A2: Antidotes in Depth

INTRODUCTION

To alter xenobiotic pharmacokinetics, the approach to a poisoned patient may include administration of gastrointestinal (GI) evacuants. Selected patients may benefit from minimizing systemic exposure by decreasing GI transit time and increasing rectal expulsion. The most effective process of evacuating the GI tract in poisoned patients is referred to as whole-bowel irrigation (WBI). WBI is typically accomplished using polyethylene glycol with a balanced electrolyte lavage solution (PEG-ELS). A detailed discussion of the merits of WBI in the context of various decontamination strategies is provided in Chap. 8.

HISTORY

In 1625 while endeavoring to recover from febrile “Hungarian disease,” Johann Glauber drank from a well from which he later isolated sal mirabile, now known as sodium sulfate, Na₂SO₄.⁴⁷ He advocated its use as a purgative and determined a synthetic production method.⁴⁷ In 1675, Nehemiah Grew first observed the presence of a purgative salt in the springs at Epsom, later determined to be magnesium sulfate.¹¹³ Phosphate of soda, called “tasteless purging salt,” was found in the urine by Hellot in 1737 and introduced into clinical practice as a purgative by George Pearson some 50 years later.¹⁰⁷ In 1882 to 1883, Hay reported on a series of experiments that provided the basis for the understanding of the mechanism of action of the saline cathartics. He identified the viscus as the main source of bowel fluid, which was secretory in nature, and established a dose–response principle of decreased time to stool as salt concentrations were increased.^43,44 PEG was introduced in 1957 as a nonabsorbable marker for the study of human fat, carbohydrate, and protein absorption.¹⁵ Experimental studies of intestinal lavage in normal human subjects appeared in 1968.⁷⁸ In 1973, Hewitt and colleagues reported on WBI in clinical practice, their method of “whole-gut irrigation” with a solution of sodium chloride, potassium chloride, and sodium bicarbonate in distilled water to prepare the large bowel for surgery.⁴⁶ WBI was used therapeutically for poisoning in 1976 in a patient ingesting 300 lead airgun pellets who was unresponsive to oral magnesium sulfate purgation.¹⁴⁷

PHARMACOLOGY

Nomenclature

Xenobiotics that promote intestinal evacuation are referred to as laxatives, cathartics, purgatives, promotility agents, and evacuants. Depending upon dose, the same xenobiotic may accomplish some or all of these tasks, with differing side effect profiles. Laxatives promote a soft-formed or semifluid stool within 6 hours to 3 days. Cathartics promote a rapid, watery evacuation within 1 to 3 hours.¹¹⁹ The term purgatives relates the force associated with bowel evacuation. Evacuants are commonly used for pre-procedural bowel cleansing, with an onset of action of as little as 30 to 60 minutes, but typically require 4 hours for a more complete effect. Promotility agents stimulate GI motor function via the enteric nervous system via acetylcholine, serotonin, motilin, or intestinal chloride channels.