Medicinal Chemistry

3. Direct vasodilators: reduce pressure by dilating resistance vessels (arteries) by
   vascular smooth muscle relaxation (e.g., Ca^2 +channel blockers such as verapamil
   (4.133) or nifedipine (5.151); vasodilators such as dihydralazine (5.152))


4. Diuretics: lower blood pressure by reducing blood volume and promoting sodium
   depletion (e.g., diuretics such as hydrochlorothiazide (5.153))

From a practical clinical perspective, the initial therapy of hypertension involves the
selection of an agent from one of the following four starter groups:

1. Diuretics


2. Beta-blockers


3. ACE inhibitors or AT 1 antagonists


4. Ca^2 +channel antagonists

If the therapeutic results are inadequate, the option is either to change to another drug
in one of the remaining three groups (maintaining one-drug therapy or monotherapy) or
to combine with a drug from one of the remaining three groups (initiating polytherapy).
In severe cases of hypertension, combination therapy is achieved by combining one or

380 MEDICINAL CHEMISTRY