(Hypertension. 2001;37:e24.)
© 2001 American Heart Association, Inc.
Letter to the Editor |
Normalization of Blood Pressure in a Patient With Severe Orthostatic Hypotension and Supine Hypertension Using Clonidine
Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia
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To the Editor:
A 78-year-old woman presented to us with a 4-year
history of recurrent dizzy spells, which had increased in frequency
over past 12-months. Past medical history included hypertension and
glaucoma. Current medications were oral perindopril (an ACE
inhibitor), aspirin, and 3 eye drops—brimonidine (a
2-adrenergic agonist), betaxolol (a topical
ß1-adrenergic blocking agent), and latanoprost
(a selective prostanoid F2-receptor
agonist)—for glaucoma.
Cardiovascular examination revealed an aortic ejection systolic murmur; supine blood pressure was 180/100 mm Hg. There was no clinical evidence of autonomic dysfunction, parkinsonian features, or gross neurological abnormalities.
She had 4 presyncopal episodes over 5 days, with no arrhythmia on telemetry. She had mild aortic stenosis (peak and mean gradients of 19 and 11 mm Hg, respectively) and normal left ventricular function by echocardiography. Exercise stress test was negative. Tilt table test and routine blood pressure observations revealed significant postural hypotension (180/100 mm Hg supine to 120/90 mm Hg erect with no significant change in her heart rate).
Treatment with oral perindopril was stopped after 4 days
because of worsening of postural drop and continuing symptoms.
Brimonidine tartrate is a 2-adrenergic
agonist that is 1000 times more selective for
2-adrenoceptor than the
1-adrenergic receptor. Topical administration
of brimonidine tartrate decreases intraocular pressure with minimal
effects on cardiovascular parameters,
although bradycardia and hypotension are known to occur in neonates.
Caution is advised with concomitant use of sympathomimetic agents or
agonists or antagonists of adrenergic receptor because
brimonidine eye drops may reduce blood
pressure.1 Betaxolol
hydrochloride is a topical ß1-adrenergic
blocking agent that has been shown to have a minor effect on heart rate
and blood pressure in clinical studies; caution is advised in treating
patients with a history of cardiac failure or heart
block.1 Latanoprost is a
selective prostanoid F2-receptor agonist that
reduces intraocular pressure with no adverse effects on heart rate or
blood pressure.1 The
combination of brimonidine and betaxolol eye drops could have
contributed to her symptoms. Betaxolol eye drops were stopped with
little effect on her blood pressure. We could not stop both her eye
drops because of the fear of making her glaucoma worse. Thus, she
presented with a not uncommon but vexing problem of severe
supine hypertension with symptomatic postural hypotension.
The use of standard agents (eg, fludrocortisone or
midodrine2 3 4
for postural hypotension may have resulted in worsening of her
hypertension.
She was started on low-dose clonidine (50 µgm/d), with almost immediate and marked improvement in both her supine hypertension and postural hypotension and with cessation of presyncopal episodes within 24 hours. By 48 hours, there was virtually no postural drop in blood pressure with good control of hypertension (136/70 mm Hg), and she was symptom free. She was discharged home on clonidine therapy (50 µgm/d) and has remained well since.
Clonidine has a predominant central action on
2-adrenoceptors. This results in the
inhibition of bulbar sympathetic cardio-accelerator and sympathetic
vasoconstrictor centers and, thereby, a decrease in heart rate. There
is also an increase in baroreceptor activity that leads to reduction in
blood pressure. Additionally, it acts on peripheral
postsynaptic 2-adrenoceptors and also
stimulates peripheral
1-adrenergic receptors, leading to
vasoconstriction, increased venous return, and increased blood
pressure.
There are limited previous reports on its use in the treatment of orthostatic hypotension.5 6 Robertson et al5 tried higher doses (400 to 800 µgm) in 4 patients with severe idiopathic orthostatic hypotension with good results. They postulated that the predominance of the pressor response over the depressor effect may have been due to a reduction in sympathetic outflow in elderly patients, and low circulating catecholamine levels were documented. A combination of these 2 opposing effects may have led to the normalization of blood pressure in our patient.
We suggest that clonidine should be considered as a possible agent in the treatment of symptomatic idiopathic orthostatic hypotension concomitant with supine hypertension.
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References |
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1. E-MIMS. St Leonards, NSW, Australia: Havas MultiMedia International; 1996–2001. Updated February 2001.
2. Midodrine for orthostatic hypotension. The Medical Letter. 1997;39:59–60.
3.
Low PA, Gilden JL,
Freeman R. Efficacy of midodrine vs placebo in neurogenic
orthostatic hypotension: a randomized, double-blind
multicenter study. JAMA. 1997;277:1046–1051.
4.
Kaufman HD, Brannan
T, Krakoff L. Treatment of orthostatic hypotension due to
autonomic failure with a peripheral -adrenergic agonist
(midodrine). Neurology. 1988;38:951–956.
5. Robertson D, Goldberg MR, Hollister AS, Wade D, Robertson RM. Clonidine raises blood pressure in severe idiopathic orthostatic hypotension. Am J Med. 1983;74:2193–2200.
6. Gaffrey FA, Lane LB, Pettinger W, Blomqvist CG. Effects of long-term clonidine administration on the hemodynamic and neuroendocrine postural responses of patients with dysautonomia. Chest. 1983 Feb;83:436–238.
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