Antihypertensive drugs compensatory responses

The value of diuretics lies in their ability to reverse the Na retention commonly associated with many antihypertensive drugs that probably induce Na retention and fluid volume expansion as a compensatory response to blood pressure reduction. 

When the diagnosis is correct and the drug is appropriate, an unsatisfactory therapeutic response can often be traced to compensatory mechanisms in the patient that respond to and oppose the beneficial effects of the drug. Compensatory increases in sympathetic nervous tone and fluid retention by the kidney, for example, can contribute to tolerance to antihypertensive effects of a vasodilator drug. In such cases, additional drugs may be required to achieve a useful therapeutic result. 

Vasodilators work best in combination with other antihypertensive drugs that oppose the compensatory cardiovascular responses. (See Resistant Hypertension Polypharmacy.)... 

Hydralazine was one of the first orally active antihypertensive drugs marketed in the United States. Its structure is shown in Figure 12.4. Initially, the drug was used infrequently because of its propensity to produce reflex tachycardia and tachyphylaxis. However, with a better understanding of the compensatory cardiovascular responses that accompany use of arteriolar vasodilators (the drug has little or no effect on venous smooth muscle), hydralazine was combined with sympatholytic agents and diuretics with greater therapeutic success. 

Describe the compensatory responses to each of the four major types of antihypertensive drugs. 

Diuretics are covered in greater detail in Chapter 15 but are mentioned in this chapter because of their importance in hypertension. These drugs lower blood pressure by reduction of blood volume and by a direct vascular effect that is not fully understood. The diuretics most important for treating hypertension are the thiazides (eg, hydrochlorothiazide) and the loop diuretics (eg, furosemide). Thiazides may be adequate in mild hypertension, but the loop agents are used in moderate, severe, and malignant hypertension. Compensatory responses to blood pressure lowering by diuretics are minimal (Table 11-2). When thiazides are given, the maximum antihypertensive effect is often achieved with doses that are below the maximum diuretic doses. 

Table 11-2. Compensatory responses to antihypertensive drugs and some of their adverse effects.

E. Adrenoceptor Blockers Alpha -selective agents (eg, prazosin) and beta-blockers (eg, propranolol) are effective antihypertensive drugs. Alpha-blockers reduce vascular resistance and venous return. The nonselective alpha-blockers (phentolamine, phenoxybenzamine) are of no value in chronic hypertension because of excessive compensatory responses, especially tachycardia. Alpha,-selective adrenoceptor blockers are relatively free of the severe adverse effects of the nonselective alpha-blockers and postganglionic nerve terminal sympathoplegic agents. 

Skill Keeper Compensatory Responses to Antihypertensive Drugs (see Chapter 6)... 

---