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Biomedical subjects

G T McInnes

Publications and source records attributed to G T McInnes.

At least 73 records · Page 4Linked to original sources
PubMed1989

Twice-daily low-dose captopril in diuretic-treated hypertensives.

Twice-daily captopril (25 mg) and placebo were compared in ten hypertensive patients who were already receiving bendrofluazide. After six weeks therapy, captopril produced significant antihypertensive effects one to six hours after dosing but these did not persist at eleven to twelve hours. Plasma renin concentration was increased for twelve hours after captopril but inhibition of angiotensin II activity was lost by twelve hours. During the period when captopril reduced blood pressure significantly, effective renal plasma flow and hepatic blood flow were unchanged although renal vascular resistance was reduced. There was no evidence that captopril altered plasma sodium, potassium or magnesium concentrations following bendrofluazide. Thus, in thiazide-treated patients, captopril 25 mg produces significant blood pressure reduction for at least six hours after dosing, without impairing renal or hepatic blood flow. However, twice-daily low-dose captopril does not adequately control blood pressure throughout the dosage interval.

Adult↗
PubMed1988

Simple high-performance liquid chromatographic method for the measurement of amiloride in body fluids.

A simplified rapid high-performance liquid chromatographic (HPLC) procedure has been developed for the measurement of amiloride in plasma or urine. Solid-phase extraction columns provide quick, clean and simple sample preparation, allowing ten samples to be processed in less than 5 min. The HPLC system uses a standard reversed-phase (C18) column with detection by ultraviolet absorption at 365 nm. The assay has been used to define plasma amiloride concentration-time profiles and to quantitate urine amiloride recovery in healthy men after repeated administration at two doses.

Adult↗
PubMed1988

Evaluation of two oxprenolol oral osmotic (OROS) delivery systems in patients with essential hypertension.

The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS. At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses. However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade. The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration. These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.

Administration, Oral↗
PubMed1988

Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.

1 The effect of sodium valproate (VPA; 500 mg thrice daily for 7 days) and matched placebo on the disposition and psychomotor profile of a single dose of carbamazepine (CBZ; 10 mg kg-1) was studied in eight healthy male subjects using a randomised balanced crossover design. 2 VPA alone had no effect on antipyrine clearance, urinary 6 beta-hydroxycortisol excretion and a battery of psychomotor function tests after 3 days' treatment despite achieving a mean steady-state concentration (90 +/- 6 mg 1(-1)) well within the target range (50-100 mg 1(-1)) for the drug. 3 VPA pre-treatment did not alter total CBZ area under the concentration-time curve (AUC 0-59 h) but did prolong CBZ elimination half life by 12% (P less than 0.01). AUC 0-59 h for free plasma CBZ was 13% higher (P less than 0.02) and half-life of unbound CBZ 16% longer (P less than 0.02) during VPA treatment. CBZ-10,11 epoxide (CBZ-E) levels (52%) and CBZ-E/CBZ ratios (45%) were both elevated by concurrent VPA (P less than 0.05) and free CBZ fraction was increased by 7% (P less than 0.02). 4 The sole effect of VPA on the psychomotor profile of CBZ was prolongation of card sorting time (P less than 0.05), although CBZ-related side effects were reported as more severe when VPA was also taken (P less than 0.01). 5 These data suggest that VPA displaces CBZ from plasma protein binding sites and inhibits the metabolism of both the parent drug and its epoxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Concentration-effect relationships for oxprenolol in patients with essential hypertension.

1. Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2. Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P less than 0.001), but differences were slight. 3. Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4. The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.

Adult↗
PubMed1988

Drug interactions that matter. A critical reappraisal.

Drug interactions are ubiquitous but those with proven clinical relevance are much less common. Only when the combined effects of the interacting drugs are greater or less than the arithmetic sum of their individual actions can the event be considered a true interaction. This eliminates many candidate 'interactions' which in reality merely describe the summation of similar or opposing, but independent, drug effects. An appreciation of those drug interactions that really do matter can be best achieved by combining a practical knowledge of the pharmacological mechanisms involved with awareness of the most vulnerable patients (those with little reserve capacity) and the drugs associated with the greatest risk (those with a narrow therapeutic index). This review follows these guidelines and provides an account of well documented drug interactions categorised according to mechanism.

Animals↗
PubMed1988

Does therapeutic reduction of diastolic blood pressure cause death from coronary heart disease?

Mortality data from 3350 patients who attended the Glasgow Blood Pressure Clinic between 1968 and the end of 1982 were used to examine the hypothesis that lowering diastolic blood pressure (DBP) below 85 mmHg causes death from coronary heart disease (CHD). Analysis of 257 coronary deaths in quintiles of treated DBP showed a significantly nonlinear relation, with the lowest mortality from CHD occurring in the middle quintile (91-98 mmHg). This finding persisted after adjustment for risk at entry, and was independent of sex and pre-existing CHD. In contrast, the relations between treated systolic blood pressure and death from CHD, and treated DBP and death from stroke were linear. For 2355 patients who were untreated at referral there was no relation between the change in DBP during treatment and death from CHD. In our view, however, these findings do not necessarily support the hypothesis that lowering of DBP below 85 mmHg with treatment causes death from CHD. Evidence for this is indirect and inconsistent, and should not, at present, be used as a basis for any change in treatment practice.

Antihypertensive Agents↗
PubMed1987

Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes.

1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink. 2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol. 3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels. 4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink. 5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol. 6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin-angiotensin systems after alcohol.

Adolescent↗
PubMed1987

Effects of calcium antagonism and beta-blockade on haemodynamic responses to stress.

The influences of verapamil, propranolol and their combination on blood pressure and heart rate during cold pressor testing and isometric exercise were examined in 13 patients with essential hypertension. Verapamil modified the peak pressor responses to each stimulus while the major action of propranolol was on heart rate. Together the drugs attenuated both haemodynamic responses. Combined calcium antagonism and beta-blockade may modify favourably surges in blood pressure and heart rate in ambulant hypertensives.

Adult↗
PubMed1986

Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction.

Verapamil (120 mg three times a day) was given as adjunctive therapy to six patients with refractory partial epilepsy who were receiving carbamazepine (CBZ). Within a few days symptoms of CBZ neurotoxicity developed in all six patients. There was a mean rise of 46% in total and 33% in free plasma CBZ concentrations in five of these patients (p less than 0.01), and a simultaneous fall of 36% in the ratio of the principal metabolite, CBZ-10,11-epoxide, to CBZ (p less than 0.001). Two patients with mild symptoms were rechallenged with a lower verapamil dosage (120 mg twice a day) and showed similar rises in CBZ concentration and recurrent neurotoxic symptoms. Verapamil increased the area under the CBZ concentration/time curve during a dose interval by 42% in another patient. Withdrawal of verapamil was associated with a decline in circulating CBZ concentration from 12 mg/l to 7 mg/l and seizure breakthrough in a further patient who was receiving both drugs long term. These results suggest that verapamil inhibits the metabolism of CBZ to an extent likely to have important clinical repercussions.

Adult↗
PubMed1986

Effect of simple short term dietary control on urine electrolyte excretion in normal men.

Normal diet and a simple short term prescribed diet were compared with respect to mean excretion of urine electrolytes and the variability in these responses in 12 healthy male subjects. Urine was collected from 7 to 15 h (overnight) and 15 to 25 h (daytime) after the start of dietary control. Differences in mean responses were slight. For sodium and potassium excretion, however, there were tendencies for responses in subjects with high excretion on normal diet to decrease and for responses in those with low excretion on normal diet to increase towards the overall mean during the prescribed diet. The prescribed diet reduced markedly the variability in electrolyte responses and for log transformed data reductions in variability were statistically significant in the daytime urine collections. The results of this study have confirmed quantitatively the benefit of a short period of simple dietary control. The marked reduction in the variability of sodium and potassium excretion improves considerably the precision and sensitivity of studies of urine electrolyte composition.

Adult↗
PubMed1986

Trends in psychotropic prescribing in general practice and general medical patients.

Psychotropic drug prescribing in 1280 medical inpatients between 1973-75 was compared with that in 1200 similar patients during 1982-83. Three benzodiazepines accounted for 64% of prescriptions in 1973-75 and nine benzodiazepines for 82% of prescriptions in 1982-83. Over the decade, use of psychotropic drugs fell from 56% to 38% (P less than 0.001), primarily due to a reduction in patients treated only in hospital (34% vs 16%, P less than 0.001). Before admission, the proportions of patients receiving these drugs were similar (17% vs 18%). During admission, concomitant administration of similar drugs declined from 22% of patients in 1973-75 to 11% in 1982-83 (P less than 0.001), while concurrent prescribing before admission increased from 13 to 19%. The marked fall in psychotropic drug use and in inappropriate concomitant therapy indicates an encouraging trend towards more rational drug use at least in hospital. This was achieved without fiscal control and further rationalization of prescribing habits may be achieved by self-audit within the profession without legislative action.

Adolescent↗