Management of hypertensive crises in the el(8)

Clevidipine had also achieved significant reduction in BP in patients with acute HTN when compared to placebo in the ESCAPE I & II trials.[56,57]When compared to nitroglycerin, nitroprusside, and nicardipine in ECLIPSE trial, it showed comparable safety profile to them, and a significant reduction in mortality.[40]Indeed, it was more effective than nitroglycerin (P =0.0006) and nitroprusside (P =0.003) in maintaining BP within the predetermined range.[40]This agent was as effective as nicardipine, in maintaining BP within a predetermined range.[40]The VELOCITY trial showed a rapid and effective reduction in BP, with a decrease of 6% of BP within three minutes, 15% within 9.5 minutes and a 27% reduction in BP 18 hours after infusion initiation.[58]Clevidipine does not induce a reflex increase in heart rate. It has coronary vasodilatory properties.[53]These anti ischemic properties make clevidipine one of the best options for elderly patients presenting with hypertensive crises.

5.6 Labetalol

Labetalol is a combined α1-adrenergic and β-adrenergic receptors blocker, with greater effect on β-receptors as compared to α-receptors.[1]Labetalol can be administered either as a bolus or continuous infusion.[59]It has negative chronotropic and inotropic effects, which made it one of the preferred agents in the management of hypertensive crises in acute aortic dissection.[16,23]Labetalol was compared with nicardipine in the CLUE trial; and results showed that nicardipine is more likely than labetalol to achieve target blood pressure within 30 minutes.[60]Reported side effects include hypotension, bradycardia nausea, vomiting, scalp tingling, and burning sensation in the groin.[61]In elderly, labetalol’s side effects are even more significant, mainly due to delayed clearance of the agent in elderly.[62]

5.7 Esmolol

Esmolol is an ultrashort cardioselective beta-blocker.[16]It is mainly used for post-operative HTN; and in combination with nicardipine or nitroglycerin to maintain hemodynamic stability in the perioperative period.[63]

Esmolol is well tolerated in patients with myocardial in-farction and patients with contraindications for other beta- blockers.[64]This agent is contraindicated in congestive heart failure, bradycardia, and chronic obstructive pulmonary disease.[32,64]In the authors’ experience, these contraindica-tions are relative.[34]Esmolol is particularly useful in situa-tions in which the cardiac output, BP, and heart rate are increased.[28]The onset of action is within 60 seconds, and the duration of action is upon 20 minutes.[16]The loading dose is 0.5–1 mg/kg over 1 minute, and the maintenance is infusion of 50 μg/kg/min.[28]The metabolism of esmolol is through hydrolysis of ester linkages by esterases of eryth-rocytes.[34]Esmolol is safe in elderly patients because it can be easily titrated.[65]

5.8 Clonidine

Clonidine was first used as a nasal decongestant, but be--cause of its other effects, such as hypotension, bradycardia, and sedation, is now used in other conditions.[66]This drug is an alpha2-adrenergic agonist (affinity 200:) and an agonist at the imidazoline receptors.[67]Its hypotensive effect is secondary to stimulation of the al-pha-adrenergic receptors in the vasomotor center of medulla oblongata, and a decrease in renin and aldosterone.[67]These effects are elicited within 30 minutes of oral administration, with peak plasma levels achieved within 2–4 hours, and half-life is 12 to 16 hours.[28,34,65]However, the antihyper-tensive effects may persist 24 hours or more.[68]Clonidine is almost completely absorbed after oral administration.[66]The metabolism of this agent is primarily by hepatic (-50%) and the excretion is 40%–60% in the urine, and 20% in feces.[69]Clonidine is used in severe HTN associated with pain and anxiety, due to its sedative-analgesic effects. Rapid with-drawal from this medication may cause rebound HTN.[28,34,65]This agent must be used with caution in the elderly, as con-fusion may be a significant side effect.[70]

5.9 Fenoldopam

Fenoldopam is a selective dopamine type-1 receptor agonist that works by increasing renal blood flow, improving renal function, and stimulating natriuresis.[71,72]This drug has an onset of action of 5–10 minutes with a half-life of five min.[73]It is rapidly metabolized by hepatic methylation without participation of cytochrome P450 enzymes, and the excretion is mostly by urine (90%).[65]Fenoldopam is preferred in hypertensive emergencies mediated by renal arterial disease, glomerulonephritis, or vascular diseases with impaired renal function.[23]Fenoldopam can be used also in hypertensive emergencies in perioperative situations.[32]Recommended dosage of this agent is 0.01–1.5 μg/kg/min and the titration is recommended by increase of 0.05–0.1 μg/kg/min every 15 min.[34]

Intravenous fenoldopam has no effect on the central nervous system, and does not cross the blood-brain barrier.[32]Due to its properties, it is considered a choice of treatment in elderly to reduce BP in severe HTN with acute kidney injury, heart failure, and in perioperative situations, specifi-cally in vascular surgery.[32]

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