Several antihypertensive drugs with different sites and mechanisms of action are now available. Nevertheless, none can be said to be the ideal antihypertensive drug. Drug choice should aim to maximize blood-pressure-lowering effectiveness and minimize patient side effects.
The most appropriate choice of initial drug therapy depends on the age and racial origin of the patient, as well as the presence of other medical conditions.
Some of the drugs used to treat hypertension include:
The ACEIs block conversion of angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. This helps blood vessels relax and reduces blood pressure.
ACEIs also block degradation of bradykinin and stimulate the synthesis of other vasodilating substances, including prostaglandin E2 and prostacyclin.
Examples of ACEIs used in the management of hypertension include
β-Blockers have several direct effects on the cardiovascular system. They can decrease cardiac contractility and cardiac output (CO), lower heart rate, blunt sympathetic reflex with exercise, reduce central release of adrenergic substances, inhibit norepinephrine release peripherally, and decrease renin release from the kidney.
All these contribute to their antihypertensive effects.
Examples of β-Blockers include
Diuretics, also called water pills, are drugs that are employed to facilitate elimination of extracellular fluid from the body. They exert their effect directly on the kidneys and lower BP by causing diuresis.
While ACEIs block conversion of angiotensin I to angiotensin II, ARBs modulate the Renin-Angiotensin-Aldosterone System (RAAS) by directly blocking the angiotensin II type 1 receptor site, preventing angiotensin II-mediated vasoconstriction and aldosterone release.
Examples of Angiotensin II receptor blockers include
These medications reduce calcium entry into smooth muscles, which causes coronary and peripheral vasodilation and lowers BP. The dihydropyridine group work almost exclusively on L-type calcium channels in the peripheral arterioles and reduce blood pressure by reducing total peripheral resistance.
In contrast, the effect of verapamil and diltiazem are primarily on the heart, reducing heart rate and cardiac output.
Other examples of CCBs include
These agents antagonise α-adrenoceptors in the blood vessel wall and, thus, prevent noradrenaline (norepinephrine) induced vasoconstriction. As a result, they reduce total peripheral resistance and blood pressure.
Central α2-agonists work in the vasomotor centres of the brain where they stimulate inhibitory neurons and decrease sympathetic outflow from the central nervous system (CNS). The resultant decrease in peripheral vascular resistance (PVR) and CO lowers BP.
These drugs cause direct arteriolar smooth muscle relaxation. They decrease total peripheral resistance and thus correct the hemodynamic abnormality that is responsible for the elevated blood pressure in primary hypertension.
In addition, because they act directly on vascular smooth muscle, the vasodilators are effective in lowering blood pressure, regardless of the etiology of the hypertension.
Similar to ACEIs or ARBs, direct renin inhibitors target the rate-limiting step in the RAAS. Aliskiren, approved in 2007, is the only direct renin inhibitor.
Many of the cautions and adverse effects seen with ACE inhibitors and ARBs apply to aliskiren.
Aldosterone exerts its effects at the nephron through mineralocorticoid receptors, which translocate to the nucleus upon aldosterone binding and exert genomic effects leading to increased sodium reabsorption.
Potent blockade of the aldosterone receptor inhibits sodium and water retention and inhibits vasoconstriction. These agents are also considered potassium-sparing diuretics.
Examples of aldosterone antagonists include: