Monotherapy, for hypertension

ADVERSE EFFECTS The use of doxazosin as monotherapy for hypertension increases the risk of developing congestive heart failure. This may be an adverse effect of all of the adrenergic receptor antagonists. 

THERAPEUTIC USES Receptor antagonists are not recommended as monotherapy for hypertensive patients. They rather are used primarily in conjunction with diuretics, /3 blockers, and other antihypertensive agents. /3 Receptor antagonists enhance the efficacy of the blockers. 

Initial drug therapy is monotherapy for Stage 1 and Stage 2 hypertension. Preferred because a reduction in morbidity and mortality has been demonstrated. 

Beta-blockers can no longer be considered as first line monotherapy for uncomplicated hypertension in older patients since some studies suggest they are less effective than diuretics and no better than placebo in reducing cardiovascular outcomes. Their use in elderly with hypertension probably should be confined to those with other indications such as angina, following myocardial infarction or with heart failure. 

Potassium-sparing diuretics, such as amiloride and triamterene. These agents reduce at the tubular level the reabsorption of sodium and water, whereas the excretion of potassium is diminished. Their primary effects are independent of aldosterone. They are slow-acting and weak diuretics, which are unsuitable as monotherapy of hypertension or heart failure. For this reason, they are always combined with thiazide or loop diuretics. Several combined preparations are commercially available. 

The first use of lithium for therapeutic purposes began in the mid-19th century to treat gout. Lithium had a relatively brief period of use as a substitute for sodium chloride in hypertensive patients in the 1940s, but it proved too toxic when available without monitoring and was banned. In 1949, Cade discovered that lithium was an effective treatment for bipolar disorder, engendering a series of controlled trials which confirmed its efficacy as monotherapy for the manic phase of bipolar disorder. 

Drng costs can acconnt for over 70% of the total cost of hypertensive care. One model for calcnlating the cost-effectiveness of varions initial monotherapies for mild to moderate hypertension fonnd that the cost of life-year saved ranged from 10,900 with a generic -blocker to 72,100 with a brand-name ACE inbhitor. ... 

Edelson JT, Weinstein MC, Tosteson AN, et al. Long-term cost-effectiveness of various initial monotherapies for mild to moderate hypertension. JAMA 1990 263 407 13. 

Initial therapy choices for hypertension in diabetes mellitus usually include angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker due to their well documented renoprotective effects. Currently, angiotensin receptor blockers have less robust data to support cardiovascular reduction compared to other therapeutic choices, yet the data that exists appears to be positive in patients with type 2 DM. Also, diuretics have shown superior results to an ACE inhibitor in the ALLHAT trial. The ADA currently recommends the use of any class (ACE inhibitors, angiotensin receptor blockers, /3-blockers, diuretics, or calcium channel blockers) of antihypertensive medication that has shown benefit in prevention of poor cardiovascular outcomes. Choice of monotherapy may not be important, as an average of two to three antihypertensive medications are needed to reach blood pressure goals. 

THERAPEUTIC USES The CNS effects prevent this class of drugs from being a leading option for monotherapy of hypertension. These drugs effectively lower blood pressure in some patients who have not responded adequately to combinations of other agents. Enthusiasm for these drugs is further diminished by the paucity of evidence demonstrating reduction in risk of adverse cardiovascular events. 

In the treatment of hypertension, ACE inhibitors are as effective as diuretics, (3-adrenoceptor antagonists, or calcium channel blockers in lowering blood pressure. However, increased survival rates have only been demonstrated for diuretics and (3-adrenoceptor antagonists. ACE inhibitors are approved for monotherapy as well as for combinational regimes. ACE inhibitors are the dtugs of choice for the treatment of hypertension with renal diseases, particularly diabetic nephropathy, because they prevent the progression of renal failure and improve proteinuria more efficiently than the other diugs. 

Two types of diuretics are used for volume management in HF thiazides and loop diuretics. Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and metolazone block sodium and chloride reabsorption in the distal convoluted tubule. Thiazides are weaker than loop diuretics in terms of effecting an increase in urine output and therefore are not utilized frequently as monotherapy in HF. They are optimally suited for patients with hypertension who have mild congestion. Additionally, the action of thiazides is limited in patients with renal insufficiency (creatinine clearance less than 30 mL/minute) due to reduced secretion into their site of action. An exception is metolazone, which retains its potent action in patients with renal dysfunction. Metolazone is often used in combination with loop diuretics when patients exhibit diuretic resistance, defined as edema unresponsive to loop diuretics alone. 

When drugs from the main available classes are used as monotherapy at the recommended doses, they produce very similar BP reductions. In general, the sizes of the BP reductions increase with the initial level of BP, but typically the placebo-adjusted reductions average about 4-8% for both SBP-DBP. Thus, for patients with blood pressures of about 160/95 mmHg, the usual reduction produced by monotherapy would be about 7-13 mmHg systolic and 4-8 mmHg diastolic. Clearly, for many patients with hypertension, such reductions in BP would not restore optimal or even nonhypertensive blood pressure levels. 

C. Although still highly controversial, the initial use of a thiazide diuretic for monotherapy has been recommended by the Joint National Committee on Detection, Evaluation and treatment of High Blood Pressure. Triamterene and Aldactone are rarely used alone and exhibit no antihypertensive activity. A recent study found that the loop diuretics bumetanide and furosemide effectively reduced blood pressure. Serum lipid levels were less affected than with thiazide diuretics or chlorthalidone. However, thiazide diuretics are a more conservative and approved approach for the initial treatment of hypertension that avoid the more dramatic fluid and electrolyte shifts that occur with loop diuretics. 

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