Biomedical subjects

D G McDevitt

Publications and source records attributed to D G McDevitt.

At least 73 records · Page 4Linked to original sources

PubMed1990

Electrocardiographic changes induced by inhaled salbutamol after treatment with bendrofluazide: effects of replacement therapy with potassium, magnesium and triamterene.

1. Twelve normal subjects were given 5 days' treatment with (a) placebo; (b) 5 mg of bendrofluazide; (c) 5 mg of bendrofluazide plus 24 mmol of potassium; (d) 5 mg of bendrofluazide plus 24 mmol of magnesium; (e) 5 mg of bendrofluazide plus 24 mmol of potassium plus 24 mmol of magnesium; (f) 5 mg of bendrofluazide plus 50 mg of triamterene. 2. After each treatment period, subjects were given two doses of inhaled salbutamol (each of 1 mg), and measurements were made 25 min after each dose. 3. Treatment with bendrofluazide plus salbutamol produced a lower absolute level of plasma potassium than salbutamol alone, although the addition of potassium, magnesium or triamterene did not attenuate this effect. Plasma magnesium was unchanged by salbutamol. 4. Salbutamol was associated with significant electrocardiographic effects, including T-wave flattening, Q-Tc interval prolongation and, in some subjects, U-waves and S-T segment depression. 5. Prior treatment with bendrofluazide potentiated the electrocardiographic effects of salbutamol. Supplementation with potassium and magnesium had no effect on electrocardiographic changes, and the addition of triamterene to bendrofluazide only attenuated electrocardiographic responses in some subjects.

Adult↗

PubMed1990

Treatment of heart failure in the elderly.

Heart failure is a syndrome of breathlessness, fatigue and oedema. The effects of ageing on myocardial function and the prevalence of often multiple cardiac pathologies makes heart failure a disease of the elderly, usually characterized by primary or secondary myocardial systolic dysfunction. Appropriate treatment, which requires precise diagnosis, involves correction of precipitating or aggravating factors and the rational use of drug therapy. Diuretics and ACE inhibitors offer a combination of both symptom control and improvement in prognosis. Other agents such as digoxin, xamoterol and nitrates may be particularly useful in the treatment of patients with associated problems such as atrial fibrillation and angina. Because both ageing and heart failure may alter pharmacokinetics and pharmacodynamics, safe and effective treatment of heart failure in the elderly requires understanding of the clinical pharmacology of the drugs used.

Aged↗

PubMed1990

Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension.

1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects.

Adolescent↗

PubMed1990

A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single doses of betaxolol.

1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20 mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was assessed by reductions in exercise heart rate. Betaxolol produced dose-related reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20, 116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was assessed by attenuation of finger tremor and cardiovascular responses to graded infusions of i.v. isoprenaline. Dose-response curves were constructed and the doses required to increase heart rate by 25 beats min-1, finger tremor by 200%, calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10 mm Hg, after each treatment were calculated. These were then compared with placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor showed significant attenuation by all doses of betaxolol (compared with PL): B10 1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55 +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40 6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1990

Central effects of the angiotensin-converting enzyme inhibitor, captopril. I. Performance and subjective assessments of mood.

1. Central effects of single doses of captopril (12.5, 25 and 50 mg) were studied in fourteen healthy male subjects. Two placebos and an active control drug, oxazepam (15 mg), were included, together with a single dose of atenolol (100 mg). The drugs were administered double-blind at 11.00 h, and performance and subjective feelings were assessed before and from 1.5-2.5 h and 3.5-4.5 h after ingestion. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. 3. Captopril did not impair performance on any of the tests, but improved short-term memory (P less than 0.05) and increased the number of letters cancelled (P less than 0.05). Oxazepam reduced the number of substitutions completed in the digit symbol test (P less than 0.01), accuracy on continuous attention (P less than 0.05), number of letters cancelled (P less than 0.05), and rate of finger tapping (P less than 0.05), and increased choice reaction time (P less than 0.001). Atenolol reduced the rate of finger tapping (P less than 0.05), but increased the number of letters cancelled (P less than 0.05). 4. No effects on mood or on subjective feelings were evident with captopril. Oxazepam reduced subjective alertness (P less than 0.05), and atenolol increased feelings of sleepiness (P less than 0.05). 5. Although these observations suggest that central effects may exist with captopril, no adverse consequences have been established on performance or on subjective assessment of mood. Captopril may, therefore, be an appropriate drug for hypertensive patients engaged in skilled activity.

Adult↗

PubMed1990

Central effects of the angiotensin-converting enzyme inhibitor, captopril. II. Electroencephalogram and body sway.

1. Effects of single doses of captopril (12.5, 25 and 50 mg) on the electroencephalogram (EEG) and on body sway were studied in fourteen healthy male subjects. Oxazepam (15 mg), as an active control, and two placebos were included in the study, together with a single dose of atenolol (100 mg). Medication was administered double-blind at 11.00 h, and assessments made before and at 2 and 4 h after drug ingestion. 2. There were no changes in the EEG with captopril. Oxazepam reduced the circadian rise in alpha activity, while atenolol decreased beta power. Delta activity was modified by both oxazepam and atenolol. 3. A reduction in lower frequencies of body sway (0.05-1 Hz) occurred with captopril, while the spectra were unaffected by oxazepam. Atenolol increased (P less than 0.05) activity in the frequency range 0.75-2.75 Hz. 4. These observations suggest that captopril is free of central effects such as sedation that may occur with beta-adrenoceptor antagonists. Reduced body sway with captopril could reflect improved integration of central and peripheral control of posture.

Atenolol↗

PubMed1990

Comparison of the effects of prolonged treatment with low and high doses of inhaled terbutaline on beta-adrenoceptor responsiveness in patients with chronic obstructive pulmonary disease.

Eleven patients with chronic obstructive pulmonary disease (age, 61 +/- 2 yr; FEV1, 1.36 +/- 0.24 L, 46 +/- 7% predicted) were given 4 wk of treatment with either a conventional low dose of inhaled terbutaline (LDT), 500 micrograms four times a day, or a high dose of inhaled terbutaline (HDT), 2,000 micrograms four times a day, delivered by a spacer. A randomized double-blind crossover design was used with 2-wk run-in and washout periods, when ipratropium bromide was substituted for inhaled beta-agonists. Dose response curves (DRC) to cumulative doubling doses of inhaled terbutaline (125 to 4,000 micrograms) were constructed after each treatment period, and baseline spirometry, finger tremor (Tr), plasma potassium (K), plasma cAMP, and ECG (HR and T wave) were measured at each dose step of the DRC. Daily PEFR measurements (A.M. and P.M.) and Holter ECG were performed during run-in and treatment periods. Baseline values for FEV1 were not significantly different during run-in, treatment, or washout periods. There were dose-related increases in FEV1 (p less than 0.0001) with no significant differences between DRC after treatment with HDT compared with those with LDT: delta FEV1 max, 0.46 +/- 0.14 L, 15.5 +/- 3.7% predicted (HDT); 0.50 +/- 0.11 L, 16.0 +/- 3.1% predicted (LDT). There were also no differences between DRC for delta FVC: 1.08 +/- 0.22 L, 31.1 +/- 5.4% predicted (HDT); 0.99 +/- 0.14 L, 28.5 +/- 3.8% predicted (LDT). There were no significant changes in K or HR in response to cumulative doses of terbutaline after either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1990

Hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy. Protection by conventional doses of spironolactone but not triamterene.

Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs.

Adult↗

PubMed1990

Beta-adrenoceptor-blocking drugs in the elderly.

Beta-adrenoceptor function appears to be diminished in the elderly, although the exact mechanisms are still uncertain. Some evidence suggests that this attenuation is predominantly of beta1-receptor activity, with beta2-receptor activity remaining intact. Pharmacokinetic changes also occur in the elderly with beta-blockers. Absorption is unchanged but bioavailability may be increased, particularly with lipophilic drugs such as propranolol that are subject to "first-pass" effects. Both hepatic and renal clearance may be diminished, and this suggests that, in general, elderly patients will require smaller doses than those normally given to younger ones. Although antihypertensive response to beta-blockers has been linked to renin status, clinical trial evidence indicates that beta-blockers are effective antihypertensive agents in the elderly, and clinical experience suggests that this is true also for ischemic heart disease. Provided attention is given to patient selection, associated diseases, and dosage, in general, beta-blockers appear to be well tolerated in the elderly. However, careful clinical supervision is required, particularly during treatment initiation.

Adrenergic beta-Antagonists↗

PubMed1990

Doxazosin in 'resistant' hypertension.

A study of doxazosin added to baseline therapy with a beta-adrenoceptor blocker plus a diuretic in the treatment of patients 'resistant' to the baseline therapy, showed that it was effective and generally well tolerated. The study was, however, open-label and lacked comparison with other third-line drugs.

Adrenergic beta-Antagonists↗

PubMed1989

Beta-adrenoceptor responses to inhaled salbutamol in normal subjects.

The aim of the present study was to quantify and compare the airways and systemic beta-adrenoceptor responses to inhaled salbutamol in normal subjects. Seven non-atopic, normal subjects were given cumulative doubling doses of inhaled salbutamol (100 micrograms to 4000 micrograms) or placebo in a single-blind cross-over design. Airways (sGaw, FEF 50%, FEF 25%), tremor, haemodynamic and metabolic responses were measured at each dose increment. There were dose-related changes in sGaw, FEF 50% and FEF 25% up to a plateau at 1.0 mg. Analysis of individual responses showed that most subjects required either 1.0 or 2.0 mg for maximum bronchodilatation, independent of the parameter of airflow. There was no correlation between maximum bronchodilatation, independent of the parameter of airflow. There was no correlation between maximum response and baseline airway calibre. In contrast to airways effects, systemic beta-adrenoceptor responses did not occur until 500 micrograms, and a ceiling in the dose-response curve was not reached. There were significant correlations between airways, tremor and haemodynamic responses, and between different metabolic variables. The intraindividual variability was greatest for tremor and sGaw, although this was small in comparison to the size of maximum change with salbutamol. The converse applied to the hypomagnesaemic response.

Administration, Inhalation↗

PubMed1989

The biochemical effects of high-dose inhaled salbutamol in patients with asthma.

We have studied the biochemical effects of high doses of inhaled salbutamol in 14 asthmatic patients age 38 years, FEV1 62%. Cumulative doubling doses of inhaled salbutamol were given every 20 min as follows: 100 micrograms, 200 micrograms, 500 micrograms, 1000 micrograms, 2000 micrograms, 4000 micrograms. Plasma glucose, potassium, and magnesium were measured at each step of the dose-response curve. Salbutamol produced significant hypokalaemic and hyperglycaemic effects, but no significant change in magnesium. There were linear log-dose responses for both glucose (r = 0.58) and potassium (r = -0.46). There were wide individual variations in maximum responses to salbutamol 4000 micrograms (as means and 95% confidence intervals): delta glucose 1.46 (0.83 to 2.09) mmol/l, delta potassium -0.38 (-0.64 to -0.12) mmol/l. Thus, hypokalaemic and hyperglycaemic effects may occur with doses of salbutamol similar to those currently used for nebulizer therapy (2.5-5 mg). We postulate that during acute exacerbations of airflow obstruction these changes may be accentuated and become clinically relevant.

Administration, Inhalation↗

PubMed1989

Pharmacokinetics, efficacy and adverse effects of sublingual salbutamol in patients with asthma.

Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 micrograms (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggest that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.

Administration, Inhalation↗

PubMed1989

Single dose and steady-state pharmacokinetics of 4 mg and 8 mg oral salbutamol controlled-release in patients with bronchial asthma.

Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion. At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0-12) were 4507 ng.min.ml-1 and 8980 ng.min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572. There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.

Adult↗

PubMed1989

Evaluation of the metabolic responses to inhaled salbutamol in the measurement of beta 2-adrenoceptor blockade.

The aim of the present study was to evaluate whether metabolic responses to inhaled salbutamol may be used to measure the cardioselectivity of beta-adrenoceptor antagonists. We therefore studied the effects of oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40), and placebo (Pl) on the hypokalaemic (K) and hyperglycaemic (Glu) responses to inhaled salbutamol in five healthy subjects. Increasing doses of atenolol were associated with a progressive attenuation of delta K compared with placebo: -0.72 mmol.l-1 (Pl) vs -0.20 mmol.l-1 (A200). However, delta K with A200 was significantly different from the response with P40: +0.12 mmol.l-1. There were partial reductions in the hyperglycaemic response with the beta-adrenoceptor antagonists, although this was only significant (compared with Pl) for P40: delta Glu 1.92 mmol.l-1 (Pl) vs 0.76 mmol.l-1 (P40). These results show that beta 2-adrenoceptor blockade by atenolol is a dose-dependent phenomenon, which may be measured by the attenuation of salbutamol-induced hypokalaemia. However, beta 2-adrenoceptor blockade by atenolol 200 mg was less than that by propranolol 40 mg. The glucose response to salbutamol was only partially blocked by propranolol and may therefore not be suitable to assess beta 2-adrenoceptor antagonism.

Administration, Inhalation↗

PubMed1989

Prior treatment with diuretic augments the hypokalemic and electrocardiographic effects of inhaled albuterol.

PURPOSE: High doses of inhaled albuterol produce substantial improvements in bronchodilatation but are associated with dose-related systemic side effects including hypokalemia and hypomagnesemia. Concomitant diuretic therapy also produces these metabolic sequelae and may therefore precipitate cardiac arrhythmias in patients taking this combination of drugs. The purpose of this study was to investigate the electrocardiographic (ECG) effects of high-dose inhaled albuterol, and to evaluate whether potentiation occurs with bendrofluazide. PATIENTS AND METHODS: Ten normal subjects (mean age [+/- SEM]: 29 +/- 2 years, four women, six men) received seven days of treatment with either bendrofluazide 5 mg or identical placebo in a single-blind, randomized, cross-over design, with a 10-day washout period. After each treatment period, responses (potassium, magnesium, ECG) to cumulative doubling doses of inhaled albuterol (100 micrograms to 2,000 micrograms) were measured. RESULTS: Baseline potassium levels (mean and 95% confidence intervals) were lower after pretreatment with bendrofluazide compared with placebo (3.07 mmol/L [2.89 to 3.25 mmol/L] versus 3.78 mmol/L [3.62 to 3.93 mmol/L]; p less than 0.001). The combination of bendrofluazide and albuterol produced a lower absolute level of potassium than did placebo and albuterol: (2.72 mmol/L [2.50 to 2.95 mmol/L] versus 3.18 mmol/L [3.09 to 3.27 mmol/L]; p less than 0.001). Mean (+/- SEM) potassium fell to a lower level with bendrofluazide and albuterol in women than in men (2.45 +/- 0.04 mmol/L versus 2.90 +/- 0.13 mmol/L; p less than 0.005). Albuterol alone produced a small but significant fall in magnesium (0.842 mmol/L [0.815 to 0.869 mmol/L] to 0.789 mmol/L [0.757 to 0.820 mmol/L]; p less than 0.001), but no further change after bendrofluazide. Pretreatment with bendrofluazide increased the frequency (p less than 0.001) and amplitude (p less than 0.05) of U waves due to albuterol. Albuterol also attenuated T-wave amplitude (p less than 0.001) and prolonged the Q-Tc interval (p less than 0.001), with no additive effect from bendrofluazide. ST-segment depression (p less than 0.001) occurred in five subjects who inhaled albuterol. CONCLUSION: These findings show that treatment with bendrofluazide augments the hypokalemic and ECG effects of high-dose inhaled albuterol. The arrhythmogenic potential of this interaction may be important in patients with acute exacerbations of chronic airflow obstruction, who have concomitant hypoxemia and ischemic heart disease.

Administration, Inhalation↗

PubMed1989

In vivo studies on the function of cardiac beta-adrenoceptors in man.

The original Lands classification considered cardiac beta-adrenoceptors to be predominantly beta 1 in type and to respond to both noradrenaline and adrenaline. Radioligand binding studies subsequently identified substantial numbers of beta 2-adrenoceptors in cardiac tissue. Studies in man employing intensive exercise, isoprenaline testing and a variety of selective and non-selective beta-adrenoceptor antagonists would now suggest that under certain circumstances these receptors may be functionally active. Severe exercise, as a sympathetic stimulus, is associated with high circulating noradrenaline concentrations, and appears to produce tachycardia predominantly by cardiac beta 1-adrenoceptor activity. In contrast, isoprenaline testing increases heart rate by a number of mechanisms: it stimulates beta 1-adrenoceptor activity in the sinoatrial node; it may result in reflex vagal withdrawal; and it appears to stimulate cardiac beta 2-adrenoceptors directly. In addition, isoprenaline also facilitates noradrenaline release by presynaptic beta 2-adrenoceptors. Thus the effects of isoprenaline would appear to mimic stress in man with the subsequent release of adrenaline from the adrenal medulla and its complex interaction directly and indirectly with both cardiac beta 1 and beta 2-adrenoceptors. These differing circumstances may also influence the relative efficacy of beta 1-selective and non-selective beta-adrenoceptor agonists and antagonists.

Humans↗

PubMed1989

Effects of atenolol, verapamil, and xamoterol on heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation.

The aim of the study was to compare the effects of atenolol (50 mg b.i.d.), verapamil (80 mg b.i.d.), xamoterol (200 mg b.i.d.), and matching placebo on heart rate (HR) and exercise tolerance in digitalised patients with chronic atrial fibrillation. Each treatment was taken for 4 weeks, and digoxin was continued throughout the study. During treatment with placebo (digoxin alone), the mean postexercise heart rate was 164 beats/min, and four subjects had rates of greater than or equal to 170 beats/min. Atenolol, verapamil, and xamoterol achieved significantly better control of exercise-induced tachycardia, mean postexercise heart rates being reduced to 120, 131, and 130 beats/min, respectively (p less than 0.01 for each). However, minimum HRs less than or equal to 45 beats/min occurred during treatment with placebo, atenolol, and verapamil, whereas treatment with xamoterol was associated with a minimum heart rate of 56 beats/min. Treatment with atenolol was associated with a marked reduction in maximum treadmill walking distance (mean 356 m) as compared both with placebo (mean 421 m, p less than 0.01) and verapamil (mean 439 m, p less than 0.01). Xamoterol reduced maximum walking distances as compared with verapamil (402 vs. 439 m; p less than 0.05) but not placebo (402 vs. 421 m; NSS). Thus, atenolol, verapamil, and xamoterol achieved better control of exercise-induced tachycardia than digoxin, but atenolol clearly impaired exercise tolerance whereas verapamil did not. Xamoterol achieved more even control of ventricular response rates and prevented the resting bradycardias that occurred with the other treatments. However, walking distances were significantly lower than those noted during treatment with verapamil.

Adrenergic beta-Agonists↗