Biomedical subjects

L G Howes

Publications and source records attributed to L G Howes.

112 records · Page 7Linked to original sources

PubMed1983

Age related changes of noradrenaline content in brain regions of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WK) rats.

Noradrenaline (NA) was assayed in brain regions of male and female WK and SHR of 6 to 40 weeks of age, using high performance liquid chromatography with electrochemical detection (HPLC-ECD). The change of levels with age was similar in brain regions of both strains except in brainstem and thoracic spinal cord where levels fell progressively with age in SHR but not in WK rats. The fall in NA content in these two regions is associated with a rise in blood pressure with age in the SHR and suggests a relationship between NA levels and hypertension. The demonstration of different patterns of change in NA levels with age between WK and SHR represents a new approach to resolving the problem of the lack of appropriate control animals for genetic models of disease. However, the data also emphasise that differences in catecholamine metabolism may occur between in-bred strains of rat such as the WK and SHR, and between male and female rats, unrelated to differences in blood pressure.

Age Factors↗

PubMed1980

Hypertensive responses induced by phenylpropanolamine in anorectic and decongestant preparations.

The acute effects of a single capsule of each of two phenylpropanolamine-containing preparations were determined in a group of healthy young adults, by means of a double-blind comparison with matching placebo preparations. Supine diastolic blood-pressure rose to 100 mm Hg or more in 12 out of 37 subjects taking an anorectic preparation ('Trimolets'; 85 mg phenylpropanolamine per capsule) and in 4 out of 34 subjects taking a decongestant preparation ('Contac 500'; 50 mg phenylpropanolamine per capsule). 20 of the subjects taking trimolets reported adverse side effects. The frequency and extent of the hypertensive response to high-dose phenylpropranolamine-containing preparations suggest that clinical use of such preparations should be reviewed and that their availability without prescription may not be appropriate.

Adult↗

PubMedDate not supplied

Pharmacokinetic comparison of a combination tablet of enalapril and hydrochlorothiazide with enalapril and hydrochlorothiazide tablets administered together and separately.

Enalapril and hydrochlorothiazide (HCT) are established single agent treatments for mild hypertension and cardiac failure and are a potent combination in more severe or resistant cases. We have compared the pharmacokinetics of enalaprilat (the active metabolite of enalapril) and HCT in a four-way comparison of a combination tablet of enalapril (10 mg)/HCT (25 mg) with a single dose of an enalapril tablet (10 mg), a single dose of a HCT tablet (25 mg) and simultaneous administration of separate tablets of enalapril (10 mg) and HCT (25 mg) in normotensive volunteers (n = 12, 21-26 years). Each subject received all four treatments and the study was conducted as a randomized, latin square, open design with at least 1 week washout between studies. Overall, HCT was bioequivalent under all conditions and enalaprilat was bioequivalent when given in combination with HCT either as one tablet or as two separate tablets. However, when given with HCT, the mean AUC and Cmax of enalaprilat were reduced up to 20 per cent compared with enalapril administered alone. This is unlikely to be of clinical significance as the differences did not reach statistical significance and the total enalaprilat excreted in the urine over 96 h was similar after all treatments.

Adult↗

PubMedDate not supplied

Effects of antihypertensive drugs on coronary artery disease risk: a meta-analysis.

1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical significance of these effects and the extent to which they persist during long-term therapy is uncertain. 2. We performed a meta-analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a beta-blocker with beta 2-adrenoceptor intrinsic sympathomimetic activity), enalapril, nifedipine and doxazosin on plasma cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure (BP). 3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations. 4. While there were no differences in antihypertensive efficacy between the drugs, atenolol significantly (P < 0.05) reduced HDL-C and increased total cholesterol, LDL-C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine. 5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 years for celiprolol). 6. The improvement in Framingham equation point scores (systolic BP formula) was significantly (P < 0.05) less for atenolol (-0.54; confidence intervals (CI) -0.29-(-0.78)) than for celiprolol (-1.69; CI -0.68-2.70), doxazosin (-1.67; CI -1.11-(-2.23)), enalapril (-1.43; CI 0.23-(-3.07)) and nifedipine (-1.91; CI -1.22-(-2.59)). Similar results were obtained for the Framingham diastolic BP formula. 7. These results suggest that the adverse effects of atenolol ]on plasma lipids do not improve with prolonged therapy and are theoretically great enough to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect plasma lipids. However it must be emphasized that these are theoretical effects. In order to determine the actual differences between these drugs on CAD end points, studies using these end points are required.

Antihypertensive Agents↗