Hypertension



Hypertension


Kelly Barranger

Diane E. Hadley



Hypertension or high blood pressure (BP) is one of the common chronic conditions managed by primary care providers and other health practitioners. It increases the risk for cardiovascular disease and chronic kidney disease (CKD). Heart disease is a prevalent cause of death in the United States, thus making management of a patient’s BP crucial. Approximately, 70 million Americans or one out of three adults in the United States has hypertension. The total costs associated with hypertension in 2011 in the United States were approximately $46 billion in health care services, medications, and missed days of work (Mozzafarian et al., 2015). Despite these alarming numbers, many people are unaware that they have hypertension because the disease can be asymptomatic; therefore, the disease is appropriately nicknamed “the silent killer.”

The prevalence of hypertension continues to grow due to the increasing age of our population, obesity, and high dietary salt intake. According to the Centers for Disease Control and Prevention (CDC), approximately 69% of adults 20 years and older are overweight and 35% of adults age 20 years and older are obese. Obesity, impaired renal function, and diabetes mellitus are all associated with resistant hypertension (Vongpatanasin, 2014).

Hypertension increases with age and affects all ethnic groups. However, blacks suffer disproportionately from hypertension and its effects, leading to high rates of cardiovascular morbidity and mortality. Hypertension in blacks occurs at an earlier age, is more severe, and results in organ damage such as coronary heart disease, stroke, and end-stage renal disease more often than it does in whites.


CAUSES

Hypertension is classified as primary or essential, secondary, or idiopathic when there is no identifiable cause for elevation in BP. Approximately 95% of adults have primary or essential hypertension, and the exact cause of primary hypertension is not known. Environmental factors (excess salt, obesity, and sedentary lifestyle) and genetic factors (inappropriately high activity of the renin-angiotensin-aldosterone system [RAAS] and the sympathetic nervous system) are hypothesized contributing factors and are being studied. An additional cause of hypertension is secondary to aorta artery stiffening secondary to increasing age. This is referred to as isolated or predominant systolic hypertension. It is characterized by high systolic blood pressure (SBP) with normal diastolic blood pressure (DBP) and is found primarily in elderly people.

Secondary hypertension, where the cause of high BP can be identified, accounts for 5% of all hypertensions. The main types of secondary hypertension are CKD (anemia, low GFR, small kidney), renovascular hypertension (abdominal bruit, elevated plasma renin activity, greater than 30% elevation of creatinine with starting BP-lowering agents), hypothyroidism (elevated TSH), hyperparathyroidism (elevated calcium), pheochromocytoma, sleep apnea, and primary aldosteronism (hypokalemia, ratio serum aldosterone/plasma renin activity greater than 25:30).

Furthermore, medications can serve as a factor that may increase BP. Examples include oral contraceptives, nicotine, steroids, appetite suppressants, tricyclic antidepressants, the antidepressant venlafaxine (Effexor), cyclosporine (Sandimmune),
nonsteroidal anti-inflammatory drugs (NSAIDs), and some nasal decongestants (which include over-the-counter preparations). Herbal products that affect BP include capsicum, goldenseal, licorice root, ma huang (Ephedra), Scotch broom, witch hazel, and yohimbine.




DIAGNOSTIC CRITERIA

Hypertension is defined as an elevation in SBP and/or DBP. As suggested by the 2014 Eighth Report of the Joint National Committee (JNC 8) guidelines, hypertension is defined as a BP of 150/90 mm Hg or higher in adults 60 years and older. The guidelines also highlights that a BP of 140/90 or higher in adults younger than 60 is defined as hypertension. Two studies within the primary literature, SHEP and Syst-EUR, used placebo-controlled approaches to evaluate people over the age of 60 with systolic hypertension and the HYVET study evaluated patients over the age of 80. The JNC 8 panel could not recommend a lower threshold value for those over 60 since no evidence existed that less than 140 mm Hg was better than less than 150 mm Hg for protecting patients from harm. Additionally, the ASH (American Society of Hypertension) and ISH (International Society of Hypertension) recommend an SBP of less than 150 (as opposed to less than 140 mm Hg) be used only in those over 80 years of age.

The biggest difference between JNC 7 and JNC 8 were the defined BP treatment goals. Additionally, another difference between JNC 7 and JNC 8 is that prehypertension was not addressed in JNC 8. This was well defined in JNC 7 as SBP ranging from 120 to 139 mm Hg and DBP ranging from 80 to 89 mm Hg and therefore remains valid. Another distinct difference was the use of very specific compelling indications within JNC 7 while JNC 8 used broader compelling indications. Finally, JNC 8 guidelines are more evidence based utilizing randomized controlled trials and have clear target ranges.

Hypertension is not diagnosed on an initial reading; rather, it is confirmed after three readings at least 1 week apart. BP measurements should be obtained after the patient has had time to relax for at least 5 minutes. Patients should be seated in a chair, back supported, rather than on an examination table, with feet on the floor, uncrossed, and arm supported at heart level. Patients should avoid smoking cigarettes 30 minutes before the reading, should not exercise heavily immediately before the reading, should not drink caffeine during the hour preceding the reading, and should avoid adrenergic stimulants, such as phenylephrine. For an accurate reading, the appropriate-size sphygmomanometer cuff should be used. The cuff should encompass 80% of the arm, and the width of the cuff should be at least 40% of the length of the upper arm (Screening for high blood pressure, 2007). At the initial evaluation, BP should be measured in both arms. If the readings are different, the arm with the higher reading should be used for measurements thereafter. It is preferable to take two readings, 1 to 2 minutes apart and use the average of these measurements. In older people, it is useful to obtain standing BP, after 1 minute and again after 3 minutes, to check for postural effects.

The diagnosis of hypertension should be confirmed at an additional patient visit, usually 1 to 4 weeks after the first
measurement. On both occasions, the SBP and DBP should be higher than recommendations listed above per age. The U.S. Preventive Services Task Force (USPSTF) recommends BP monitoring in adult patients over the age of eighteen. If the BP is very high (SBP greater than 180), initiate the appropriate triage and treatment should occur. If available resources are not adequate to permit a convenient second visit, the initial diagnosis can be made and treatment can be started.

Ambulatory BP monitoring (ABPM) is recommended for patients with suspected variable BP. Contributing factors can include “white coat hypertension,” episodic hypertension, hypertension resistant to increasing medication regimens, hypotensive symptoms while taking antihypertensive medications, and autonomic dysfunction. Patients with “white coat hypertension” have a persistently elevated BP in the doctor’s office but a persistently normal BP at other times. ABPM readings correlate better with target organ damage than clinical measurements. ABPM also identifies patients in whom BP does not drop significantly during sleep. More aggressive treatment may be necessary for these patients, who are known to be at higher cardiovascular risk. An elevated systolic BP is a more potent cardiovascular risk factor than an elevated diastolic BP.



Diagnostic Tests

The following laboratory tests should be routinely performed: electrocardiogram, blood glucose, hemoglobin, hematocrit, complete urinalysis, and complete chemistry panel especially serum potassium, creatinine, estimated glomerular filtration rate, liver function tests, calcium and magnesium, glycosylated hemoglobin (hemoglobin A1c), and fasting lipid panel (9- to 12-hour fast), which includes total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Further testing should be performed based on clinical findings.


INITIATING THERAPY


Goals of Drug Therapy

Treatment guidelines are cumbersome due to the different classifications of hypertensive patients with or without comorbidities of diabetes and/or CKD and also elderly versus nonelderly patients. Per JNC 8 guidelines, treatment should be initiated when BP is 140/90 or higher in adults younger than 60 and treated to a goal of less than 140/90 mm Hg. Similarly, the National Institute for Health and Care Excellence (NICE) 2013 guidelines support the same BP goal; however, they recommend this for patients 80 and younger. In adult patients with hypertension and diabetes, pharmacologic treatment should be initiated when BP is 140/90 mm Hg or higher, regardless of age, per the JNC 8 guidelines and the American Diabetes Association (ADA) 2015 Standards of Medical Care in Diabetes guidelines. The JNC 8 goal for diabetic patients, regardless of race, is less than 140/90 mm Hg. The ADA guidelines state as a caveat, however, that younger patients can be considered for a more aggressive BP target of ≤130/80 mm Hg if this can be achieved without side effects. The American College of Cardiology (ACC), American Heart Association (AHA), and the CDC also recommend a BP goal of less than 140/90 mm Hg for diabetic patients (Go et al., 2014).

Furthermore, the National Kidney Foundation (KDOQI) 2012 commentary on the 2012 KDIGO clinical practice guidelines for nondiabetic patients with hypertension and CKD with normal to mild albuminuria states the BP goal is ≤140/90 mm Hg. However, for severe albuminuria patients, the BP goal is ≤130/80 mm Hg. Thus, BP treatment per the KDOQI guidelines would be initiated at the respective targets listed above (Taler et al., 2013). The current 2014 JNC 8 guidelines recommend treatment in adult CKD patients with BP of 140/90 mm Hg or higher and their goal is a BP less than 140/90 mm Hg. Lastly, for elderly patients, JNC 8 recommends treatment for BP of 150/90 mm Hg or higher in adults 60 years and older to aim at a BP goal of less than 150/90 mm Hg. In contrast, the NICE guidelines from 2013 state that for patients above the age of 80 years old, their BP goal is less than 150/90 mm Hg.

The goal of antihypertensive therapy is to manage hypertension and reduce cardiovascular disease (including lipid disorders, glucose intolerance or diabetes, obesity, and smoking) and renal disease. The treatment goal of SBP is less than 140 mm Hg and DBP less than 90 mm Hg with special note of higher goals for elderly patients as listed above. In the past, guidelines have recommended treatment values of less than 130/80 mm Hg for patient with diabetes, CKD, and coronary artery disease. However, evidence to support this lower target is lacking and recent guidelines, such as JNC 8, have increased
the BP target goal. For instance, the ACCORD trial, BP trial arm, demonstrated that aggressive reduction of BP target (less than 120/80 mm Hg) in type 2 DM patients did not reduce combined cardiovascular and renal outcomes compared with usual care (target BP less than 140/90 mm Hg) (Cushman et al., 2010). Among secondary outcomes, strokes were reduced by the lower BP goals but at the expense of twice as many serious side effects. Several meta-analyses have demonstrated that lowering BP to below 130 mm Hg systolic does not reduce mortality rates or most cardiovascular outcomes (Mancia et al., 2013). It is important to inform patients that the treatment of hypertension is usually expected to be a lifelong commitment and can be dangerous for them to terminate treatment without first consulting their provider.






FIGURE 19.1 Modified JNC VIII Treatment for hypertension. (CKD, chronic kidney disease.) (Adapted from James, P., Oparil, S., Carter, B., et al. (2014). 2014 Evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Journal of the American Medical Association, 311, 507-520; Pharmacist’s Letter. (2014). Treatment of hypertension: JNC 8 and more. Pharmacist’s Letter/Prescriber’s Letter, Feb. 2014, Detail-Document #300201.)

Figure 19.1 summarizes widely used guidelines for hypertension treatment.



Overview of Pharmacological Antihypertensive Agents


Diuretics

There are five classes of diuretics: carbonic anhydrase inhibitors (which are not used for hypertension because of their weak antihypertensive effects), thiazides, thiazide-like diuretics, loop diuretics, and potassium-sparing diuretics. Diuretics decrease BP by causing diuresis, which results in decreased plasma volume, stroke volume, and cardiac output (see Table 19.1). During chronic therapy, their major hemodynamic effect is reduction of peripheral vascular resistance. As a result of drug-induced diuresis, adverse effects of hypokalemia and hypomagnesemia may lead to cardiac arrhythmias. Patients at greatest risk are those receiving digitalis therapy, those with LVH, and those with ischemic heart disease.


Thiazide Diuretics


Mechanism of Action

Thiazide diuretics work by increasing the urinary excretion of sodium and chloride in equal amounts (see Table 19.1). They inhibit the reabsorption of sodium and chloride in the thick ascending limb of the loop of Henle and the early distal tubules. The antihypertensive action requires several days to produce effects. The duration of action of the thiazides requires a single daily dose to control BP. Thiazide diuretics cause an increase potassium and bicarbonate excretion and decrease calcium excretion. Additionally, they cause uric acid retention; therefore, caution should be used in patients with a history of gout. Diuretic-induced hyperuricemia may produce gouty arthritis or uric acid stones.



Adverse Events

Side effects include hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, and hyperglycemia. As a result of drug-induced diuresis, hypokalemia occurs in 15% to 20% of patients taking low-dose thiazide diuretics; therefore, potassium supplements can be utilized by some patients. Combination therapy with thiazide and potassium-sparing diuretics (e.g., hydrochlorothiazide [Microzide] and triamterene [Dyrenium]) may be prudent when potassium levels are less than 4.0 mEq/L and the patient is taking a thiazide diuretic or when a low potassium level may potentiate drug toxicity, as in patients concurrently taking digoxin (Lanoxin). Other side effects include tinnitus, paresthesia, abdominal cramps, nausea, vomiting, diarrhea, muscle cramps, weakness, and sexual dysfunction.


Loop Diuretics


Mechanism of Action

Loop diuretics are indicated in the presence of edema associated with congestive heart failure, hepatic cirrhosis, and renal disease (see Table 19.1). This class of drug is useful when greater diuresis is desired compared to thiazide diuretics. In general, loop diuretics should be reserved for hypertensive patients with chronic renal insufficiency and/or need more severe diuresis.

Furosemide and ethacrynic acid inhibit the reabsorption of sodium and chloride, not only in proximal and distal tubules but also in the loop of Henle. In contrast, bumetanide is more chloruretic than natriuretic and may have an additional action in the proximal tubule.



Adverse Events

Loop diuretics may cause the same side effects as thiazides, although the effects on serum lipids and glucose are not as significant, and hypocalcemia may occur instead (see Table 19.1). The metabolic abnormalities, such as hyperlipidemia and hyperglycemia, usually occur with high doses of diuretics and can be avoided by using low doses of the drug. Loop diuretics may lead to electrolyte and volume depletion more readily than thiazides; they have a short duration of action, but the thiazide diuretics are more effective than loop diuretics in reducing BP in patients with normal renal function. Therefore, loop diuretics should be reserved for hypertensive patients with renal dysfunction (serum creatinine of more than 2.5).


Potassium-Sparing Diuretics

In the kidney, potassium is filtered at the glomerulus and then absorbed parallel to sodium throughout the proximal tubule and thick ascending limb of the loop of Henle, so that only minor amounts reach the distal convoluted tubule. As a result, potassium appearing in urine is secreted at the distal tubule and collecting duct. The potassium-sparing diuretics interfere with sodium reabsorption at the distal tubule, thus decreasing potassium secretion (see Table 19.1). This drug can be used



as a possible agent for HTN; however, its true benefit is indicated within heart failure. Secondary to the Randomized Spironolactone Evaluation Study (RALES), in 1999, showed the benefits of low-dose spironolactone (Aldactone) to improve morbidity and mortality rates in patients with severe heart failure (Pitt et al., 1999). Potassium-sparing diuretics have the potential for causing hyperkalemia and hyponatremia, especially in patients with renal insufficiency or diabetes and in patients receiving concurrent treatment with an ACE inhibitor (ACEI), NSAIDs, or potassium supplements.








TABLE 19.1 Overview of Selected Antihypertensive Agents

















































































































































































































































































































Generic (Trade) Name and Dosage


Selected Adverse Events


Contraindications


Special Considerations


Selected Diuretics


THIAZIDE AND THIAZIDE-LIKE


chlorthalidone 12.5-100 mg qd


Hyperuricemia, hypokalemia, hypomagnesemia, hyperglycemia, hyponatremia, hypercalcemia, hypercholesterolemia, hypertriglyceridemia, rashes, and other allergic reactions


High doses are relatively contraindicated in patients with hyperlipidemia, gout, and diabetes.


Preferred in patients with creatinine clearance >30 mL/min


hydrochlorothiazide (Microzide) 12.5-25 mg qd


Same as chlorthalidone


Same as chlorthalidone


Same as chlorthalidone


indapamide (Lozol) 1.25-5 mg qd


metolazone (Zaroxolyn) 2.5-5 mg qd


Same as chlorthalidone


Less or no hypercholesterolemia


Same as chlorthalidone


Same as chlorthalidone


LOOP DIURETICS


bumetanide (Bumex) 0.5-5 mg bid-tid


Dehydration, circulatory collapse, hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia, metabolic alkalosis, and hyperuricemia (short duration of action, no hypercalcemia)


High doses are relatively contraindicated in patients with hyperlipidemia, gout, and diabetes.


Effective in patients with creatinine clearance <30 mL/min


ethacrynic acid (Edecrin) 25-100 mg bid-tid


Same as bumetanide (only nonsulfonamide diuretic, ototoxicity)


Same as bumetanide


Same as bumetanide


furosemide (Lasix) 20-320 mg qd


Same as bumetanide


Same as bumetanide


Same as bumetanide


torsemide (Demadex) 5-20 mg qd


Short duration of action and no hypercalcemia


Same as bumetanide


Same as bumetanide


POTASSIUM-SPARING DIURETICS


amiloride (Midamor) 5-10 mg qd-bid


Hyperkalemia, GI disturbances, and rash


High doses are relatively contraindicated in patients with hyperlipidemia, gout, and diabetes.


Effective in patients with creatinine clearance <30 mL/min


spironolactone (Aldactone) 12.5-100 mg qd-bid**


eplerenone (Inspra) 50 mg qd to 50 mg bid**


Hyperkalemia, GI disturbances, rash, gynecomastia, hirsutism, and menstrual irregularities


Hyperkalemia, GI disturbances, rash, gynecomastia, hirsutism, and menstrual irregularities


Same as amiloride


Same as amiloride


Ideal in patients with heart failure; in GFR < 30, use is not recommended.


Not recommended in CrCl < 30 mL/min


triamterene (Dyrenium) 50-150 mg qd-bid


Hyperkalemia, GI disturbances, and nephrolithiasis


Same as amiloride


Effective in patients with creatinine clearance <30 mL/min


** Also known as an aldosterone receptor antagonist


Beta-Adrenergic Blocking Agents


SELECTED BETA-BLOCKERS


atenolol (Tenormin) 25-100 mg qd


Fatigue, depression, bradycardia, decreased exercise tolerance, congestive heart failure, aggravates peripheral arterial insufficiency, bronchospasm, masks signs and symptoms of hypoglycemia, Raynaud phenomenon, insomnia, vivid dreams or hallucinations, acute mental disorder, and impotence; sudden withdrawal can lead to exacerbation of angina and MI.


Contraindicated in first trimester of pregnancy and heart failure (except carvedilol, bisoprolol, and metoprolol succinate); relatively use in caution with patients with asthma (prefer low-dose cardioselective agents).


Abrupt cessation should be avoided; taper the dose of beta-blocker over a 2-wk period.


Advantageous in patients with angina, tachycardia, and acute MI; hypertensive patients with left ventricular hypertrophy


bisoprolol (Zebeta) 2.5-10 mg qd


Same as atenolol


Same as atenolol


Same as atenolol


metoprolol tartrate (Lopressor) 50-100 qd-bid


Same as atenolol


Same as atenolol


Same as atenolol


nadolol (Corgard) 40-120 mg qd


Same as atenolol


Same as atenolol


Same as atenolol


propranolol (Inderal, Inderal LA) 40-160 mg bid and 60-180 mg bid


Same as atenolol


Same as atenolol


Same as atenolol


metoprolol succinate (Toprol-XL) 50-100 mg qd-bid


Same as atenolol


Same as atenolol


Same as atenolol; one of the agents recommended for heart failure patients


pindolol (Visken) 10-40 mg bid


Same as atenolol, but with less resting bradycardia and lipid changes


Same as atenolol


Same as atenolol


acebutolol (Sectral) 200-600 mg bid


Same as atenolol, but with less resting bradycardia and lipid changes; positive antinuclear antibody test and occasional drug-induced lupus


Same as atenolol


Same as atenolol


ALPHA- AND BETA-BLOCKERS


carvedilol (Coreg) 12.5-50 mg bid


Similar to atenolol but more postural hypotension and bronchospasm


Same as atenolol


Same as atenolol; one of the agents recommended for heart failure patients


labetalol (Trandate) 200-800 mg bid


Hepatotoxicity


Same as atenolol


Same as atenolol; does not affect serum lipids


Angiotensin-Converting Enzyme (ACE) Inhibitors


SELECTED ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS


benazepril (Lotensin) 10-40 mg qd-bid


Common: cough; hypotension, particularly with a diuretic or volume depletion; hyperkalemia; rash; loss of taste; leukopenia; angioedema; neutropenia; and agranulocytosis in <1% of patients


Contraindicated in pregnancy; avoid in patients with bilateral renal artery stenosis or unilateral stenosis.


First line in hypertensive diabetic patients with proteinuria; congestive heart failure patients with systolic dysfunction


captopril (Capoten) 25-100 mg bid-tid


Same as benazepril; rash in 10% of patients; loss of taste


Same as benazepril


Same as benazepril


enalapril maleate (Vasotec) 2.5-40 mg qd-bid


Same as benazepril


Same as benazepril


Same as benazepril


fosinopril (Monopril) 10-40 mg qd


Same as benazepril


Same as benazepril


Same as benazepril


lisinopril (Prinivil, Zestril) 10-40 mg qd


Same as benazepril


Same as benazepril


Same as benazepril


moexipril (Univasc) 7.5-30 mg qd


Same as benazepril


Same as benazepril


Same as benazepril


quinapril (Accupril) 10-80 mg qd


Same as benazepril


Same as benazepril


Same as benazepril


ramipril (Altace) 2.5-20 mg qd


Same as benazepril


Same as benazepril


Same as benazepril


trandolapril (Mavik) 1-4 mg qd


Same as benazepril


Same as benazepril


Same as benazepril


Angiotensin II Receptor Blockers


*Selected agents are listed.


losartan (Cozaar) 25-100 mg qd-bid


Similar to ACE inhibitors but causes cough rarely; angioedema (very rare) and hyperkalemia


valsartan (Diovan) 80-320 mg qd


candesartan cilexetil (Atacand) 8-32 mg qd


irbesartan (Avapro) 150-300 mg qd


telmisartan (Micardis) 20-80 mg qd


eprosartan (Teveten) 400-800 mg qd-bid


olmesartan (Benicar) 20-40 mg qd


Calcium Channel Blocking Agents


*Selected agents are listed.


NONDIHYDROPYRIDINES


diltiazem HC1 (Cardizem SR, Cardizem CD, Dilacor XR, Tiazac) 180-420 mg qd and (Diltia XR) 120-480 mg qd


Dizziness, headache, edema, and constipation (especially verapamil); lupus-like rash with diltiazem; conduction defects, worsening of systolic dysfunction, and gingival hyperplasia (nausea, headache)


Avoid in patients with AV node dysfunction (second- or third-degree heart block) or left ventricular (systolic) dysfunction.


Swallow whole; do not chew, divide, or crush.


verapamil HC1 (Isoptin SR, Calan SR, Verelan) 120-480 mg qd


Constipation


Same as diltiazem


Swallow whole; do not chew, divide, or crush.


DIHYDROPYRIDINES


amlodipine (Norvasc) 2.5-10 mg qd


Dizziness, headache, rash, peripheral edema, flushing, headache, and gingival hypertrophy



Swallow whole; do not chew, divide, or crush. Elderly patients with isolated systolic hypertension


felodipine (Plendil) 2.5-20 mg qd


Same as amlodipine



Swallow whole; do not chew, divide, or crush.


isradipine (DynaCirc) 2.5-10 mg bid and (DynaCirc CR) 5-10 mg bid


Same as amlodipine



Swallow whole; do not chew, divide, or crush.


nicardipine (Cardene SR) 60-120 mg bid


Same as amlodipine



Swallow whole; do not chew, divide, or crush.


nifedipine (Procardia XL) 30-60 mg qd


Same as amlodipine



Swallow whole; do not chew, divide, or crush. Do not use sublingually.


nisoldipine (Sular) 10-40 mg qd


Same as amlodipine



Swallow whole; do not chew, divide, or crush.


Alpha-Blockers


doxazosin (Cardura) 1-16 mg qd


First-dose phenomenon, postural hypotension, lassitude, vivid dreams, depression, headache, palpitations, fluid retention, weakness, priapism, and drowsiness



Administer initially at bedtime; start with low dose and titrate slowly. Ideal for hypertensive patients with benign prostatic hypertrophy


prazosin (Minipress) 2-20 mg bid-tid


Same as doxazosin



Same as doxazosin


terazosin (Hytrin) 1-20 mg qd-bid


Same as doxazosin



Same as doxazosin


Central Agonists


clonidine (Catapres) 0.1-0.8 mg bid-tid


Sedation, dry mouth, bradycardia, withdrawal hypertension, bradycardia, and heart block


Avoid prescribing for noncompliant patients.


Do not stop therapy abruptly without consulting healthcare provider first.


transdermal (Catapres TTS) one patch weekly (0.1-0.3 mg/d)


guanabenz (Wytensin) 4-64 mg bid


Similar to clonidine


Similar to clonidine


Tolerance of alcohol may decrease.


guanfacine (Tenex) 0.5-2.0 mg qd


Similar to clonidine


Similar to clonidine


Take at bedtime.


methyldopa (Aldomet) 250-1000 mg bid


Drowsiness, sedation, fatigue, depression, dry mouth, orthostatic hypotension, bradycardia, heart block, and autoimmune disorders, including colitis; hepatitis and hemolytic anemia <1% of patients



Urine may darken after voiding when exposed to air.


Direct Vasodilators


hydralazine (Apresoline) 25-100 mg bid


Tachycardia, aggravation of angina, headache, dizziness, fluid retention, lupus-like syndrome, dermatitis, drug fever, hepatitis, and peripheral neuropathy



Beneficial use in black patients with heart failure


minoxidil (Loniten) 2.5-80 mg qd-bid


Tachycardia, aggravation of angina, dizziness, fluid retention, and hypertrichosis


Avoid in patients taking nitrates.


Restrict to patients with refractory hypertension.


Adrenergic Antagonists


guanadrel (Hylorel) 10-75 mg bid


Postural hypotension, exercise hypotension, diarrhea, weight gain, syncope, and retrograde ejaculation



Restrict to patients with refractory hypertension.


guanethidine (Ismelin) 10-50 mg qd


reserpine (Serpasil) 0.5-0.25-0.1 mg qd


Similar to guanadrel, but greater incidence of diarrhea


Nasal stuffiness, drowsiness, GI disturbances, bradycardia, and nightmares with high doses


Relatively contraindicated in depression


Maximal effect not seen for 2-4 wk. Avoid doses above 0.25 mg daily in patients with depression.

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Nov 11, 2018 | Posted by in PHARMACY | Comments Off on Hypertension

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