Document Detail


Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure.
MedLine Citation:
PMID:  20837887     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Orthostatic hypotension affects patients with autonomic failure producing considerable disability because of presyncopal symptoms. Severely affected patients may have residual sympathetic tone that can be engaged to increase blood pressure (BP) with the α-2 adrenergic antagonist yohimbine. This medication activates sympathetic outflow centrally and unrestrains norepinephrine release from noradrenergic neurons. Alternatively, the acetylcholinesterase inhibitor, pyridostigmine, can increase sympathetic tone by improving ganglionic cholinergic neurotransmission. Our purpose was to compare these complementary approaches and to explore whether the combination would lead to synergistic increases in BP. We compared the effects of 60 mg of pyridostigmine and 5.4 mg of yohimbine in a single-blind, randomized, placebo-controlled, crossover fashion. In a subset of patients we tested the combination of pyridostigmine and yohimbine. Our primary outcome was the change in standing diastolic BP 60 minutes after drug administration from baseline. We studied a total of 31 patients with severe autonomic failure. Yohimbine significantly improved standing diastolic BP as compared with placebo (11±3 mm Hg [95% CI: 6 to 16 mm Hg]; P<0.001). On the contrary, pyridostigmine did not increase the standing diastolic BP (0.6±3 mm Hg [95% CI: -5 to 5 mm Hg]; P=0.823). Only yohimbine showed a significant improvement in presyncopal symptoms. Sixteen patients received the combination of pyridostigmine and yohimbine, but no evidence of synergistic pressor effect was found. Engaging residual sympathetic tone with yohimbine is a more effective approach to improve orthostatic hypotension as compared with pyridostigmine in patients with severe orthostatic hypotension.
Authors:
Cyndya Shibao; Luis E Okamoto; Alfredo Gamboa; Chang Yu; Andre' Diedrich; Satish R Raj; David Robertson; Italo Biaggioni
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2010-09-13
Journal Detail:
Title:  Hypertension     Volume:  56     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-21     Completed Date:  2010-11-10     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  847-51     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00223691
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Antagonists / therapeutic use
Aged
Analysis of Variance
Blood Pressure / drug effects*
Cholinesterase Inhibitors / therapeutic use
Cross-Over Studies
Female
Heart Rate / drug effects
Humans
Hypotension, Orthostatic / complications,  drug therapy*,  physiopathology
Male
Middle Aged
Pure Autonomic Failure / complications*,  physiopathology
Pyridostigmine Bromide / therapeutic use*
Single-Blind Method
Yohimbine / therapeutic use*
Grant Support
ID/Acronym/Agency:
KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; KL2-RR024977/RR/NCRR NIH HHS; P01 HL056693/HL/NHLBI NIH HHS; P01 HL56693/HL/NHLBI NIH HHS; R01 NS055670/NS/NINDS NIH HHS; R01 NS055670/NS/NINDS NIH HHS; TL1 RR024978/RR/NCRR NIH HHS; TL1 TR000447/TR/NCATS NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 TR000445/TR/NCATS NIH HHS; UL1-RR24975/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Cholinesterase Inhibitors; 2Y49VWD90Q/Yohimbine; KVI301NA53/Pyridostigmine Bromide
Comments/Corrections
Comment In:
Hypertension. 2010 Nov;56(5):811-3   [PMID:  20837880 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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