●Introduction 185
●Pathophysiology and sites of drug action 185
●General principles of managing essential
hypertension 187●Drugs used to treat hypertension 187
●Other antihypertensive drugs 193CHAPTER 28
HYPERTENSION
INTRODUCTION
Systemic arterial hypertension is one of the strongest known
modifiable risk factors for ischaemic heart disease, stroke,
renal failure and heart failure. It remains poorly treated. As an
asymptomatic disorder, people are understandably reluctant
to accept adverse drug effects in addition to the inconvenience
of long-term treatment. In this regard, modern drugs represent
an enormous improvement.
Figure 28.1 shows the relationship between the usual mean
diastolic blood pressure and the risks of coronary heart disease
and of stroke. A meta-analysis of published randomized con-
trolled trials showed that the reduction in diastolic blood pres-
sure achieved by drug treatment reduced the risk of stroke by
the full extent predicted, and reduced the risk of coronary dis-
ease by about 50% of the maximum predicted, within approxi-
mately 2.5 years. These impressive results form a secure clinical
scientific evidence base for the value of treating hypertension
adequately.
1234576 84 91 98 1050.250.501.002.004.00Relative risk of strokeApproximate mean usual DBP (mmHg)1234576 84 91 98 1050.250.501.002.004.00Relative risk of CHDApproximate mean usual DBP (mmHg)Figure 28.1:Risks of stroke and coronary heart disease (CHD) in relation to diastolic blood pressure (DBP). (Redrawn with permission
from MacMahon et al. Lancet1990; 335 : 765–4. © The Lancet Ltd.)
PATHOPHYSIOLOGY AND SITES OF DRUG
ACTIONHypertension is occasionally secondary to some distinct dis-
ease. However, most patients with persistent arterial hyper-
tension have essential hypertension.
Arterial blood pressure is determined by cardiac output,
peripheral vascular resistance and large artery compliance.
Peripheral vascular resistance is determined by the diameter
of resistance vessels (small muscular arteries and arterioles) in
the various tissues (see Figure 28.2). One or more of a ‘mosaic’
of interconnected predisposing factors (including positive
family history, obesity and physical inactivity among others)
are commonly present in patients with essential hypertension,
some of which are amenable to changes in diet and other
habits. The importance of intrauterine factors (the ‘Barker
hypothesis’) is supported by the finding that hypertension in
adult life is strongly associated with low birth weight.