Studies on side effect profile of treated hypertensives on selected pharmacotherapy
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Date
2001
Authors
Ismail, Marina
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Background: Hypertension is a major public health problem because of its
consequences. Its treatment is crucial and goals include to decrease ~orbidity
and mortality associated with hypertension by decreasing blood pressure using
drugs that have good tolerance, dosing convenience and low cost. As many
antihypertensives are now available, it is important to choose the most
appropriate drug in terms of efficacy and with least side effect in order to
improve compliance and the patient's quality of life. In HUSM, metoprolol is a
widely used. Its metabolism is mediated by the polymorphic debrisoquinehydroxylase
that exhibits large inter ethnic difference. As most of its adverse
reactions could be due to excessive plasma concentrations, its use among our
local population may therefore be associated with adverse effects due to reduced
capacity of the local population to metabolise the drug. The objedives of this
study were therefore to investigate the use of metoprolol in the treatment of
hypertension in relation to the incidence of adverse drug reactions it caused. We
would also determine whether patients who experienced adverse reactions
suffered reduced quality of life. As controls, we used patients who received
enalapril or enalapril combined with metoprolol in the treatment of their
hypertension. Method: Two hundred hypertensive patients treated with metoprolol and/or
enalapril at the Hypertensive Clinic, HUSM were recruited. Those excluded were
patients diagnosed to have diabetes mellitus, ischaemic heart disease, chronic
renal failure, congestive cardiac failure and those who suffered from other
chronic diseases for example malignancy, which may interfere with the proper
use of the investigation instrument. Patients' demography were recorded and
biochemical profile were taken. The clinical observation were recorded during the
first visit and at follow up. Their quality of life assessment were assessed using
questionnaire.
Result: Two hundred hypertensive patients treated with metoprolol
andlon enalapril were enrolled. The majority were Malays. Their age
averaged 53.4 years and half were males. Seventy-seven received
metoprolol as their primary antihypertensive drug, 99 were on enalapril
and 24 were on combination metoprolol-enalapril therapies. 48% had
systolic blood pressure (SBP) that averaged 140 mmHg or below and
28o/o had diastolic blood pressure (DBP) that averaged 80 mmHg or
below. 42% metoprolol patients, 43o/o enalapril patients and 40%
combined-therapy patients had blood pressure control (average SBP =s;;
140 mmHg and average DBP s 90 mmHg) p=0.979. No statistical significant difference in blood chemistries occurred among
the study groups. Adverse events were reported frequently by the
patients and were most frequently reported by patients on combinationtherapy.
Some adverse effects were more significant with patients on
metoprolol. These included bradycardia, cold extremities, nocturia, and
palpitation. Almost all however reported that they were satisfied with their
lives but those who said that they were not satisfied came from the
metoprolol group.
Conclusion: Our study showed that less than half of our patients treated with
either metoprolol, enalapril or metoprolol-enalapril combination achieved
satisfactory blood pressure controls. Many however reported adverse effects.
Dose-related side effects appeared to occur commonly in patients given
metoprolol and this could have lead to reduced compliance and hence
inadequate blood pressure control. This could be due to reduced ability to
metabolise metoprolol that could have occurred with some patients due to
debrisoquine hydroxylase genetic polymorphism. Further work involving
phenotyping and genotyping for the polymorphism may provide insights into this
problem.
Description
Keywords
Hypertension