Osmotic laxatives

Lactulose (Constulose, Generlac, Enulose, Others) [Laxative/ Osmotic] Uses Hepatic encephalopathy constipation Action Acidifies the colon, allows ammonia to diffuse into colon Dose Acute hepatic encephalopathy. 30-45 mLPO qlh until soft stools, then tid-qid Chronic laxative therapy 30-45 mL... 

Laxative Osmotic effect primarily in small intestine. Draws water into intestinal lumen, produces distention, promotes peristalsis, bowel evacuation... 

Bulk-forming laxatives Stimulant laxatives Osmotic laxatives ... 

Lactulose (e.g., Chronulac) Cramps, flatulance, nausea, vomiting. PO. Metabolized in intestine to lactate which acts as a laxative osmotically and by lowering pH. 

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. 

Polyethylene glycol (PEG, MiraLax) is an osmotic laxative available only by prescription. It is useful in patients who are experiencing acute constipation and who have had inadequate response to more traditional agents. Principal adverse effects include upset stomach, bloating, cramping, and gas. 

Slow-transit constipation can be treated with chronic administration of osmotic laxatives. Tegaserod maleate 6 mg orally twice daily is an acceptable treatment. Senna, bisacodyl, and other stimulants should be used only when the others fail to deliver the desired effect. 

Lactulose is the foundation of pharmacologic therapy to prevent and treat hepatic encephalopathy. It is a non-digestible synthetic disaccharide laxative that is hydrolyzed in the gut to an osmotically-active compound that draws water into the colon and stimulates defecation. Lactulose also lowers colonic pH, which favors the conversion of ammonia (NH3) to ammonium (NHf).48 Ammonium is ionic and cannot cross back into systemic circulation it is eliminated in the feces. Lactulose is usually initiated at 15 to 30 mL two to three times per day and titrated to a therapeutic goal of two to four soft bowel movements daily.20 49 50... 

Agents that cause softening of feces in 1-3 days Bulk-forming agents/osmotic laxatives Methylcellulose 4-6 g/day... 

Metabolism via normal metabolic pathways or fast excretion without metabolism are desirable characteristics. Some intense sweeteners are excreted unchanged while others are metabolised. Bulk sweetener absorption is lower and slower than for carbohydrates and results in reduced caloric availability which is partly due to metabolites formed by intestinal bacteria. Such metabolites and osmotic effects of not fully absorbed bulk sweeteners can cause laxative effects. Generally, the calorific value of bulk sweeteners is lower than for carbohydrates. Intense and bulk sweeteners are, as far as they are metabolised, not dependent on insulin. They are therefore acceptable for diabetics as part of a suitable diet. 

Duphalac is a proprietary preparation of lactulose, an osmotic laxative. Lactulose, which is a semi-synthetic disaccharide, is not absorbed from the gastrointestinal tract and produces an osmotic diarrhoea of low faecal pH, which discourages the proliferation of ammonia-producing organisms. 

Bisacodyl is a stimulant laxative that does not take long to act and is therefore useful in acute constipation. The bulk-forming laxative ispaghula husk takes longer to act when compared with bisacodyl but is useful for long-term administration. Lactulose, which is an osmotic laxative, has a lag time of about 48 hours before onset of action. Loperamide and kaolin and morphine mixture are antidiarrhoeals used in acute diarrhoea. 

Lactulose is an osmotic laxative acting by retaining fluid in the bowel. It takes a long time to act, generally up to 48 hours, and may cause abdominal discomfort. 

Since food has a buffering effect, antacids are taken between meals (e.g., 1 and 3 h after meals and at bedtime). Nonabsorbable antacids are preferred. Because Mg(OH)2 produces a laxative effect (cause osmotic action, p. 170, release of cholecystokinin by Mg, or both) and Al(OH)3 produces constipation (cause astringent action of AP, p. 178), these two antacids are frequently used in combination. 

Osmotically active laxatives (C) are soluble but nonabsorbable particles that retain water in the bowel by virtue of their osmotic action. The osmotic pressure (particle concentration) of bowel contents always corresponds to that of the extracellular space. The intestinal mucosa is unable to maintain a higher or lower osmotic pressure of the luminal contents. Therefore, absorption of molecules (e.g., glucose, NaQ) occurs isoosmotically, i.e., solute molecules are followed by a corresponding amount of water. Conversely, water remains in the bowel when molecules cannot be absorbed. 

Osmotic laxative effects are also produced by the polyhydric alcohols, mannitol and sorbitol, which unlike glucose cannot be transported through the intestinal mucosa, as well as by the non-hydrolyzable disaccharide, lactubse. Fermentation of lactulose by colon bacteria results in acidification of bowel contents and microfloral damage. Lactulose is used in hepatic failure in order to prevent bacterial production of ammonia and its subsequent absorption (absorbable NH3 nonabsorbable NH4+), so as to forestall hepatic coma. 

Cholekinetics stimulate the gallbladder to contract and empty, e.g., egg yolk the osmotic laxative MgS04, the cholecystokinin-related ceniletide (given parenterally). Cholekinetics are employed to test gallbladder function for diagnostic purposes. 

Polyethylene Glycol [PEG] 3350 (MiraLax) [Laxative] Uses Occasional constipation Action Osmotic laxative Dose 17 g powder (1 heaping tbsp) in 8 oz (1 cup) of H2O drink max 14 d Caution [C, ] R/0 bowel obst before use Contra GI obst, allergy to PEG Disp Powder for recons bottle cap... 

Saline laxatives like MgS04, Mg(OH)2, Mg2 Citrate and Na+ Phosphates act via their osmotic pressure to retain water in the colon. Other osmotic laxatives are carbohydrates such as lactulose, glycerin, sorbitol, and mannitol. They are not absorbed and are resistant to digestion in the small intestine. Most agents are orally administered. It should be noted however that glycerin, sodium phosphates and sorbitol are formulated for rectal use. From lactulose lactic and acetic acids are formed by intestinal bacteria and apart from its osmotic effects it thus acidifies the content of the colon. The reduction of the pH stimulates motility and secretion. 

Macrogol is also an osmotic laxative. Macrogol 4000 is a long linear polymer, also known as polyethylene glycol. It is not absorbed from the gut into the bloodstream, but remains in the gut where it causes water to be drawn into the lower bowel. Anaphylaxis to macrogol has been described. 

If drugs are used, the first choice should be a bulk laxative, e.g. isphagula or sterculia gum. Nonabsorbent carbohydrates with osmotic activity also work well but often cause flatulence. Salinic laxatives like polyethylene glycol and magnesium oxide are very effective but often cause stomach upsets like flatulence and abdominal pain. Tegaserod, a 5-HT4 partial agonist, appears to improve the frequency of bowel movements in those with chronic constipation (see Evans et ah, 2007). 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

Polyethylene glycol (Miralax) is another osmotic laxative that is colorless and tasteless once it is mixed. 

Sorbitol has also been used in injectable and topical products, and has a therapeutic use as an osmotic laxative. 

---