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Otc lec (23) Agents for constipation -Now in bulk forming laxatives we must notice if they are sugar free or not. -if they are sugar free >>the amount of fiber per gram Weigh is larger (more). -if it was sugar free ,so there is no sugar , as a compensation the fiber quantity increases per gram . Which means : If any one want to switch from regular to sugar free bulk forming laxative , he must take in consideration that less quantity most likely to be required . -with sugar free he must reduce the quantity because it contains more fiber. -many of the available products may vary substantially in their potency ,for instance sugar free metamucil have twice the potency of the standard metamucil . (metamucil which contains psyllium). -here as we talked there is less sugar so they add a fibers as a compensation , because they are really inexpensive to add so its easy to add them as an extra ingredient. -theoretical consideration suggest that the use of fermentable fiber 1 which increase short chain fatty acid concentration in the colonel lumen may have other health benefits as suppose to (methyl cellulose). Which means : With natural ones like psyllium there are other reported health benefit (such as decreasing (LDL cholesterol) in the blood but this is really not substantiated by evidence , because it is a very slight reduction we can not depend on them as a main source for decreasing the cholesterol . they also decrease the blood sugar and blood pressure . other Claims that these fibers decrease the colorectal cancer. -the only thing established with these fibers that they act as bulk forming laxatives. -they help regulate the bowel movement and prevent constipation. -there onset of action needs (24-72) hours , so the first thing here that this impaction absolutely inappropriate. so we can not use them in acute constipation , they are more likely to be used as maintenance or prevention . -to avoid patient non compliance due to the development of cramping and loathing that accompany changing the dietary fiber ,fiber supplementation should be started at low (sub therapeutic dose) which means: 2 Here the dose is 3.5 grams (one to three times daily) , to avoid excessive GI upset and abdominal cramps with these agents (typically) we start with sub therapeutic dose and increase the dose weekly(titrated upward on weekly bases until the reach to the desired effect or maximum recommendation dose ,we should not increase the dose a above the maximum because there is no additional therapeutic effect but it increases the side effects. -if we reach the desired effect before we reach to the maximum dose we stop here and don't increase it anymore. - users must pay attention for the water intake, these agents (fiber containing laxatives) must be taken with a large amount of water (at least 8 glasses per day) . Ok, the next group is saline and osmotic laxatives -they work by creating an osmotic gradient to push the water into small and large intestines ,which leads to distention of the intestinal lumen and increase in peristalsis. The two agents work by the same mechanism but the difference: Osmotic laxatives :organic compounds Saline: inorganic solvents -saline laxatives has an added effect , they increase the activity 3 of enzyme called cholecystokinin-pancreozymin (minor effect). -this enzyme increase the secretion of fluids into GIT ,but this is a minor effect. -onset of action varies depending on the ingredients and dosage forms. -generally in rectal formulations (suppositories and enemas) onset of action (5-30 min). -oral preparations have onset of action (3-6 hours) depending on the dose and the ingredients of the used drug . -it could be more than 6 hours ,that the patient take the tablet at bed time and bowel movements occurs at morning. but rectal dosage forms always have a faster onset of action. -saline laxatives: inorganic (sodium or magnesium salts) Na salts: rarely used in oral preparations because it may be absorbed excessively and cause increase in the blood pressure. - sodium phosphate is the most common active ingredient used in enemas because it has a fast onset of action . -in oral preparations they use magnesium salts. -as enemas i need quick onset of action ,so i use sodium salts and here there is no excessive absorption occurs because of the quick elimination . -about 20℅ of magnesium may be absorbed ,so it is used cautiously 4 in patients with renal impairment. -there is 3 types of magnesium salts used as laxatives: 1-magnisuim citrate 2-magnisuim hydroxide 3-magnisuim sulphate -the most potent is magnesium sulphate (Epsom salt) (English salt) we use it at small quantities. -magnesium sulphate : it is a drug also found as IV for arrhythmia third degree block (TDB) , refractory bronchospasm not responded to B2 agonist to help relax the muscles. -orally :magnesium salts are laxatives. -magnesium hydroxide is antacid but at higher doses it act as laxative. -magnesium hydroxide is known as (milk of magnesia), it found as suspension of magnesium hydroxide only and it is white in color. -here in Jordan the most likely one is (maalox) which is a suspension of aluminum and magnesium hydroxide ,But here because it contains aluminum hydroxide ,we don't use maalox as a laxative ,its laxative effect is very mild. -magnesium citrate gives a clear solution ,but the problem here that i need a huge amount to give the desired effect . -for adults: the bottle contains (300-350) ml , patient must drink all 5 the bottle or at least half of it to see the effect of magnesium citrate. -in Jordan these preparations are not found ,we can find them as a mixture with other agents. -in Jordan , we don't have saline laxatives but the alternative is osmotic laxative ,they act by the same mechanism but they are organic compounds. -osmotic laxatives: Glycerin Lactulose PEG( poly ethylene glycol) Sorbitol -glycerin Through rectal : Adults: 3 g suppositories Children:1.5 g suppositories For infants : we take the suppository of children ,cut it in half and use the tip of it. -lactulose also used to decrease blood ammonia levels in patients with hepatic encephalopathy but here it used as laxative. -may cause flatulence and cramping ,should be taken with fruit juice or milk to improve the palatability. 6 Adult dose:15-30 ml given one to two times daily. -sorbitol :we can find it in sugar free gums. -it is an osmotic laxative. -in theory too much sugar free gums will result in diarrhia . - it is found internationally in a preparations of: Orally:70℅ solution Rectally :as enemas contain 25% solution -orally :adult dose :15 ml -rectally :adult dose 120ml -sorbitol is more potent than lactulose but here in Jordan we have lactulose . -PEG (poly ethylene glycol) it is more effective than sorbitol and lactulose , it is used if other treatments failed ,it can be used for more than one week. -generally ,laxatives especially stimulant laxatives must not be used for more than 7 days . -to decrease the effect of these laxatives on peristaltic movement ,laxatives must not be used for more than one week. -there is 3 exceptions in this rule: two of these exceptions are not laxatives ,the first one is bulk forming laxatives (in fact they are not laxatives) , second one is emollients ( they are also not laxatives) ,the third one is PEG and lactulose. 7 -PEG and lactulose can be used for more than a week even for chronic constipation . -PEG dose: for adults 17g per day (as available product in Jordan (movicol) which is found as (13.5 gram per package ) , here we can mix 2 packages and drink them once, or drink a package at morning and another in the evening. -PEG : Too much of it may cause cathartic effect by flushing out of the bowel (they use it in colonoscopy)to flush out the bowel. -not every laxative must have a cathartic effect , to give cathartic effect it must be able to flush out the bowel at certain dose. the third group is stimulant laxatives -stimulant laxatives used badly in weight loss formulations. -the most dangerous laxatives if it used more than a week. -they cause irritation in the walls of the intestines (damage in the walls) as a result of this irritation our bodies considered these as a toxins and stimulate the peristaltic movement. -using these agents more than one week may cause megacolon which is : with the damage in the intestine and normal flora ,there will be infection which leads to abscess and increase in the volume of the colon , and it may cause rapture in the colon and this bacteria will reach to the blood and cause septic shock. -no matter how much weight loss has achieved ,no weigh loss worth 8 the risk of megacolon. -even if it didn't cause megacolon ,it will disrupt the regularity and it may cause laziness in the peristaltic movement. -it may cause enough damage to impair the neurological control of peristaltic movement. -but , in Lowe doses it has effective faster onset of action . -here in Jordan the most famous ones are (sennosides) . -sennosides dose for the adults is (12-15 mg)twice daily. -evacarbon :the active ingredient is sennosides not activated charcoal ,it has a tiny amount of charcoal , so it is more likely stimulant laxative rather than antidote. -cascara anthraquinones(not used anymore because they are toxic). -bisacodyl (dulcolax) is the most gentle (weakest) of the stimulant laxatives ,we can find them as enteric coated tablets because they are originally irritant ,so tablets shouldn't be crushed. -it shouldn't be taken with milk or antacid , because we don't want to release the tablet before it reaches the intestine. -oral dose :5-15 mg/day Rectal dose:10mg -commercial strength of the tablets is 5 mg ,so the patient can take (1-3 tablets )at bed time. -castor oil : it is the strongest in this class , it works mainly on small 9 intestine .(laxative effect is strong). -so ,it increases the peristaltic movement of the small intestine and decreases the absorption of water and nutrients . -because most of the absorption occurs in the small intestine , so as castor oil it produces very strong laxative effect. -its onset of action :2-6 hours.(but it could be much much faster ). -patients who want to drink castor oil must know that there will be abdominal cramps and GI upset last for many hours. *lactulose also cause abdominal cramps and GI upset but at less extent than castor oil. -adult dose:15-16 ml once daily. -how can we know if this castor oil is inauthentic or not? Castor oil is gel like in its nature ,it is not liquid , so we can judge by the consistency of the oil. -castor oil is not recommended to use it as a laxative. -other uses of castor oil: 1-in cosmetics ,it stimulates hair growth. 2-in topical analgesics to improve the penetration. Note : Castor oil itself has not any analgesic effect but it increases the penetration by increasing the blood flow (it gives warm effect ). -some times many people advice pregnant women to drink castor oil 10 before the labor to facilitate it ,this is totally wrong (castor oil is a pregnancy category x and it must not be given to the last day of pregnancy because it is toxic substance and it may cause nurologic damage to the fetus . -The forth group is emollient laxatives: -they act as surfactants by allowing the absorption of water into the stool which make soften stool easier to pass , this is a very important laxative. -sodium docusate is an example on this group which is also found in ear wax drops but we can not find it in Jordan. -it has a very good effect if it used with other laxatives because it dose not work on the frequency it works on softening the hard feces. -Dose(in America): as a soft gel capsule (colace) 50-100 mg twice daily . -because it works as a surfactant we shouldn't use it with mineral oil. -mineral oil works by increasing the water retention in the stool to soften the stool. -from the name(lubricant laxatives) it covers the walls of the intestine ( it works as a lubricant (facilitating the passing out of fecal matter)). -mineral oil (liquid) : we can find it in baby oil it is (100% )mineral oil, it is a good laxative , it can decrease the retention of fat soluble 11 vitamins and it affects the absorption of any lipophilic drug. -mineral oil shouldn't be given to elderly and children less than 6 years or patients with rectal bleeding or appendicitis. -if we give mineral oil to a patient with bleeding , mineral oil may reach the circulation and it may forms a fat embolisms and it is very serious. ممكن تعمل جلطة وصعب عالجها النها ما بتذوب -generally if the patient has hard feces what is the recommendation? Using a stool softener , if it is not available use a glycerin suppositories which is an osmotic laxative ( glycerin itself has an emollient effect locally so here as glycerin suppositories it will give osmotic action and emollient effect , but if the stool softener is available it will be better than glycerin because here the fecal matter may be extended upward to the colon not just in the rectal. -if there is soft stool but poor anal tone ( no full evacuation) we give the patient (stimulant laxative) . -any one with decreased frequency>> give stimulant laxatives. -any one takes opioids or agents that decrease the peristaltic movement >>stimulant laxatives. -anyone with normal stool but decreased frequency (the stool is not hard) >>stimulant laxatives. - bulk forming laxatives are not effective for disimpaction. -the first stage is to induce the disimpaction 12 -the second stage is to prevent the recurrence, and here it depends mainly on life style modifications , increase in the fluid intake and so on , but if the patient suffers from a disease which cause constipation or from a medications in this case we give lactulose or PEG but in the first one or two days we give stimulant laxative to induce the bowel movement or we can give a PEG in the doses of disimpaction (very high doses) (1 g /kg body weight). -if the bulk forming laxatives were not effective , we move to the stronger saline and osmotic laxatives (PEG is the strongest ) , if I need an agent stronger than osmotic laxatives , I give stimulant laxatives. -Now , if we have products like lubiprostone (amitizia)(prostaglandin related drug )it is approved in certain cases of chronic constipation ,when there is non functional constipation (there is an organic cause). - a general rule for the daily amount of fiber for all children :(5 g + the child's age).(important rule ) -some experts recommend that for children who have had constipation in the past , the amount should be increased to 10 g plus the child's age.(not important) -for adults (less than 50 in age) : for males 38 g , for females 25 g -adults (more than 50 in age) :for male 30 g , for female 20-21 g 13 GOOD LUCK Randa almousa 14