Diarrhea intestinal motility

Approximately 1 to 1.5 L of fluid is ingested per day, and coupled with secretions from the stomach, pancreas, and proximal duodenum, approximately 8 L of chyme enters the jejunum per day. Reabsorption of 6 to 7 L occurs within the small bowel, leaving a residual of 1.5 L fluid, 90% of which is reabsorbed in the colon. This pattern of liquid reabsorption permits the elimination of fecal waste containing an average of 0.1 to 0.2 L fluid per day. Diarrhea occurs if there is an altered rate of intestinal motility, if mucosal function or permeability is altered, or if the fluid load entering the colon overwhelms colonic reabsorption. Constipation may occur if intestinal movement is inhibited or if there is a fixed obstruction. 

Drugs that increase intestinal motility or induce diarrhea may decrease riboflavin absorption. Hyperthyroidism and the administration of thyroxine also reduce riboflavin absorption. 

A9-Tetrahydrocannabinol (A9-THC) is considered to be the predominant compound in preparations of C. sativa (marijuana, hashish, bhang) that is responsible for the central nervous system effects in humans. The recognized central nervous system responses to these preparations include alterations in cognition and memory, euphoria, and sedation. Potential therapeutic applications of cannabis preparations that are of either historical or contemporary interest include analgesia, attenuation of the nausea and vomiting of cancer chemotherapy, appetite stimulation, decreased intestinal motility of diarrhea, decreased bronchial constriction of asthma, decreased intraocular pressure of glaucoma, antirheumatic and antipyretic actions, and treatment of convulsant disorders. These effects have been reviewed recently (Howlett, 1995). 

Inhibition of 5-HT3 receptors in the gastrointestinal tract results in modulation of visceral afferent pain sensation and intestinal motility. Alosetron is a 5-HT3 antagonist that has been approved for the treatment of patients with severe irritable bowel syndrome with diarrhea (Figure 63-5). Three other 5-HT3 antagonists (ondansetron, granisetron, dolasetron) have been approved for the prevention and treatment of nausea and vomiting (see Antiemetics) however, their efficacy in the treatment of irritable bowel syndrome has not been determined. The relative differences between these 5-HT3 antagonists that determine their pharmacodynamic effects have not been well studied. 

Four general pathophysiologic mechanisms disrupt water and electrolyte balance, leading to diarrhea. These four mechanisms are the basis of diagnosis and therapy. They are (1) a change in active ion transport by either decreased sodium absorption or increased chloride secretion (2) a change in intestinal motility (3) an increase in luminal osmolarity and (4) an increase in tissue hydrostatic pressure. These mechanisms have been related to four broad clinical diarrheal groups secretory, osmotic, exudative, and altered intestinal transit. 

Gastrointestinal discomfort is not unusual in patients receiving chloroquine, and diarrhea can occur. Changes in intestinal motility may be to blame intramuscular injection of chloroquine caused a shortened orofecal time in the five cases in which this was measured. Overdosage can cause vomiting. 

The safety and efficacy of senna have been reviewed (31). Its rhein-anthrone-induced laxative effects occur through two distinct mechanisms, an increase in intestinal fluid transport, which causes accumulation of fluid intra-luminally, and an increase in intestinal motility. Senna can cause mild abdominal complaints, such as cramps or pain. Other adverse effects are discoloration of the urine and hemorrhoidal congestion. Prolonged use and overdose can result in diarrhea, extreme loss of electroljdes, especially potassium, damage to the surface epithelium, and impairment of bowel function by damage to autonomic nerves. Abuse of senna has also been associated with melanosis coli, but resolution occurs 8-11 months after withdrawal. Tolerance and genotoxicity do not seem to be problems associated with senna, especially when used periodically in therapeutic doses. 

Altered intestinal motility produces diarrhea by three mechanisms reduction of contact time in the small intestine, premature emptying of the colon, and bacterial overgrowth. Chyme must be exposed to intestinal epithelium for a sufficient time period to enable normal absorption and secretion processes to occur. If this contact time decreases, diarrhea results. Intestinal resection or bypass surgery and drugs (such as metoclopramide) cause this type of diarrhea. On the other hand, an increased time of exposure allows fecal bacteria overgrowth. A characteristic small intestine diarrheal pattern is rapid, small, coupling bursts of waves. These waves are inefficient, do not allow absorption, and rapidly dump chyme into the colon. Once in the colon, chyme exceeds the colonic capability to absorb water. 

Loperamide hydrochloride is an antidiarrheal agent that slows intestinal motility, affects water and electrolyte movement through intestine, inhibits peristalsis, reduces daily fecal volume, increases viscosity and bulk density of stool, and diminishes loss of fluid and electrolytes. It is indicated in the control and symptomatic relief of acute nonspecific or chronic diarrhea and in the reduction in volume of ileostomy output. 

Diarrhea can be caused by an increased osmotic load within the intestine (resulting in retention of water within the lumen) excessive secretion of electrolytes and water into the intestinal lumen exudation of protein and fluid from the mucosa and altered intestinal motility resulting in rapid transit (and decreased fluid absorption). In most instances, multiple processes are affected simultaneously, leading to a net increase in stool volume and weight accompanied by increases in fractional water content. 

OPIOIDS Opioids continue to be widely used in the treatment of diarrhea. They act principally through either p- or 5-opioid receptors on enteric nerves, epithelial cells, and muscle (see Chapter 21). These mechanisms include effects on intestinal motility (p receptors), intestinal secretion (5 receptors), or absorption (p and Preceptors). Commonly used antidiarrheals such as diphenoxylate, difenoxin, and loperamide act principally via peripheral /t-ofrioid receptors and are preferred over opioids that penetrate the CNS. 

Bisacodyl (e.g., Dulcolax) Increases water and electrolytes in feces and increases intestinal motility. Continuous use may cause severe diarrhea. PO. Softens feces in 6-8 hrs. 

Izzo, A.A., Mascolo, N., Pinto, L., Capasso, R., and Capasso, E (1999) The role of cannabinoid receptor in intestinal motility, defaecation and diarrhea in rats, Eur. J. Pharmacol. 384 37-42. 

The tricyclic diterpene salvinorin A (14) is a trans-clerodane diterpenoid isolated from the Mexican plant Salvia divinorum. It acts as a kappa opioid receptor agonist and it is the first non-aUcaloid compound acting on this receptor [27]. Salvinorin A is the most potent hallucinogen isolated from plants and it is also capable of inhibiting excess intestinal motility (e.g., diarrhea), through a combination of k-opioid and cannabinoid receptors. 

Hypersecretion. Intestinal distension from hypersecretion stimulates stretch receptors, which respond with increased intestinal motility. The combination of hypersecretion and hypermotility may result In severe and explosive diarrhea. 

Phyto chemicals can be used to either stimulate or inhibit motility of the GIT. For example, caffeine and other phytochemicals stimulate motility (Lis-Balchim etal, 2001 Boekema et al, 1999), whereas motility is slowed by peppermint oil (Beesley et al, 1996), protease inhibitors (Schwartz et al., 1994) and several other phytochemicals (Abdullahi et al, 2001 Odetola and Acojenu, 2000 Rojas et al, 1999 Amos et al, 1998). Many of the traditional herbal medicines used for treatment of diarrhea are based on aqueous extracts that slow small intestine transit and increase residence time for digesta (Lin et al, 2002). The opiates and derivatives are particularly noteworthy (Williams et al., 1997). 

Patients who have had multiple intestinal resections due to CD may have diarrhea related to the inability to reabsorb bile salts. Cholestyramine has been demonstrated to improve diarrheal symptoms in this population.8,15 NSAIDs should be avoided for pain management due to their ability to worsen IBD symptoms. Narcotic analgesics should be used with caution, as they may significantly reduce GI motility. 

Increased motility results in decreased contact between ingested food and drink and the intestinal mucosa, leading to reduced reabsorption and increased fluid in the stool. Diarrhea resulting from altered motility is often established after other mechanisms have been excluded. IBS-related diarrhea is due to altered motility. 

V. cholerae is a gram-negative bacillus. Vibrios pass through the stomach to colonize the upper small intestine. Vibrios have filamentous protein extensions that attach to receptors on the intestinal mucosa, and their motility assists with penetration of the mucus layer.2 The cholera enterotoxin consists of two subunits, one of which (subunit A) is transported into the cells and causes an increase in cyclic AMP, which leads to a deluge of fluid into the small intestine.20 This large volume of fluid results in the watery diarrhea that is characteristic of cholera. The stools are an electrolyte-rich isotonic fluid, the loss of which results in blood volume depletion followed by low blood pressure and shock.2 Of note, the diarrheal fluid is highly infectious. 

Loperamide is presently used more often as an antidiarrheal drug than as an analgesic, and it is also included in the list of over-the-counter drugs because of its insignificant action on the CNS. It reduces intestinal smooth muscle tone and motility as a result of binding to intestinal opiate receptors. It is used for symptomatic treatment of severe and chronic diarrhea of various origins. The most popular synonym for loperamide is imodium. 

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