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Central sympatholytics Clonidine Catapres 01 mg twice daily 01 mg/d patch weekly 4 mg twice daily 1 mg once daily 250 mg twice daily 02 06 mg in 2 doses 01 03 mg/ d patch weekly 8 64 mg in 2 doses 1 3 mg daily $022/ 01 mg $3242/ 02 mg $098/4 mg $087/1 mg $063/ 500 mg $1320 (01 mg twice daily) $12968 (02 mg weekly) $5880 (4 mg twice daily) $2610 (1 mg daily) $3780 (500 mg twice daily) Sedation, dry mouth, sexual dysfunction, headache, bradyarrhythmias; side effects may be less with guanfacine Contact dermatitis with clonidine patch Methyldopa also causes hepatitis, hemolytic anemia, fever Rebound hypertension may occur even after gradual withdrawal Methyldopa should be avoided in favor of safer agents

1:

Peripheral neuronal antagonists Reserpine Serpasil 005 mg once daily 005 025 mg daily $032/ 01 mg $960 (01 mg daily) Depression (less likely at low dosages, ie, < 025 mg), night terrors, nasal stuffiness, drowsiness, peptic disease, gastrointestinal disturbances, bradycardia

Direct vasodilators Hydralazine Apresoline 25 mg twice daily 5 mg once daily 50 300 mg in 2 4 doses 5 40 mg qd $051/ 25 mg $3060 (25 mg twice daily) $3870 (10 mg qd) GI disturbances, tachycardia, headache, nasal congestion, rash, LElike syndrome Tachycardia, fluid retention, headache, hirsutism, pericardial effusion, thrombocytopenia May worsen or precipitate angina

Average wholesale price (AWP, for AB-rated generic when available) for quantity listed Source: Red Book Update, Vol 26, No 3, March 2007 AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions GI, gastrointestinal; LE, lupus erythematosus

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able to subtle asymmetries in blood pressure control rather than to any inherent advantages of one agent over another Therefore, experts recommend thiazide diuretics as the firstline treatment of older and perhaps all patients with hypertension because these agents are very effective and less expensive than the newer drugs Exceptions are appropriate for individuals who have specific indications for another class of agent, such as postmyocardial infarction patients ( blockers, ACE inhibitors), patients with diabetic nephropathy (ACE inhibitors, ARBs), or other comorbid conditions Table 11 4 provides suggestions for individualizing first-line treatment based on compelling indications As discussed above, many experts would suggest that blockers no longer be considered ideal first-line drugs in the treatment of hypertension without compelling indications for their use However, theoretical considerations suggest that the newer vasodilator -blockers may be superior to the older drugs, but this possibility remains to be tested For the purpose of devising an optimal treatment regimen, drugs can be divided into two complementary groups easily remembered as AB and CD A and B refer to drugs that interrupt the renin-angiotensin system (ACE/ ARB and -blockers) and C and D refer to those that do not (calcium channel blockers and thiazide diuretics) Combinations of drugs between these groups are likely to be more potent in lowering blood pressure than combinations within a group Drugs A/B are more effective in young, white persons, in whom renins tend to be higher, and drugs C/D are more effective in old or black persons, in whom renin levels are generally lower It is also important to note that antihypertensive treatment is effective at reducing cardiovascular risk at all ages, including the very elderly Figure 11 3 illustrates guidelines established by the BHS for developing a rational antihypertensive regimen In these guidelines, B is placed in parentheses to reflect the increasingly prevalent view that -blockers should no longer be considered an ideal first-line agent In trials that include patients with systolic hypertension, most patients require two or more medications and even then a substantial proportion fail to achieve the goal systolic blood pressure of < 140 mm Hg (< 130 mm Hg in high-risk persons) In diabetic patients, three or four drugs are usually required to reduce systolic blood pressure to < 140 mm Hg In many patients, blood pressure cannot be maintained at the recommended goal of < 130 mm Hg with any combination As a result, debating the appropriate first-line agent is less relevant than determining the most appropriate combinations of agents This has led many experts and practitioners to reconsider the use of fixed-dose combination antihypertensive agents as first-line therapy in patients with substantially elevated systolic pressures (> 160/100 mm Hg) or difficult-to-control hypertension (associated diabetes or renal dysfunction) Based both on antihypertensive efficacy and complementarity, combinations of a diuretic and an ACE inhibitor (or an ARB if patient is intolerant of ACE inhibitor) are recommended In younger white patients, the best choice is probably a combination of an ACE inhibitor and a calcium channel blocker The initial use of low-dose combinations.

A (or B*)

A (or B*)

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