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Nurse practitioners who are responsible for the clinical management of patients with hypertension must choose antihypertensive medications that minimize side effects. Nurse practitioners must be aware of the drugs’ potential influences on physiologic and psychological variables and include adequate assessment of these responses in patients during treatment. Pindolol, propranolol, and hydrochlorothiazide were equally effective in reducing systolic and diastolic blood pressure in essential hypertensives, although pindolol and hydrochlorothiazide did not affect resting heart rate (an advantage in some patients). Hydrochlorothiazide was associated with a trend for several negative mood changes in black subjects; depression scores of black subjects were significantly increased with hydrochlorothiazide. The results of this study indicate the need to consider race and other factors in research about antihypertensive mood responses.