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

784 Stop Hypertension (DASH) diet may be particularly
useful (Champagne, 2006).
• For some patients, restriction of ethanol intake to
modest levels may lower blood pressure.
• Increased physical activity may improve control of
hypertension.
SECTION III
MODULATION OF CARDIOVASCULAR FUNCTION
SELECTION OF ANTIHYPERTENSIVE
DRUGS IN INDIVIDUAL PATIENTS
Choice of antihypertensive drugs for individual patients
may be complex; there are many sources of influence
that modify therapeutic decisions. While results derived
from randomized controlled clinical trials are the optimal
foundation for rational therapeutics, it may be difficult
to sort through the multiplicity of results and address
how they apply to an individual patient. While therapeutic
guidelines can be useful in reaching appropriate therapeutic
decisions, it often is difficult for clinicians to
apply guidelines at the point of care, and guidelines often
do not provide enough information about recommended
drugs. In addition, intense marketing of specific drugs to
both clinicians and patients may confound optimal decision
making. Moreover, persuading patients to continue
taking sometimes expensive drugs for an asymptomatic
disease is a challenge. Clinicians may be reluctant to prescribe
and patients reluctant to consume the number of
drugs that may be necessary to adequately control blood
pressure. For these and other reasons, perhaps one-half of
patients being treated for hypertension have not achieved
therapeutic goals in blood pressure lowering.
Choice of an antihypertensive drug should be
driven by the likely benefit in an individual patient, taking
into account concomitant diseases such as diabetes
mellitus, problematic adverse effects of specific drugs,
and cost.
National guidelines (Chobaniry et al, 2003) recommend
diuretics as preferred initial therapy for most
patients with uncomplicated stage 1 hypertension (Table
27–4) who are unresponsive to nonpharmacological
measures. Patients also are commonly treated with other
drugs: β-receptor antagonists, ACE inhibitors/AT 1
-receptor
antagonists, and Ca 2+ channel blockers. Patients with
uncomplicated stage 2 hypertension will likely require
the early introduction of a diuretic and another drug from
a different class. Subsequently, doses can be titrated
upward and additional drugs added to achieve goal blood
pressures (blood pressure <140/90 mm Hg in uncomplicated
patients). Some of these patients may require four
different drugs to reach the goal.
An important and high-risk group of patients with
hypertension are those with compelling indications for
specific drugs on account of other underlying serious
cardiovascular disease (heart failure, post-MI, or with
high risk for coronary artery disease), chronic kidney
disease, or diabetes (Chobanian et al., 2003). For example,
a hypertensive patient with congestive heart failure
ideally should be treated with a diuretic, β receptor
antagonist, ACE inhibitor/AT 1
-receptor antagonist, and
(in selected patients) spironolactone because of the benefit
of these drugs in congestive heart failure, even in the
absence of hypertension (see Chapter 28). Similarly,
ACE inhibitors/AT 1
-receptor antagonists should be firstline
drugs in the treatment of diabetics with hypertension
in view of these drugs’ well-established benefits in
diabetic nephropathy.
Other patients may have less serious underlying
diseases that could influence choice of antihypertensive
drugs. For example, a hypertensive patient with symptomatic
benign prostatic hyperplasia might benefit from
having an α 1
receptor antagonist as part of his or her therapeutic
program, because α 1
antagonists are efficacious
in both diseases. Similarly, a patient with recurrent
migraine attacks might particularly benefit from use of
a β receptor antagonist because a number of drugs in
this class are efficacious in preventing migraine attacks.
On the other hand, in pregnant hypertensives, some
drugs that are otherwise little used (methyldopa) may
be preferred and popular drugs (ACE inhibitors)
avoided on account of concerns about safety.
Patients with isolated systolic hypertension (systolic
blood pressure >160 mm Hg and diastolic blood
pressure <90 mm Hg) benefit particularly from diuretics
and also from Ca 2+ channel blockers and ACE
inhibitors. These should be first-line drugs in these
patients in terms of efficacy, but compelling indications
as noted earlier need to be taken into account.
These considerations apply to patients with
hypertension that need treatment to reduce long-term
risk, not patients in immediately life-threatening settings
due to hypertension. While there are very limited
clinical trial data, clinical judgment favors rapidly lowering
blood pressure in patients with life-threatening
complications of hypertension, such as patients with
hypertensive encephalopathy or pulmonary edema due
to severe hypertension. However, rapid reduction in
blood pressure has considerable risks for the patients; if
blood pressure is decreased too quickly or extensively,
cerebral blood flow may diminish due to adaptations in
the cerebral circulation that protect the brain from the
sequelae of very high blood pressures. The temptation