THE THERAPY OF HYPERTENSION

M.T. PIASCIK, PHA 622

JAN 22, 2008

 

 

            A) Definition of  Hypertension

 

 

            B) Clinical Management of Hypertension

 

The therapy of hypertension poses a challenge because the disease is asymptomatic.  Patients can live for many years without knowledge of elevated blood pressure.  However, untreated hypertension can lead to stroke, congestive heart failure and other cardiovascular diseases. Numerous clinical trials have shown that the reduction in blood pressure is associated with a decrease in risk of the morbidity and mortality of other cardiovascular diseases.  There are over 100 drug products (individual agents and fixed dose combinations) that are available for the treatment of hypertension.  Of the top 300 drugs by prescription sales (see http://www.rxlist.com) nearly 10 percent are used to treat hypertension. Another goal of therapy is to minimize the number of drugs prescribed as well as the times that drugs have to be taken.  Hypertension is a unique clinical problem because of its asymptomatic nature.  Therefore, if therapy with antihypertensive drugs causes unpleasant side effects, patient compliance could be reduced.

 

 

 

 

 

 

 

 

 

 

 

            B1) Diuretics

 

The major diuretic class used in the long term treatment of hypertension is the thiazides.  Thiazides are one of the cornerstones of hypertensive therapy and are considered first line agents in the treatment of elevated blood pressure.  Numerous clinical studies have shown these agents to decrease the risks of other cardiovascular diseases.  Diuretics can be used as monotherapy for mild hypertension as well as in combination with other antihypertensives.  For examples see the above list of combination products for hypertension.   Many, but not all, antihypertensive agents induce water and salt retention.  Diuretics counter this increase in fluid retention.  This allows for lower concentrations of both drugs to be used.  Thiazide diuretics are particularly effective in African Americans and the elderly.  These agents are available as generics, thus are not very expensive.

 

            B2) Sympatholytics

 

Beta blockers are first line agents in the treatment of hypertension.  These drugs have diverse effects on cardiovascular function and have a variety of cardiovascular and noncardiovascular uses.  They  also block the release of renin (mediated by beta1-receptors).   There are selective and nonselective beta blockers.  Prominent side effects include sedation, fatigue, and bradycardia.  Prazosin, terazosin and doxazosin are selective alpha1-receptor blockers.  These drugs are of particular benefit in hypertensive males who have BPH. Treatment with these drugs can result in fluid retention as a response to the lowering of blood pressure.  The hypotensive action of prazosin is decreased as a result of the expansion of plasma volume. Another side effect is first dose syncope and orthostatic hypotension.  These agents are considered second line antihypertensive agents.

 

            B3) Calcium Channel Blockers

 

The Calcium Channel Blockers

The calcium channel blockers are of three classes, the dihydropyridines (nifedipine and amlodipine), benzothiazepines (diltiazem) and phenyalkylamines (verapamil).   The dihydropyridines are arterial vasodilators and decrease blood pressure by decreasing peripheral vascular resistance.  Diltiazem and verapamil have negative inotropic and chronotrophic activity.  Therefore, these drugs would decrease blood pressure by decreasing cardiac output and heart rate. 

 

            B4) Inhibitors of the Renin Angiotensin System

 

 

 

 

 

There are numerous ACE-inhibitors and AT1-receptor antagonists. Captopril is a prototype for ACE-inhibitors and Losartan is a prototype for AT-1 antagonists.  These drugs work by decreasing peripheral vascular resistance and decreasing the actions of aldosterone.  Aldosterone promote sodium retention and increase fluid volume.   ACE inhibitors and AT1- receptor antagonists are first line agents for the treatment of hypertension.  These drugs might have particular benefit in patients who also have congestive heart failure or following myocardial infarction.  AT-1receptor antagonists have fewer side effects than the ACE inhibitors.

 

 

 

            B5) Vasodilators

Hydralazine and minoxidil are vasodilators that can reduce blood pressure.  However, the are second line agents employed when first line agents are not effective.  These drugs tend to cause increases in heart rate and fluid retention.  As a consequence, they should be given with a beta blocker (to block the tachycardia) and a diuretic (to block the increase in fluid volume)

 

 

C) THE TREATMENT OF HYPERTENSIVE CRISIS

Hypertensive crisis is an elevation in blood pressure in which diastolic pressure exceeds 120 mmHg.  In the presence of ongoing end-organ damage this is referred to as a hypertensive emergency.  Without such complications, it is referred to as a hypertensive urgency.  Hypertensive emergencies require blood pressure to be reduced within a few hours.  The blood pressure in hypertensive urgencies can be lowered over a period of 1-2 days.  Intravenous medications are often used to treat these conditions.  Some agents are used in the chronic treatment of hypertension while some are reserved for hypertensive crises.