Pharmacokinetic-pharmacodynamic relationships of alpha-adrenoceptor antagonists.

Competitive alpha1-adrenoceptor antagonists are effective in the treatment of both hypertension and cardiac failure. Prazosin has both a short half-life and a short duration of action, but other related quinazoline derivatives, such as doxazosin and terazosin, have pharmacokinetic and pharmacodynamic profiles which make them potentially suitable for once-daily administration. Acute reductions in blood pressure have been correlated with plasma concentrations of prazosin but in most instances, particularly during long term therapy, there is no simple, direct relationship between drug concentration and the fall in blood pressure.

Clinical pharmacological evaluation of calcium antagonists and other drugs modifying myogenic tone in essential hypertension.

The factors determining the acute and long-term response to calcium antagonists have been studied in controlled trials in essential hypertension. The importance of dose and plasma level in determining the response has been confirmed. The blood pressure response has been modelled and mathematically described, with drug concentrations related to blood pressure falls by linear or Emax (maximum fall in blood pressure) models.

Endothelin stimulates phosphatidylinositol hydrolysis in rat vascular smooth muscles.

The ability of endothelin to stimulate phosphatidylinositol hydrolysis in rings of rat aorta was studied. Endothelin 10(-8)-10(-5) mol/l caused increases of 200-1000% in inositol phosphate levels. However, physiological responses to endothelin have been reported in the concentration range 10(-10)-10(-8) mol/l.

A controlled study of combined hormonal and psychological treatment for sexual unresponsiveness in women.

Thirty couples, whose presenting complaint was general sexual unresponsiveness in the female partner, were randomly allocated to one of three treatment groups: testosterone plus sexual counselling; placebo plus the same form of counselling; or testosterone alone. Therapy was time-limited to 16 weeks, and assessments were conducted pre-treatment, at the end of treatment and at a four-month follow-up. There were no notable differences in outcome between the two counselling groups, both of which showed significantly greater improvement on a number of measures of sexual and general interpersonal adjustment and attitude change than the group that received testosterone alone.

Rhabdomyolysis and listeria monocytogenes.

Non-traumatic rhabdomyolysis occurs as a complication of a wide variety of infections and is often discovered as a result of the associated renal failure. We report a case of meningitis due to Listeria monocytogenes, an uncommon cause of infection in adults which was associated with rhabdomyolysis. This confirms a recent first case report of this association.

Peptic ulcer perforation: a complication of double contrast barium meal examination.

This is a case report of peptic ulcer perforation as a complication of double contrast Barium meal examination in the presence of gastric outlet obstruction.

Basal platelet intracellular free calcium concentrations in untreated hypertensive patients and normotensive controls.

Basal platelet intracellular free calcium concentrations were measured in 18 untreated essential hypertensive patients and 18 age and sex matched normotensive controls. No significant difference was observed between the mean platelet intracellular free calcium concentrations for these two groups. There was a weak, but significant positive correlation between both systolic and diastolic BP and basal platelet intracellular free calcium concentration.

The cardiovascular actions of clonidine and neuropeptide-Y in the ventrolateral medulla of the rat.

1. The cardiovascular responses to neuropeptide-Y (NPY) (25 and 50 pmol) and clonidine (10 and 20 nmol) were examined following microinjection into the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Mean arterial pressure (MAP) and heart rate (HR) were measured in anaesthetized rats, pre- and post-injection.

Hysteroscopic endometrial ablation with the neodymium-YAG laser.

Over the past 3 years a series of patients referred to the gynaecological department at Stobhill Hospital with menorrhagia have been treated, as an alternative to hysterectomy, by endometrial ablation with the neodymium-YAG laser. The results in the first 25 patients with a follow-up of over 6 months are presented. The overall success rate was only 52%, but by increasing the power output of the laser energy used to 80 W the rate of success increased to 83%.

A simple, rapid assay for plasma oxalate in uraemic patients using oxalate oxidase, which is free from vitamin C interference.

An enzymatic assay for the determination of oxalate in plasma was developed which is specific, simple, rapid and requires no specialised equipment; interference from vitamin C was removed by incubation of acidified plasma ultrafiltrate with ascorbate oxidase prior to oxalate estimation. Recoveries were 93 +/- 11% and the inter-batch coefficient of variation for 31 determinations at an oxalate level of 24 mumol/l was 10%. The assay is linear up to 300 mumol/l with a detection limit of 2 mumol/l.

Management of achalasia and laryngo-tracheal compression.

A case of severe airway obstruction due to laryngo-tracheal compression associated with achalasia is presented. Local anaesthetic tracheostomy has an important role in some cases.

The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis.

1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2.

Blood coagulation profile in long-term hormone replacement therapy with mestranol.

The coagulation profile of oophorectomised women on long-term (15 yr) hormone replacement therapy with mestranol (30 micrograms/day) is compared to that of women on long-term placebo. Analysis of these data showed no significant difference in prothrombin time, partial thromboplastin time or in anti-thrombin III level in these groups.

Electrocardiographic evidence of myocardial salvage after thrombolysis in acute myocardial infarction.

There is a need for a simple clinical measurement that will indicate the extent of myocardial salvage after successful thrombolysis. This study examined whether coronary artery reperfusion reduced the infarct size as assessed electrocardiographically after thrombolytic treatment. The sum of the (sigma) ST segment area in leads showing ST segment elevation in the 12 lead electrocardiogram at presentation was used as an index of potential myocardial injury (initial ischaemic index).

Twenty-four-hour intragastric acidity in duodenal ulcer patients during dosing with placebo, and 150 mg ranitidine twice or four times daily.

Twenty-four-hour intragastric acidity was measured in 10 patients with a past history of duodenal ulcer on the fourth day of dosing with placebo, and either 150 mg ranitidine given twice or four times daily. The order of the treatments was randomized and a double-blind design was employed. Ranitidine (150 mg) b.

Pharmacokinetics of perindopril: therapeutic consequences.

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril.

First-line and combination treatment for hypertension.

Conventional stepped-care approaches for the control of high blood pressure based on the use of diuretics and beta-blockers have had a disappointing impact on coronary heart disease, the major cause of death in hypertension. Drug therapy for blood pressure should be complementary to attempts to control other risk factors and should not adversely affect other factors. A range of drugs, including calcium antagonists, angiotensin-converting enzyme inhibitors, and alpha-blockers, can be considered as possible first-line treatment.

Endocarditis in intravenous drug abusers with staphylococcal septicaemia.

The case reports of 186 intravenous drug abusers admitted over a three year period were studied. Nineteen had proven staphylococcal septicaemia. Echocardiography showed tricuspid vegetations in seven and aortic vegetations in two.

Impact of a policy of direct admission to a coronary care unit on use of thrombolytic treatment.

Because thrombolytic treatment is effective only if it is given within six hours of acute myocardial infarction it is vital to admit patients to the coronary care unit as soon as possible after the acute event. A policy of admitting patients to the coronary care unit at the request of the patient's general practitioner by a telephone line that is independent of the hospital switchboard significantly reduced the delay. Those admitted via the accident and emergency department at the same hospital reached the coronary care unit 1 h 32 min after being seen by the general practitioner whereas the patients admitted directly took only 43 minutes [corrected].

Skeletal muscle beta 2-adrenoreceptors and the effect of adrenergic drugs on plasma potassium in perinephritis hypertension in rabbits.

1. It has been suggested that beta 2-adrenoreceptors in skeletal muscle regulate plasma potassium. The possibility that alterations in the function and/or density of these receptors occurs in perinephritis hypertension in rabbits was studied.

Lipoprotein and apolipoprotein levels in postmenopausal women on continuous oestrogen/progestogen therapy.

Levels of serum lipoproteins and apolipoproteins were monitored for 48 weeks in two groups of women taking part in a double-blind trial of continuous oestrogen/progestogen with and without oestriol. There were no differences between the effects of the two treatments on the substances measured. Triglycerides did not change and there was a transient fall in very low density lipoprotein cholesterol.