At least 19 recordsLinked to original sources
PubMed1991

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes.

Despite the fact that beta blockers were introduced into clinical practice 25 years ago, new beta blockers with differing kinetic and dynamic profiles continue to be developed and marketed. This overview assesses some of the more extensively studied agents from the point of view of proof of utility and the validity of claims for therapeutic advances. The clinical data suggests that despite the expectations of improvements based on kinetic and dynamic consideration, none of the newer agents have been shown unequivocally, either in terms of efficiency or tolerability, to be an advance over the reference agents, the beta 1 antagonists atenolol and metoprolol. This may be either because such improvements will not occur or because of shortcomings in the design and duration of comparative studies. There are trends to suggest that celiprolol has lesser effects on bronchial function and that it has a lesser impact on lipoprotein profiles. Approaches are suggested that might enable clinicians to appraise for themselves the validity of claims for the improved efficiency of new beta blockers.

Adrenergic beta-Antagonists↗
PubMed1988

Age-related effects of beta-blockers and hypertension.

The literature relating to the effect of age on the blood pressure response to beta-blockade is critically reviewed. It is concluded that although there may be an interaction, the appropriate clinical studies have not, as yet, been performed. There is no evidence of an increase in adverse events with age.

Adrenergic beta-Antagonists↗
PubMed1985

The possible role of the ancillary properties of beta adrenoceptor antagonists in the management of angina pectoris.

Beta adrenoceptor antagonists are effective in the symptomatic management of angina pectoris. This paper examines critically the possible influence of the ancillary properties of beta 1 selectivity, partial agonism and membrane-stabilizing action on the response in anginal patients. The response is categorized according to experimental, pharmacological and clinical endpoints, placing emphasis on the possible errors which may arise from extrapolation from the former to the latter. It is concluded: That selective beta adrenoceptor antagonism confers limited, but tangible advantages over non-selective antagonists in regard to patients with reversible airways obstruction, and also in the metabolic and haemodynamic response to acute hypoglycaemia. Cardioselectivity does not influence the central haemodynamic response to exercise, but lessens adrenaline-mediated hypertensive responses to smoking and hypoglycaemia. Non-selective partial agonists cause less reduction in resting ventricular function, but their effects on cardiac output during exercise are indistinguishable from full antagonists. Membrane stabilizing properties have a marked influence on the tolerability of these agents in terms of unwanted, nonspecific central nervous system symptoms. Unresolved questions relate to the influence of partial agonism on fatigue, metabolic responses, especially blood lipids and glucose, and the possibility of lesser efficacy in angina compared to full antagonists.

Adrenergic alpha-Antagonists↗
PubMed1978

Studies on the pharmacokinetics and pharmacodynamics of atenolol in man.

The non-stimulant cardioselective beta adrenocepter antagonist atenolol has been studied in volunteers in order to define its pharmacokinetic characteristics. Atenolol (100 and 200 mg orally) is rapidly absorbed, reductions in heart rate and systolic pressure being observed in 30 min. The effect persists for up to 8 h. Over 85% of an intravenous dose is excreted in urine within 24 h but only 50% of an oral dose. The bioavailability of approximately 50% is due to reduced absorption. Peak blood levels are observed at 2-4 h and the half life of atenolol given orally is 5-6 h. Atenolol reduces the cardiac response to standing and head-up tilt. It does not reduce circulating levels of renin but slightly impairs the renin response to tilt. Atenolol both orally and intravenously reduces supine diastolic pressure about four hours after administration, the effect persisting for up to 24 h.

Administration, Oral↗
PubMed1978

Aerosol therapy with Sch 1000. Short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects.

The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.

Adult↗
PubMed1977

Oral and intravenous propranolol during exercise.

The intrinsic sinoatrial (SA) rate at rest and during exercise was measured in 5 normal male subjects after prolonged oral and acute intravenous administration of propranolol and atropine. At rest, the intrinsic SA rate was similar after both oral and intravenous propranolol. At the higher levels of power output on a cycle ergometer, cardiac rate was slower after oral than after intravenous propranolol. When the intravenous study was repeated with the use of an additional dose of propranolol, cardiac rate was lower at comparable levels of power output, but not as low as that after oral propanolol. Differences in responses were interpreted as reflecting varying degrees of beta blockade, the most complete being that after prolonged oral propranolol administration of 320 mg daily. The intravenous dose of propranolol usually used to obtain the "pharmacologically isolated heart" at rest is too small to induce full beta blockade in exercise.

Administration, Oral↗
PubMed1977

A comparison of the bronchodilator activity of Sch 1000 and salbutamol.

The effects of the beta 2-adrenergic agonist, salbutamol, 200 mug, and the cholinergic antagonist, Sch 1000, 40 mug, have been compared in 25 asthmatic patients using a single dose, double-blind, crossover trial design. Salbutamol aerosol produces a greater degree of bronchodilatation than Sch 1000 aerosol during the initial three hours following drug administration. There is no significant difference in the bronchodilator effects of the two drugs in the interval four to eight hours after drug administration. Nonatopic patients showed less difference in bronchodilator response to each of the two drugs than atopic patients. Neither drug showed any significant adverse effect on blood pressure, pulse rate, or electrocardiogram. In six asthmatic patients the effect of the combination of salbutamol, 200 mug, and Sch 1000, 40 mug, was evaluated. The combination produced a longer duration of bronchodilatation than either drug alone when compared to placebo.

Adult↗
PubMed1977

Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat.

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose-response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.

Acetylcholine↗
PubMed1976

Comparison of metoprolol and propranolol in modification of haemodynamic and renin-aldosterone responses to tilting in humans.

1. Acute oral administration of metoprolol and propranolol to ten normal males resulted in equal reduction in heart rate both supine and after passive tilting to 60 degrees. 2. Tilted systolic blood pressure was reduced by both agents but metoprolol alone reduced supine systolic blood pressure. 3. Tilted but not supine diastolic blood pressure was reduced by both agents. 4. Metoprolol and propranolol both reduced the rise in plasma renin activity induced by tilting. 5. No effect of tilting was observed on plasma aldosterone.

Adult↗
PubMed1976

Human pharmacokinetic and pharmacodynamic studies on the atenolo (ICI 66,082), a new cardioselective beta-adrenoceptor blocking drug.

The beta-adrenoceptor blocking effects of orally administered atenolol on tachycardia induced by intravenous isoprenaline or by exercise have been studied in normal volunteers, and compared with the effects of similar doses of propranolol. The blood levels of atenolol at various times after oral administration were determined by g.l.c. and correlated with the degree of inhibition of tachycardia. Atenolol was shown to be a beta-adrenoceptor blocker in man, as in animals, in that it antagonized the chronotropic effects of isoprenaline and of exercise. The inhibitory effect of atenolol on exercise-induced tachycardia was evident at a concentration in blood of 0.2 mug/ml and virtually complete at 0.5 mug/ml. Higher concentrations than this did not produce significantly greater blockade. The effects of atenolol on exercise-induced tachycardia were similar to those of propranolol but it was less effective in blocking the rise in heart rate and fall in diastolic blood-pressure induced by intravenous infusion of isoprenaline. This separation of effects is considered characteristic of drugs causing preferential blockade of cardiac beta-adrenoreceptors. The half-life of atenolol in blood was calculated to ablut 9 hours.

Adult↗
PubMed1976

The effect of beta-adrenoreceptive antagonists on the morbidity and mortality in cardiovascular disease.

The effect is critically reviewed of chronic administration of beta-adrenoreceptor antagonists on morbidity and mortality in angina pectoris and myocardial infarction. There is inconclusive evidence that the abrupt cessation of therapy with these agents may increase morbidity and mortality in angina pectoris. The type of anginal patient in which this may occur is not yet defined and neither is the mechanism. There is no evidence that beta-antagonists prolong the life of anginal patients. In the acute phase of experimental myocardial infarction, these drugs reduce mortality but do not do so in man. There is increasing evidence that they prolong life if administered to patients surviving the acute phase of myocardial infarction. The need for further studies is discussed.

Adrenergic beta-Antagonists↗
PubMed1976

Beta-blockade and mechanisms of disease.

In this review an attempt has been made to define the contribution of beta-antagonists to out understanding of the mechanisms of disease. It is concluded that beta-antagonists, and propranolol in particular, have clarified mechanisms in angina pectoris, cardiac arrhythmias and some aspects of essential hypertension as well as hypertrophic obstructive cardiomyopathy. The study of beta-antagonists in anxiety states shows that they can help to define the somatic component but give no clue as to central mechanisms involved. There is no substantial evidence that beta-antogonists are of value in the psychoses and these negative findings suggest that disturbances of brain catecholamines contribute little to the pathogenesis of these conditions.

Adrenergic beta-Antagonists↗
PubMed1975

Beta blocking drugs as anti-arrhythmic agents.

Fifteen years after the introduction of beta adrenergic blocking drugs into clinical medicine, there is satisfactory evidence indicating that this class of drug has significant anti-arrhythmic activity. The chief indications for using these drugs are for the control of sinus tachycardia digitalis dysrhythmias and for the control of rapid ventricular rates atrial and ventricular dysrhythmias. The mode of action is by antagonizing the cardiac actions of catecholamines on cardiac automaticity and conduction.

Action Potentials↗