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Biomedical subjects

L M Wing

Publications and source records attributed to L M Wing.

At least 73 records · Page 4Linked to original sources
PubMed1984

Failure of 'therapeutic' doses of beta-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine.

The effects of separate 1 week pre-treatments with each of the beta-adrenoceptor antagonists, propranolol (80 mg every 12 h), metoprolol (100 mg every 12 h) and atenolol (50 mg once daily), on the disposition of a single i.v. dose of tolbutamide were studied in six healthy volunteers. In addition, the effects of a 1 week pre-treatment with metoprolol (100 mg every 12 h) and atenolol (50 mg once daily) on the disposition of orally and i.v. administered lignocaine were determined in seven healthy subjects. Tolbutamide clearance, half-life, volume of distribution and plasma protein binding were not altered by the beta-adrenoceptor blocker pre-treatments. Similarly, neither metoprolol nor atenolol had a significant effect on the systemic clearance, apparent oral clearance or other dispositional parameters of lignocaine. 'Therapeutic' plasma concentrations of the beta-adrenoceptor blockers were confirmed on each study day. It is concluded that the inhibition of oxidative drug metabolism previously reported for lipophilic beta-adrenoceptor blockers may be selective for different forms of cytochrome P450 and possible concentration-dependent.

Adrenergic beta-Antagonists↗
PubMed1984

Effects of indomethacin, sulindac, naproxen, aspirin, and paracetamol in treated hypertensive patients.

Four placebo controlled, randomised crossover studies were carried out to investigate the effects of non-steroidal anti-inflammatory drugs and analgesics on blood pressure control in treated hypertensive patients. Twelve patients completed one study comparing indomethacin, 25 mg tds, with placebo in 2 six week phases; there were increases in mean blood pressure (p less than 0.01) of 9 mm Hg (casual), 8 mm Hg (supine) and 10 mm Hg (standing) in the indomethacin phase accompanied by a 50% reduction in plasma renin activity (p less than 0.05) and a 47% decrease in plasma aldosterone concentration (p less than 0.05). Similar studies on aspirin-SR, 650 mg daily (19 patients), and paracetamol, 1 g 8th hourly (20 patients), revealed only small changes in blood pressure, with a 2 mm Hg increase in supine diastolic blood pressure during aspirin therapy and a 4 mm Hg increase in supine and standing systolic blood pressure during paracetamol therapy (p less than 0.05 for both). Nineteen patients completed a study with 4 three week phases, taking placebo, naproxen 250 mg mane and 500 mg nocte, sulindac 200 mg bd, and aspirin-SR 1950 mg bd. All three active agents depressed plasma renin activity and plasma aldosterone concentration. Neither sulindac nor aspirin caused any significant increases in blood pressure, and naproxen had little effect, though it did cause a 4 mm Hg increase in standing systolic pressure (p less than 0.05). We conclude that the effects of indomethacin on control of blood pressure in treated hypertensive patients are not exhibited to the same extent by other drugs investigated, and that they are not dependent on the concomitant decreases in plasma renin activity or plasma aldosterone concentration. The importance of inhibition of prostaglandin synthesis remains unclear.

Acetaminophen↗
PubMed1984

The effect of ketanserin on blood pressure and biochemical parameters in treated patients with essential hypertension.

17 subjects with essential hypertension (14 male, 3 female - ages: 40-69 years), 13 of whom continued their previous anti-hypertensive therapy, completed a double-blind cross-over trial of ketanserin 40 mg twice daily versus placebo tablets twice daily - each treatment phase was six weeks in duration. For the group as a whole, blood pressure (BP) was reduced in the ketanserin phase compared with the placebo phase; supine mean BP decrease: 4 +/- 1 mm Hg (p less than 0.05); standing mean BP decrease: 7 +/- 1 mm Hg (p less than 0.001). Heart rate (HR) was also significantly decreased in the ketanserin phase by 5 +/- 1 beats/minute (p less than 0.001). When individual subgroups were analysed the reductions in BP and HR were greater in subjects already receiving anti-hypertensives, diuretic and/or beta blockers. Changes were observed in 24 hour urine sodium and potassium excretion - sodium (mmol/day): placebo 137 +/- 17, ketanserin 174 +/- 19 (p less than 0.05); potassium (mmol/day): placebo 74 +/- 8, ketanserin 57 +/- 5. For the group as a whole there were no significant adverse effects during the ketanserin phase, although two subjects had a dose reduction of ketanserin because of drowsiness and dizziness. Two additional subjects withdrew from the study due to adverse effects, one in the placebo phase. In conclusion ketanserin in the dose administered has a modest hypotensive effect which is best seen in subjects already receiving other anti-hypertensive agents.

Adrenergic beta-Antagonists↗
PubMed1983

Marital interaction and adjustment in patients with essential hypertension.

Twenty-five men and twenty-six women with essential hypertension, and their spouses, were compared with normotensive control couples on a questionnaire measure of marital adjustment. The marriages of the hypertensive men showed significantly raised levels of marital dissatisfaction in the spouses, and an abnormal degree of reciprocal dissatisfaction between spouses. The marriages of the female patients showed an abnormal lack of reciprocity between spouses' scores. These findings support anecdotal reports of a relationship between marital disharmony and communication problems and elevated blood pressure. It is suggested that clinicians could routinely assess marital adjustment in patients with essential hypertension, and that in some cases conjoint marital therapy might be an adjunct or alternative to anti-hypertensive medications.

Adult↗
PubMed1982

Effects of once daily indapamide and pindolol on blood pressure, plasma aldosterone concentration and plasma renin activity in a general practice setting.

Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide (2.5 mg daily) and pindolol (10 mg daily) on blood pressure, heart rate, plasma renin activity and plasma aldosterone concentration. There were four randomised test phases of eight weeks each during which patients received indapamide alone, pindolol alone, indapamide plus pindolol and no active treatment (placebo). Blood pressure and heart rate were measured every two weeks. Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase, 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase. Factorial analysis confirmed that the hypotensive effects of the two drugs were additive, without evidence of potentiation or antagonism. Indapamide caused significant reductions in plasma potassium and chloride, and increases in plasma bicarbonate and urate concentrations; it also caused increases in plasma renin activity and aldosterone concentration. These changes are similar to those observed with thiazide diuretics.

Adult↗
PubMed1982

Long-acting and short-acting diuretics in mild essential hypertension.

A randomised, placebo-controlled, double-blind crossover study was conducted in 14 patients with mild essential hypertension comparing different regimens of administration of the "short-acting" diuretic, chlorothiazide and the "long-acting" diuretic, chlorthalidone. There were 6 randomised treatment phases each of 5 weeks duration. For blood pressure recorded both at the Clinic and at home the most prominent effects were seen with standing blood pressure, for which significant reductions of mean blood pressure compared to the placebo phase were observed with chlorthalidone 25 mg once daily (-5 +/- 1 (SE) mm Hg - p less than 0.05), chlorthalidone 50 mg once daily (-7 +/- 1 mm Hg - p less than 0.01) and chlorothiazide 500 mg twice daily (-4 +/- 1 mm Hg - p less than 0.05). Blood pressure reductions with chlorothiazide 500 mg once daily and 1000 mg once daily were not significant. About half of the patients completing the trial could be described as "non-responders". The observed biochemical changes (reduced plasma potassium and chloride concentrations and increased plasma bicarbonate and urate concentrations) were most marked in the phases with the most prominent blood pressure effects. The result support the suggestion that a sustained diuretic effect is desirable when diuretics are used in the treatment of hypertension. This can be obtained by selection of the appropriate dosage regimen for a particular diuretic, such as once daily administration for "long-acting" and twice daily for "short-acting" thiazide-type diuretics.

Adult↗
PubMed1981

Comparison of indapamide with thiazide diuretics in patients with essential hypertension.

The effect of the new diuretic antihypertensive drug, indapamide (2.5 mg a day), was compared with the effect of thiazide diuretics in 24 patients with hypertension (seven of whom were receiving a diuretic alone, six were taking a beta-blocker plus a diuretic, and 11 received other combinations of drugs, including a diuretic in all cases). The randomized crossover study with two six-week phases indicated that indapamide is an effective hypotensive agent with potency similar to that of the thiazide diuretics in lowering the blood pressure and in increasing the excretion of potassium.

Benzothiadiazines↗
PubMed1980

Comparison of labetalol, hydrallazine, and propranolol in the therapy of moderate hypertension.

The efficacy of labetalol, an alpha and beta adrenoceptor blocking drug, has been compared with that of placebo, of propranolol alone, of hydrallazine alone, and of hydrallazine plus propranolol in combination in a randomized double-blind, fixed-dose crossover trial. Labetalol (300 mg twice a day) was equally effective with propranolol (80 mg twice a day), and more effective than hydrallazine (50 mg twice a day) alone. The effect of labetalol was comparable with that of hydrallazine plus propranolol when the patient was standing, but less potent with the patient in the supine position. Side effects were few.

Antihypertensive Agents↗
PubMed1980

The simultaneous determination of theophylline, theobromine and caffeine in plasma by high performance liquid chromatography.

A high performance liquid chromatographic procedure for the stimultaneous micro-scale determination of theophylline, theobromine and caffeine in plasma is described. After a single dichloromethane extraction of 0.5--0.2 ml of acidified plasma, the evaporated residue is chromatographed on a reverse-phase gC-18) column. With a mobile phase of acetate buffer (pH 4)--acetonitrile (88:12) at a flow-rate of 2.0 ml/min., the three methylxanthines are separated within six minutes. Detection at xanthines are separated within six minutes. Detection at 276-280 nm enables quantitation of 0.1 mg/1 of drug in a 0.1 ml sample. The method is reproducible, correlates well with EMIT for plasma theophylline, and is applicable to the routine monitoring of both paediatric and adult patients as well as to metabolic studies.

Adult↗
PubMed1980

The effect of metoclopramide and atropine on the absorption of orally administered mexiletine.

The effect of pretreatment with intravenous metoclopramide (10 mg) and atropine (0.6 mg), both separately and combined, on the absorption rate and relative oral bioavailability of the antiarrhythmic drug, mexiletinee (400 mg) was studied in eight fasting healthy males using a Latin Square design for order of pretreatment administration. The time (Tmax) of the maximum mexiletin plasma concentration (Cpmax) was reduced by metoclopramide (P < 0.001) and was increased by atropine (P < 0.01) compared with saline control. Tmax was not significantly altered by combined metoclopramide and atropine pretreatment. Atropine pretreatment was associated with a significant reduction of Cpmax (P < 0.05) and of elimination half-life (P < 0.05). The area under the mexiletine plasma concentration-time curve was not affected by any of the pretreatments. The results suggested that metoclopramide enhanced and atropine decreased the rate of mexiletine absorption without altering the relative oral bioavailability. When the pretreatments were administered in combination, metoclopramide reversed the delay in mexiletine absorption produced by atropine.

Administration, Oral↗
PubMed1979

Effects of allopurinol on theophylline metabolism and clearance.

The effects of allopurinol on the plasma clearance and metabolism of theophylline in man were investigated under single-dose and multiple-dosing conditions. No change in theophylline clearance was found with the concomitant use of allopurinol but 1-methylxanthine (1MX), a theophylline metabolite not previously described in man, was detected in urine during control and allopurinol treatment phases under both single- and multiple-dosing conditions. 1MX excretion increased at the expense of 1-methyluric acid (1MU) during the allopurinol treatment phase. It is proposed that the secondary biotransformation of 1MX to 1MU is mediated by xanthine oxidase.

Adult↗
PubMed1979

Antihypertensive effects of clonidine in tetraplegic subjects devoid of central sympathetic control.

1. The effects of 300 microgram of oral clonidine on blood pressure, heart rate, plasma noradrenaline and adrenaline concentrations were studied in seven tetraplegic subjects with physiologically complete cervical spinal cord transections. 2. Clonidine did not significantly change resting blood pressure during the 8 h of the study. Resting heart rate fell. Resting plasma noradrenaline and adrenaline concentrations, when measured 2 h after clonidine, were not significantly lower. 3. Urinary bladder stimulation resulted in a marked rise in blood pressure accompanied by an elevation in plasma noradrenaline but not adrenaline. The hypertensive response to bladder stimulation was substantially reduced by clonidine, the maximum suppression occurring 2-4 h after administration of the drug. The plasma noradrenaline response to bladder stimulation, when measured 2 h after clonidine, was significantly lower than the response before clonidine. In two tetraplegic subjects with indwelling catheters the rise in intravesical pressure caused by bladder stimulation was unchanged by clonidine. 4. The pressor response to intravenous noradrenaline in two tetraplegic subjects and to intravenous phenylephrine in a further two tetraplegic subjects was unchanged by clonidine. 5. Clonidine may have additional antihypertensive effects which occur independently of actions in the brain. These effects may be exerted by an action either on sympathetic neurones in the spinal cord or on presynaptic alpha-adrenoreceptors in the periphery.

Adult↗
PubMed1977

Pharmacokinetic and concentration-effect relationships of clonidine in essential hypertension.

The effect of oral doses of 300 microgram of clonidine hydrochloride on blood pressure, sedation and saliva production in 5 essential hypertensives were qualitatively similar to the effects in normotensive subjects. Peak plasma clonidine concentration (1.34 +/- 0.28 ng/ml) and plasma half-life (10.0 +/- 0.8 h) were similar to normotensives. During chronic oral dosing there was no evidence of drug accumulation. Some tolerance to the sedative and salivary flow effects occurred but no tolerance to the hypotensive effect was observed. There was a linear relationship between reduction in saliva flow and plasma levels of clonidine. The hypotensive effect was also related to plasma level at low concentrations. At plasma levels greater than 1.5 ng/ml the hypotensive effect was diminished. This loss of effect at high plasma concentration may be related to the peripheral, post-synaptic alpha-adrenoceptor agonist action of the drug.

Blood Pressure↗