Hypertension is the elevated pressure exerted by the blood on the walls of the blood vessels. A sustained arterial pressure of 140/90 mm Hg (systolic pressure of 140 mm Hg and/or diastolic pressure of 90 mm Hg) or more is conventionally considered to be hypertension. It is the most common cardiovascular disease in the United States affecting over 20% of the American population.
Hypertension is primarily of two types, the primary or essential hypertension and the secondary hypertension. Essential hypertension is the most common type accounting for more than 90% of all hypertensive patients. The exact cause of essential hypertension is not clearly understood and it is considered to develop as a result of multiple factors. There are numerous types of drugs available to effectively control essential hypertension but no single drug has been successful in curing the disease. Secondary hypertension is a raised blood pressure that is associated with a definite recognizable cause like some other underlying disease. Many of the causes of secondary hypertension can be treated leading to complete cure of hypertension.
How does hypertension medication work?
Hypertension medication (antihypertensive drugs) work by lowering the elevated blood pressure by various mechanisms. Irrespective of the specific mechanism, the hypertension medication reduces blood pressure by decreasing cardiac output or the peripheral vascular resistance. These are the two major factors that contribute to the blood pressure. It is explained in detail under Explain Hypertension.
The cardiac output in turn depends on heart rate, force of contraction of heart, and amount of blood returning to heart through veins. The drugs that reduce any of these factors in a significant way is expected to have prominent antihypertensive effect. The primary purpose of treating hypertension is to reduce the cardiovascular risk. Effective antihypertensive therapy has been found to markedly reduce the risk of stroke, heart failure, and renal insufficiency due to hypertension.
The cardiovascular risk reduction in hypertension is further assisted by dietary and non-pharmacological interventions along with hypertension medication. Dietary intervention includes restricting salt, alcohol and fat intake. Other non-pharmacological interventions include weight loss (in obese individuals), smoking cessation, increasing aerobic exercise and adopting relaxation techniques. Mild hypertension may be controlled with these interventions alone. Those patients who do not respond to these lifestyle changes require hypertension medication along with the lifestyle changes.
The hypertension drugs can be grouped into four broad categories based on the prominent mechanism of action.
- Angiotensin II modulators
- Sympathetic (adrenergic) blocking drugs
Angiotensin II Modulators
Angiotensin II is a powerful vasoconstrictor that is normally formed in the body. It is formed in the body from angiotensin I by action of an enzyme called as angiotensin-converting enzyme (ACE). Angiotensin I in turn is formed from angiotensinogen by the action of renin. In addition to constriction of blood vessels angiotensin II can also cause an increase in the levels of aldosterone. Increased aldosterone levels lead to salt and water retention in the body. These two actions of angiotensin contribute significantly to the blood pressure.
In people with hypertension, reduction in the actions of angiotensin can effectively lower the blood pressure. Angiotensin II modulators drugs reduce blood pressure by reducing peripheral vascular resistance and also possibly the blood volume. These drugs that interfere with angiotensin II production or action are currently one of the first-line agents in treatment of hypertension. The actions of angiotensin II can be reduced by different mechanisms. The angiotensin II modulating drugs useful in hypertension are grouped based on the mechanism of action. The various drugs altering production or action of angiotensin II are categorized into three groups :
- Angiotensin converting enzyme (ACE) inhibitiors
- Angiotensin II receptor blockers (ARBs)
- Renin inhibitors
Sympathetic (Adrenergic) Blocking Drugs
The sympathetic nervous system is a part of the autonomic nervous system of the body. It has prominent effect on the heart and the blood vessels. Beta adrenergic receptors are present on the heart. When stimulated it increases the heart rate and force of contraction of heart. Alpha adrenergic receptors are present on the blood vessels. When alpha receptors are stimulated, the blood vessels are constricted increasing the blood pressure. Blocking the sympathetic system results in reduced heart rate and force of contraction, and dilation of blood vessels with pooling of blood in veins. This reduces the cardiac output and the peripheral resistance, thereby the blood pressure.
The sympathetic system can be blocked at different levels. The central sympathetic outflow, autonomic ganglions, sympathetic nerve terminals, and adrenergic receptors (alpha and beta) can be blocked. The various groups of sympathetic system blockers are :
- Centrally acting sympathetic blockers
- Autonomic ganglion blockers
- Sympathetic nerve terminal blockers
- Adrenergic receptor (alpha and beta) blockers
Diuretics (‘Water Pills’)
Diuretics are drugs that increase the urine output thereby reducing the sodium and water levels in the body. This reduces the blood volume and hence the cardiac output and the peripheral resistance which ultimately helps in reducing the blood pressure. Other unclear mechanisms involving peripheral vascular resistance are also believed to be involved in the sustained antihypertensive action of diuretics like thiazides.
Diuretics can effectively lower blood pressure by 10 to 15 mm Hg in most patients. Diuretics alone can provide adequate treatment for mild or moderate primary hypertension. In severe hypertension, diuretics may be used in combination with other antihypertensive drugs. It is best combined with adrenergic blocking drugs or vasodilator drugs. Diuretic therapy for hypertension is inexpensive and used to be the first line until a few years back. Currently the diuretics are more of a second-line drug but still a major component of combination therapy.
The important diuretics used in treatment of hypertension are :
- Thiazides and thiazide-like diuretics
- Potassium-sparing diuretics
- Loop diuretics
Dilation of blood vessels is a major mechanism of hypertension medication. Many drugs directly act on the blood vessels causing dilation of the arteries as well as veins. Dilation of the arteries results in reduction in the peripheral resistance while dilation of veins reduces the venous return to the heart. The vasodilators cause the dilation by a variety of mechanism and these drugs are grouped accordingly. The major groups of vasodilators are :
- Calcium channel blockers (CCBs)
- Potassium channel openers
- Other vasodilators