Intestinal motility, altered

Disturbed intestinal motility appears to be a central feature of IBS, which leads to altered stool consistency. Studies suggest that the colon of IBS sufferers is abnormally sensitive to normal stimuli.13 This enhanced visceral sensitivity manifests as pain, especially related to gut distention. 

A summary of how physiological factors affect the dissolution rate is given in Table 21.2. The effective surface area will be affected by the wetting properties of the bile acids and other surface-active agents in the gastrointestinal tract. The dif-fusivity of a drug molecule in the intestinal juice will be altered by changes in viscosity that are induced, for instance, by meal components. An increased dissolution rate could be obtained at more intense intestinal motility patterns or increased... 

Vagal neuropathy in diabetes mellitus [145, 146] and truncal vagotomy [147] may markedly change intestinal motility, as do heart-lung transplantation [148]. Spinal cord lesions also alter gut function, but the outlet obstruction due to failure of the striated muscles involved in defecation is more important than the enteric smooth muscle effects [149]. 

Radiation Injury. Late radiation enteropathy is associated with alterations of small intestinal motility [154], intestinal pseudoobstruction [154, 155] and Gram-negative colonization of the small bowel in patients with impaired small bowel motility [12], In patients with severe injury, alterations in the motility and microflora are of main importance for the clinical symptoms [154],... 

Dysmotility has been reported in Lyme disease [166] and in postviral syndromes associated with cytomegalovirus and herpes simplex virus [167], Altered intestinal motility can also be part of infectious mononucleosis [168]. 

Intestinal motility can be altered by reduced contact time in the small intestine, premature emptying of the colon, and by bacterial overgrowth. 

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. 

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). 

Because drugs are often taken orally at the same time, the GI tract is a relatively common site for drug interactions to occur. Possible interactions during absorption include changes in local pH (e.g., antacids), altered gastric emptying and intestinal motility, and the formation of complexes. 

CRITICAL ASSESSEMENT OF THE METHOD In general pharmacological studies during anesthesia should be assessed appropriately due to the possible interaction between the test compound and the used anesthetic as well as due to the reduced tone of the autonomic nervous system. Enteral administration of the candidate compound should be avoided, because enteral absorption of the test compound might be reduced due to the impaired intestinal motility during anesthesia. With respect to the effect of the aesthetic compound itself on intermediary metabolism the barbiturate pentobarbital sodium is the most inert anesthetic and does not cause alterations of metabolic blood and tissue parameters. In contrast, e.g. urethane as well as isoflurane (inhalation aesthetic) influences by itself substantially metabolic parameters over time (hours). 

Diarrhoea associated with deranged motility. In order for nutrients and water to be efficiently absorbed, the intestinal contents must be adequately exposed to the mucosal epithelium and retained long enough to allow absorption. Disorders in motility that accelerate transit time can decrease absorption, resulting in diarrhoea. Alterations in intestinal motility (usually increased propulsion) are observed in many types of diarrhoea. What is not usually clear, and is very difficult to demonstrate, is whether primary alterations in motility are the cause of diarrhoea or simply an effect. 

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. 

Altered gastrointestinal motility can result from many disorders, not all of which primarily affect the gut. For instance, endotoxemia, regardless of its origin, can depress intestinal motility. Motility is also probably affected by diet, subclinical endoparasitism and even exercise. 

How it works Binds with opioid receptors within CNS, altering processes affecting pain perception, emotional response to pain. Decreases intestinal motility by local and central actions. 

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. 

Many disease states can cause individual variation in response to drugs. Any disease that results in alteration in the pharmacokinetics of a drug will create these variations. Diseases of the liver and kidney, any disease that affects intestinal motility, mal-absorption syndromes and any condition that reduces plasma protein concentration are all implicated. Some diseases can alter the physiological sensitivity to a drug at its site of action. 

Under normal circumstances, these quantities are well within the range of the total absorptive capacity of the small bowel ( 16 L) and colon (4-5 L). Neurohumoral mechanisms, pathogens, and drugs can alter these processes, resulting in changes in either secretion or absorption of fluid by the intestinal epithelium. Altered motility also contributes to this process, as the extent of absorption parallels transit time. With decreased motility and excess fluid removal, feces can become inspissated and impacted, leading to constipation. When the capacity of the colon to absorb fluid is exceeded, diarrhea will occur. 

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. 

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