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Table 4 Doses, pharmacokinetics, and pharmacodynamics of the intravenous antihypertensive agents most frequently used in intensive care units

From: Control of hypertension in the critically ill: a pathophysiological approach

Drugs Intravenous dose Onset/peak of action Half-life/duration of action Metabolism/excretion Main side effects Main clinical indications
Sympatholytic drugs       
β-blockers       
Propranolol (β1- and β2-receptor blocker) 1-3 mg every 2–5 min (over 1–30 min) Onset: 5 min Half-life: 3–5 h Metabolism: hepatic CYP450 Hypotension, heart failure, heart block, dizziness, fatigue, confusion, depression, bronchospasm, Raynaud´s phenomenon, diarrhea, pruritus, rash Cardiac ischemic syndromes with arterial hypertension and normal heart function. Avoid in pheochromocytoma crises
Max dose: 5 mg   Duration: 6–12 h Excretion: urine (96-99%)
Infusion: not recommended    
Metoprolol (selective β1-receptor blocker) 5 mg every 3 min (over 1–30 min) Onset: 5–10 min Half-life: 3–7 h Metabolism: hepatic CYP2D6 Hypotension, heart failure, heart block, dizziness, fatigue, depression, bronchospasm, diarrhea, pruritus, rash Cardiac ischemic syndromes with arterial hypertension and normal heart function
Max dose: 15 mg   Duration: 5–8 h Excretion: urine (5-10% unchanged)
Infusion: not recommended    
Labetalol (α1, β1, and β2-receptor blocker) Bolus: 20–80 mg every 10 min. Max dose: 300 mg Onset: 5–10 min Half-life: 6 h Metabolism: hepatic glucuronide conjugation Nausea, scalp tingling, bronchospasm, dizziness, heart block, orthostatic hypotension Most hypertensive emergencies, good for hypertension in neurocritically ill patients and pregnancy; caution in heart failure
Infusion: 0.5-2.0 mg/min Peak: 5–15 min Duration: 3–18 h Excretion: urine 50% (<5% unchanged), feces 50%
Esmolol (selective β1-receptor blocker) Bolus: 500 μ g/Kg (over 1 min) Onset: 1–2 min Half-life: 9 min Metabolism: plasma esterases Arterial hypotension, bronchospasm, heart block, heart failure Hypertensive emergencies with normal or high cardiac output, and aortic dissection in particular. Contraindicated in pheochromocytoma crisis
Max dose: 300 μg/Kg/min Peak: 6–10 min Duration: 10–30 min Excretion: urine 70-90% (<1% unchanged)
Infusion: 50–300 μg/Kg/min    
α-Adrenergic antagonists       
Phentolamine (peripheral α-receptor antagonist) Bolus: 5–20 mg Onset: 1–2 min Half-life: 19 min Metabolism: hepatic Tachycardia, flushing, headache, orthostatic hypotension, dizziness, nasal congestion, pulmonary hypertension Hypertensive emergencies associated with excessive catecholamine levels
Max dose: 15 mg Peak: 10–20 min Duration: 15–30 min Excretion: urine (10% unchanged)
Infusion: not recommended    
Urapidil (peripheral α1-receptor antagonist and central serotonin antagonist) Bolus: 12.5-25 mg Onset: 3–5 min Half-life: 2–4.8 h Metabolism: hepatic Headache, hypotension, dizziness Hypertensive emergencies in postoperative and pregnant patients
  Max dose: 50 mg Peak: 0.5-6 h Duration: 4–6 h Excretion: urine (15-20% unchanged), feces 10%   
Infusion: 5–40 mg/h    
Centrally acting agents       
Clonidine (central α2 receptor agonist) Bolus: not recommended Onset: 5–10 min Half-life: 12 h Metabolism: Hepatic CYP450 Eye and mouth dryness, sedation, erectile dysfunction, orthostatic hypotension, bradycardia, drowsiness. Hypertensive emergencies, particularly in the context of withdrawal syndrome and pain
Max dose: 7.2 μg/min (or 450 μg/2 h) Peak: 2–4 h Duration: 6–10 h Excretion: Urine (50% unchanged), feces/bile 20%
Infusion: 1.2-7.2 μg/min    
Methyldopa (central α2 receptor agonist) 250-1000 mg every 6-8h Onset: >1 h Half-life: 2 h Metabolism: Hepatic CYP450 and central adrenergic neurons Peripheral edema, fever, depression, sedation, dry mouth, bradycardia, hepatitis, hemolytic anemia, lupus-like syndrome Hypertensive emergencies, particularly in pregnant patients. Use limited by adverse effects
Max dose: 1000 mg every 6h Peak: 6–8 h Duration: 12–24 h Excretion: urine (85% metabolites), feces
Infusion: not recommended    
Dexmedetomidine (central α2receptor agonist) Bolus: 1 μg/Kg/min over 10 min (not necessary in sedated patients) Onset: 6–15 min Half-life: 2–2.5 h Metabolism: hepatic Hypotension, bradycardia, fever, nausea, vomiting, hypoxia, anemia Hypertensive urgencies associated with hyperactive delirium or withdrawal syndrome
Max dose: 1.5 μg/Kg/h Peak: 1 h Duration: 4 h Excretion: urine (metabolites)
Infusion: 0.2-0.7 μg/Kg/h    
Calcium channel blockers       
Nicardipine Bolus: not recommended Onset: 5–10 min Half-life: 2–4 h Metabolism: hepatic CYP3A4 Tachycardia, headache, flushing, peripheral edema, angina, nausea, AV block, dizziness Most hypertensive emergencies; caution in heart failure
Max dose: 30 mg/h Peak: 30 min Duration: 4–6 h Excretion: urine 60% (<1% unchanged), feces 35%
Infusion: 5–15 mg/h    
Clevidipine Bolus: not recommended Onset: 1–2 min Half-life: 1–15 min Metabolism: plasma and tissue esterases Atrial fibrillation, nausea, fever, insomnia, headache, acute renal failure All hypertensive emergencies, particularly postoperative hypertension
Max dose: 32 mg/h Peak: 3 min Duration: 5–15 min Excretion: urine 63-74%, feces 7-22%
Infusion: 1–2 mg/h    
Diltiazem Bolus: 0.25 mg/Kg (over 2 min) Onset: 2–7 min Half-life: 3.4 h Metabolism: hepatic CYP3A4 Bradycardia, AV block, hypotension, cardiac failure, peripheral edema, headache, constipation, hepatic toxicity Hypertensive emergencies associated with normal heart function and tachyarrhythmia
Max dose: 15 mg/h Peak: 7–10 min Duration:30 min-10 h (median 7 h) Excretion: bile, urine (2-4% unchanged)
Infusion: 5–15 mg/h (≤24 h)    
ACE inhibitor       
Enalaprilat Bolus: 1.25-5 mg every 6 h Onset: 15–30 min Half-life: 11 h Metabolism: hepatic biotransformation Hypotension, headache, worsening of renal function, hyperkalemia, angioedema, cough, agranulocytosis Hypertensive emergencies associated with left ventricular dysfunction; caution in hypovolemia
Max dose: 5 mg every 6 h Peak: 3–4.5 h Duration: 6–12 h Excretion: urine (60-80%)
Infusion: not recommended    
Arterial vasodilators       
Hydralazine (arteriolar vasodilator) Bolus: 10–20 mg every 4–6 h Onset: 5–20 min Half-life: 2–8 h Metabolism: Hepatic acetylation Hypotension, tachycardia, headache, facial flushing, angina pectoris, vomiting, paradoxical hypertension, lupus-like syndrome Hypertensive emergencies, especially severe hypertension in pregnancy
Max dose: 40 mg per dose Peak: 30–60 min Duration: 1–8 h Excretion: urine 52-90% (14% unchanged), feces 10%
Infusion: not recommended    
Fenoldopam (selective dopamine type 1-receptor agonist) Bolus: not recommended Onset: 5–10 min Half-life: 5 min Metabolism: Hepatic methylation Hypotension, tachycardia, headache, nausea, facial flushing, angina, ST-T wave changes, elevated intraocular pressure Hypertensive emergencies, especially severe hypertension in patients with acute renal failure
Max dose: 1.6 μg/Kg/min Peak: 15 min Duration:30–60 min Excretion: urine 90%, feces 10%.
Infusion: 0.05-1.6 μg/Kg/min    
Mixed arterial/venous vasodilators       
Nitroprusside (nitric oxide donor) Bolus: not recommended Onset: 1–2 min Half-life: <10 min (nitroprusside), 3 days (thiocyanate) Metabolism: erythrocytes, hepatic methylation Hypotension, tachycardia, headache, cyanide and thiocyanide intoxication, nausea, flushing, vomiting, muscle spasm, pulmonary shunt Hypertensive emergencies, especially aortic dissection. Caution in renal and hepatic failure
Max dose: 10 μg/Kg/min (<1 h) Peak: 15 min   Excretion: urine
Infusion: 0.25-4 μg/Kg/min   Duration: 1–10 min  
Nitroglycerin (nitric oxide donor with predominant venular action) Bolus: not recommended Onset: 2–5 min Half-life: 1–3 min Metabolism: erythrocytes, hepatic, vessel wall Hypotension, headache, dizziness, vomiting, tachyphylaxis, methemoglobinemia Hypertensive emergencies, especially those associated with acute coronary syndrome, volume overload, or pulmonary edema
Max dose: 300 μg/min Peak: 5 min Duration: 5–10 min Excretion: urine
Infusion: 5–300 μg/min    
Diuretics       
Furosemide (inhibits reabsorption of Na/Cl in the ascending loop of Henle) Bolus: 20–40 mg Onset: 5 min Half-life: 30–60 min Metabolism: hepatic Hypokalemia, hypovolemia, hypotension, metabolic alkalosis, ototoxicity, thrombocytopenia, pancreatitis, interstitial nephritis, hyperglycemia, hyperuricemia Hypertensive emergencies, especially those associated hypervolemia and/or heart failure
Max dose: 200 mg/dose or 160 mg/h Peak: 1–2 h Duration: 2 h Excretion: urine 88%, bile/feces 12%.
Infusion: 10–40 mg/h    
Bumetanide (inhibits reabsorption of Na/Cl in the ascending loop of Henle) Bolus: 0.5-1 mg/dose up to 2 times/day Onset: 2–3 min Half-life: 1–1.5 h Metabolism: hepatic Hypokalemia, hypovolemia, hypotension, metabolic alkalosis, ototoxicity, thrombocytopenia, pancreatitis, interstitial nephritis, hyperglycemia, hyperuricemia Hypertensive emergencies, especially those associated with hypervolemia and/or heart failure
Max dose: 10 mg/day Peak: 1–4 h Duration:4–6 h Excretion: urine 81%, bile 2%
  Infusion: 0.5-2 mg/h      
  1. ACE angiotensin-converting enzyme.