Biomedical subjects

D G McDevitt

Publications and source records attributed to D G McDevitt.

At least 37 records · Page 2Linked to original sources

PubMed1994

Bronchodilator subsensitivity after chronic dosing with eformoterol in patients with asthma.

PURPOSE: The aim of the present study was to evaluate in vivo and in vitro beta 2-adrenoceptor responsiveness after chronic inhaled therapy with the long-acting beta 2-agonist eformoterol or placebo, given twice daily, in patients with mild to moderate asthma. PATIENTS AND METHODS: Seven asthmatic patients, age 34 +/- 5 years were evaluated. Mean forced expiratory volume in 1 second (FEV1) (% predicted) at entry was 58 +/- 5%. After at least 2 weeks run-in without beta 2-agonist therapy, patients were randomized to receive regular treatment with eformoterol 24 micrograms twice daily or placebo twice daily given by metered-dose inhaler for 4 weeks, in a double-blind, crossover design. Dose-response curves (DRC) to eformoterol (cumulative dose 6 micrograms to 126 micrograms) for airways and systemic beta 2-responses were constructed at the end of each treatment period. Responses were measured at baseline, 30 minutes after each dose, and for 6 hours after the last dose. In addition, in vitro parameters of lymphocyte beta 2-receptor function were evaluated prior to the DRC after each treatment period. RESULTS: There was a nonsignificant trend towards higher baseline values after eformoterol compared with placebo for FEV1: 0.16 L (95% CI -0.04 to 0.36) and forced expiratory flow (FEF25-75): 0.27 L/sec (95% CI -0.08 to 0.62). The peak bronchodilator response from the DRC and response 6 hours after the last dose were both significantly (P < 0.05) attenuated after chronic therapy with eformoterol compared with placebo. The mean differences between eformoterol and placebo for delta FEV1 were as follows: peak: 0.26 L (95% CI 0.09 to 0.43), and at 6 hours: 0.39 L (95% CI 0.20 to 0.58). Corresponding values for delta FEF25-75 were as follows: peak: 0.41 L/sec (95% CI 0.10 to 0.71), 6 hours 0.52 L/sec (95% CI 0.22 to 0.82). Systemic responses were likewise significantly blunted after eformoterol treatment compared with placebo. There was also subsensitivity of lymphocyte beta 2-adrenoceptor function after treatment with eformoterol compared with placebo. CONCLUSIONS: Our results suggest that chronic therapy with eformoterol produces (1) tachyphylaxis to its bronchodilator response, which was greatest at 6 hours after the last dose, (2) tachyphylaxis of extrapulmonary beta 2-mediated responses, and (3) subsensitivity of in vitro beta 2-adrenoceptor function.

Adrenergic beta-Agonists↗

PubMed1994

Beta-adrenoceptor subtypes mediating the metabolic effects of BRL 35135 in man.

1. The aim of the present study was to evaluate the metabolic responses produced in man by the beta 3-adrenoceptor agonist BRL 35135, and to determine which of these responses are beta 3-, rather than beta 1- or beta 2-, mediated. 2. Eight normal male subjects received single oral doses of BRL 35135 (8 mg) or the selective beta 2-adrenoceptor agonist salbutamol (8 mg) after pretreatment with placebo, bisoprolol (5 mg) as a selective beta 1-antagonist or nadolol (20 mg) to block beta 1- and beta 2-, but not beta 3-adrenoceptors. 3. BRL 35135 and salbutamol produced a significant fall in serum potassium concentration compared with placebo, in keeping with beta 2-adrenoceptor stimulation. Both drugs also produced a significant increase in serum glucose, insulin and lactate concentrations, which mirrored the hypokalaemic response, being unaffected by selective beta 1-blockade (bisoprolol), but completely blocked by nadolol. BRL 35135 (but not salbutamol) also produced a significant rise in serum free fatty acid and glycerol concentrations, which appeared to be beta 2-mediated. 4. A significant increase in basal metabolic rate occurred with both BRL 35135 and salbutamol. In the case of salbutamol, this effect appeared to be mediated solely by beta 2-adrenoceptors, whereas BRL 35135 produced a thermogenic response which could only be partially accounted for by a combination of beta 1- and beta 2-adrenoceptor stimulation. 5. These results infer the possibility of thermogenic beta 3-adrenoceptors in man, although these do not appear to be involved in the control of carbohydrate or fat metabolism.

Adrenergic beta-Agonists↗

PubMed1994

Cardiac effects of the beta 3-adrenoceptor agonist BRL35135 in man.

The aim of the present study was to evaluate the cardiac effects of the beta 3-adrenoceptor agonist BRL35135, and determine whether beta 3-receptors are involved in mediating chronotropic or inotropic responses in man. Eight normal males received single oral doses of BRL35135 8 mg (BRL) or the selective beta 2-adrenoceptor agonist salbutamol 8 mg (SAL), after pretreatment with either placebo (PL), bisoprolol 5 mg (B5) as a selective beta 1-adrenoceptor antagonist, or nadolol 20 mg (N20) to block beta 1- and beta 2- but not beta 3-receptors. Both BRL and SAL produced a significant increase in postural finger tremor in keeping with beta 2-adrenoceptor stimulation, and this response was totally abolished by pretreatment with N20. Significant increases in systolic blood pressure and Doppler stroke distance occurred with BRL and SAL which were unaffected by pretreatment with B5 and completely blocked by N20, in keeping with beta 2-mediated effects. BRL and SAL produced significant chronotropic and minute distance responses which were unaffected by beta 1-adrenoceptor blockade. However, whereas N20 blocked these responses to SAL, a small but significant response occurred with BRL in comparison with placebo despite complete blockade of co-existing beta 2-mediated effects. Compared with PL, the mean responses to N20/BRL, and the 95% confidence interval for the differences between the means were 7.4 beats min-1 [3.2 to 11.6] (P = 0.002) for heart rate, and 208.8 cm [38.3 to 379.3] (P = 0.02) for minute distance responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Influence of sex-steroid hormones on the regulation of lymphocyte beta 2-adrenoceptors during the menstrual cycle.

1. Up to 40% of female asthmatic subjects suffer a premenstrual deterioration in their condition which may be ameliorated by progesterone supplementation, although the mechanism responsible for this phenomenon is not understood. In vitro studies have shown that female sex-steroid hormones potentiate the bronchorelaxant effect of isoprenaline, whilst in vivo it has been shown that females exhibit greater sensitivity of systemic beta 2-adrenoceptor responses. 2. The aim of the present study was to determine whether cyclical alterations in beta 2-adrenoceptor expression, occurring under the influence of ovarian sex-steroid hormones, may offer an explanation for these findings. In vitro parameters of lymphocyte beta 2-adrenoceptor function were investigated in nine normal female subjects (aged 24 +/- 2 years) during the follicular (day 2-4) and luteal (day 21-23) phases of their menstrual cycle, and results were compared with those of nine age-matched healthy male controls studied at the same time intervals. 3. In female subjects there were significant increases in serum concentrations of oestradiol (3.3-fold) and progesterone (10.6-fold) between the follicular and luteal phases of the menstrual cycle, whereas no changes occurred in males. 4. In females during the luteal phase, the increase in sex-steroid hormones was mirrored by an increase in lymphocyte beta 2-adrenoceptor density (Bmax) and in maximal cyclic AMP response to isoprenaline (Emax), which were significantly higher than in male subjects. Mean differences (95% CI) between male and female subjects on visit 2 were 1.09 (0.49 to 1.69) fmol/10(6) cells (P = 0.001) for Bmax, and 3.42 (0.80 to 6.04) pmol/10(6) cells (P = 0.02) for Emax.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Central effects of the diuretic, bendrofluazide.

1. Central effects of the diuretic, bendrofluazide (2.5, 5 and 10 mg) were studied in 12 healthy volunteers. Two placebos and an active control drug, oxazepam (15 mg), were included. Single doses were administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 and 3.5-4.5 h after ingestion, and recording of the electrical activity of the brain (EEG) and body sway carried out. 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. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. 3. Bendrofluazide (10 mg) increased the number of errors at letter cancellation and reduced the rate of finger tapping (P < 0.05), while oxazepam increased the number of errors and reduced accuracy at continuous attention (P < 0.01), and increased the number of involuntary rest pauses during tapping (P < 0.05). 4. There were no effects of drugs on subjective assessment of mood. 5. No changes in the electrical activity of the brain were observed with bendrofluazide. In recordings with eyes open, oxazepam reduced delta (0.5-3 Hz), theta (3.5-7 Hz) and alpha 2 (10.5-13 Hz) while increasing beta 1 (13.5-21 Hz) activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Primary non-compliance with prescribed medication in primary care.

OBJECTIVE: To determine the rate of patients not redeeming their prescriptions (primary noncompliance) and assess the factors influencing this. DESIGN: Observational study comparing copies of prescriptions written by general practitioners with those dispensed by pharmacists and subsequent case record review. SETTING: A large rural general practice in Tayside. SUBJECTS: All 4854 patients who received prescriptions (20,921) written between January 1989 and March 1989. MAIN OUTCOME MEASURES: The rate of non-redemption of prescriptions. RESULTS: Seven hundred and two patients (14.5%) did not redeem 1072 (5.2%) prescriptions during the study period, amounting to 11.5% of men and 16.3% of women. Non-redemption was highest in women aged 16-29 (27.6% of women) and men aged 40-49 (18.3% of men). Of prescriptions issued to women for oral contraceptives 24.8% were not redeemed during the study period. In those who redeemed prescriptions 17% were not exempt from prescription charges compared with 33% of patients who failed to redeem them. The non-redemption rate was highest for prescriptions issued at the weekends, although this was a small proportion of all prescribing. Prescriptions issued by trainee general practitioners were also less likely to be redeemed. CONCLUSIONS: Non-redemption varies with age, sex, general practitioner, exemption status, and with day of the week the prescription was written. Observational studies of drug exposure can be more accurately estimated from dispensing rather than prescribing data.

Adolescent↗

PubMed1993

Central effects of combined bendrofluazide and atenolol administration. A single dose study in normal subjects.

Twelve normal male subjects received single oral doses of atenolol 100 mg (AT), bendrofluazide 5 mg (BFZ), combined atenolol 100 mg and bendrofluazide 5 mg (AT/BFZ), diazepam 5 mg (Dz), or one of two matching placebos, on each of 6 study days. Tests of psychomotor performance [digit symbol substitution (DSST), letter cancellation (LCT), continuous attention, choice reaction time (CRT), finger tapping, short-term memory, body sway], physiological measurements [critical flicker fusion (CFF), two-flash fusion (2FF)] and subjective assessments using visual analogue scales (VAS), were performed at 2 and 4 hours post-ingestion. Dz (active control) significantly worsened VAS scores at 2 h (+0.68) and reduced DSST scores at both 2 h (-15.0) and 4 h (-11.0). AT and BFZ given alone, each produced significant worsening of VAS at 2 h [AT +1.0; BFZ +1.38], but had no significant effects on performance. In combination however, AT/BFZ at 4 h produced significant impairment of DSST scores (-10.4), reduced finger tapping (-16.5) and increased involuntary rest pauses (+16.5). Despite these effects, no change in VAS scores occurred. In summary, we have demonstrated significant impairment of psychomotor performance in normal subjects with the AT/BFZ combination, which was not evident with the single agents and which occurred in the absence of a change in subjective awareness. These central effects may have important clinical implications for patients taking combined antihypertensive medication.

Adult↗

PubMed1993

Comparison of the extrapulmonary beta2-adrenoceptor responses and pharmacokinetics of salbutamol given by standard metered dose-inhaler and modified actuator device.

1. Ten healthy subjects were randomised to inhale salbutamol via a standard metered-dose inhaler (MDI), or via a modified metered-dose actuator device (MA). Previously published radiolabelled aerosol data had shown that the MA device produced a lower aerosol velocity, reduced oropharyngeal deposition, but with unchanged pulmonary deposition. 2. Dose-response curves (DRC) were constructed with the following cumulative doses of salbutamol: 200 microg, 600 microg (200 microg + 400 microg), 1400 microg (600microg + 800 microg) ad 2600 microg (1400 + 1200 microg). Dose increments were made every 30 min and measurements of extrapulmonary beta2-adrenoceptor responses were performed 20 min after each dose. In addition, plasma salbutamol concentrations were also measured immediately before and for up to 60 min after the last dose. 3. Baseline values were not significantly different between the two study days for any of the measured parameters. 4. Cmax (ng ml(-1)) for plasma salbutamol (as means and 95% CI for difference between MA and MDI) was: 2.0 (0.3-3.7), P = 0.03. Values for t(max) (min), median and range: MA 5 (5-10) vs MDI 5 (5-10); and AUC 0-60, (ng ml(-1) min, mean and 95% CI for difference between MA and MDI): 69 (-5-143), were not significantly different between the two devices. 5. There was a significant (P < 0.01) left shift in the DRC with the MA device compared with the MDI, for hypokalaemic, finger tremor, chronotropic and electrocardiographic (Twave, Q-Tc) responses to salbutamol. Values for the hypokalaemic response (mmol l(-1)) at 2600 microg were (as change from baseline, means and 95% CI for difference between MA and MDI): 0.23 (0.10-0.36). 6. Thus, the MA device produced greater systemic absorption of salbutamol, and associated extrapulmonary beta2-adrenoceptor responses compared with a standard MDI. These results, therefore, suggest that data from radiolabelled aerosol deposition studies may not predict the systemic absorption of inhaled beta2-adrenoceptor agonists.

Absorption↗

PubMed1993

Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.

BACKGROUND: The aim of the present study was to compare the dose related effects of fenoterol and salbutamol on cardiac beta 1 and beta 2 receptors using the beta 1 selective antagonist atenolol, in order to dissect out relative beta 1/beta 2 mediated responses. METHODS: Fourteen normal volunteers were randomised to receive pretreatment with either atenolol 25 mg or placebo, followed by inhaled fenoterol or salbutamol in equal doses by weight (cumulative doses of 1 mg and 4 mg). Measurements were made 30 minutes after inhaling each dose of beta 2 agonist. Values (mean and 95% CI) were expressed as a change from baseline. RESULTS: At 4 mg fenoterol produced equivalent falls in serum potassium and increases in tremor to salbutamol. The mean (95% CI) increase in heart rate (beats/min) with fenoterol at 4 mg after placebo was 47 (41-53) and after atenolol was 34 (28-40), with values for salbutamol being 46 (40-52) after placebo and 30 (24-36) after atenolol. The inotropic response (stroke distance) after atenolol at the 4 mg dose was 5.0 (3.9-6.1) cm for fenoterol and 4.7 (3.5-5.9) cm for salbutamol. There were no significant differences in heart rate or stroke distance response between the two drugs after either placebo or atenolol. Furthermore, ECG effects (Q-Tc and T wave) of fenoterol and salbutamol were comparable at both doses. CONCLUSIONS: These results show that there is no difference in the respective chronotropic or inotropic activities of fenoterol and salbutamol on cardiac beta 1 or beta 2 receptors when given at higher than conventional doses.

Administration, Inhalation↗

PubMed1993

The risks of symptomatic vaginal candidiasis after oral antibiotic therapy.

It is generally accepted that antibiotic use can result in vaginal fungal overgrowth, although evidence estimating the extent to which this causes symptomatic vaginitis is scant. In a study using the prescription of vaginal antifungal preparations as a surrogate measure of vaginal candidiasis, a cohort of women taking antibiotics had a higher incidence of vaginal candidiasis after antibiotic exposure than beforehand (relative risk 2.3; 95% confidence interval 1.9-3.0); this risk was highest in those aged 36-40 years (RR 6.0, 95% CI 2.9-12.5). The attributable risk was highest among those who were taking cephalosporins (AR 12.8%, 95% CI 9.1-16.5). In a case-control study, comparing previous antibiotic exposure among women using vaginal antifungal agents and matched controls, antibiotic exposure was higher among those using vaginal antifungal agents during the previous 28 days, with an odds ratio of 5.5 (95% CI 3.8-7.9).

Administration, Oral↗

PubMed1993

Do beta 3-adrenoceptors mediate metabolic responses to isoprenaline.

We investigated whether the putative beta 3-adrenoceptors mediated metabolic responses to isoprenaline. Seven normal volunteers received infusions of isoprenaline, a (beta 1, beta 2 and beta 3-agonist), at 0.5-3.0 micrograms/min. They were pretreated with either placebo, 25 mg atenolol (a selective beta 1 antagonist), or 5, 20 and 80 mg nadolol (which blocks beta 1 and beta 2 but not beta 3-adrenoceptors). Isoprenaline markedly (30.6%) increased basal metabolic rate (BMR): this increase was significantly reduced by 25 mg atenolol but not by 5 mg nadolol. Significant beta 2-blockade (from tremor data) occurred with 5 mg nadolol but not with 25 mg atenolol. This suggests that beta 1 but not beta 2-adrenoceptors are involved in the mediating thermogenic effects of isoprenaline. However, the rise in BMR was not totally blocked even by 80 mg nadolol (9.5%), which produced complete beta 1/beta 2 blockade, as evidenced by the elimination of the chronotropic effect of isoprenaline. This implies that the thermogenic response has a non-beta 1/beta 2-mediated component. There were also significant increases in plasma free fatty acids, glycerol, glucose, insulin and lactate, but these were completely abolished by beta 1/beta 2 blockade. Overall, isoprenaline produced an increase in BMR which is only partly due to stimulation of beta 1-adrenoceptors, and which is not associated with beta 1/beta 2-mediated effects on carbohydrate and fat metabolism. This suggests the possibility of thermogenic beta 3-adrenoceptors in man, although their location and role remain unknown.

Adult↗

PubMed1993

Investigation of putative cardiac beta 3-adrenoceptors in man.

The purpose of the present study was to investigate the presence of putative cardiac beta 3-adrenoceptors mediating chronotropic and inotropic responses in normal subjects. Isoprenaline (a known beta 1, beta 2 and beta 3-agonist) was infused to stimulate cardiac beta-adrenoceptors in the presence of antagonists at beta 1 (atenolol 25 mg) and beta 1/beta 2 (nadolol 5 mg, 20 mg and 80 mg) adrenoceptor subtypes. Dose-ranging with nadolol was performed to evaluate the lowest dose required to produce significant beta 2-blockade, since the higher doses might conceivably cause beta 3-blockade. Doppler echocardiography was used to evaluate stroke distance and minute distance, which are the linear analogues of stroke volume and cardiac output respectively. Nadolol 5 mg produced almost complete blunting of finger tremor (beta 2-blockade) whilst atenolol 25 mg had no significant effect. Chronotropic and Doppler minute distance responses to isoprenaline were consistent with stimulation of both beta 1 and beta 2-adrenoceptors with no evidence of a beta 3-mediated effect. However, isoprenaline produced an increase in systolic blood pressure and left ventricular stroke distance that was not attenuated by a dose of nadolol (20 mg) which produced complete blunting of beta 1 and beta 2-mediated responses. This infers the possibility of functional inotropic or lusitropic beta 3-adrenoceptors in the human heart. This study also brings into question possible differences in the validity of using stroke distance and systolic blood pressure as measures of inotropic response to beta-adrenoceptor stimulation and advocates the use of Doppler echocardiography as an additional tool for this purpose.

Adult↗

PubMed1993

Echocardiography in chronic heart failure in the community.

A total of 128 patients from a single practice population who were receiving loop diuretics for treatment of presumptive cardiac failure were identified from prescribing data captured by the Medicines Monitoring Unit. A subgroup of 78 patients underwent echocardiography to determine the prevalence of true left ventricular systolic dysfunction in this population and the validity of the diagnosis of cardiac failure in primary care. A further 50 patients were studied to assess the workload generated by these patients for both primary health care and hospital services. The estimated prevalence of left ventricular systolic dysfunction was 0.84%, whereas 1.6% of the population received loop diuretics for this indication. A false-positive diagnosis occurred in 47% and was more likely in females (73%) than males (37%). Of all consultations 79% were seen by GPs, 14% as hospital out-patients and 7% as in-patients. Within the hospital general physicians have most contact with these patients. In summary chronic heart failure is common within the community, although the false-positive rate for diagnosis of this condition is high. GPs and general physicians treat the majority of these patients and should therefore receive continuing education regarding recent advances in this area. Echocardiography should be performed early in the management of all patients suspected of having cardiac failure.

Adult↗

PubMed1992

Inhaled beta 2-adrenoceptor agonists in asthma: help or hindrance?

Conventional low doses of inhaled beta 2-adrenoceptor agonists produce effective bronchodilation without systemic effects. Higher doses of inhaled beta 2-adrenoceptor agonists may produce substantial improvements in bronchodilator response, which may be helpful to patients with more severe airway obstruction. At higher than recommended doses, in asthmatic patients, fenoterol appears to cause greater dose-related systemic beta 2-responses compared with salbutamol or terbutaline, although there is no evidence to suggest that fenoterol is any less beta 2-selective in vivo. Furthermore, tolerance develops to systemic but not to bronchodilator effects during chronic treatment with inhaled beta 2-adrenoceptor agonists. The link between asthma mortality and systemic adverse effects of inhaled beta 2-adrenoceptor agonists at present remains unproven. A critical reappraisal of the regular use of inhaled beta 2-adrenoceptor agonists including long-acting drugs is now indicated in the light of their possible adverse effects on disease control. Patients requiring regular use of inhaled beta 2-adrenoceptor agonists should be given additional anti-inflammatory therapy with inhaled corticosteroids.

Administration, Inhalation↗

PubMed1992

Evaluation of in vivo partial beta 1/beta 2-agonist activity: a dose-ranging study with carteolol.

1. The aims of this study were to investigate the partial agonist profile of carteolol and evaluate methodology for differentiating relative beta 1 and beta 2 partial agonist activity (PAA) in vivo. 2. Eight normal subjects received single oral doses of carteolol 10 mg, 30 mg and 60 mg; nadolol 40 mg; pindolol 30 mg and placebo, given in a single-blind, randomised crossover design. 3. beta 1-PAA was demonstrated with carteolol by dose-related increases in resting heart rate and systolic blood pressure, and a plateau in the dose-response curve for attenuation of exercise tachycardia. beta 2-PAA with carteolol was evidenced by a dose-related increase in resting finger tremor and progressive attenuation of exercise-induced hyperkalaemia. beta 2-adrenoceptor antagonism was shown by attenuation of terbutaline induced hypokalaemic, chronotropic and finger tremor responses. 4. Carteolol behaved as a non-selective beta-adrenoceptor antagonist with both beta 1 and beta 2-PAA components. In the standard clinical dose range of 10-30 mg, its in vivo PAA effects were relatively beta 1-selective. Thus at low doses, there appeared to be a dissociation between selectivity of antagonist and partial agonist activity. 5. Attenuation of exercise hyperkalaemia appears to be a novel and sensitive method for the evaluation of beta 2-PAA in vivo.

Adrenergic beta-Agonists↗

PubMed1992

Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects.

1. The aims of this study were to assess the relative beta 1/beta 2 selectivity of the antagonist and partial agonist activity (PAA) of celiprolol in man. 2. Eight normal males received single oral doses of celiprolol 200 mg (C200), 400 mg (C400) and 800 mg (C800); atenolol 50 mg (A50), 100 mg (A100) and 200 mg (A200); nadolol 40 mg (N40) and placebo (PL), administered in a single-blind, randomised crossover design. 3. At rest, in the presence of low levels of circulating adrenaline and noradrenergic tone, a low dose of celiprolol (C200) showed evidence of beta 1-PAA by significant increases in systolic blood pressure and resting heart rate. At higher doses (C400, C800), beta 2-PAA became evident by a significant increase in postural finger tremor, whereas C200 had no effect. 4. In the presence of a beta 1-adrenoceptor agonist, as assessed by reduction of exercise tachycardia, increasing doses of celiprolol produced significantly less beta 1-adrenoceptor blockade compared with atenolol. Furthermore, there was no increase in beta 1-adrenoceptor blockade beyond C400. 5. In the presence of a beta 2-adrenoceptor agonist, as assessed by blunting of terbutaline-induced chronotropic, hypokalaemic and finger tremor responses, celiprolol exhibited less beta 2-adrenoceptor blockade than comparable doses of atenolol used in clinical practice. 6. Exercise hyperkalaemia was blunted significantly by C400 and C800 in comparison with all doses of atenolol and nadolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline.

BACKGROUND: Gender differences in the chronotropic effects of infused isoprenaline have previously been described. The aim of the present study was to investigate possible gender differences in hypokalaemic, chronotropic, and electrocardiographic effects of inhaled terbutaline. METHODS: Twenty healthy volunteers (10 female) were recruited (mean age 24 years for women (F) and 22 years for men (M). Subjects were given either inhaled terbutaline 5 mg or placebo in single blind, randomised crossover fashion and the following measurements were made for four hours after inhalation: (a) serum potassium concentration; (b) heart rate; (c) electrocardiographic sequelae (T wave amplitude, Q-Tc interval). The effects of terbutaline on serum potassium was chosen as the primary end point for detecting a 0.3 mmol/l difference between sexes, with a beta error of 0.2 and alpha set at 0.05. RESULTS: The hypokalaemic effects of terbutaline were significantly greater in women, the potassium results (means and 95% CI) being as follows: lowest potassium concentration--F 3.12 (2.96-3.28) mmol/l v M 3.65 (3.49-3.81) mmol/l; percentage change from baseline at one hour--F 15.4% (11.5-19.3%) v M 8.5% (4.6-12.3%); average potassium concentration during the four hours--F 3.39 (3.33-3.46) mmol/l v M 3.78 (3.72-3.85) mmol/l. There was no significant regression between body weight and the potassium response to terbutaline. There were also significant sex differences for T wave, Q-Tc, and heart rate response. The percentage fall in T wave amplitude 30 minutes after terbutaline was: F 44.6% (32.1-57.0%) v M 22.4% (9.9-34.8%). CONCLUSIONS: Women are more sensitive to the hypokalaemic, chronotropic, and electrocardiographic sequelae of inhaled terbutaline.

Administration, Inhalation↗