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Biomedical subjects

G T McInnes

Publications and source records attributed to G T McInnes.

At least 55 records · Page 3Linked to original sources
PubMed1993

A comparison of the potassium and magnesium-sparing properties of amiloride and spironolactone in diuretic-treated normal subjects.

1. The relative potencies of amiloride (5 and 20 mg) and spironolactone (25 and 100 mg) for plasma and erythrocyte electrolytes were investigated in a double-blind, randomised, balanced, crossover study in 12 normal men treated concomitantly with hydrochlorothiazide 100 mg daily for 1 week. 2. Participants satisfied an a priori requirement for a fall in plasma potassium concentration of at least 0.5 mmol l-1 after 7 days of treatment with hydrochlorothiazide alone. 3. After hydrochlorothiazide alone, plasma potassium and sodium concentrations fell (P < 0.001). There were associated reductions in erythrocyte sodium (P < 0.01). Plasma magnesium concentration did not change, although erythrocyte magnesium decreased (P < 0.001). 4. Both amiloride and spironolactone attenuated the thiazide-induced fall in plasma potassium (relative potency, amiloride:spironolactone 10:1, 95% confidence interval 6.3-16.2:1). Amiloride but not spironolactone was associated with a dose-related increase in plasma magnesium; a relative potency estimation was precluded. There was little evidence of influences of amiloride or spironolactone on erythrocyte electrolytes. 5. On a weight basis, amiloride is ten times more potent than spironolactone as a potassium-sparing agent in diuretic-treated subjects but neither agent had major effects on erythrocyte potassium. The drugs may have divergent actions on magnesium handling; hydrochlorothiazide alone had no influence on plasma magnesium.

Adult↗
PubMed1993

Effect of renal function on the pharmacokinetics and pharmacodynamics of trandolapril.

1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clearance 4-112 ml min-1 1.73 m-2). 2. The pharmacokinetics of trandolapril were unaffected by differences in renal function. 3. In contrast, there was a close correlation between the renal clearance (0-96 h) of trandolaprilat and creatinine clearance (r = 0.95, P = 0.0001). The maximum plasma concentration of trandolaprilat, and the area under the concentration curve (0-96 h) correlated inversely with creatinine clearance (r = -0.59, P < 0.001; and r = -0.61, P < 0.001 respectively). 4. Significant changes in plasma trandolaprilat concentrations were seen only in patients with creatinine clearances of 30 ml min-1 1.73 m-2 or less, suggesting that a dose reduction in trandolapril might be advisable in severe renal impairment. 5. However, the majority of parameters of ACE inhibition were unrelated to creatinine clearance, although area under the curve for ACE inhibition (0-336 h) showed a weak negative correlation (r = -0.49, P < 0.01). Similarly, weighted mean changes in blood pressure were not influenced by renal function. 6. Therefore, while the pharmacokinetic parameters of trandolaprilat correlated with creatinine clearance, pharmacodynamic measurements (ACE inhibition and blood pressure changes) in general showed no such relationship, indicating that dose adjustment of ACE inhibitors in renal impairment should be based on pharmacokinetic results only in conjunction with pharmacodynamic data.

Adult↗
PubMed1993

Patient knowledge about diuretic prescription.

1. In order to assess the prevalence and knowledge of diuretic prescription, 203 consecutive admissions to three general medical wards were interviewed. Additional information was collected on forms sent to general practitioners and hospital doctors responsible for each patient. 2. Prevalence of diuretic use was 31% (63 patients); other drugs only, 60% (121 patients); no drugs, 9% (19 patients). Patients gave an incorrect indication for 31% of diuretics prescribed, but for only 16% of other drugs (P < 0.005). 3. Compared with patients not taking diuretics, diuretic-users were older (mean +/- s.d., 70 years +/- 14 vs 54 +/- 20, P < 0.001), had lower abbreviated mental test scores (AMT scores seven or less, 21% vs 9%, chi 2 = 3.48, P = 0.06) and were prescribed more drugs (5.0 +/- 2.4 vs 3.2 +/- 2.0, P < 0.001). Increasing age and decreasing AMT score were associated with poorer knowledge of drug indication, but these factors could not explain fully the poor understanding of diuretic prescription. 4. Accurate recall of dose was the same for diuretics and for other agents. Knowledge about medication was not different if the general practitioner or hospital initiated treatment.

Adolescent↗
PubMed1993

Patients' attitudes to participation in clinical trials.

1. In order to assess attitudes of patients to participation in therapeutic trials 197 patients underwent structured interviews conducted by a single observer. Of these patients 66 were previous or current participants in clinical trials (group A), 12 had declined participation in a trial (group B), and 119 had never been invited to participate in research (group C). 2. In group A, 62% stated their motivation for participation was to help others and 39% to improve their own treatment, but in 38% participation was to comply with the doctor's request. Two-thirds of group C patients would or might participate in a future hypothetical trial; of these more than half (57%) would do so to help others, and 42% to improve their own treatment. 3. Of the 12 patients who had declined entry into a study (group B) three did not want to alter their current therapy, three had insufficient time to participate in the particular trial, and in three cases relatives objected to their participation. Group C patients who stated they would not participate in trials gave being too ill (22%), not wanting to change treatment (22%), and fear of side-effects (17%) as the commonest reasons for declining. 4. In group A, 83% felt they had adequate time to consider their participation. Nearly two-thirds of patients (60%) would have liked written information to retain for reference, whereas only 38% were provided with information in this form. Over half of these patients (54%) disliked no aspect of the study in which they participated. Venepuncture and other uncomfortable procedures were least popular.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude to Health↗
PubMed1992

Use of beta-blockade in a patient with phaeochromocytoma and asthma.

This case report describes a patient with co-existing phaeochromocytoma and bronchial asthma. She had no asthmatic symptoms at the time of diagnosis of phaeochromocytoma; her asthma recurred after adrenalectomy. Despite concern about the use of a beta-blocker in a patient with asthma, pre-operative tachycardia was successfully treated with the beta-1-selective adrenoreceptor antagonist, metoprolol.

Adrenal Gland Neoplasms↗
PubMed1992

Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension.

OBJECTIVE: To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension. DESIGN: Double-blind, placebo-controlled, parallel-group study of 28 days' duration. SETTING: Three hospital outpatient departments participating in the Glasgow Blood Pressure Clinic (Glasgow, UK). PATIENTS: Forty patients with essential hypertension with diastolic blood pressure 95-114 mmHg after a 2-4 week placebo run-in period. INTERVENTIONS: Twenty-eight days' treatment with candoxatril 200 mg twice daily or matching placebo capsules. MAIN OUTCOME MEASURES: Changes in supine and erect blood pressure, and volunteered side effects during double-blind treatment. RESULTS: When measured at the end of the dose interval, the fall in supine blood pressure following candoxatril was not significantly greater than that after placebo. Compared with placebo, a significant effect for candoxatril was seen only for systolic blood pressure in the erect posture; the fall in erect diastolic blood pressure attributable to candoxatril was insignificant. Median plasma atrial natriuretic peptide concentration increased in candoxatril-treated patients and decreased in the placebo group. No stimulation of the renin-aldosterone axis was seen. There was a non-significant trend towards greater urinary excretion of cyclic guanosine monophosphate after candoxatril. Mean plasma concentration of candoxatril at (UK 73,967--the active metabolite of candoxatril) reached a peak of 1010 +/- 437 ng/ml after acute dosing, and 1328 +/- 405 ng/ml after chronic dosing; time to maximum concentration was 2 h in each case. Candoxatril was well-tolerated; numbers of adverse events did not differ between active treatment and placebo. CONCLUSIONS: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure. Our results cast some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.

Antihypertensive Agents↗
PubMed1992

Twenty-four-hour blood pressure in junior medical staff.

Circadian variations in blood pressure in junior medical staff were compared during routine working days and days receiving medical emergencies. The overnight work commitment of junior medical staff when receiving medical emergencies causes a loss in the normal circadian blood pressure rhythm, with overnight blood pressure falling 10/11 mmHg less than on routine working days. This supports the hypothesis that circadian blood-pressure changes are activity related rather than dependent upon hormonal variation. Long-term health effects of abolishing such normal circadian rhythms are not known.

Adult↗
PubMed1991

Evaluation of potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol in normal subjects.

1. Potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol were evaluated in two double-blind, randomised, balanced, crossover studies employing the same six healthy males. 2. The first study examined the effect of repeated propranolol administration on the pharmacodynamics and pharmacokinetics of verapamil after single oral and intravenous doses. The second explored the pharmacodynamics and pharmacokinetics of verapamil and propranolol alone and in combination after single and repeated oral doses. 3. The magnitude of the prolongation of PR interval induced by oral and intravenous verapamil was not affected by pre-treatment with propranolol. When verapamil and propranolol were co-administered as single doses, effects on PR interval were additive but, following repeated doses, a trend towards greater than additive prolongation was seen. The arithmetic sum of the effects of the two drugs was 23% (95% C.I. 8-38%) but the measured increase after the combination was 40% (95% C.I. 26-54%). 4. The extent of reduction in heart rate and blood pressure at rest and after exercise following repeated doses of propranolol was not influenced by single oral or intravenous doses of verapamil. The heart rate and blood pressure responses to single and repeated oral doses of verapamil and propranolol in combination were significantly greater than those after either drug alone and approximated to the arithmetic sum of the individual responses. 5. Although repeated administration of propranolol reduced hepatic blood flow as assessed by indocyanine green clearance, there was no evidence of an interaction between the drugs at this level. 6. The pharmacokinetics of verapamil and norverapamil were not significantly affected by prior propranolol. After single doses of verapamil and propranolol in combination, the maximum plasma concentration of propranolol was increased and the oral clearance of verapamil reduced. No pharmacokinetic interaction was observed after repeated doses. 7. These findings provide little evidence of a pharmacodynamic or pharmacokinetic interaction between verapamil and propranolol in normal subjects. Most of the haemodynamic responses to these drugs in combination can be explained by additive drug effects but an interaction affecting AV conduction after repeated doses cannot be excluded. The minor pharmacokinetic interaction between the drugs is unlikely to be relevant to the pharmacodynamic changes.

Adult↗
PubMed1991

Hemodynamic effects of a single moderate dose of alcohol in elderly subjects.

The effects of 0.5 g ethanol/kg body weight and of an iso-volumic control drink were compared in eight normotensive subjects aged 70-96 years. Blood alcohol concentration reached a mean (+/- SEM) maximum of 44.4 +/- 5.0 mg/dl at 50 minutes after the start of drinking. Compared to control, alcohol increased mean sitting and standing heart rates by 3.4 +/- 1.3 (p = .08) and 5.4 +/- 1.9 (p less than .05) beats/minute, respectively; mean venous haematocrit rose by 3.9 +/- 1.3% (p less than .05). There were no significant changes in sitting or standing systolic or diastolic blood pressures after alcohol compared to the control drink. A single moderate dose of alcohol has only minor haemodynamic effects in normotensive elderly subjects. The rise in heart rate after alcohol may be a reflex response that helps to maintain blood pressure in the face of reduced circulating plasma volume due to alcohol-induced diuresis.

Aged↗
PubMed1990

Policies for managing hypertensive patients: a survey of the opinions of British specialists.

In September 1988 medically-qualified members of the British Hypertension Society were asked to complete anonymously a questionnaire relating to their views on the management of hypertensive patients. Of 149 questionnaires posted, 90 were returned (60%). There was general agreement that non-pharmacological measures, particularly weight loss and alcohol restriction, are effective treatments. However, there was wide variation in the minimum level of blood pressure considered to warrant drug treatment and little consensus regarding measurement policies or target blood pressures. The drugs of first choice were beta-blockers (54% in men, 35% in women) and thiazide diuretics (28% in men and 47% in women), and they were also the most frequent second choices with 54% of respondents advocating 'stepped-care' based on these drugs. The maximum age at which respondents would be prepared to introduce antihypertensive drugs varied widely although 63% considered that thiazide diuretics are first choice in the elderly. These findings demonstrate a broad range of opinion on the management of hypertension among British specialists, and suggest a continuing need for large clinical trials.

Adrenergic beta-Antagonists↗
PubMed1989

Lack of effect of spironolactone on hair shaft diameter in hirsute females.

Because of its anti-androgenic activity spironolactone 50-200 mg daily is advocated widely for the management of female hirsutism but this practice lacks adequately controlled experimental support. In a double-blind placebo controlled study of the efficacy of spironolactone 100 mg daily in idiopathic hirsutism we were unable to demonstrate objective benefit from spironolactone treatment. The mean effect of spironolactone given over a 9 month period was to increase hair shaft diameter by +15% with 95% CI (-0.4% to +29%). In addition there were no changes in circulating serum androgen concentrations.

Androgens↗