A number of drug classes are effective for initial and subsequent management of hypertension:
Angiotensin-converting enzyme (ACE) inhibitors Angiotensin-converting enzyme (ACE) inhibitors A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers... read more
Drug selection and use Drugs Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more 
in the treatment of stable hypertension is discussed elsewhere. For drug treatment of hypertensive emergencies, see table Parenteral Drugs for Hypertensive Emergencies Parenteral Drugs for Hypertensive Emergencies 
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(See also Overview of Hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more and Hypertensive Emergencies Hypertensive Emergencies A hypertensive emergency is severe hypertension with signs of damage to target organs (primarily the brain, cardiovascular system, and kidneys). Diagnosis is by blood pressure (BP) measurement... read more .)
Adrenergic modifiers
Adrenergic modifiers include central alpha-2-agonists, postsynaptic alpha-1-blockers, and peripheral-acting non-selective adrenergic blockers (see table Adrenergic Modifiers for Hypertension Adrenergic Modifiers for Hypertension ).
Alpha-2-agonists (eg, methyldopa, clonidine, guanabenz, guanfacine) stimulate alpha-2-adrenergic receptors in the brain stem and reduce sympathetic nervous activity, lowering blood pressure (BP). Because they have a central action, they are more likely than other antihypertensives to cause drowsiness, lethargy, and depression; they are no longer widely used. Clonidine can be applied transdermally once a week as a patch; thus, it may be useful for nonadherent patients (eg, those with dementia).
Postsynaptic alpha-1-blockers (eg, prazosin, terazosin, doxazosin) are no longer used for primary treatment of hypertension because evidence suggests no reduction in mortality. Also, doxazosin used alone or with antihypertensives other than diuretics increases risk of heart failure. However, they may be used in patients who have prostatic hypertrophy and need a 4th antihypertensive or in people with high sympathetic tone (ie, with high heart rate and spiking blood pressures) already on the maximum dose of a beta-blocker.
Angiotensin-converting enzyme (ACE) inhibitors
ACE inhibitors (see table Oral ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension Oral Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Blockers for Hypertension ) reduce blood pressure by interfering with the conversion of angiotensin I to angiotensin II and by inhibiting the degradation of bradykinin, thereby decreasing peripheral vascular resistance without causing reflex tachycardia. These drugs reduce BP in many hypertensive patients, regardless of plasma renin activity. Because these drugs provide renal protection, they are the drugs of choice for patients with diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more . They are not recommended for initial treatment in blacks, in whom they appear to increase the risk of stroke when used for initial treatment.
A dry, irritating cough is the most common adverse effect, but angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute mast cell–mediated reaction caused by exposure to drug, venom, dietary, pollen, or animal dander allergens... read more 
is the most serious and, if it affects the oropharynx, can be fatal. Angioedema is most common among blacks and smokers. ACE inhibitors may increase serum potassium and creatinine levels, especially in patients with chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more 
and those taking potassium-sparing diuretics, potassium supplements, or nonsteroidal anti-inflammatory drugs (NSAIDs). ACE inhibitors are the least likely of the antihypertensives to cause erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more . ACE inhibitors are contraindicated during pregnancy. In patients with a renal disorder, serum creatinine and potassium levels are monitored at least every 3 months. Patients who have stage 3 nephropathy (estimated glomerular filtration rate [GFR] of < 60 mL/minute to > 30 mL/minute) and are given ACE inhibitors can usually tolerate up to a 30 to 35% increase in serum creatinine above baseline. ACE inhibitors can cause acute kidney injury in patients who have hypovolemia, severe heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more 
, severe bilateral renal artery stenosis Renal Artery Stenosis and Occlusion Renal artery stenosis is a decrease in blood flow through one or both of the main renal arteries or their branches. Renal artery occlusion is a complete blockage of blood flow through one or... read more 
, or severe stenosis in the artery to a solitary kidney.
Thiazide-type diuretics enhance the antihypertensive activity of ACE inhibitors more than that of other classes of antihypertensives. Spironolactone and eplerenone also appear to enhance the effect of ACE inhibitors.
Angiotensin II receptor blockers (ARBs)
Angiotensin II receptor blockers (see table Oral ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension Oral Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Blockers for Hypertension ) block angiotensin II receptors and therefore interfere with the renin-angiotensin system Renin-angiotensin-aldosterone system Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more . Angiotensin II receptor blockers and ACE inhibitors are equally effective as antihypertensives. Angiotensin II receptor blockers may provide added benefits via tissue ACE blockade. The 2 classes have the same beneficial effects in patients with left ventricular failure or with nephropathy due to type 1 diabetes Diabetic Nephropathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more 
. An angiotensin II receptor blocker should not be used together with an ACE inhibitor, but when used with a beta-blocker may reduce the hospitalization rate for patients with heart failure. Angiotensin II receptor blockers may be safely started in people < 60 with initial serum creatinine of ≤ 3 mg/dL (≤ 265 micromol/L).
Incidence of adverse events is low; angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute mast cell–mediated reaction caused by exposure to drug, venom, dietary, pollen, or animal dander allergens... read more occurs but much less frequently than with ACE inhibitors. Precautions for use of angiotensin II receptor blockers in patients with renovascular hypertension Renovascular Hypertension Renovascular hypertension is blood pressure elevation due to partial or complete occlusion of one or more renal arteries or their branches. It is usually asymptomatic unless long-standing. A... read more 
, hypovolemia, and severe heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more are the same as those for ACE inhibitors (see table Oral ACE Inhibitors and Angiotensin II Receptor Blockers for Hypertension Oral Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Blockers for Hypertension ). Angiotensin II receptor blockers are contraindicated during pregnancy.
Beta-blockers
Beta-blockers (see table Oral Beta-Blockers for Hypertension Oral Beta-Blockers for Hypertension ) slow heart rate and reduce myocardial contractility, thus reducing blood pressure. All beta-blockers are similar in antihypertensive efficacy. In patients with diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , chronic peripheral arterial disease Peripheral Arterial Disease Peripheral arterial disease (PAD) is atherosclerosis of the extremities (virtually always lower) causing ischemia. Mild PAD may be asymptomatic or cause intermittent claudication; severe PAD... read more 
, or chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more 
(COPD), a cardioselective beta-blocker (acebutolol, atenolol, betaxolol, bisoprolol, metoprolol) may be preferable, although cardioselectivity is only relative and decreases as dose increases. Even cardioselective beta-blockers are contraindicated in patients with asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more or in patients with COPD with a prominent bronchospastic component.
Beta-blockers are particularly useful in patients who have angina Angina Pectoris Angina pectoris is a clinical syndrome of precordial discomfort or pressure due to transient myocardial ischemia without infarction. It is typically precipitated by exertion or psychologic stress... read more , who have had a myocardial infarction Acute Myocardial Infarction (MI) Acute myocardial infarction is myocardial necrosis resulting from acute obstruction of a coronary artery. Symptoms include chest discomfort with or without dyspnea, nausea, and diaphoresis.... read more 
, or who have heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more , although atenolol may worsen prognosis in patients with coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more 
(CAD). These drugs are no longer considered problematic for the elderly.
Beta-blockers with intrinsic sympathomimetic activity (eg, acebutolol, pindolol) do not adversely affect serum lipids; they are less likely to cause severe bradycardia.
Beta-blockers have central nervous system (CNS) adverse effects (sleep disturbances, fatigue, lethargy) and exacerbate depression. Nadolol affects the CNS the least and may be best when CNS effects must be avoided. Beta-blockers are contraindicated in patients with 2nd- or 3rd-degree atrioventricular block Atrioventricular Block Atrioventricular (AV) block is partial or complete interruption of impulse transmission from the atria to the ventricles. The most common cause is idiopathic fibrosis and sclerosis of the conduction... read more 
, asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , or sinus node dysfunction Sinus Node Dysfunction Sinus node dysfunction refers to a number of conditions causing physiologically inappropriate atrial rates. Symptoms may be minimal or include weakness, effort intolerance, palpitations, and... read more .
Calcium channel blockers
Dihydropyridines (see table Oral Calcium Channel Blockers for Hypertension Oral Calcium Channel Blockers for Hypertension ) are potent peripheral vasodilators and reduce blood pressure by decreasing total peripheral vascular resistance (TPR); they sometimes cause reflexive tachycardia.
The nondihydropyridines verapamil and diltiazem slow the heart rate, decrease atrioventricular conduction, and decrease myocardial contractility. These drugs should not be prescribed for patients with 2nd- or 3rd-degree atrioventricular block Atrioventricular Block Atrioventricular (AV) block is partial or complete interruption of impulse transmission from the atria to the ventricles. The most common cause is idiopathic fibrosis and sclerosis of the conduction... read more or with left ventricular failure.
Long-acting nifedipine, verapamil, or diltiazem is used to treat hypertension, but short-acting nifedipine and diltiazem are associated with a high rate of myocardial infarction and are not recommended.
A calcium channel blocker is preferred to a beta-blocker in patients with angina pectoris Angina Pectoris Angina pectoris is a clinical syndrome of precordial discomfort or pressure due to transient myocardial ischemia without infarction. It is typically precipitated by exertion or psychologic stress... read more and a bronchospastic disorder, with coronary spasms, or with Raynaud syndrome Raynaud Syndrome Raynaud syndrome is vasospasm of parts of the hand in response to cold or emotional stress, causing reversible discomfort and color changes (pallor, cyanosis, erythema, or a combination) in... read more 
.
Direct renin inhibitor
Aliskiren, a direct renin inhibitor, is used in the management of hypertension. Dosage is 150 to 300 mg orally once a day, with a starting dose of 150 mg.
As with ACE inhibitors and angiotensin II receptor blockers, aliskiren causes elevation of serum potassium and creatinine. Aliskiren should not be combined with ACE inhibitors or angiotensin II receptor blockers in patients with diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more or renal disease (estimated GFR < 60 mL/min).
Direct vasodilators
Direct vasodilators, including minoxidil and hydralazine (see table Direct Vasodilators for Hypertension Direct Vasodilators for Hypertension ), work directly on blood vessels, independently of the autonomic nervous system. Minoxidil is more potent than hydralazine but has more adverse effects, including sodium and water retention and hypertrichosis, which is poorly tolerated by women. Minoxidil should be reserved for severe, refractory hypertension.
Hydralazine is used during pregnancy (eg, for preeclampsia Preeclampsia and Eclampsia Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more ) and as an adjunct antihypertensive. Long-term, high-dose (> 300 mg/day) hydralazine has been associated with a drug-induced lupus syndrome, which resolves when the drug is stopped.
Diuretics
Main classes of diuretics used for hypertension (see table Oral Diuretics for Hypertension Oral Diuretics for Hypertension ) are
Loop diuretics
Potassium-sparing diuretics
Thiazide-type diuretics
Diuretics modestly reduce plasma volume and reduce vascular resistance, possibly via shifts in sodium from intracellular to extracellular loci.
Loop diuretics are used to treat hypertension only in patients who have lost > 50% of kidney function; these diuretics are given at least twice a day (except for torsemide which can be given once a day).
Although the potassium-sparing diuretics do not cause hypokalemia Hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more , hyperuricemia, or hyperglycemia, they are not as effective as thiazide-type diuretics in controlling hypertension and thus are not used for initial treatment. Potassium-sparing diuretics or potassium supplements are not needed when an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker is used because these drugs increase serum potassium.
Thiazide-type diuretics are most commonly used. In addition to other antihypertensive effects, they cause a small amount of vasodilation as long as intravascular volume is normal. All thiazides are equally effective in equivalent doses; however, thiazide-type diuretics have longer half-lives and are relatively more effective at similar doses. Thiazide-type diuretics can increase serum cholesterol slightly (mostly low-density lipoprotein) and also increase triglyceride levels, although these effects may not persist > 1 year. Furthermore, levels seem to increase in only a few patients. The increase is apparent within 4 weeks of treatment and can be ameliorated by a low-fat diet. The possibility of a slight increase in lipid levels does not contraindicate diuretic use in patients with dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis... read more 
.
All diuretics except the potassium-sparing distal tubular diuretics cause significant potassium loss, so serum potassium is measured monthly until the level stabilizes. Unless serum potassium is normalized, potassium channels in the arterial walls close and the resulting vasoconstriction makes achieving the blood pressure (BP) goal difficult. Patients with potassium levels < 3.5 mEq/L (< 3.5 mmol/L) are given potassium supplements. Supplements may be continued long-term at a lower dose, or a potassium-sparing diuretic (eg, daily spironolactone 25 to 100 mg, triamterene 50 to 150 mg, amiloride 5 to 10 mg) may be added. Potassium supplements or addition of a potassium-sparing diuretic is also recommended for any patients who are also taking digitalis, have a known heart disorder, have an abnormal ECG, have ectopy or arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more 
, or develop ectopy or arrhythmias while taking a diuretic.
In most patients with diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , thiazide-type diuretics do not affect control of diabetes. Uncommonly, diuretics precipitate or worsen type 2 diabetes in patients with metabolic syndrome.
A hereditary predisposition probably explains the few cases of gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing... read more 
due to diuretic-induced hyperuricemia. Diuretic-induced hyperuricemia without gout does not require treatment or discontinuation of the diuretic.
Diuretics may slightly increase mortality in patients with a history of heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more who do not have pulmonary congestion, particularly in those who are also taking an ACE inhibitor or angiotensin II receptor blocker and who do not drink at least 1400 mL (48 oz) of fluid daily. The increased mortality is probably related to diuretic-induced hyponatremia and hypotension.
More Information
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