Antihypertensive effect of prazosin in combination with methyldopa, clonidine, or propranolol

Seventeen hypertensive out-patients, more or less unresponsive to previous treatment with antihypertensive drugs, were treated in a cross-over fashion with placebo, prazosin (Pz), methyldopa (MD), Pz + MD, Pz + clonidine (C) and Pz + propranolol. The antihypertensive responses to Pz 2 mg t.i.d. and MD 250 mg t.i.d. were poor, and only modest when the drugs were combined. The combination of Pz with low doses of C was about as effective as Pz + MD, and some patients failed to respond to it. Nor was the combination of Pz + propranolol effective in those cases but the addition of a diuretic produced good responses in all patients. Side effects were few. It is concluded that a combination of central and peripheral sympathetic blockade does not necessarily produce normotension, and that a diuretic added to this combination greatly improves the response.