Water and Sudafed in Autonomic Failure

The maximal pressor response to water is reached when other pressor agents are only beginning to act. In addition to the therapeutic value of water ingestion alone, the blood pressure-raising effects of agents that increase sympathetic nervous system tone, such as phenylpropanolamine, are potentiated by water drinking. These drug interaction effects can be exploited in the treatment of orthostatic hypotension with the combination of water and a sympathomimetic potentially able to increase blood pressure to a greater extent and for a longer period of time than either water or the medication alone. However, the interaction can also lead to potentially dangerous blood pressure surges. This protocol requires an initial screening history and physical of study participants, including safety labs and EKGs, and evaluation of their autonomic nervous system status following the consent process. If the patient meets study criteria and is willing to undergo study testing, the 4-way crossover protocol will follow. Study Testing days 1 and 2 Arm 1: Pseudoephedrine 30 mg PO + 50 ml water Arm 2: Pseudoephedrine 30 mg PO + 480 ml water * Testing will be performed at the same time of day for all studies, at least 2 hours after a meal to avoid any confounding effects from postprandial hypotension. * A saline lock will be inserted for blood sampling at least 30 minutes before baseline data collection. * Participants will be asked to empty their bladders before beginning the test to avoid any effect of a full urinary bladder on peripheral sympathetic activity. * Participants will be seated comfortably in a chair. They will be asked to remain in the seated position for the duration of the study. * The Dinamap electrocardiographic and blood pressure (brachial cuff) recorder will be attached to the patient and set up for measurements every 5 minutes throughout the study with digital download into the ADC (Autonomic Dysfunction Center) BP database. * Participants will also be instrumented with EKG, finger cuff and sensor for continuous monitoring of blood pressure, heart rate, respiration, SpO2, stroke volume, systemic vascular resistance, and cardiac output, using a Nexfin system and Ivy Biomedical Vital-Guard monitor. * After a 30 minute baseline monitoring period (time -30 min to 0 min), 4 ½ teaspoons of blood will be collected for osmolality measurement and assays of hormones that regulate blood pressure. * The subject will then be given 30 mg of pseudoephedrine PO (time 0 min). Monitoring will be continued for 45 minutes. * At 45 minutes, the participant will be asked to drink 50 ml (Arm 1) or 480 ml (Arm 2) of water. * Additional blood samples (4 ½ teaspoons) for osmolality and BP-regulating hormones will be collected 30 and 60 minutes after water (+75 and +105 minutes of study). * Monitoring will be continued until + 135 min. * At 135 minutes, the study will end for the day. The timing of pseudoephedrine administration relative to water ingestion and the duration of the monitoring period are based on previous results3 and pharmacokinetic data7 reporting a Tmax for pseudoephedrine between 1 and 2 hours. Testing on study day 2 will be identical with the participant consuming the alternate water volume. Study Testing days 3 and 4 are optional Arm 3: Placebo PO + 50 ml water Arm 4: Placebo PO + 480 ml water Testing will be performed according to the same schedule as for Arms 1 and 2. Instrumentation will be limited to the Dinamap electrocardiographic and blood pressure (brachial cuff) recorder set up for measurements every 5 minutes throughout the study for Arms 3 and 4.