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Drug Selection in Hypertension ÃÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ´
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Design of a treatment regimen begins with the choice of one of 2
different approaches to treatment: "stepped care," (polypharmacy), or
Stepped care: Ordinary chronic hypertension has often been
managed using a stepped care regimen, ie, starting with the drugs of
lowest toxicity and adding drugs from other groups as needed (eg, Joint
National Committee, 1984). Use of several drugs, each from a different
group, can greatly reduce the toxicity produced by the total regimen.
Agents of differing efficacy are available in each of the groups. This
permits the use of less toxic agents in mild and responsive cases, with
the more powerful (and toxic) agents reserved for use in severe disease.
Several formulations of stepped care exist. One approach (Benowitz and
Bourne, 1987) consists of the following steps:
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1. A diuretic. A thiazide or thiazide-like agent is used as the first
drug in most cases.
2. A sympathoplegic (beta-blocker or methyldopa) is added if response to
the thiazide is inadequate.
3. A direct vasodilator (hydralazine or calcium channel blocker) is
added if response to the diuretic plus beta-blocker combination is in-
adequate at tolerated doses.
4. An angiotensin converting enzyme inhibitor (captopril or
enalapril) is substituted for, or added to, the preceding regimen if
response is still incomplete or toxicity is intolerable at the doses
required. If response to steps 1-4 is inadequate, another
sympathoplegic may be substituted for, or added to, the beta-blocker. The
most efficacious sympathoplegic, guanethidine, may be added if control
is inadequate with the preceding 4 levels.
Recent results from several large studies suggest that, in the
doses commonly used, diuretics and á-blockers were not as effective in
reducing the cardiac sequellae of hypertension as expected from the
excellent blood pressure control that had been achieved (Weinberger,
1986). A possible explanation is vascular damage associated with
the small but consistent elevation in low density lipoproteins observed
in patients receiving either thiazides or beta blockers.
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Monotherapy: As an alternative to the above stepped care regimens,
lower doses of diuretics or beta-blockers, or monotherapy with selec-
tive alpha-blockers (eg, prazosin), or angiotensin converting enzyme in-
hibitors (eg, captopril, enalapril, or lisinopril) has been proposed.
Early studies (eg, Alderman, Davis, Carroll, 1986) suggest that such
monotherapy, ie, therapy with a single agent, may be as successful in
the management of mild or moderate hypertension, with lower toxicity, as
stepped care with multiple drugs.
Most patients with hypertension can be managed on a chronic out-
patient basis. Patients with rapid progression of end-organ damage
(brain, heart, kidneys) have accelerated or malignant hypertension, and
must be treated as emergencies. Because the urgency of pressure reduc-
tion is much greater, more powerful drugs are used, and they are given
parenterally. These agents are described at the end of this chapter
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