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Biomedical subjects

P Walmsley

Publications and source records attributed to P Walmsley.

9 recordsLinked to original sources
PubMed2000

The effects of hepatic impairment on the pharmacokinetics of doxazosin.

The pharmacokinetics of doxazosin was determined in an open-label study of 12 male volunteers with hepatic impairment (stable alcoholic cirrhosis) and 12 healthy male volunteers. Participants (fasting) received a single 2 mg doxazosin tablet, and blood samples were collected over a 120-hour period. Safety assessments included laboratory and vital sign (blood pressure, pulse rate, and ECGs) measurements and recording of all reported adverse events. The mean peak plasma concentrations were 10.8 ng/mL and 12.3 ng/mL for the subjects with hepatic impairment and healthy subjects, respectively. The corresponding mean area under the plasma concentration-time curve values were 246 and 172 ng.h/mL, a 43% increase in exposure in the subjects with hepatic impairment (p = 0.02). Although the apparent oral clearance was reduced by 30% in men with hepatic impairment compared with healthy subjects (p = 0.02), the elimination halflife was not significantly changed (24 vs. 22 hours, respectively). Laboratory test results, vital signs, and the incidence of adverse events were similar for the two treatment groups. These findings indicate that the recommended dosing regimen for doxazosin is appropriate for patients with clinically mild to moderate hepatic impairment.

Blood Pressure↗
PubMed1999

Risking harm.

Explore the source record for details and available documents.

Acute Disease↗
PubMed1996

Principal results of the Hypertension and Lipid Trial (HALT): a multicenter study of doxazosin in patients with hypertension.

The Hypertension and Lipid Trial (HALT) was undertaken to assess the efficacy and safety of doxazosin, a selective alpha 1- adrenergic blocker, in patients with hypertension in a clinical practice setting. The effects of doxazosin on office blood pressure, changes in lipid profiles, and theoretic coronary disease risk were studied. In an open, noncomparative, multicenter trial, 851 patients were studied for a maximum of 16 weeks. Doxazosin significantly reduced mean sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 15.2/12.5 mm Hg and standing SBP and DBP by 16.1/12.7 mm Hg in the total study population (n = 807; p = 0.0001), with no significant effect on heart rate. Mean total cholesterol levels were significantly reduced by 2.7%, low-density lipoprotein cholesterol levels by 2.4%, and mean triglyceride levels by 3.4% (all p values < 0.05). High-density lipoprotein (HDL) cholesterol levels were essentially unchanged. The mean ratio of total to HDL cholesterol was significantly reduced (p < 0.05). Mean predicted 5-year coronary disease risk was significantly reduced with doxazosin therapy by 14.7% in previously untreated patients (p < 0.0001) and by 1.7% in patients who were previously receiving antihypertensive therapy (p < 0.05). The drug was well tolerated. This study demonstrates that antihypertensive therapy with doxazosin can favorably affect coronary disease risk factors and reduce predicted coronary disease risk.

Adult↗
PubMed1994

Nighttime dosing of doxazosin has peak effect on morning ambulatory blood pressure. Results of the HALT Study. Hypertension and Lipid Trial Study Group.

In this study the effects of a single daily dose (average 8.9 mg) of doxazosin (an alpha-adrenergic blocker) given at night were evaluated in 111 patients with mild hypertension. Patients were studied first on no medication, and a second time after being treated for up to 16 weeks with doxazosin. Blood pressure was measured by noninvasive ambulatory monitoring at the beginning and end of the study. There was a sustained reduction of both systolic and diastolic pressure throughout the day and night, but the greatest reduction occurred in the morning hours. Since the peak treatment effect was later than predicted from previous pharmacokinetic studies, it is suggested that the timing of the peak effect may depend on the prevailing level of alpha-adrenergic tone, as well as on the pharmacokinetics of the drug.

Adult↗
PubMed1994

Differential effects of doxazosin on clinic and ambulatory pressure according to age, gender, and presence of white coat hypertension. Results of the HALT Study. Hypertension and Lipid Trial Study Group.

In this study the effects of a single daily dose of doxazosin (an alpha-adrenergic blocker) given at night were evaluated in 112 patients with mild hypertension. Patients were studied first on no medication, and a second time after being treated for up to 16 weeks with doxazosin. Blood pressure (BP) was measured by noninvasive ambulatory monitoring at the beginning and end of the study. Before treatment, the white coat effect (clinic-ambulatory BP) was greater in women than in men (significant for systolic pressure but not diastolic), and greater in elderly (aged over 65 years) than in younger patients (significant for both systolic and diastolic pressure). Clinic and ambulatory BP were reduced to a similar extent in men and women by doxazosin, but in the elderly the fall in clinic BP was associated with a much smaller fall of ambulatory BP. In patients with white coat hypertension (elevated clinic but normal ambulatory BP) doxazosin lowered clinic but not ambulatory BP, while in those with sustained hypertension it lowered both.

Adult↗
PubMedDate not supplied

The natural history of liver disease in former drug users.

Three hundred and twenty drug-free former narcotic addicts were studied with regard to persistence of abnormalities of liver function and morphology, and their relation to hepatitis B infection. Hepatitis B antibody was present in 52.4 per cent, while HBs antigen was detected in only 6 per cent. Transaminase abnormalities, initially present in 39 per cent, were found in 22 per cent six months after cessation of drug abuse. Abnormalities tended to persist thereafter, although there was some continued return to normal levels. Liver biopsy findings of chronic persistent and aggressive hepatitis correlated with persistence of HBs antigenemia and transaminase elevation. Follow-up liver biopsies in seven subjects showed decreased inflammatory reaction in five. None showed progressive liver disease. We conclude that: (1) 15 to 20 per cent of former narcotics addicts have chronic persistent hepatitis or chronic aggressive hepatitis after cessation of drug absuse for six months or more; (2) serologic evidence of exposure to HBs antigen is frequent, and rapidly develops after the start of needle use; (3) although histologic ad chemical abnormalities usually persist, progression did not occur, and some individuals demonstrated spontaneous improvement.

Acute Disease↗
PubMedDate not supplied

Partial to holistic care.

This article evaluates how clients with severe and enduring mental illness in the USA and Eire are managed within the philosophy of 'partial hospitalisation', a total care package that is delivered part of the time in a mental health unit, instead of a traditional inpatient mental health service. The author visited McLean Hospital, Boston, which is a centre of excellence for the partial hospitalisation philosophy (Sederer, 1992), and Harvard Medical School, Massachusetts. This is compared with a visit to St Joseph's Hospital, County Limerick, and Newcastle Hospital, County Wicklow, which evolved from institutional care philosophies and sustained the highest bed population in the world for patients with mental illness (Commission of Inquiry, 1996).

Boston↗