General principles of antihypertensive drug therapy
Choice of a starting drug in the treatment of hypertension has been discussed above. If this single agent is not sufficiently efficacious, consideration should be given to using two drugs at relatively low doses, rather than “pushing” the dose of a single drug and increasing the risk of adverse effects. At the higher dosage range, even large dose increments produce relatively little further hypotensive effect as the top of the dose–response curve is reached. In contrast, the dose-dependent incidence of adverse effects continues to increase in the higher dosage ranges. Using two drugs in low dosage often exploits additive or synergistic efficacy between drugs, allowing maintenance of these low doses and avoidance or a minimization of adverse effects.
In poorly controlled patients with severe hypertension or those who are at high risk, add drugs, rather than substituting one class of agent for another. When blood pressure is controlled with the use of the added drug, attempts can then be made to reduce or discontinue other agents. In patients with severe hypertension, one may be unsure whether the drug is having an effect and whether the pressure would be much higher in its absence. Withdrawing a useful agent and allowing the pressure to rise might exacerbate the disease and be dangerous to the patient. In treating mild hypertension in low-risk patients, sequential use of drugs as monotherapy can help to determine empirically the most effective agent with the least toxicity in the patient, because it is quite acceptable to take months to control hypertension in these patients.
It is important to use the lowest possible doses to maintain pressure below the target blood pressure. In patients whose blood pressure is well controlled for one year or more, it may be appropriate to attempt to minimize the dosage required to keep the patient at this level (step-down therapy). Such efforts may be especially useful in patients who have undertaken nonpharmacologic approaches to lowering blood pressure, such as weight loss. Because of the implications of lifelong therapy of hypertension, maintaining patients on the lowest possible drug dosage for the longest possible time is justified.
Special settings requiring consideration for antihypertensive therapy
Very severe hypertension
Management of patients with very high blood pressure depends on the clinical setting rather than the actual levels of blood pressure. One must be able to distinguish the true hypertensive emergency from less pressing situations, because the risks of lowering blood pressure rapidly are considerable and should be avoided unless absolutely necessary.
A hypertensive emergency is a situation in which elevated blood pressure must be lowered immediately to limit and reverse damage to target organs. Hypertensive emergencies include markedly elevated blood pressure that has led to dissecting aortic aneurysm, encephalopathy, or pulmonary edema. Clinical judgment and experience, rather than controlled clinical trials, indicate that these life-threatening settings require prompt judicious lowering of blood pressure to relieve symptoms and to stop or reverse pathological changes. Hypertensive patients with severe elevations in blood pressure typically have altered cerebral blood flow autoregulation that makes them susceptible to cerebral ischemia at much higher mean arterial pressures than for normotensive subjects, as blood pressure is lowered. Accordingly, it is especially important to avoid precipitous drops in blood pressure unless the situation warrants taking such risks. It has been suggested that the initial goal of therapy in these patients should be to lower mean blood pressure by no more than 25% in the first minutes to 2 hours after start of therapy; at that point blood pressure can be lowered toward 160/100 mm Hg over 2 to 6 hours (Joint National Committee 1997). This is a consensus view, trying to balance the benefit of lowered blood pressure against the risk of precipitating cerebral, coronary, or renal ischemia from too rapid a fall in blood pressure; it is not currently feasible to test these recommendations in controlled clinical trials.
Drugs useful in the emergency treatment of hypertension are shown in Table Parenteral Drugs for Hypertensive Emergencies. The ideal drugs are given intravenously, are titratable, have rapid onset and offset of action, are predictable in their effects, and are easily monitored. Therapy should be given in such a manner to maintain blood flow to all vital organs. Sodium nitroprusside is one drug of choice. Other drugs can be considered. The use of sodium nitroprusside requires intra-arterial monitoring of blood pressure in an intensive care unit setting. Other potentially useful intravenous agents include labetalol, diazoxide, fenoldopam, or hydralazine, especially when sodium nitroprusside is not available.
| Table Parenteral Drugs for Hypertensive Emergencies. | |
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Hypertensive urgencies are defined as those situations in which it is desirable to lower blood pressure over the course of hours (Joint National Committee 1997). Some physicians believe this is appropriate for very high absolute values of blood pressure, hypertension in the setting of papilledema (so-called “malignant hypertension”) or progressive target-organ damage, and severe perioperative hypertension. In addition, many physicians believe that elevated blood pressure in its own right, in the absence of significant symptoms or new or progressive target-organ damage, should not be treated as an emergency. These types of guidelines are somewhat ambiguous, depend on clinical judgment, and have not been studied in controlled trials. However, in the absence of demonstrated benefit and the known risks of sudden lowering of blood pressure in severe hypertension, a conservative approach to lowering blood pressure cautiously over substantial periods of time seems warranted. In other words, hypertensive urgencies are probably best managed using oral medications with relatively prompt onset of action, such as β-adrenergic receptor antagonists, Angiotensin-converting enzyme inhibitors, calcium-entry blockers, and loop diuretics when appropriate. Broken capsules of nifedipine administered sublingually (actually swallowing the contents works faster) has been very extensively used in the treatment of hypertensive urgencies. However, this approach leads to particularly unpredictable large falls in blood pressure that may have severe adverse consequences in terms of tissue ischemia. These include stroke or acute myocardial infarction.
As a consequence, there is no justification for using this approach to lower blood pressure in any situation.
Finally, even in the context of very high pressures, if the patient is asymptomatic and there is no advanced retinopathy, then it is safe to slowly decrease blood pressure over days and to use oral agents in an outpatient setting provided that frequent (up to daily) monitoring is feasible if indicated.
Principles
In the absence of likely benefit, the physician should not expose patients to the risk of unnecessary treatment merely to make the numbers look better as an end in itself.
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