Management of hypertensive crises in the el(2)

Table 1. Pharmacokinetics of different medications used in the management of hypertensive crises in the (s)DosageOnsetHalf-life NitroglycerinActivation of guanylyl cyclase via NO5 to 200 μg/min2–5 min1–4 min NitroprussideActivation of guanylyl cyclase via NO0.3 to 10 mcg/kg/min< 2 min–2 min Nifedipine1st generation dihydropyridine calcium-channel blocker10 to 20 mg 3 times daily–20 min2.5–5 h Nicardipine1st generation dihydropyridine calcium-channel blocker5–25 mg/h5–15 min4–6 h Clevidipine3rd generation dihydropyridine calcium-channel blocker1–2 mg/h Increase every 10 min up to 16 mg/h2–4 min5–15 min LabetalolSelective α1-adrenergic receptor blocker and nonselective β-adrenergic blocker200–400 mg per o.s. every 2–3 h30–120 min2–6 h EsmololBeta1 receptor –1 mg/kg loading dose. 50–300 μg/kg/min infusion60 s20 min ClonidineAlpha2 adrenergic agonist and imidazoline I1 receptor agonist500 μg/kg in bolus and 25–300 μg/kg/min30 min12–16 h FenoldopamDopamine type-1 receptor –1.6 μg/Kg/ min5–10 min5 min HydralazineInhibition of calcium influx in vascular smooth muscle cells20 mg initial bolus; 20–80 mg repeat boluses5–15 min3 h

Regardless of the target BP, the pharmacological management must include agents that are titratable and easily reversible. The choice of the medications also depends on the patient’s comorbidities, availability, and end-organ involvement (Table 2).

Table 2. Specific indications and adverse effects of different drugs used in the management of acute hypertension in the IndicationsAdverse Effects NitroglycerinAcute coronary syndrome, pulmonary edema, volume overloadHeadache, vomiting reflex tachycardia and methemoglobinemia NitroprussideUse only in the elderly when other alternatives are not availableThiocyanate and cyanide intoxication, coronary steal syndrome NifedipineNot recommended in the elderly patientHypotension, coronary steal syndrome, reflex tachycardia NicardipineMost hypertensive crises as a potent vasodilatorHeadache, local phlebitis, vomiting ClevidipineMost hypertensive crisesHeadache, tachycardia, heart failure LabetalolAcute aortic dissectionHeart block and bronchoconstriction EsmololPost-operative hypertension, useful in increased cardiac output, easily titrationHeart block and heart failure ClonidineSevere hypertension associated with pain and anxietyRebound hypertension and sedative effects FenoldopamRenal arterial disease, glomerulonephritis or vascular diseases with impaired renal function, very usefulHeadache, tachycardia, nausea and exacerbation of glaucoma HydralazineNot recommended in elderly patientsReflex tachycardia and severe hypotension

In patients presenting with hypertensive urgencies, a less drastic approach can be considered. Some authors suggest a decrease of BP over a period of 24–48 hours with an oral short-acting agent, such as angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, followed by close monitoring of the patient for several hours.[1,21]

The following paragraphs describe some of the common agents used to treat this condition.

5 Common agents

5.1 Nitroglycerin

Nitroglycerin is a potent vasodilator prodrug that acts on Cyclic guanosine monophosphate (cGMP) via release of nitric oxide (NO).[27] The hypotensive effects are secondary to a decrease in the preload and cardiac output.[27–29] Based on the data from the Euro-STAT registry, nitroglycerin is the most commonly drug used for acute HTN in the intensive care unit.[30] This agent is available in different routes of administration including intravenous, oral, sublingual, and transdermal.[27] The onset action of nitroglycerin is 2–5 minutes, and it has a plasma half-life of 1–4 minutes with half-life of metabolites of 40 minu-tes.[27] It metabolizes via erythrocytes, hepatic, and vessels walls.[27] The recommended intravenous dose of nitroglyc-erin for the treatment of hypertensive crises is from 5 to 200 μg/min.[31] Tachyphylaxis is common. The most common adverse effects include headache, vomiting, reflex tachycardia and methemoglobinemia.[32] Nitroglycerin is particularly useful in clinical practice in acute coronary syndromes and pulmonary edema as an adjunctive agent.[1,4,16,33,34]

5.2 Sodium nitroprusside

Nitroprusside is a potent vasodilator that elicits its effects on both arteries and veins.[35] It is comprised of a ferrous ion center complexed with five cyanide moieties and a nitrosyl group. Once infused, it can interact with oxyhemoglobin, dissociating immediately and forming methemoglobin while releasing cyanide and NO.[35] Nitric oxide causes then vasodilation, and mediates the antihypertensive properties of the medication while cyanide can accumulate potentially to toxic levels.[36] For years, it used to be the gold standard; however, because the cyanide toxicity is so significant, the Food and Drug Administration placed a black box warning in 1991.[37] Nevertheless, this medication is still being used, although less than before.[35] In the STAT registry, nitroprusside was the 4th most commonly used drug (13%) in management of hypertensive crises with neurological manifestations.[38]

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