Hypertext Drug Manual Drug Selection in Hypertension Back to main menu: ESC ³ ³ Back to la

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ÚÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ¿ ³ Hypertext Drug Manual ³ Drug Selection in Hypertension ÃÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ´ ³ Back to main menu: ESC ³ ³ Back to last screen: <- ³ ³ Table of Contents: ³ ³ ³ ÀÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÙ Design of a treatment regimen begins with the choice of one of 2 different approaches to treatment: "stepped care," (polypharmacy), or "monotherapy." 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: (PgDn for more text) 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. (PgDn for more text) 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 (section V). (Home to return to top of file)


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