to be used, it is especially important to reduce doses in patients with volume
depletion, those who have recently used other antihypertensive drugs, and the
The acute response to oral clonidine loading is not predictive of the daily dose
required to maintain BP control. Maintenance oral therapy with clonidine is
somewhat empiric; however, total daily doses should be spread between 2 and 3
times daily dosing owing to the drug’s short half-life.
Adverse Effects and Precautions
CASE 16-1, QUESTION 4: What are the adverse effects and precautions that should be considered before
recommending the use of clonidine?
Oral clonidine is generally well tolerated. Adverse effects include orthostatic
hypotension, bradycardia, sedation, dry mouth, and dizziness. Clonidine can decrease
cerebral blood flow by up to 28%; it should not be used in patients with severe
41 Clonidine also should be avoided in patients with HF,
bradycardia, sick sinus syndrome, or cardiac conduction defects,
patients at risk of medication nonadherence because of the rebound hypertension.
CASE 16-1, QUESTION 5: M.M. has a history of HFpEF and normal renal function. Based on these
urea nitrogen or serum creatinine were elevated?
Captopril has been used both orally and sublingually to acutely lower BP.
Captopril decreases both afterload and preload, and lowers total peripheral vascular
23 For this reason, captopril and other ACE inhibitors are often considered
the drugs of choice in patients with HF with reduced ejection fraction as they have
been shown to reduce mortality in this patient population (see Chapter 14, Heart
Failure, for further discussion). M.M has HFpEF; the evidence of using ACE
inhibitors in improving cardiovascular outcomes in this patient population is not
strong. However, given that M.M. appeared to be well controlled on his enalapril
therapy before abruptly stopping his medications, it is reasonable to restart a rapid
ACE inhibitor and reinforce medication adherence issues.
After oral administration, the onset of action of captopril occurs within minutes
and peaks 30 to 90 minutes later.
46 Clinically, it reduces BP within 10 to 15 minutes,
with effects persisting for 2 to 6 hours. Sublingual captopril is as effective as
nifedipine but without reflex tachycardia in acutely reducing mean arterial pressure
in both urgent and emergent conditions.
Despite these beneficial effects, captopril, as well as long-acting ACE inhibitors,
must be used with caution in patients with renal insufficiency or volume depletion. In
most cases, an elevated blood urea nitrogen or serum creatinine will provide a clue
to the existence of these conditions; however, captopril can also induce renal failure
in patients with bilateral renal artery stenosis or renal artery stenosis in a solitary
kidney. Such conditions may not be easy to detect in the context of an acute
hypertensive emergency. Therefore, in patients in whom these conditions can be
excluded, captopril can be considered for therapy. First-dose hypotension is a
common limiting factor with captopril use. This complication is most likely to occur
in the elderly and in patients with high renin levels such as those who are volume
depleted or those receiving diuretics. Under these circumstances, initial doses should
not exceed 12.5 mg, with repeat doses an hour or more later if necessary. Therefore,
captopril would be a reasonable choice as initial therapy in M.M., which can later be
replaced by a longer-acting ACE inhibitor.
CASE 16-1, QUESTION 6: What other oral agents are used in the treatment of hypertensive urgency?
Minoxidil, a potent oral vasodilator, has been used successfully in the treatment of
49,50 An oral loading dose of 10 to 20 mg produces a maximal
BP response in 2 to 4 hours and can be followed by a dose of 5 to 20 mg every 4
hours if necessary. Unfortunately, its onset of action is slower than that of clonidine
or captopril. Another complicating factor is that
β-blockers and loop diuretics generally must be used concomitantly to counteract
minoxidil-induced reflex tachycardia and fluid retention.
should only be prescribed by those who have experience with prescribing this agent
and managing these adverse effects. These adverse effects make this agent a less than
ideal choice in M.M. because of his history of HF. Minoxidil should be used only in
patients presenting with hypertensive urgency who are not responding to other
antihypertensive therapies or who have previously been taking this agent.
Oral labetalol, a combined α- and β-receptor antagonist, is an alternative to oral
clonidine or captopril for the treatment of severe hypertension, but the most
appropriate dosing regimen remains to be determined.
mg may provide a sustained response for up to 4 hours.
hourly intervals to a maximum dose of 1,200 mg) was comparable to oral clonidine
in reducing mean arterial pressure.
54 An alternative regimen using 300 mg initially
followed by 100 mg at 2-hour intervals to a maximum of 500 mg was also successful
53 Other literature has reported that a single loading dose of
200 to 400 mg does not appear to be effective in achieving an adequate BP
55 Because labetalol can cause profound orthostatic hypotension, patients
should remain in the supine position and should be checked for orthostasis before
ambulation. In addition, labetalol should be avoided in patients with asthma,
bradycardia, or advanced heart block.
QUESTION 1: M.R., a 55-year-old African American man, presents to the emergency department with a 3-
narrowing and arteriovenous nicking without hemorrhages, exudates, or papilledema. No jugular venous
midclavicular line with no thrills or heaves. The rhythm is regular with an S3
noted. The remainder of M.R.’s examination is within normal limits.
Significant laboratory values include the following:
White blood cell count and differential, within normal limits
moderate cardiomegaly and bilateral fluffy infiltrates.
What aspects of M.R.’s history and physical examination are characteristic of an emergent need to
Hypertensive crisis occurs most often in African American men and in individuals
between the ages of 40 and 60. Furthermore, many patients who present with
hypertensive crisis have a recent history of discontinuing the use of their
13,15 as is the case with M.R. in Case 16-2 and M.M. in Case 16-1.
Recent-onset severe headache, nausea, and vomiting are consistent with central
nervous system signs of severe hypertension, as are the acute onset of angina
(substernal pain) and acute HF (shortness of breath, increased pulse and respiratory
, and chest radiographic findings of pulmonary edema). The
absence of signs of right-sided HF such as jugular venous distention or hepatomegaly
suggests an acute onset of HF caused by hypertension as opposed to a gradual
worsening of chronic HF. M.R.’s urinary sediment is relatively unimpressive at this
time, especially in light of his history, and his ocular complications are minimal.
M.R.’s presentation is considered hypertensive emergency because of the presence of
HF symptoms; M.R. should be admitted to the hospital as intravenous (IV)
antihypertensive therapy is warranted.
What alternatives to nitroprusside are available?
M.R.’s arterial pressure should be lowered with parenteral medications, which
have a rapid onset of action. Nitroprusside, fenoldopam, and IV nitroglycerin all
decrease total peripheral resistance rapidly with minimal effect on myocardial
oxygen consumption and heart rate. Of these agents, either nitroprusside or
fenoldopam would be preferred in patients with hypertension accompanied by
decompensated HF in the absence of MI. Parenteral nitroglycerin is similar to
nitroprusside except that it has a relatively greater effect on the venous circulation
and less effect on arterioles. It is most useful in patients presenting with angina
secondary to coronary insufficiency, ischemic heart disease, MI, or hypertension
after coronary bypass surgery (also see Case 16-3, Question 6). In addition,
nitroprusside and IV nitroglycerin may both decrease elevated left ventricular
diastolic pressures in patients presenting with hypertensive emergency. Although
nitroglycerin would be helpful for someone who is experiencing chest pain in the
setting of an MI, this patient is not having an acute coronary syndrome, which is
confirmed by negative troponins and electrocardiogram. Before considering
nitroprusside, it is important to consider the etiology of the chest pain. As described
above, the chest pain is likely due to acute-onset HF due to severe hypertension.
Based on the signs and symptoms, it is not likely to have been caused by ischemic
heart disease. In the setting of coronary ischemia, nitroglycerin has been shown to be
more beneficial than nitroprusside; however, this patient does not have evidence of
active coronary ischemia. Because the clinical presentation is more consistent with
is important to focus on reducing peripheral resistance and decreasing elevated
left ventricular diastolic pressures. Nitroprusside provides an advantage here
because it provides both arterial and venous vasodilation, allowing for further
reduction in peripheral resistance and left ventricular diastolic pressures.
Nitroglycerin has a relatively greater effect on venous circulation, especially at
lower doses. Thus, nitroprusside would be preferred in this patient.
Fenoldopam and nitroprusside are equally efficacious in acutely lowering BP.
Both medications have an immediate onset, are easily titratable, have a short duration
of action, and are relatively well tolerated.
60–63 Unlike nitroprusside, fenoldopam
does not cause cyanide or thiocyanate toxicity. However, fenoldopam is associated
with dose-related tachycardia and should be avoided in those with active coronary
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