NCLEX: Antihypertensives

Hypertension is defined as either a sustained systolic blood pressure of greater than 140 mm Hg or a sustained diastolic blood pressure of greater than 90 mm Hg. Hypertension results from increased peripheral vascular arteriolar smooth muscle tone, which leads to increased arteriolar resistance and reduced capacitance of the venous system. In most cases, the cause of the increased vascular tone is unknown. Elevated blood pressure is a common disorder, affecting approximately 30% of adults in the United States.

Although many patients have no symptoms, chronic hypertension can lead to heart disease and stroke, the top two causes of death in the world. Hypertension is also an important risk factor in the development of chronic kidney disease and heart failure. The incidence of morbidity and mortality significantly decreases when hypertension is diagnosed early and is properly treated. In recognition of the progressive nature of hypertension, hypertension is classified into four categories for the purpose of treatment management.








Focus topic: Antihypertensives

Although hypertension may occur secondary to other disease processes, more than 90% of patients have essential hypertension (hypertension with no identifiable cause). A family history of hypertension increases the likelihood that an individual will develop hypertension. The prevalence of hypertension increases with age, but decreases with education and income level.

Non-Hispanic blacks have a higher incidence of hypertension than do both non-Hispanic whites and Hispanic whites. Persons with diabetes, obesity, or disability status are all more likely to have hypertension than those without. In addition, environmental factors, such as a stressful lifestyle, high dietary intake of sodium, and smoking, may further predispose an individual to hypertension.


Focus topic: Antihypertensives

Arterial blood pressure is regulated within a narrow range to provide adequate perfusion of the tissues without causing damage to the vascular system, particularly the arterial intima (endothelium). Arterial blood pressure is directly proportional to cardiac output and peripheral vascular resistance. Cardiac output and peripheral resistance, in turn, are controlled mainly by two overlapping control mechanisms: the baroreflexes and the renin–angiotensin–aldosterone system. Most antihypertensive drugs lower blood pressure by reducing cardiac output and/or decreasing peripheral resistance.

A. Baroreceptors and the sympathetic nervous system

Baroreflexes act by changing the activity of the sympathetic nervous system. Therefore, they are responsible for the rapid, moment-tomoment regulation of blood pressure. A fall in blood pressure causes pressure-sensitive neurons (baroreceptors in the aortic arch and carotid sinuses) to send fewer impulses to cardiovascular centers in the spinal cord. This prompts a reflex response of increased sympathetic and decreased parasympathetic output to the heart and vasculature, resulting in vasoconstriction and increased cardiac output.

B. Renin–angiotensin–aldosterone system

The kidney provides long-term control of blood pressure by altering the blood volume. Baroreceptors in the kidney respond to reduced arterial pressure (and to sympathetic stimulation of β1-adrenoceptors) by releasing the enzyme renin. Low sodium intake and greater sodium loss also increase renin release. Renin converts angiotensinogen to angiotensin I, which is converted in turn to angiotensin II, in the presence of angiotensin-converting enzyme (ACE). Angiotensin II is a potent circulating vasoconstrictor, constricting both arterioles and veins, resulting in an increase in blood pressure. Angiotensin II exerts a preferential vasoconstrictor action on the efferent arterioles of the renal glomerulus, increasing glomerular filtration. Furthermore, angiotensin II stimulates aldosterone secretion, leading to increased renal sodium reabsorption and increased blood volume, which contribute to a further increase in blood pressure. These effects of angiotensin II are mediated by stimulation of angiotensin II type 1 (AT1) receptors.






Focus topic: Antihypertensives

The goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality. The relationship between blood pressure and the risk of cardiovascular events is continuous, and, thus, lowering of even moderately elevated blood pressure significantly reduces cardiovascular disease. The classification of “prehypertension” recognizes this relationship and emphasizes the need for decreasing blood pressure in the general population by education and the adoption of blood pressure–lowering behaviors.

For most patients, the blood pressure goal when treating hypertension is a systolic blood pressure of less than 140 mm Hg and a diastolic blood pressure of less than 90 mm Hg. Mild hypertension can sometimes be controlled with monotherapy, but most patients require more than one drug to achieve blood pressure control. Current recommendations are to initiate therapy with a thiazide diuretic, ACE inhibitor, angiotensin receptor blocker (ARB), or calcium channel blocker.

If blood pressure is inadequately controlled, a second drug should be added, with the selection based on minimizing the adverse effects of the combined regimen and achieving goal blood pressure. Patients with systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg (or systolic blood pressure greater than 20 mm Hg above goal or diastolic blood pressure more than 10 mm Hg above goal) should be started on two antihypertensives simultaneously.

A. Individualized care

Hypertension may coexist with other diseases that can be aggravated by some of the antihypertensive drugs or that may benefit from the use of some antihypertensive drugs independent of blood pressure control. In such cases, it is important to match antihypertensive drugs to the particular patient shows preferred therapies in hypertensive patients with concomitant diseases, and shows the frequency of concomitant disease in the hypertensive population.

In addition to the choice of therapy, blood pressure goals may also be individualized based on concurrent disease states. For instance, in patients with diabetes, some experts recommend a blood pressure goal of less than 140/80 mm Hg. Likewise, in patients with chronic kidney disease and proteinuria, lower goals of less than 130/80 mm Hg may be considered. Elderly patients may have less stringent goals (for example, less than 150/90 mm Hg).

B. Patient compliance in antihypertensive therapy

Lack of patient compliance is the most common reason for failure of antihypertensive therapy. The hypertensive patient is usually asymptomatic and is diagnosed by routine screening before the occurrence of overt end-organ damage. Thus, therapy is generally directed at preventing future disease sequelae rather than relieving current discomfort. The adverse effects associated with the hypertensive therapy may influence the patient more than the future benefits.

For example, β-blockers can cause sexual dysfunction in males, which may prompt discontinuation of therapy. Thus, it is important to enhance compliance by selecting a drug regimen that reduces adverse effects and also minimizes the number of doses required daily. Combining two drug classes in a single pill, at a fixed-dose combination, has been shown to improve patient compliance and the number of patients achieving goal blood pressure.





Antihypertensives: DIURETICS

Focus topic: Antihypertensives

Thiazide diuretics can be used as initial drug therapy for hypertension unless there are compelling reasons to choose another agent. Regardless of class, the initial mechanism of action of diuretics is based upon decreasing blood volume, which ultimately leads to decreased blood pressure. Low-dose diuretic therapy is safe, inexpensive, and effective in preventing stroke, myocardial infarction, and heart failure. Routine serum electrolyte monitoring should be done for all patients receiving diuretics.

A. Thiazide diuretics

Thiazide diuretics, such as hydrochlorothiazide [hye-droe-klor-oh-THYE-a-zide] and chlorthalidone [klor-THAL-ih-done], lower blood pressure initially by increasing sodium and water excretion. This causes a decrease in extracellular volume, resulting in a decrease in cardiac output and renal blood flow. With long-term treatment, plasma volume approaches a normal value, but a hypotensive effect persists that is related to a decrease in peripheral resistance.

Thiazides are useful in combination therapy with a variety of other antihypertensive agents, including β-blockers, ACE inhibitors, ARBs, and potassium-sparing diuretics. With the exception of metolazone [me-TOL-ah-zone], thiazide diuretics are not effective in patients with inadequate kidney function (estimated glomerular filtration rate less than 30 mL/min/m2). Loop diuretics may be required in these patients. Thiazide diuretics can induce hypokalemia, hyperuricemia and, to a lesser extent, hyperglycemia in some patients.

B. Loop diuretics

The loop diuretics (furosemide, torsemide, bumetanide, and ethacrynic acid) act promptly by blocking sodium and chloride reabsorption in the kidneys, even in patients with poor renal function or those who have not responded to thiazide diuretics. Loop diuretics cause decreased renal vascular resistance and increased renal blood flow. Actions of thiazide diuretics Like thiazides, they can cause hypokalemia. However, unlike thiazides, loop diuretics increase the Ca2+ content of urine, whereas thiazide diuretics decrease it. These agents are rarely used alone to treat hypertension, but they are commonly used to manage symptoms of heart failure and edema.

C. Potassium-sparing diuretics

Amiloride [a-MIL-oh-ride] and triamterene [tri-AM-ter-een] (inhibitors of epithelial sodium transport at the late distal and collecting ducts) as well as spironolactone [speer-on-oh-LAK-tone] and eplerenone [eh-PLEH-reh-none] (aldosterone receptor antagonists) reduce potassium loss in the urine. Aldosterone antagonists have the additional benefit of diminishing the cardiac remodeling that occurs in heart failure (see Chapter 19). Potassium-sparing diuretics are sometimes used in combination with loop diuretics and thiazides to reduce the amount of potassium loss induced by these diuretics.





Focus topic: Antihypertensives

β-Blockers are a treatment option for hypertensive patients with concomitant heart disease or heart failure.

A. Actions

The β-blockers reduce blood pressure primarily by decreasing cardiac output (Figure 17.8). They may also decrease sympathetic outflow from the central nervous system (CNS) and inhibit the release of renin from the kidneys, thus decreasing the formation of angiotensin II and the secretion of aldosterone. The prototype β-blocker is propranolol [proe PRAN-oh-lol], which acts at both β1 and β2 receptors. Selective blockers of β1 receptors, such as metoprolol [met-OH-pro-lol] and atenolol [ah-TEN-oh-lol], are among the most commonly prescribed β-blockers.

Nebivolol is a selective blocker of β1 receptors, which also increases the production of nitric oxide, leading to vasodilation. The selective β-blockers may be administered cautiously to hypertensive patients who also have asthma. The nonselective β-blockers, such as propranolol and nadolol, are contraindicated in patients with asthma due to their blockade of β2-mediated bronchodilation.




B. Therapeutic uses

The primary therapeutic benefits of β-blockers are seen in hypertensive patients with concomitant heart disease, such as supraventricular tachyarrhythmia (for example, atrial fibrillation), previous myocardial infarction, angina pectoris, and chronic heart failure. Conditions that discourage the use of β-blockers include reversible bronchospastic disease such as asthma, second- and third-degree heart block, and severe peripheral vascular disease.

C. Pharmacokinetics

The β-blockers are orally active for the treatment of hypertension. Propranolol undergoes extensive and highly variable first-pass metabolism. Oral β-blockers may take several weeks to develop their full effects. Esmolol, metoprolol, and propranolol are available in intravenous formulations.

D. Adverse effects

  • Common effects: The β-blockers may cause bradycardia, hypotension, and CNS side effects such as fatigue, lethargy, and insomnia. The β-blockers may decrease libido and cause erectile dysfunction, which can severely reduce patient compliance.
  • Alterations in serum lipid patterns: Noncardioselective β-blockers may disturb lipid metabolism, decreasing high-density lipoprotein cholesterol and increasing triglycerides.
  • Drug withdrawal: Abrupt withdrawal may induce angina, myocardial infarction, and even sudden death in patients with ischemic heart disease. Therefore, these drugs must be tapered over a few weeks in patients with hypertension and ischemic heart disease.




Antihypertensives: ACE INHIBITORS

Focus topic: Antihypertensives

The ACE inhibitors, such as enalapril [e-NAL-ah-pril] and lisinopril [lye-SIN-oh-pril], are recommended as first-line treatment of hypertension in patients with a variety of compelling indications, including high coronary disease risk or history of diabetes, stroke, heart failure, myocardial infarction, or chronic kidney disease.

A. Actions

The ACE inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output, heart rate, or contractility. These drugs block the enzyme ACE which cleaves angiotensin I to form the potent vasoconstrictor angiotensin II. ACE is also responsible for the breakdown of bradykinin, a peptide that increases the production of nitric oxide and prostacyclin by the blood vessels. Both nitric oxide and prostacyclin are potent vasodilators. ACE inhibitors decrease angiotensin II and increase bradykinin levels.

Vasodilation of both arterioles and veins occurs as a result of decreased vasoconstriction (from diminished levels of angiotensin II) and enhanced vasodilation (from increased bradykinin). By reducing circulating angiotensin II levels, ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. ACE inhibitors reduce both cardiac preload and after load, thereby decreasing cardiac work.

B. Therapeutic uses

Like the ARBs, ACE inhibitors slow the progression of diabetic nephropathy and decrease albuminuria and, thus, have a compelling indication for use in patients with diabetic nephropathy. Beneficial effects on renal function may result from decreasing intraglomerular pressures, due to efferent arteriolar vasodilation. ACE inhibitors are a standard in the care of a patient following a myocardial infarction and first-line agents in the treatment of patients with systolic dysfunction.

Chronic treatment with ACE inhibitors achieves sustained blood pressure reduction, regression of left ventricular hypertrophy, and prevention of ventricular remodeling after a myocardial infarction. ACE inhibitors are first-line drugs for treating heart failure, hypertensive patients with chronic kidney disease, and patients at increased risk of coronary artery disease. All of the ACE inhibitors are equally effective in the treatment of hypertension at equivalent doses.

C. Pharmacokinetics

All of the ACE inhibitors are orally bioavailable as a drug or prodrug. All but captopril [KAP-toe-pril] and lisinopril undergo hepatic conversion to active metabolites, so these agents may be preferred in patients with severe hepatic impairment. Fosinopril [foe-SIN-oh-pril] is the only ACE inhibitor that is not eliminated primarily by the kidneys and does not require dose adjustment in patients with renal impairment. Enalaprilat [en-AL-a-pril-AT] is the only drug in this class available intravenously.

D. Adverse effects

Common side effects include dry cough, rash, fever, altered taste, hypotension (in hypovolemic states), and hyperkalemia. The dry cough, which occurs in up to 10% of patients, is thought to be due to increased levels of bradykinin and substance P in the pulmonary tree and resolves within a few days of discontinuation. The cough occurs more frequently in women. Angioedema is a rare but potentially life-threatening reaction that may also be due to increased levels of bradykinin.

Potassium levels must be monitored while on ACE inhibitors, and potassium supplements and potassium-sparing diuretics should be used with caution due to the risk of hyperkalemia. Serum creatinine levels should also be monitored, particularly in patients with underlying renal disease. However, an increase in serum creatinine of up to 30% above baseline is acceptable and by itself does not warrant discontinuation of treatment. ACE inhibitors can induce fetal malformations and should not be used by pregnant women.





Focus topic: Antihypertensives

The ARBs, such as losartan [LOW-sar-tan] and irbesartan [ir-be-SARtan], are alternatives to the ACE inhibitors. These drugs block the AT1 receptors, decreasing the activation of AT1 receptors by angiotensin II. Their pharmacologic effects are similar to those of ACE inhibitors in that they produce arteriolar and venous dilation and block aldosterone secretion, thus lowering blood pressure and decreasing salt and water retention. ARBs do not increase bradykinin levels.

They may be used as first-line agents for the treatment of hypertension, especially in patients with a compelling indication of diabetes, heart failure, or chronic kidney disease. Adverse effects are similar to those of ACE inhibitors, although the risks of cough and angioedema are significantly decreased. ARBs should not be combined with an ACE inhibitor for the treatment of hypertension due to similar mechanisms and adverse effects. These agents are also teratogenic and should not be used by pregnant women.

Antihypertensives: RENIN INHIBITOR

Focus topic: Antihypertensives

A selective renin inhibitor, aliskiren [a-LIS-ke-rin], is available for the treatment of hypertension. Aliskiren directly inhibits renin and, thus, acts earlier in the renin–angiotensin–aldosterone system than ACE inhibitors or ARBs. It lowers blood pressure about as effectively as ARBs, ACE inhibitors, and thiazides. Aliskiren should not be routinely combined with an ACE inhibitor or ARB. Aliskiren can cause diarrhea, especially at higher doses, and can also cause cough and angioedema, but probably less often than ACE inhibitors. As with ACE inhibitors and ARBs, aliskiren is contraindicated during pregnancy. Aliskiren is metabolized by CYP 3A4 and is subject to many drug interactions.


Focus topic: Antihypertensives

Calcium channel blockers are a recommended treatment option in hypertensive patients with diabetes or angina. High doses of short-acting calcium channel blockers should be avoided because of increased risk of myocardial infarction due to excessive vasodilation and marked reflex cardiac stimulation.

A. Classes of calcium channel blockers

The calcium channel blockers are divided into three chemical classes, each with different pharmacokinetic properties and clinical indications.

  • Diphenylalkylamines: Verapamil [ver-AP-a-mil] is the only member of this class that is available in the United States. Verapamil is the least selective of any calcium channel blocker and has significant effects on both cardiac and vascular smooth muscle cells. It is also used to treat angina and supraventricular tachyarrhythmias and to prevent migraine and cluster headaches.
  • Benzothiazepines: Diltiazem [dil-TYE-a-zem] is the only member of this class that is currently approved in the United States. Like verapamil, diltiazem affects both cardiac and vascular smooth muscle cells, but it has a less pronounced negative inotropic effect on the heart compared to that of verapamil. Diltiazem has a favorable side effect profile.
  • Dihydropyridines: This class of calcium channel blockers includes nifedipine [nye-FED-i-peen] (the prototype), amlodipine [am-LOE-di-peen], felodipine [fe-LOE-di-peen], isradipine [is-RADi- peen], nicardipine [nye-KAR-di-peen], and nisoldipine [nye-ZOLdi-peen]. These agents differ in pharmacokinetics, approved uses, and drug interactions. All dihydropyridines have a much greater affinity for vascular calcium channels than for calcium channels in the heart. They are, therefore, particularly beneficial in treating hypertension. The dihydropyridines have the advantage in that they show little interaction with other cardiovascular drugs, such as digoxin or warfarin, which are often used concomitantly with calcium channel blockers.




B. Actions

The intracellular concentration of calcium plays an important role in maintaining the tone of smooth muscle and in the contraction of the myocardium. Calcium enters muscle cells through special voltage sensitive calcium channels. This triggers release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium. Calcium channel antagonists block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral arteriolar vasculature. This causes vascular smooth muscle to relax, dilating mainly arterioles. Calcium channel blockers do not dilate veins.

C. Therapeutic uses

In the management of hypertension, CCBs may be used as an initial therapy or as add-on therapy. They are useful in the treatment of hypertensive patients who also have asthma, diabetes, and/or peripheral vascular disease, because unlike β-blockers, they do not have the potential to adversely affect these conditions. All CCBs are useful in the treatment of angina. In addition, diltiazem and verapamil are used in the treatment of atrial fibrillation.

D. Pharmacokinetics

Most of these agents have short half-lives (3 to 8 hours) following an oral dose. Sustained-release preparations are available and permit once-daily dosing. Amlodipine has a very long half-life and does not require a sustained-release formulation.

E. Adverse effects

First-degree atrioventricular block and constipation are common dose dependent side effects of verapamil. Verapamil and diltiazem should be avoided in patients with heart failure or with atrioventricular block due to their negative inotropic (force of cardiac muscle contraction) and dromotropic (velocity of conduction) effects. Dizziness, headache, and a feeling of fatigue caused by a decrease in blood pressure are more frequent with dihydropyridines. Peripheral edema is another commonly reported side effect of this class. Nifedipine and other dihydropyridines may cause gingival hyperplasia.






Focus topic: Antihypertensives

Prazosin [PRA-zoe-sin], doxazosin [dox-AH-zoe-sin], and terazosin [ter-AH-zoe-sin] produce a competitive block of α1-adrenoceptors. They decrease peripheral vascular resistance and lower arterial blood pressure by causing relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Therefore, long-term tachycardia does not occur, but salt and water retention does.

Reflex tachycardia and postural hypotension often occur at the onset of treatment and with dose increases, requiring slow titration of the drug in divided doses. Due to weaker outcome data and their side effect profile, α-blockers are no longer recommended as initial treatment for hypertension, but may be used for refractory cases. Other α1-blockers with greater selectivity for prostate muscle are used in the treatment of benign prostatic hyperplasia.


Focus topic: Antihypertensives

Labetalol [la-BAY-ta-lol] and carvedilol [kar-VE-di-lol] block α1, β1, and β2 receptors. Carvedilol, although an effective antihypertensive, is mainly used in the treatment of heart failure. Carvedilol, as well as metoprolol succinate, and bisoprolol have been shown to reduce morbidity and mortality associated with heart failure. Labetalol is used in the management of gestational hypertension and hypertensive emergencies.


Focus topic: Antihypertensives

A. Clonidine

Clonidine [KLON-i-deen] acts centrally as an α2 agonist to produce inhibition of sympathetic vasomotor centers, decreasing sympathetic outflow to the periphery. This leads to reduced total peripheral resistance and decreased blood pressure. Clonidine is used primarily for the treatment of hypertension that has not responded adequately to treatment with two or more drugs. Clonidine does not decrease renal blood flow or glomerular filtration and, therefore, is useful in the treatment of hypertension complicated by renal disease.

Clonidine is absorbed well after oral administration and is excreted by the kidney. It is also available in a transdermal patch. Adverse effects include sedation, dry mouth, and constipation. Rebound hypertension occurs following abrupt withdrawal of clonidine. The drug should, therefore, be withdrawn slowly if discontinuation is required.

B. Methyldopa

Methyldopa [meth-ill-DOE-pa] is an α2 agonist that is converted to methylnorepinephrine centrally to diminish adrenergic outflow from the CNS. The most common side effects of methyldopa are sedation and drowsiness. Its use is limited due to adverse effects and the need for multiple daily doses. It is mainly used for management of hypertension in pregnancy, where it has a record of safety.

Antihypertensives: VASODILATORS

Focus topic: Antihypertensives

The direct-acting smooth muscle relaxants, such as hydralazine [hye-DRAL-a-zeen] and minoxidil [min-OX-i-dill], are not used as primary drugs to treat hypertension. These vasodilators act by producing relaxation of vascular smooth muscle, primarily in arteries and arterioles. This results in decreased peripheral resistance and, therefore, blood pressure. Both agents produce reflex stimulation of the heart, resulting in the competing reflexes of increased myocardial contractility, heart rate, and oxygen consumption.

These actions may prompt angina pectoris, myocardial infarction, or cardiac failure in predisposed individuals. Vasodilators also increase plasma renin concentration, resulting in sodium and water retention. These undesirable side effects can be blocked by concomitant use of a diuretic and a β-blocker. For example, hydralazine is almost always administered in combination with a β-blocker, such as propranolol, metoprolol, or atenolol (to balance the reflex tachycardia) and a diuretic (to decrease sodium retention).

Together, the three drugs decrease cardiac output, plasma volume, and peripheral vascular resistance. Hydralazine is an accepted medication for controlling blood pressure in pregnancy induced hypertension. Adverse effects of hydralazine include headache, tachycardia, nausea, sweating, arrhythmia, and precipitation of angina. A lupus-like syndrome can occur with high dosages, but it is reversible upon discontinuation of the drug. Minoxidil treatment causes hypertrichosis (the growth of body hair). This drug is used topically to treat male pattern baldness.


Focus topic: Antihypertensives

Hypertensive emergency is a rare but life-threatening situation characterized by severe elevations in blood pressure (systolic greater than 180 mm Hg or diastolic greater than 120 mm Hg) with evidence of impending or progressive target organ damage (for example, stroke, myocardial infarction). [Note: A severe elevation in blood pressure without evidence of target organ damage is considered a hypertensive urgency.] Hypertensive emergencies require timely blood pressure reduction with treatment administered intravenously to prevent or limit target organ damage.

A variety of medications are used, including calcium channel blockers (nicardipine and clevidipine), nitric oxide vasodilators (nitroprusside and nitroglycerin), adrenergic receptor antagonists (phentolamine, esmolol, and labetalol), the vasodilator hydralazine, and the dopamine agonist fenoldopam. Treatment is directed by the type of target organ damage present and/or comorbidities present.


Focus topic: Antihypertensives

Resistant hypertension is defined as blood pressure that remains elevated (above goal) despite administration of an optimal three-drug regimen that includes a diuretic. The most common causes of resistant hypertension are poor compliance, excessive ethanol intake, concomitant conditions (diabetes, obesity, sleep apnea, hyperaldosteronism, high salt intake, and/or metabolic syndrome), concomitant medications (sympathomimetics, nonsteroidal anti-inflammatory drugs, or antidepressant medications), insufficient dose and/or drugs, and use of drugs with similar mechanisms of action.

Antihypertensives: COMBINATION THERAPY

Focus topic: Antihypertensives

Combination therapy with separate agents or a fixed-dose combination pill may lower blood pressure more quickly with minimal adverse effects. Initiating therapy with two antihypertensive drugs should be considered in patients with blood pressures that are more than 20/10 mm Hg above the goal. A variety of combination formulations of the various pharmacologic classes are available to increase ease of patient adherence to treatment regimens that require multiple medications to achieve the blood pressure goal.





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