Intestinal secretion

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

Diphenoxylate Hydrochloride. l-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxyhc acidmonohydrochlorhydrate [3810-80-8] (Lomotil) (13) is a white, odorless, crystalline powder that melts at 220—226°C. It is soluble ia methanol, spariagly soluble ia ethanol and acetone, slightly soluble ia water and isopropyl alcohol, freely soluble ia chloroform, and practically iasoluble ia ether and hexane. The method of preparation for diphenoxylate hydrochloride is available (11). Diphenoxylate hydrochloride [3810-80-8] (13) is an antidiarrheal that acts through an opiate receptor. It has effects both on propulsive motility and intestinal secretion. Commercial forms are mixed with atropiae to discourage abuse. 

Approximately 0.05 to 0.2% of vitamin > 2 stores are turned over daily, amounting to 0.5—8.0 )J.g, depending on the body pool size. The half-life of the body pool is estimated to be between 480 and 1360 days with a daily loss of vitamin > 2 of about 1 )J.g. Consequentiy, the daily minimum requirement for vitamin B22 is 1 fig. Three micrograms (3.0 J.g) vitamin B22 are excreted in the bile each day, but an efficient enterohepatic circulation salvages the vitamin from the bile and other intestinal secretions. This effective recycling of the vitamin contributes to the long half-life. Absence of the intrinsic factor intermpts the enterohepatic circulation. Vitamin > 2 is not catabolized by the body and is, therefore, excreted unchanged. About one-half of the vitamin is excreted in the urine and the other half in the bile. 

CAPASSO R, IZZO A, BORRELLI F, RUSSO A, SAUTEBIN L, PINTO A, CAPASSO F, MASCOLO N (2002) Effect of pipeline, the active ingredient of black pepper, on intestinal secretion in mice. Life Sci. 71 2311. 

Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. It is indicated for the treatment of patients younger than 65 years of age who experience chronic idiopathic constipation. The most common adverse effects include headache, abdominal pain, diarrhea, and nausea. 

During normal processes, approximately 9 liters of fluid traverse the gastrointestinal tract daily. Of this amount, 2 liters represent gastric juice, 1 liter is saliva, 1 liter is bile, 2 liters are pancreatic juice, 1 liter is intestinal secretions, and 2 liters are ingested. Of these 9 L of fluid presented to the intestine, only about 150 to 200 mL remain in the stool after reabsorptive processes occur. 

Tegaserod maleate (Zelnorm) stimulates 5-HT4 receptors in the GI tract, thereby increasing intestinal secretion, peristalsis, and small bowel transit. It also reduces sensitivity related to abdominal distention. It has been shown to be more effective than placebo in improving global IBS symptoms and altered bowel habits in constipation-predominant IBS.21 Diarrhea is a possible adverse effect. 

D. The Role of Metabolism and Intestinal Secretion Reaction-Transport Coupling... 

Water and electrolytes. Each day in an average adult, about 5.51 of food and fluids move from the stomach to the small intestine as chyme. An additional 3.5 1 of pancreatic and intestinal secretions produce a total of 9 1 of material in the lumen. Most of this (>7.5 1) is absorbed from the small intestine. The absorption of nutrient molecules, which takes place primarily in the duodenum and jejunum, creates an osmotic gradient for the passive absorption of water. Sodium may be absorbed passively or actively. Passive absorption occurs when the electrochemical gradient favors the movement of Na+ between the absorptive cells through "leaky" tight junctions. Sodium is actively absorbed by way of transporters in the absorptive cell membrane. One type of transporter carries a Na+ ion and a Cl ion into the cell. Another carries a Na+ ion, a K+ ion, and two Cl ions into the cell. 

Hunter, J., Hirst, B. H., Intestinal secretion of drugs the role of P-glycoprotein and related drug efflux systems in limiting oral drug absorption, A dr. Drug Del. Rev. 1997, 25, 129-157. 

Gramatte, T., Oertel, R., Terhaag, B., Kirch, W., Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans, Clin. Pharmacol. Ther. 1996, 59, 541-549. 

Gramatte, T., Oertel, R., Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil,... 

H., Mutschler, E., Terhaag, B., Rosch, W., Langguth, P., Evidence for intestinal secretion as an additional clearance pathway of Talinolol enantiomers concentration and dose dependent absorption in vitro and in vivo, Pharm. Res. 1996, 13, 514-522. 

By the end of the small intestine, deposition is almost complete and there is no need for intestinal secretions to aid assimilation. The principal role of the colon is to resorb water and reclaim sodium, which it does very efficiently. In fact, for every 2 L of water entering the colon, the residual water in the stools will be <200 mL. The environment becomes problematic for delivery past the hepatic flexure as the lack of water will restrict dispersion and dissolution. The flow of chyme from the ileum to the colon in healthy human beings is 1-2 L h 1. 

Kauffinann, H.M., Schrenk, D., Terhaag, B., Kroemer, H.K. and Siegmund, W. (2000) Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings a new type of... 

H-bonding potential Molecular weight/size PSA Intestinal metabolism Transport mechanisms Native surfactants Intestinal secretions, e.g. mucous, enzymes Intestinal blood/lymph flow Excipient effects... 

Devries MH, Rademaker CM, Geerlings C, Vandijk A and Noordhoek J (1989) Pharmacokinetic Modeling of the Effect of Activated-Charcoal on the Intestinal Secretion of Theophylline, Using the Isolated Vascularly Perfused Rat Small-Intestine. J Pharm Pharmacol 41 pp 528-533. 

Lipka E, Spahn-Langguth S, Mutschler E and Amidon GL (1998) In Vivo Non-Linear Intestinal Permeability of Celiprolol and Propranolol in Conscious Dogs Evidence for Intestinal Secretion. EurJ Pharm Sci 6 pp 75-81. 

Naruhashi K, Tamai I, Inoue N, Muraoka H, Sai Y, Suzuki N, Tsuji A (2001) Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein. J Pharm Pharmacol 53 699-709. 

Digestive system g agonists decrease secretion of stomach acid, reduce gastric motility, and prolong gastric emptying. Pancreatic, biliary, and intestinal secretions are reduced. Intestinal transit is also slowed. Peristaltic movements are reduced, but tone is increased, sometimes causing spasm. As a result, constipation is a frequent problem with opioid use. Bile duct pressure is also increased by opioids. 

Buffer — support the pH constancy of serum, spinal liquor and intestinal secretions ... 

P-glycoprotein-mediated efflux is a potential source of pecuHarities in drag pharmacokinetics, such as non-Hnearity. This includes dose-dependent absorption, drug-drag interactions, intestinal secretion and limited access to the brain. Assays are in development to quantify the interaction between transporters and drugs. One of the first is a 96-weU plate assay for P-gp binding [33, 34] and an MDRl ATPase test [35]. 

Small-intestinal secretions. The glands of the small intestine (the Lieberkuhn and Brunner glands) secrete additional digestive enzymes into the bowel. Together with enzymes on the microvilli of the intestinal epithelium (peptidases, glycosidases, etc.), these enzymes ensure almost complete hydrolysis of the food components previously broken down by the endoenzymes. 

Increase salivation, intestinal secretions, lacrimation, urinary urgency, hyperperistalsis, sweating... 

Antimotility drugs are opioid drugs. They increase small bowel smooth muscle tone and segmentation activity. They also reduce propulsive movements and decrease intestinal secretions while increasing absorption. They mediate these actions through p receptors. 

Octreotide inhibits intestinal secretion and has dose-related effects on bowel motility. In low doses (50 meg subcutaneously), it stimulates motility, whereas at higher doses (eg, 100-250 meg subcutaneously), it inhibits motility. Octreotide is effective in higher doses for the treatment of diarrhea due to vagotomy or dumping syndrome as well as for diarrhea caused by short bowel syndrome or AIDS. Octreotide has been used in low doses (50 meg subcutaneously) to stimulate small bowel motility in patients with small bowel bacterial overgrowth or intestinal pseudo-obstruction secondary to scleroderma. 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

After oral administration, doxycycline is rapidly and well absorbed from the gastrointestinal tract. It has a half-life of 15-22 h, which is longer than that of other tetracyclines. Following administration by various routes, doxycycline is widely distributed in the body, with highest levels in kidney and liver, besides bones and dentine. Doxycycline may be metabolized for up to 40%, and is largely excreted in feces via bile and intestinal secretion. 

Glycogen and starch ingested in the diet are hydrolyzed by a-amylases, enzymes in saliva and intestinal secretions that break (al—>4) glycosidic bonds between glucose units. Most animals cannot use cellulose as a fuel source, because they lack an enzyme to hydrolyze the (fil—>4) linkages. Termites readily digest cellulose... 

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