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R.J. is a 63-year-old woman with a 20-year history of type 2 diabetes mellitus. The patient has hyperglycemia, hypertension, and hyperlipidemia for which she is taking metformin, amlodipine, benazepril, and atorvastatin. She has a history of neuropathic ulcers at the first metatarsal head on the plantar surfaces of both feet. The most recent ulcer achieved full wound closure 5 months ago. Two weeks ago, R.J. was diagnosed with gastroparesis and prescribed metoclopramide as a prokinetic. Last week, the healed neuropathic ulcer on the first left metatarsal head reulcerated. R.J. was referred to physical therapy for wound evaluation and possible foot orthotics to prevent further breakdown.


Drugs that are swallowed pass through the gastrointestinal (GI) system prior to reaching the systemic circulation. Thus, drugs used to treat GI conditions have the potential to interfere with all other orally administered drugs leading to drug-drug interactions. These interactions may result in a decreased therapeutic effect due to decreased absorption of non-GI drugs, or adverse effects from higher drug plasma concentration due to decreased metabolism of non-GI drugs. Many drugs used to treat GI disorders may be obtained over-the-counter (OTC). Use of OTC drugs complicates accurate assessment of the drug history because it is not unusual for patients to forget to include OTC drugs when asked by the healthcare provider about medications. A classic example is the very common use of antihistamines used in acid-peptic disease.


The various components of the GI tract serve several functions, including digestive, excretory, endocrine, and exocrine. Control of these functions requires neuronal activity from both local and higher centers. The digestive system is innervated through connections with the central nervous system (CNS) and by a collection of highly organized neurons called the enteric nervous system (ENS) located within the intestinal walls. The ENS is often considered a third division of the autonomic nervous system. The ENS contains hundreds of millions of neurons, the majority of which are contained in the myenteric and submucosal plexuses. The ENS receives preganglionic fibers from the parasympathetic system as well as postganglionic sympathetic axons. There is bidirectional communication between the CNS and ENS and between the ENS and sympathetic prevertebral ganglia. Fibers from the cell bodies in these plexuses travel to the smooth muscle of the gut to control motility. Other motor fibers go to the secretory cells. The ENS also receives sensory input from within the wall of the gut. Sensory fibers transmit information from the mucosa and from stretch receptors to motor neurons in the plexuses and to postganglionic neurons in the sympathetic ganglia. The parasympathetic and sympathetic fibers that synapse on enteric plexus neurons appear to play a modulatory role.

Multiple neurotransmitters, neuromodulators, and autocoids are present in the GI system and control many functions. Because autocoids are typically produced and ...

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