Contrasting actions of pressor agents in severe autonomic failure.
BACKGROUND
Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response.


METHODS
In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg).


RESULTS
There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels.


CONCLUSIONS
We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.
Jordan
J
J
Clinical Research Center, Franz Volhard Clinic, Berlin, Germany.
Shannon
J R
JR
Biaggioni
I
I
Norman
R
R
Black
B K
BK
Robertson
D
D
D000368:Aged; D001337:Autonomic Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000627:therapeutic use; D002395:Catecholamines / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007052:Ibuprofen / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D010665:Phenylpropanolamine / Q000627:therapeutic use; D012044:Regression Analysis; D016037:Single-Blind Method; D015016:Yohimbine / Q000627:therapeutic use
D001337:Autonomic Agents; D002395:Catecholamines; D008774:Methylphenidate; D015016:Yohimbine; D010665:Phenylpropanolamine; D002110:Caffeine; D007052:Ibuprofen; D007213:Indomethacin