Hypertension

Gary L. Schwartz, M.D.
Mayo Medical School

Sheldon G. Sheps, M.D.
Mayo Clinic

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Prehypertension

• SBP: 120–139 mm Hg
• DBP: 80–89 mm Hg

Essential Hypertension

• Stage 1
  • SBP: 140–159 mm Hg
  • DBP: 90–99 mm Hg
• Stage 2
  • SBP: ≥ 160 mm Hg
  • DBP: ≥ 100 mm Hg
• Age at onset: 40–60 yr
• Family history of hypertension
• BP at diagnosis: < 180/< 110 mm Hg
• Asymptomatic
• Normal history, physical exam, and routine laboratory studies (no target-organ damage) at time of diagnosis
• BP control achieved with lifestyle changes and 1 or 2 drugs
• BP control maintained once achieved in a compliant patient

Secondary Hypertension

• Age at onset: < 30 yr or > 50 yr
• BP: > 180/110 mm Hg at diagnosis
• Significant target-organ damage at diagnosis
• Hemorrhages and exudates on retinal examination
• Renal insufficiency
• Left ventricular hypertrophy
• Poor response to appropriate 3-drug therapy (which includes a diuretic)
• Accelerated or malignant hypertension
• Sudden worsening of hypertension at any age

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Differential Diagnosis

• Isolated clinic ("white-coat") hypertension
• Secondary hypertension

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Best Tests

Essential Hypertension

BP Measurement

• At least two clinic visits 1–2 mo apart (shorter period if initial BP is severely elevated) with two standardized readings at each visit averaging ≥ 140/90 mm Hg
• Patient self-measured BP ≥ 135/85 mm Hg
  • Elevated office BP with self-measured BP < 130/80 mm Hg identifies isolated clinic (white-coat) hypertension
• Ambulatory BP monitoring to distinguish sustained hypertension from isolated clinic (white-coat) hypertension and to assess the following:
  • Hypotension
  • Episodic hypertension
  • Masked hypertension
  • Suspected autonomic dysfunction in patients with postural hypotension

Lab Tests

• Identify CV risk factors
  • Cholesterol (LDL and HDL)
  • Triglycerides
  • Fasting blood glucose
• Identify target-organ injury
  • Chest x-ray
  • ECG
  • Urinalysis
  • Serum creatinine or BUN
  • Uric acid
• Potassium
• Calcium
• Urinalysis
• If initial assessment suggests renal dysfunction, evaluate for chronic kidney disease by measuring 24-hour urinary protein excretion and estimating glomerular filtration rate (GFR):
  • GFR = (140 – age in yr) × (weight in kg) × 0.85 (if patient is female)/72 × serum creatinine (mg/dl)

Screening Tests for Secondary Hypertension (Sensitivity/Specificity)

Renovascular Hypertension

• Captopril radionuclide renal scan (75% sens./85% spec.)
  • Advantage: no contrast exposure
  • Disadvantages: renal dysfunction impairs interpretation; may miss bilateral, accessory-, or branch-vessel disease
• Duplex ultrasound (80%–90% sens./90% spec.)
  • Advantages: no contrast or radiation exposure; renal dysfunction does not impair interpretation; calculation of resistive index identifies subset of patients with renal dysfunction likely to benefit from intervention (RI < 0.80)
  • Disadvantages: failure to visualize both renal arteries (15%–20% of cases); may miss accessory- or branch-vessel disease
• Spiral CT angiography
  • Advantages: excellent images of renal arteries; can identify dissection, accessory vessels, and fibromuscular disease
  • Disadvantages: considerable contrast load precludes use in presence of renal dysfunction; expensive
• Magnetic resonance angiography (85%–100% sens./79%–98% spec.)
  • Advantages: no contrast or radiation exposure; renal dysfunction does not impair interpretation
  • Disadvantages: cost; may overstate degree of stenosis; claustrophobic patients may not tolerate test
• Renal angiography: gold standard
  • Advantages: identifies accessory- and branch-vessel disease; percutaneous interventions can be performed as part of study
  • Disadvantages: cost; contrast exposure; invasive (atheroemboli)

Primary Aldosteronism

• Measurement of serum sodium, potassium, plasma renin activity (PRA), and plasma aldosterone concentration (PAC)
• 24-hr urinary aldosterone, sodium, and PRA after 3 days of a 200 mEq–sodium diet
• Screening: ratio of PAC/PRA > 20
  • Diagnosis confirmed if U_Na > 200 mEq, U_aldo > 12, and PRA < 1.0 after 3 days of high-sodium diet
  • Advantage: 30% of patients with primary aldosteronism are normokalemic at presentation; ratio is easy to obtain
  • Disadvantages: many antihypertensive drugs can influence values of PRA and PAC; sensitivity and specificity of ratio not established

Pheochromocytoma

• Plasma-free metanephrines (99% sens./89% spec.)
  • 24-hr fractionated urinary metanephrines (77% sens./93% spec.)
  • Use plasma test if degree of suspicion is high or familial syndrome is suspected

Cushing Syndrome

• 24-hr urinary free cortisol (95%–100% sens./97%–100% spec.)
  • Diagnosis certain if 24-hr urinary free cortisol level > 3 times normal
  • Diagnosis excluded if level normal
  • Use low-dose dexamethasone suppression test if elevation < 3 times normal

Coarctation of the Aorta

• Chest x-ray; transesophageal echocardiogram
• CT or MRI of the aorta
• Diagnostic findings on chest x-ray
  • "3" sign from dilation of aorta above and below the coarctation
  • Rib notching from collateral vessels

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Best Therapy

Prehypertension

• Monitor BP annually
• Lifestyle adjustments to lower BP and CV risk and prevent progression to hypertension
• In patients with diabetes or renal disease, treat with lifestyle adjustments and antihypertensive drugs if systolic BP > 130 mm Hg or diastolic BP > 80 mm Hg

Essential Hypertension: Risk Stratification and Initial Treatment in Hypertensive Patients by Blood Pressure Stage (mm Hg)

Risk Group A (No CV Risk Factors, No Target-Organ Disease or Clinical Cardiovascular Disease)

• Prehypertension (120–139/80–89): lifestyle modification
• Stage 1 (140–159/90–99): lifestyle modification (up to 12 mo)
• Stage 2: (≥ 160/≥ 100): lifestyle modification + drug therapy

Risk Group B (≥ 1 CV Risk Factor, Not Including Diabetes; No Target-Organ Disease or Clinical Cardiovascular Disease)

• Prehypertension (120–139/80–89): lifestyle modification
• Stage 1 (140–159/90–99): lifestyle modification (up to 6 mo); consider adding drugs initially
• Stage 2: (≥ 160/≥ 100): lifestyle modification + drug therapy

Risk Group C (Target-Organ Disease or Clinical Cardiovascular Disease and/or Diabetes ± Other CV Risk Factors)

• Prehypertension (120–139/80–89)
  • Lifestyle modification
  • Drug therapy: use drugs if SBP > 130 or if DBP > 80 and patient has heart failure, chronic kidney disease, or diabetes
• Stage 1 (140–159/90–99): lifestyle modification + drug therapy
• Stage 2: (≥ 160/≥ 100): lifestyle modification + drug therapy
• Treatment goals
  • Reduce risk of CV morbidity and mortality
  • Lower BP to < 140/90; lower to < 130/80 in patients with heart failure, diabetes, renal disease; lower to < 140 mm Hg in older patients with isolated systolic hypertension
• Coexisting CVD risk factors should be addressed
• Consider low-dose aspirin once BP is controlled
• Encourage self-measurement of BP

Treatment for Patients with Essential Hypertension

• Continue lifestyle modifications
• Start with lowest recommended dose of a once-daily drug
  • Combination drug therapy is appropriate if BP > 20/10 above goal
  • Thiazide diuretic + one of the following as second agent: beta blocker; ACE inhibitor; angiotensin receptor blocker; calcium antagonist
  • If no response or significant side effects at 2–4 wk, substitute another drug from a different class
  • If partial response at 2–4 wk and drug is well tolerated, increase dose of initial drug or add agent from a different class (diuretic if not chosen initially)
  • If not at goal BP in 2–4 more wk, continue titrating doses and adding agents from other classes at regular follow-up visits
  • If patient on three drugs and goal BP not reached, review considerations for resistant hypertension; consider referral to hypertension specialist

Lifestyle Modification

• Weight reduction if overweight
• Reduce sodium intake to ≤ 100 mmol/day: 2.4 g sodium, 6 g salt
• Increase aerobic exercise: 30–45 min/day
• Limit alcohol intake to ≤ 1 oz/day
• Maintain adequate intake of potassium: 90 mmol/day
• Eat a diet rich in fruits, vegetables, and low-fat dairy products but reduced in saturated and total fat
• Discontinue tobacco use (reduce CVD risk)

Pharmacologic Therapy

• Thiazide diuretics are initial drugs of choice for most patients with uncomplicated hypertension
• Common comorbid conditions may dictate choice
• Long-acting agents preferable because compliance and consistency of BP control are superior with once-a-day dosing
• When monotherapy is unsuccessful, add second agent of a different class
• Initiate treatment with combination therapy (two drugs) if BP > 20/10 above goal
• Include a diuretic appropriate for level of renal function
• Refractory/resistant hypertension: consider the following: noncompliance, interfering substances, inappropriate regimens, office hypertension, secondary hypertension

Diuretics

• General side effects of diuretics: hyponatremia; hypokalemia; hypomagnesemia; hyperglycemia; hypercalcemia (decrease in urinary calcium excretion); hyperuricemia; increase in triglycerides and cholesterol; decrease in lithium secretion
• Contraindications: diuretics should be avoided in pregnancy and in patients with gout
• Hydrochlorothiazide (HCTZ)
  • First choice in uncomplicated hypertension and isolated systolic hypertension
  • Initial dose: 12.5 mg/day; range: 12.5–50 mg/day; cost/mo: $9
• Chlorthalidone
  • First choice in uncomplicated hypertension and isolated systolic hypertension
  • Initial dose: 12.5 mg/day; range: 12.5–25 mg/day; cost/mo: $9
• Indapamide
  • Use in presence of renal insufficiency
  • Initial dose: 1.25 mg/day; range: 1.25–5.0 mg/day; cost/mo: $16
• Metolazone
  • Use in presence of renal insufficiency
  • Initial dose: 1.25 mg/day; range: 1.25–5.0 mg/day; cost/mo: $66
• Furosemide
  • Alternate diuretic in renal insufficiency
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 20 mg/day; range: 20–320 mg/day; cost/mo: $11
• Bumetanide
  • Alternate diuretic in renal insufficiency
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 0.5 mg/day; range: 0.5–5.0 mg/day; cost/mo: $37
• Ethacrynic acid
  • Alternate diuretic in renal insufficiency or sulfa-based diuretic allergy
  • Only non–sulfa-based diuretic
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 25 mg/day; range: 25–100 mg/day; cost/mo: not available
• Torsemide
  • Alternate diuretic in renal insufficiency
  • Long-acting loop diuretic
  • Side effects: same as other diuretics but increases urinary calcium excretion
  • Initial dose: 5 mg/day; range: 5–20 mg/day; cost/mo: $23
• Spironolactone (also available combined with HCTZ)
  • Potassium sparing
  • Aldosterone antagonist
  • Avoid in renal insufficiency
  • Specific side effects: hyperkalemia, hyponatremia, painful gynecomastia, menstrual irregularities
  • Initial dose: 25 mg/day; range 25–100 mg/day; cost/mo: $40
• Eplerenone
  • Potassium sparing
  • Aldosterone antagonist
  • Fewer antiandrogen side effects than spironolactone
  • Avoid in renal insufficiency
  • Specific side effects: hyperkalemia, hyponatremia
  • Reduce dose by half if patient is on verapamil
  • Initial dose: 50 mg/day; range: 50–100 mg/day; cost/mo: $108
• Triamterene (also available combined with HCTZ)
  • Potassium sparing
  • Usually used for prevention of diuretic-induced hypokalemia
  • Specific side effects: hyperkalemia, nephrolithiasis
  • Initial dose: 50 mg/day; range: 50–150 mg/day; cost/mo: $18
• Amiloride (also available combined with HCTZ)
  • Potassium sparing
  • Usually used for prevention of diuretic-induced hypokalemia
  • Specific side effect: hyperkalemia
  • Initial dose: 5 mg/day; range: 5–10 mg/day; cost/mo: $36

Calcium Antagonists (Alternative First-Line Drugs)

• General side effects of calcium antagonists: headache, edema, gingival hyperplasia
• Diltiazem extended-release (many versions available)
  • Additional side effects: constipation, AV block, bradycardia, heart failure
  • Initial dose: 120 mg/day; range: 120–480 mg/day; cost/mo: $34
• Verapamil extended-release (many versions available)
  • Additional side effects: constipation, AV block, bradycardia, heart failure
  • Initial dose: 120 mg/day; range: 120–480 mg/day; cost/mo: $26
• Nifedipine extended-release
  • Additional side effects: flushing, tachycardia
  • Initial dose: 30 mg/day; range: 30–120 mg/day; cost/mo: $66
• Amlodipine
  • Additional side effects: flushing, tachycardia
  • Initial dose: 2.5 mg/day; range: 2.5–10 mg/day; cost/mo: $61
• Nicardipine extended-release
  • Additional side effects: flushing, tachycardia
  • Initial dose: 60 mg/day; range: 60–120 mg/day; cost/mo: $98
• Felodipine
  • Additional side effects: flushing, tachycardia
  • Initial dose: 2.5 mg/day; range: 2.5–10 mg/day; cost/mo: $60
• Isradipine extended-release
  • Additional side effects: flushing, tachycardia
  • Initial dose: 5 mg/day; range: 5–10 mg/day; cost/mo: $67
• Nisoldipine
  • Additional side effects: flushing, tachycardia
  • Initial dose: 10 mg/day; range: 10–60 mg/day; cost/mo: $96

• General side effects of beta blockers: fatigue; bradycardia; reduced exercise tolerance; bronchospasm; vivid dreams; reduction in HDL cholesterol; increase in triglycerides; insomnia; mask symptoms and delay recovery from hypoglycemia in diabetics
• Propranolol
  • Initial dose: 40 mg/day; range: 40–240 mg/day; cost/mo: $19
• Propranolol extended release
  • Initial dose: 60 mg/day; range: 60–240 mg/day; cost/mo: $112
• Metoprolol (fumarate)
  • Initial dose: 50 mg/day; range: 50–200 mg/day; cost/mo: $14
• Metoprolol (succinate)
  • Initial dose: 50 mg/day; range: 50–400 mg/day; cost/mo: $118
• Atenolol
  • Initial dose: 25 mg/day; range: 25–100 mg/day; cost/mo: $11
• Bisoprolol
  • Initial dose: 5 mg/day; range: 5–20 mg/day; cost/mo: $68
• Nadolol
  • Initial dose: 20 mg/day; range: 20–320 mg/day; cost/mo: $55
• Timolol
  • Initial dose: 10 mg/day; range: 10–40 mg/day; cost/mo: $32
• Acebutolol
  • Additional side effects: intrinsic sympathomimetic activity, resulting in less bradycardia and lipid changes
  • Associated with positive ANA and drug-induced lupus
  • Initial dose: 200 mg/day; range: 200–1,200 mg/day; cost/mo: $58
• Pindolol
  • Additional side effects: intrinsic sympathomimetic activity, resulting in less bradycardia and lipid changes
  • Initial dose: 10 mg/day; range: 10–60 mg/day; cost/mo: $38
• Labetalol
  • Alpha₁-blocking activity
  • Additional side effects: orthostatic hypotension, hepatotoxicity
  • Initial dose: 200 mg/day; range: 200–1,200 mg/day; cost/mo: $78
• Carvedilol
  • Alpha₁-blocking activity
  • Additional side effects: orthostatic hypotension, hepatotoxicity
  • Initial dose: 12.5 mg/day; range: 12.5–50 mg/day; cost/mo: $95

• General side effects of ACE inhibitors: cough; angioedema; hyperkalemia; acute renal failure if there is bilateral renal artery stenosis
• Contraindicated in pregnancy
• Captopril
  • Additional side effects: taste disturbance; leukopenia; proteinuria with membranous glomerular lesion secondary to sulfhydryl group
  • Only sulfa-based ACE inhibitor
  • Initial dose: 12.5 mg/day; range: 12.5–100 mg/day; cost/mo: $9
• Enalapril
  • Initial dose: 2.5 mg/day; range: 2.5–40 mg/day; cost/mo: $22
• Lisinopril
  • Initial dose: 5 mg/day; range: 5–40 mg/day; cost/mo: $25
• Benazepril
  • Initial dose: 10 mg/day; range: 10–80 mg/day; cost/mo: $24
• Fosinopril
  • Initial dose: 10 mg/day; range: 10–40 mg/day; cost/mo: $30
• Moexipril
  • Initial dose: 7.5 mg/day; range: 7.5–30 mg/day; cost/mo: $46
• Perindopril
  • Initial dose: 4 mg/day; range: 4–8 mg/day; cost/mo: $49
• Quinapril
  • Initial dose: 5 mg/day; range: 5–80 mg/day; cost/mo: $72
• Ramipril
  • Initial dose: 1.25 mg/day; range: 1.25–20 mg/day; cost/mo: $93
• Trandolapril
  • Initial dose: 1 mg/day; range: 1–4 mg/day; cost/mo: $30

• General side effects of angiotensin II receptor antagonists: renal dysfunction (particularly in heart failure); angioedema (rare)
• These drugs do not cause cough
• Losartan
  • Initial dose: 25 mg/day; range: 25–100 mg/day; cost/mo: $58
• Valsartan
  • Initial dose: 80 mg/day; range: 80–320 mg/day; cost/mo: $63
• Irbesartan
  • Initial dose: 150 mg/day; range: 150–300 mg/day; cost/mo: $53
• Candesartan
  • Initial dose: 8 mg/day; range: 8–32 mg/day; cost/mo: $56
• Eprosartan
  • Initial dose: 400 mg/day; range: 400–800 mg/day; cost/mo: $61
• Telmisartan
  • Initial dose: 40 mg/day; range: 40–80 mg/day; cost/mo: $46
• Olmesartan
  • Initial dose: 20 mg/day; range: 20–40 mg/day; cost/mo: $43

• General side effects of alpha₁ blockers: orthostatic hypotension; edema; syncope with first dose (take at bedtime)
• Prazosin
  • Initial dose: 1 mg/day; range: 1–20 mg/day; cost/mo: $52
• Doxazosin
  • Initial dose: 1 mg/day; range: 1–16 mg/day; cost/mo: $48
• Terazosin
  • Initial dose: 1 mg/day; range: 1–20 mg/day; cost/mo: $28

• General side effects of central alpha-adrenergic agonists: sedation, fatigue, dry mouth, bradycardia, heart block, fluid retention, rebound hypertension with sudden discontinuance
• Clonidine
  • Initial dose: 0.1 mg/day; range: 0.1–0.6 mg/day; cost/mo: $12
• Clonidine transdermal patch
  • Rebound HTN less likely than with oral form
  • Additional side effect: contact dermatitis from patch
  • Initial dose: 0.1 mg/day; range, 0.1–0.3 mg/day; cost/mo: $121
• Methyldopa
  • Additional side effects: can cause hepatitis, Coombs-positive hemolytic anemia, lupuslike syndrome, blood dyscrasias
  • Initial dose: 250 mg/day; range: 250–2,000 mg/day; cost/mo: $25
• Guanfacine
  • When taken at bedtime, lessens sedation side effect; cost/mo: $61
• Guanabenz
  • Initial dose: 4 mg/day; range: 4–64 mg/day; cost/mo: $362

• General side effects of direct vasodilators: headache, fluid retention
• Hydralazine
  • Additional side effects: flushing, tachycardia, nasal congestion, hepatitis, lupuslike syndrome
  • Initial dose: 40 mg/day; range: 40–200 mg/day; cost/mo: $11
• Minoxidil
  • Use for resistant HTN
  • Additional side effects: tachycardia; significant fluid retention requiring loop diuretic for control; pericardial effusion; hair growth
  • Initial dose: 2.5 mg/day; range: 2.5–40 mg/day; cost/mo: $72

• No comorbid conditions: thiazide diuretics
• Isolated systolic hypertension (elderly patients): thiazide diuretics (preferred) (compelling indication [CI]); calcium antagonists (dihydropyridine [DHP]) (CI)
• Angina: beta blockers (CI); calcium antagonists (non–short-acting DHP) (specific indication [SI])
• Angina with diabetes or LV dysfunction: ACE inhibitors (SI) (in addition to beta blockers and calcium antagonists)
• Atrial fibrillation: beta blockers (CI); calcium antagonists (diltiazem, verapamil) (CI, SI)
• Cough with ACE inhibitors: ARBs (CI)
• Type 1 diabetes mellitus with proteinuria: ACE inhibitors (CI); calcium antagonists (non-DHP); diuretics; beta blockers (SI)
• Type 2 diabetes mellitus with proteinuria: angiotensin II receptor blockers (ARBs) (CI, SI); calcium antagonists (non-DHP) (SI); diuretics (SI); beta blockers (SI)
• Essential tremor: noncardioselective beta blockers (SI)
• Heart failure, LV dysfunction: ACE inhibitors; beta blockers; diuretics; aldosterone antagonists (CI); ARBs (SI)
  • Generally, an ACE inhibitor is first choice, ± a beta blocker in asymptomatic patients
  • Diuretic used to treat congestion
  • Aldosterone antagonist used only in advanced disease in combination with other agents (creatinine < 2.5 mg/dl and serum potassium < 5.0 mg/dl)
  • ARB should not be used in patients on ACE inhibitor and beta blocker
• Patient at high risk for CV disease or type 2 diabetes: ACE inhibitor (SI)
• Hyperlipidemia: alpha blockers (not considered first-line therapy) (SI)
• Intolerance to other antihypertensive drugs: ARBs (SI)
• Left ventricular hypertrophy (by ECG): ARBs (SI)
• Migraine: noncardioselective beta blockers (SI); calcium antagonists (verapamil) (SI)
• Myocardial infarction: beta blocker (without intrinsic sympathomimetic activity) most often drug of choice, with ACE inhibitor added if LV function impaired (CI); aldosterone antagonist can be added to standard therapy in patients with LV dysfunction (CI); diltiazem (non–Q wave infarction; avoid if heart failure) (SI); verapamil (avoid if heart failure) (SI)
• Osteoporosis: thiazide diuretics (SI)
• Peripheral vascular disease: calcium antagonists (SI)
• Preoperative hypertension if at increased CV risk: beta blockers (SI)
• Previous stroke: diuretic + ACE inhibitor (CI)
  • ACE inhibitor as monotherapy had no effect on BP or outcome; benefit noted only with combination that lowered BP
• Prostatism: alpha blockers (not considered first-line therapy) (SI)
• Renal insufficiency with proteinuria from any cause: ACE inhibitors; ARBs; calcium antagonists (non-DHP) (SI)

• Acute, severe elevation in BP, with DBP often > 130 mm Hg
• Retinal hemorrhages, exudates, and papilledema
• Encephalopathy (headache, confusion, somnolence, stupor, visual loss, focal neurologic deficits, seizure, or coma)
• Oliguria and azotemia
• Nausea, vomiting, dyspnea
• Physical findings of heart failure

• Hospitalize patient in ICU
• Begin parenteral therapy to lower mean BP by 20% in the first hour (DPB should be reduced to 100–110 mm Hg)
• If patient stable, reduce BP further over the next 24 hr; oral therapy can be started, and parenteral therapy gradually discontinued
• Monitor patient for evidence of worsening cerebral, renal, or cardiac function
• Once the patient is stabilized, evaluate for causes of secondary hypertension

• Sodium nitroprusside
  • General drug of choice
  • Produces direct arteriolar and venous dilation
  • Immediate onset and offset
  • Side effects: metabolic acidosis, nausea, vomiting, agitation, psychosis, tremor (monitor thiocyanate levels)
  • Dose: 0.25–10.0 µg/kg/min I.V. infusion
• Labetalol
  • Combination alpha/beta blocker
  • Onset 5–10 min, offset 3–6 hr
  • Useful in most settings, especially postoperative state, hypertensive crisis of pregnancy
  • Avoid in acute heart failure
  • Take beta-blocker precautions
  • Side effects: scalp tingling, vomiting, heart block, orthostatic hypotension
  • Dose: repetitive I.V. boluses of 20–80 mg q. 10 min or constant infusion of 0.5–2.0 mg/min
• Glyceryl trinitrate
  • Produces direct arteriolar and venous dilation
  • Onset 5–10 min, offset 3–5 min
  • Especially useful in acute coronary ischemia, CHF
  • Tolerance with prolonged infusion
  • Side effects: headache, flushing, nausea, methemoglobinemia
  • Dose: 5–100 µg/min I.V. infusion
• Esmolol
  • Cardioselective beta blocker
  • Onset 1–2 min, offset 10–20 min
  • Especially useful in postoperative state, aortic dissection, ischemic heart disease
  • Take beta-blocker precautions
  • Side effects: bradycardia, nausea
  • Dose: 50–300 µg/kg/min I.V.
• Hydralazine
  • Causes direct arteriolar vasodilation
  • Onset 10–20 min, offset 3–8 hr
  • Used primarily for hypertensive crisis of pregnancy
  • Avoid in acute MI, angina, aortic dissection
  • Side effects: headache, flushing, nausea, vomiting, tachycardia, angina
  • Dose: 10–20 mg I.V. bolus
• Enalapril
  • ACE inhibitor
  • Onset 15 min, offset 6 hr
  • Especially useful in acute heart failure in postoperative state
  • Lower doses in renal disease
  • Side effects: precipitous decline in BP (high-renin states), acute renal failure (presence of renal vascular disease)
  • Dose: 1.25–5 mg I.V. bolus, q. 6 hr
• Nicardipine
  • Dihydropyridine calcium antagonist
  • Onset 5–10 min, offset 1–4 hr
  • Especially useful in postoperative state
  • Avoid in acute heart failure
  • Side effects: headache, nausea, flushing, phlebitis
  • Dose: 5–15 mg/hr I.V. infusion
• Fenoldopam
  • Dopamine (DA1) agonist
  • Onset 5 min, offset 30–60 min
  • Especially useful in patients with impaired renal function
  • Side effects: nausea, vomiting, headache, flushing
  • Dose: 0.1–1.6 µg/kg/min I.V. infusion
• Phentolamine
  • Alpha blocker
  • Onset instantaneous, offset 3–10 min
  • Drug of choice for pheochromocytoma crisis
  • Side effects: flushing, tachycardia
  • Dose: 5–15 mg I.V. bolus
• Trimethaphan
  • Ganglionic blocker
  • Onset 1–5 min, offset 10 min
  • Tachyphylaxis common with prolonged infusion
  • Side effects: urinary retention, paralytic ileus, dry mouth, blurred vision, orthostatic hypotension
  • Dose: 0.5–15 mg/min I.V. infusion

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Best References

Chobanian A, et al: Hypertension 42:1206, 2003 [PMID 14656957]

European Society of Hypertension – European Society of Cardiology Guidelines Committee: J Hypertens 21:1011, 2003 [PMID 12777938]

Williams B, et al: J Hum Hypertens 18:139, 2004 [PMID 14973512]

July 2006