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G T McInnes

Publications and source records attributed to G T McInnes.

106 records · Page 6Linked to original sources
PubMed1981

Steady-state relative potency of aldosterone antagonists: spironolactone and prorenoate.

The dose ratio approach was used to define the steady-state relative potency of the competitive mineralocorticoid antagonists prorenoate potassium and spironolactone in six healthy male subjects using fludrocortisone as mineralocorticoid agonist. Log fludrocortisone dose-response relationships in the presence or absence of antagonists did not differ from linearity and parallelism, supporting the theoretical basis of the method. Urinary sodium and plasma potassium responses appeared to behave according to the law of mass action, which made possible estimation of the potency of prorenoate relative to spironolactone on a weight basis-4.2:1 (95% C.L. 2.7-6.9:1) and 2.68:1 (95% C.L. 0.71-6.57:1, respectively. The steady-state relative potency for sodium excretion was greater than previously estimated after single doses. Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.

Adult↗
PubMed1981

Quantitative comparison of aldosterone antagonists in normal human subjects: prediction of therapeutic potency.

1 The potency of single doses of the aldosterone antagonist SC8109 relative to spironolactone in reversing the urinary electrolyte effects of fludrocortisone was examined in a double-blind, balanced, crossover study in six healthy volunteers. 2 For the urinary ratio log10 10Na/K, the relative potency of SC8109; spironolactone on a weight basis was 0.08:1 (95% confidence limits 0.04--0.13:1). 3 The potency of SC8109 relative to spironolactone for natriuresis and antikaliuresis was 0.10:1 and 0.05:1, respectively. 4 The results show excellent agreement with clinical experience where SC8109 was considered to have one tenth the potency of spironolactone. We suggest that the human bioassay employed in this study provides quantitative information which should be predictive of the therapeutic potency of aldosterone antagonists.

Adult↗
PubMed1981

Acute adverse reactions attributed to allopurinol in hospitalised patients.

Of 29 524 hospitalised medical patients monitored in a drug surveillance programme 1835 (6.2%) received the xanthine oxidase inhibitor allopurinol. After the exclusion of skin reactions adverse effects were attributed to this drug in 33 (1.8%) patients, the most frequent being haematological abnormalities (11 patients, 0.6%) and diarrhoea and drug fever (5 each, 0.3%). Adverse effects were dose-related. Reactions were unrelated to age, weight, reason for therapy, admission blood urea, or albumin concentrations. Acute exacerbation of gout was troublesome in 3 patients (1 in 600 exposed).

Aged↗
PubMed1980

Activity of sulfur-containing intermediate metabolites of spironolactone.

The renal antimineralocorticoid activity of single administration of 2 sulfur-containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes indiced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 alpha-thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 alpha-thio-spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 alpha-thiomethyl-spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur-containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone.

Adult↗
PubMed1978

Bumetanide and frusemide: a comparison of dose-response curves in healthy men.

1 Log dose-responses for the loop diuretics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as regards urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46:1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20:1 reported when the drugs are used at high dosage in patients with renal failure.

Adult↗
PubMedDate not supplied

Effect of micronization on the bioavailability and pharmacologic activity of spironolactone.

The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of these tablets were identical. After 200-mg single doses, the bioavailability of micronized tablets was significantly higher than that of standard tablets. Furthermore, as assessed by 24-hour urine log10 10 Na/K ratio, the pharmacologic activity of micronized spironolactone was significantly greater than that of the standard formulation. The significant influence on renal antimineralocorticoid activity of raised plasma and urinary levels of canrenone, quantitatively the major active metabolite of spironolactone in man, emphasizes the clinical importance of the bioavailability of spironolactone preparations. Since this study, the process used in the manufacture of spironolactone (Aldactone) tablets has been under review.

Biological Availability↗
PubMedDate not supplied

Mortality amongst patients of the Glasgow Blood Pressure Clinic was high in the 1970s and 80s but has fallen since, why?

Established in 1968 the Glasgow Blood Pressure Clinic has over 11,000 patients on its computer record. Up to 1980, mortality from all-causes and from cardiovascular causes was high: relative risks compared with two local control populations were greater than 2.0. Since 1980, all-cause mortality has decreased to 1.31 (859 deaths, CI 1.23-1.39). Lower mortality from cardiovascular causes, particularly coronary heart disease, contributes to the decrease. Reasons for the decrease are under investigation currently. Referral of patients with slightly lower blood pressure contributes, as may better blood pressure control with newer antihypertensive drugs. ACE inhibitors and calcium channel blockers were introduced in 1980 and during the 16-year period to 1995, all-cause mortality has decreased most in patients taking ACE inhibitor. A decrease also occurred in patients taking antihypertensive drugs other than ACE inhibitor.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Is cancer related to hypertension or to its treatment?

Three questions related to cancer and blood pressure are discussed. (i) Is cancer related in some way to hypertension, or to blood pressure? Several studies show a relation of blood pressure and cancer in populations. However, our own experience, based on a cohort of 15,411 subjects with BP measured in the 1970s and with 1,392 fatal cancers since, shows no relation of cancer risk and diastolic pressure. Nor were cancer numbers (n=72) observed in the 1,078 untreated hypertensives of the Glasgow Blood Pressure Clinic different from those expected (n=71.2) in a control population matched for age, sex and smoking habit. (ii) Do antihypertensive drugs promote cancer? Atenolol and calcium channel blockers have been suspected of this, but evidence of larger studies, including two of our own, is negative: relative risk for cancer in our patients taking CCB was 1.02 (CI 0.82-1.27). (iii) Do antihypertensive drugs protect against cancer? A study of ours based on the Glasgow Clinic raises this possibility: relative risk for incident cancer amongst 1,559 patients taking ACE inhibitor was 0.72 (CI 0.55-0.92).

Adrenergic beta-Antagonists↗