Does physostigmine (anticholinesterase inhibitor) affect the small intestine (small bowel)?

From the Guidelines

Physostigmine does work on the small bowel, as it is an acetylcholinesterase inhibitor that increases acetylcholine levels in the body, enhancing gastrointestinal motility, including in the small intestine. The mechanism of action of physostigmine involves preventing the breakdown of acetylcholine, allowing this neurotransmitter to accumulate and stimulate muscarinic receptors in the gut, which increases smooth muscle contractions and peristalsis in the small bowel 1. This makes it potentially useful for treating conditions involving decreased intestinal motility, such as postoperative ileus or certain forms of intestinal pseudo-obstruction.

Key Points to Consider

• Typical dosing for gastrointestinal applications ranges from 0.5-2 mg administered intravenously or intramuscularly.
• Physostigmine has a narrow therapeutic window and can cause significant side effects including bradycardia, hypersalivation, bronchospasm, and seizures.
• Other prokinetic agents like metoclopramide or erythromycin are often preferred in clinical practice due to the side effects associated with physostigmine 1.
• The management of adult patients with severe chronic small intestinal dysmotility involves a comprehensive approach, including determining and ordering primary symptoms, excluding mechanical obstruction, evaluating contributing factors, and starting nutritional treatment 1.

Clinical Implications

• Physostigmine may be considered for patients with severe chronic small intestinal dysmotility who have not responded to other treatments.
• However, its use should be carefully weighed against the potential risks and benefits, and patients should be closely monitored for side effects.
• A therapeutic plan should be established to address the patient's symptoms, nutritional status, psychosocial issues, and quality of life, and regular review and reconsideration of the diagnosis should be performed as the clinical situation changes 1.

From the FDA Drug Label

Physostigmine Salicylate Injection should not be used in the presence of ... mechanical obstruction of the intestine The mechanical obstruction of the intestine warning in the drug label implies that physostigmine may affect the small intestine.

• The label does not specify the nature of this effect, but it suggests that physostigmine could potentially exacerbate or interact with existing intestinal conditions.
• As an anticholinesterase inhibitor, physostigmine increases acetylcholine levels in the body, which can stimulate muscle contractions in the small intestine.
• However, without more direct information, it is unclear what specific effects physostigmine may have on the small intestine in the absence of a mechanical obstruction 2.

From the Research

Physostigmine's Effect on the Small Intestine

• There is limited direct evidence on the effect of physostigmine on the small intestine.
• However, studies have reported gastrointestinal side effects associated with physostigmine use, such as nausea, vomiting, diarrhea, and abdominal cramps 3, 4.
• These side effects suggest that physostigmine may have an impact on the small intestine, possibly due to its cholinergic effects.
• One study reported that physostigmine was associated with a higher number of patients suffering from gastrointestinal complaints, such as nausea, vomiting, and diarrhea 3.
• Another study found that physostigmine was effective in reversing anticholinergic delirium, but also reported gastrointestinal side effects, including emesis and abdominal cramps 4, 5.

Mechanism of Action

• Physostigmine is a reversible cholinesterase inhibitor, which means it increases the concentration of acetylcholine in the synaptic cleft 6.
• This increase in acetylcholine can stimulate the muscarinic receptors in the small intestine, leading to increased motility and secretions.
• The exact mechanism of physostigmine's effect on the small intestine is not fully understood and requires further study.

Clinical Implications

• The gastrointestinal side effects associated with physostigmine use should be carefully monitored in patients receiving this medication 3, 4.
• Patients with pre-existing gastrointestinal conditions, such as irritable bowel syndrome or gastroesophageal reflux disease, may be more susceptible to these side effects.
• Further research is needed to fully understand the effects of physostigmine on the small intestine and to develop strategies to minimize gastrointestinal side effects.