DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

766 Hypertension is defined conventionally as a sustained
increase in blood pressure ≥140/90 mm Hg, a criterion
that characterizes a group of patients whose risk of
hypertension-related cardiovascular disease is high
enough to merit medical attention. Actually, the risk of
both fatal and nonfatal cardiovascular disease in adults is
lowest with systolic blood pressures of <120 mm Hg and
diastolic BP <80 mm Hg; these risks increase progressively
with higher systolic and diastolic blood pressures.
Recognition of this continuously increasing risk provides
a simple definition of hypertension (Chobanian et al.,
2003) (Table 27–4). Although many of the clinical trials
classify the severity of hypertension by diastolic pressure,
progressive elevations of systolic pressure are similarly
predictive of adverse cardiovascular events; at every
level of diastolic pressure, risks are greater with higher levels
of systolic blood pressure. Indeed, beyond age
50 years, systolic blood pressure predicts outcome better
than diastolic blood pressure. Systolic blood pressure
tends to rise disproportionately greater in the
elderly due to decreased compliance in blood vessels
associated with aging and atherosclerosis. Isolated systolic
hypertension (sometimes defined as systolic BP
>140-160 mm Hg with diastolic BP <90 mm Hg) is
largely confined to people older than 60 years of age.
SECTION III
MODULATION OF CARDIOVASCULAR FUNCTION
At very high blood pressures (systolic ≥210 mm Hg and/or
diastolic ≥120 mm Hg), a subset of patients develops fulminant arteriopathy
characterized by endothelial injury and a marked proliferation
of cells in the intima, leading to intimal thickening and
ultimately to arteriolar occlusion. This is the pathological basis of
the syndrome of immediately life-threatening hypertension, which is
associated with rapidly progressive microvascular occlusive disease
in the kidney (with renal failure), brain (hypertensive encephalopathy),
congestive heart failure, and pulmonary edema. These patients
typically require in-hospital management on an emergency basis for
prompt lowering of blood pressure. Interestingly, isolated retinal
changes with papilledema in an otherwise asymptomatic patient with
very high blood pressure (formerly called “malignant hypertension”)
may benefit from a more gradual lowering of blood pressure over
days rather than hours.
Table 27–4
Criteria for Hypertension in Adults
BLOOD PRESSURE (mm Hg)
CLASSIFICATION SYSTOLIC DIASTOLIC
Normal <120 and <80
Prehypertension 120-139 or 80-89
Hypertension, stage 1 140-159 or 90-99
Hypertension, stage 2 ≥160 or ≥100
The presence of pathological changes in certain target organs
heralds a worse prognosis than the same level of blood pressure in a
patient lacking these findings. Consequently, retinal hemorrhages,
exudates, and papilledema in the eyes indicate a far worse short-term
prognosis for a given level of blood pressure. Left ventricular hypertrophy
defined by electrocardiogram, or more sensitively by echocardiography,
is associated with a substantially worse long-term
outcome that includes a higher risk of sudden cardiac death. The risk
of cardiovascular disease, disability, and death in hypertensive
patients also is increased markedly by concomitant cigarette smoking,
diabetes, or elevated low-density lipoprotein; the coexistence of
hypertension with these risk factors increases cardiovascular morbidity
and mortality to a degree that is compounded by each additional
risk factor. Because the purpose of treating hypertension is to
decrease cardiovascular risk, other dietary and pharmacological
interventions may be required to treat these conditions.
Pharmacological treatment of patients with hypertension
decreases morbidity and mortality from cardiovascular
disease. Effective antihypertensive therapy
markedly reduces the risk of strokes, cardiac failure, and
renal insufficiency due to hypertension. However, reduction
in risk of MI may be less impressive.
Principles of Antihypertensive Therapy. Nonpharmacological
therapy is an important component of treatment of all
patients with hypertension. In some stage 1 hypertensives
(see Table 27–4), blood pressure may be adequately
controlled by a combination of weight loss (in
overweight individuals), restricting sodium intake,
increasing aerobic exercise, and moderating consumption
of alcohol. These lifestyle changes, though difficult
for many to implement, may facilitate pharmacological
control of blood pressure in patients whose responses to
lifestyle changes alone are insufficient.
Arterial pressure is the product of cardiac output
and peripheral vascular resistance. Drugs lower blood
pressure by actions on peripheral resistance, cardiac output,
or both. Drugs may decrease the cardiac output by
inhibiting myocardial contractility or by decreasing ventricular
filling pressure. Reduction in ventricular filling
pressure may be achieved by actions on the venous tone
or on blood volume via renal effects. Drugs can decrease
peripheral resistance by acting on smooth muscle to
cause relaxation of resistance vessels or by interfering
with the activity of systems that produce constriction of
resistance vessels (e.g., the sympathetic nervous system,
the renin–angiotensin system [RAS]). In patients with
isolated systolic hypertension, complex hemodynamics
in a rigid arterial system contribute to increased blood
pressure; drug effects may be mediated by changes in
peripheral resistance but also via effects on large artery
stiffness (Franklin, 2000). Antihypertensive drugs can