Document Detail

Effects of promethazine and midodrine on orthostatic tolerance.
MedLine Citation:
PMID:  21235099     Owner:  NLM     Status:  In-Process    
INTRODUCTION: Astronauts experience both orthostatic hypotension and space motion sickness during re-entry. Midodrine, an alpha1-adrenergic agonist, is used to treat orthostatic hypotension. Promethazine, a histamine H1-receptor antagonist, is prescribed for space motion sickness. Many astronauts need both midodrine and promethazine. This study evaluated the interactive effects of midodrine and promethazine on hemodynamic responses to upright tilt.
METHODS: Subjects (5 men; 3 women) were studied four times: control (no drug); midodrine only; promethazine only; or midodrine plus promethazine. Hemodynamic parameters, plasma norepinephrine, renin activity, and aldosterone were measured supine and upright.
RESULTS: Rates of presyncope were 38% with no drug; 0% with midodrine alone; 100% with promethazine alone; and 63% with both drugs. Supine to upright decreases in systolic pressure were greater with promethazine alone than control (P < 0.01); midodrine (P < 0.05) or both drugs (P < 0.05). Supine to upright increases in plasma norepinephrine, renin activity, and aldosterone all were significantly reduced with promethazine alone compared to control (P < 0.05, P < 0.05, P < 0.05) and midodrine alone (P < 0.05, P < 0.01, P < 0.01). Cardiac output fell more with promethazine alone than with no drug (P < 0.05) or with midodrine plus promethazine (P < 0.05).
DISCUSSION: Promethazine significantly increased the incidence of orthostatic hypotension in subjects, even when combined with midodrine. Inhibition of sympathetic responses, likely via enhancement of the inhibitive effects of GABA, by promethazine may underlie the increased orthostatic hypotension. Promethazine also appears to inhibit responses of the renin angiotensisn system during orthostatic challenge.
Shang-Jin Shi; Steven H Platts; Michael G Ziegler; Janice V Meck
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Aviation, space, and environmental medicine     Volume:  82     ISSN:  0095-6562     ISO Abbreviation:  Aviat Space Environ Med     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501714     Medline TA:  Aviat Space Environ Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9-12     Citation Subset:  IM; S    
National Aeronautics and Space Administration, Johnson Space Center, Houston, TX 77058, USA.
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