Neostigmine and Glycopyrrolate by Iontophoresis to Induce Bowel Evacuation
Abstract
According to the National Spinal Cord Injury Statistical Center, approximately 285,000 people with traumatic (injury-related) spinal cord injury (SCI) are currently living in the United States. From data collected from surveys conducted by the Christopher & Dana Reeve Foundation, more than 1 million people in the United States have SCI or spinal cord disease. When the spinal cord is damaged, many changes occur to the body that result from interruption of nerve transmission to a part of the body or disrupt to the ability to walk; occasionally, both conditions may act to reduce the function of an organ system. After SCI, the gastrointestinal tract no longer functions normally, which has been termed by the medical profession as neurogenic bowel disorder. However, both the inability to walk, along with the interruption of nervous impulses to the bowel from the brain, are responsible for not being able to adequately propel stool through the large bowel to evacuate its contents. Thus, marked constipation is all too often a major problem for Veterans with SCI. Trying to reduce bowel problems associated with this condition often requires strict dietary prescriptions, adequate fluid intake, laxatives, enemas, and bowel care for several hours, two or three times a week, often with a caregiver. Despite these almost heroic measures, these efforts to have a normal and regular bowel movement are frequently unsatisfactory, resulting in incomplete stool evacuation and incontinence, which can severely limit an individuals ability to work and function independently, and may be a constant source of great humiliation. The ability to move the bowel contents along to the rectum was severely impaired primarily because of poor gut contractions on the left side of the colon, as shown by our team of investigators. To address this problem, a dual medication combination (neostigmine and glycopyrrolate) was developed that safely and predictably caused the bowel to empty after delivering these drugs into a vein (intravenously) or into the muscle bed (intramuscularly). Because no one likes needles, and because of the practical limits of administering medications on a routine basis by the use of needles, especially in persons with SCI because of their other health considerations, the investigators have devised a new approach: driving these medications across the skin and into the circulation of the body by applying an electrical current that is too small to feel (iontophoresis). However, much is still unknown about the appropriate dose of neostigmine (the medicine that causes the bowel to have contractions and drive its contents along) to result in bowel evacuation or the correct ratio of neostigmine to glycopyrrolate (the medicine that prevents many of the untoward side-effect of neostigmine, especially on the heart and lung). As such, studies have been designed in this proposal to address these questions. The concentrations of each of these medications will be measured sequentially in the circulation after administration through the skin by iontophoresis and related to bowel evacuation and untoward side-effects. The current work that was performed by iontophoretic administration of drugs used skin patches that were connected by wires to a controller box. There is a wireless iontophoresis device that is commercially available and appropriate for this purpose that could be tested to assess the safety and effectiveness of delivering these medications. It is quite possible that the investigators could interest a manufacturer of wireless iontophoresis devices to design an iontophoresis system that is better adapted to deliver the medications of interest in a more user-friendly manner. If this could be accomplished, then persons with SCI could have more control over their bowels, have predictable and complete bowel evacuations, prevent stool incontinence, and lead more healthy and normal lives. The proposed research project to determine the correct dose
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910770
Entities
People
- Mark Korsten
Organizations
- James J. Peters VA Medical Center
- United States Army