There are several types of drugs to treat hypertension and the use of each is dependent on the severity, duration and type of hypertension. Other underlying diseases also have to be taken into account when prescribing the most appropriate antihypertensive drug, even if the condition is not directly contributing to the raised blood pressure. Antihypertensive drugs work by either reducing the peripheral vascular resistance, cardiac output and/or fluid volume in the body.

The four main groups of antihypertensives based on different mechanisms of action. Hypertension medication may have different names depending on the class of drugs but fall into one or more of these categories  :

  • Angiotensin II modulators
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Angiotensin II receptor blockers
    • Renin inhibitors
  • Sympathetic (adrenergic) blockers
    • Centrally acting sympathetic blockers
    • Autonomic ganglion blockers
    • Sympathetic nerve terminal blockers
    • Adrenergic receptor blockers
      • Alpha blockers
      • Beta blockers
  • Diuretics
    • Thiazides and thiazide-like diuretics
    • Potassium-sparing diuretics
    • Loop diuretics
  • Vasodilators
    • Calcium channel blockers (CCBs)
      • Vaso-selective blockers
      • Cardio-selective blockers
    • Nitrates
    • Potassium channel openers
    • Other antihypertensives

Angiotensin Converting Enzyme (ACE) Inhibitors

ACE inhibitors  inhibit formation of angiotensin II from angiotensin I. This includes drugs like captopril, enalapril, lisinopril, benazepril, quinapril, ramipril and perindopril.

ACE inhibitors reduce the constricting actions of angiotensin II on blood vessels and reduces the release of aldosterone. These two effects of reduced angiotensin II levels is primarily responsible for the blood pressure lowering action of ACE inhibitors. Bradykinin is a powerful dilator of blood vessels and it reduces peripheral vascular resistance. ACE inhibitors also inhibits break down of bradykinin and increases the levels of bradykinin. This also assists with lowering the the blood pressure.

ACE inhibitors are most useful in hypertensive patients with concomitant heart failure, diabetes mellitus, diabetic renal diseases (diabetic nephropathy), or hyperlipidemia and following a myocardial infarction (heart attack).

ACE inhibitors are not indicated in hypertensive patients with hypovolemia (low blood volume) as it can cause very low blood pressure (hypo. Use of ACE inhibitors in patients with narrowed renal arteries (renal stenosis) is not recommended as it can further damage the kidney. It is also contraindicated in pregnant women. Most common side effects of ACE inhibitors are a dry cough (due to increased levels of bradykinin) and hyperkalemia (increased levels of potassium of in blood).

Angiotensin II receptor blockers (ARBs)

Angiotensin II receptor blockers reduce blood pressure by blocking the actions of angiotensin II. This includes drugs like  losartan, valsartan, irbesartan, candesartan, telmisartan and olmesartan.

The efficacy, beneficial effects and side effect profile of angiotensin II receptor blockers are similar to that of ACE inhibitors. Unlike ACE inhibitors, the angiotensin II receptor blockers do not have any effect on bradykinin levels. This has resulted in minimal incidence of dry cough associated with angiotensin II receptor blockers.

Renin inhibitors

Renin inhibitor aliskiren decreases the conversion of angiotensin I to angiotensin II and is therefore useful in the treatment of hypertension. The side effects of rennin inhibitor are similar to that of ACE inhibitors.

Centrally Acting Sympathetic Blockers

Centrally acting sympathetic blockers reduce central sympathetic outflow and reduce norepinephrine release from adrenergic nerve endings. This includes drugs like clonidine and methyldopa.

These drugs are useful in treatment of hypertension. Clonidine is also use for treating symptoms of withdrawal from abused drugs and a prominent side effect of its use is sedation. Methyldopa is safe for use in pregnant women with hypertension.

Autonomic Ganglion Blockers

Autonomic ganglion blockers block the ganglionic nicotinic receptors of acetylcholine. These includes drugs like trimethaphan which causes a fall in blood pressure. It is also associated with a wide spread action not limited to cardiovascular system. These drugs are not regularly used for treatment of hypertension.

Sympathetic Nerve Terminal Blockers

Sympathetic nerve terminal blockers reduce sympathetic flow at the sympathetic nerve terminals by interfering with storage and release of noradrenaline. This includes drugs like reserpine and guanethedine.

It is effective in reducing blood pressure but is rarely used at present because of side effects. Reserpine is associated with toxicities like severe depression with suicidal thoughts and drug–induced Parkinsonism.

Adrenergic Receptor Blockers

Alpha blockers

Alpha blockers are effective in treatment of hypertension. This includes drugs like prazosin and terazosin. Alpha blockers are considered to be third-line agents in hypertension.

Alpha blockers reduce the blood pressure by preventing the normal alpha receptor (sympathetic) mediated blood vessel constriction. Alpha blockers also relieve the difficulty in passing urine in patients with prostate enlargement. Alpha blockers are thus ideal for older men with hypertension and prostate enlargement. The most prominent drawback of alpha blockers is the postural hypotension.

Beta blockers

Beta blockers are one of the most important groups of antihypertensive drugs. The group includes drugs like propranolol, atenolol, metoprolol, pindolol, bisoprolol and carvediolol.

Beta blockers reduce blood pressure by reducing the heart rate and its force of contraction. Some of the drugs among them (like atenolol and metoprolol) are very selective in its action on heart. Drugs like propranolol are not selective for heart and have some additional constricting action on bronchi. Beta blockers are useful in treatment of hypertension, cardiac arrhythmias and in controlling symptoms of hyperthyroidism. It is also useful in long term prophylaxis against ischemic heart disease (IHD).

Carvediolol has additional alpha blocking action and is also useful in conditions like heart failure. Use of other beta blockers in heart failure can worsen it. Beta blockers are generally not recommended in patients with concomitant bronchial asthma. It can interfere with awareness and recovery from hypoglycemia (low blood sugar levels) resulting from use of anti-diabetic medicines. Hence, its use in diabetic patients has to be done very cautiously. Beta blockers can also dangerously reduce heart rate in patients with heart block and when combined with other cardiac depressant drugs (like verapamil).

Thiazides and Thiazide-like Diuretics

Thiazide diuretics (like hydrochlorothiazide) are the most important antihypertensive diuretic group. Thiazide diuretics are usually used in combination with potassium-sparing diuretics like spironolactone.

Thiazides are known to cause hypokalemia (low potassium levels), which is countered or prevented with the use of potassium-sparing diuretics. Glucose intolerance and lipid level abnormalities are other common adverse effects of thiazides. It is used in mild to moderate primary hypertension. It is also of use in patients with concomitant mild heart failure.

Potassium-sparing Diuretics

Potassium-sparing diuretics (like spironolactone, eplerenone, amiloride etc) are used along with thiazides or loop diuretics. These drugs combinations act synergistically in lowering blood pressure and in reducing or preventing hypokalemia.

Loop Diuretics

Loop diuretics are less commonly used in long term management of hypertension and includes drugs like furosemide. It may be used along with potassium-sparing diuretics in management of severe hypertension along with other antihypertensive drugs. It may be also be used in patients with concomitant heart failure.

Calcium channel blockers (CCBs)

Calcium channel blockers are important group antihypertensive drugs. Some of the calcium channel blockers block the entry of calcium into vascular smooth muscle cells. This causes vasodilation due to relaxation of the vascular smooth muscle cells. These drugs are called vaso-selective calcium channel blockers.

Some of the CCBs inhibit the calcium channels in the cardiac muscle cells. This results in depression of cardiac functions and subsequent fall in blood pressure. These are called cardio-selective calcium channel blockers.

Vasoselective calcium channel blockers

Vaso-selective CCBs include amlodipine, felodipine, isradipine, nicardipine, nimodipine and nifedipine. These drugs primarily reduce blood pressure by dilating the blood vessels. This group of drug is used in treatment of hypertension. Hypertensive patients with concomitant peripheral vascular diseases also benefit from vaso-selective CCBs.

Postural hypotension is a common side effect for these drugs. It can also cause increase in heart rate, flushing, edema, and sometimes precipitate cardiac pain (ischemic attack). This group of CCBs can be safely combined with other cardiac suppressant drugs like beta blockers and other drugs like diuretics.

Cardio-Selective Calcium Channel Blockers

Cardio-selective CCBs include verapamil and diltiazem. These drugs reduce blood pressure by suppressing the cardiac function. Heart rate and force of contraction of the heart is therefore also reduced.

This group of drug is used in treatment of hypertension, cardiac arrhythmias and angina pectoris. Heart rate can be dangerously reduced by these drugs occasionally as a side effect. Combining with other cardiac depressants like beta blockers is contraindicated. The group is also contraindicated in heart failure patients.

Nitrates

Nitrates have very potent dilating action on blood vessels but are not used for regular management of hypertension. Nitrates lower blood pressure very quickly and are preferred drugs in hypertensive emergencies (acute development of very high blood pressure). It can be administered intravenously for hypertensive emergencies. Important antihypertensive nitrates include sodium nitroprusside and nitroglycerine. Use of nitrates is associated with severe headache, sweating, palpitation and postural hypotension.

Potassium channel openers

Potassium channel openers like minoxidil produce blood pressure lowering effects by dilation of the blood vessels resulting from relaxation of the vascular smooth muscles. Potassium channel openers are less commonly used as antihypertensive drugs.

Minoxidil is more commonly used for treatment of male-pattern baldness. The use of these drugs as antihypertensive drugs is associated with hirsutism (abnormal facial hair growth in women), sweating, palpitations, and postural hypotension.

Others Antihypertensives

Several other drugs are known to have antihypertensive actions. Hydralazine, diazoxide, and fenoldapam are some of these other types of hypertensives. Hydralazine is available as tablets and for intravenous use. Hydralazine tablets are now rarely used for regular treatment of hypertension. The intravenous preparation is useful in hypertensive emergencies. Diazoxide and fenoldapam are also available as intravenous preparations for use in hypertensive emergencies.


Article reviewed by Dr. Greg. Last updated on December 3, 2011