Constipation – Causes, Symptoms, Diagnosis, Treatment Constipation refers to bowel movements that are infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Complications from constipation may include hemorrhoids, anal fissure or fecal impaction. The normal frequency of bowel movements in adults is between three per day and three per week. Babies often have three to four bowel movements per day while young children typically have two to three per day. Constipation is a health problem that influences almost 20% of the world’s population[rx]. It is a bothersome disorder which negatively affects the quality of life and increases the risk of colon cancer[rx]. There are a wide-range of treatment methods. Lifestyle modification, such as increased fluid intake or exercise, is usually recommended as first-line treatment, but data on the effectiveness of these measures are limited[rx]. Laxatives are most commonly used for the treatment of constipation, but frequent use of these drugs may lead to some adverse effects[rx,rx], alternative treatment measure is, therefore, needed. Soluble fiber absorbs water to become a gelatinous, viscous substance and is fermented by bacteria in the digestive tract. Insoluble fiber has a bulking action[rx]. Dietary fiber is the product of healthful compounds and has demonstrated some beneficial effect. The increase of dietary fiber intake has been recommended to treat constipation in children and adults[rx–rx]. In a large-population case-control study, Rome found that dietary fiber intake was independently negatively correlated with chronic constipation, despite the age range and the age at onset of constipation[rx]. Epidemiology of Constipation is the most common chronic gastrointestinal disorder in adults. Depending on the definition employed, it occurs in 2% to 20% of the population. It is more common in women, the elderly and children. Specifically constipation with no known cause affects females more often affected than males. The reasons it occurs more frequently in the elderly is felt to be due to an increasing number of health problems as humans age and decreased physical activity. 12% of the population worldwide reports having constipation. Chronic constipation accounts for 3% of all visits annually to pediatric outpatient clinics. Constipation-related health care costs total $6.9 billion in the US annually. More than four million Americans have frequent constipation, accounting for 2.5 million physician visits a year. Around $725 million is spent on laxative products each year in America. Causes of Constipation People’s regular toilet habits can be affected by many things, including. Busy lifestyles Changes of routine, including holidays, starting school Not eating enough fibre Not drinking enough water or fluids Not taking enough exercise, being sedentary Ignoring natural urges to go to the toilet, sometimes due to not being near a toilet you are comfortable using Emotional and psychological problems Health conditions, including Parkinson’s disease, an under-active thyroid gland and depression Age and circumstances Bottle-feeding for babies Some medications, including narcotic-type pain killers such as codeine, iron supplements and some drugs used to control blood pressure. Causing Secondary Constipation [stextbox id=’custom’] Congenital malformations Structural causes or mechanical obstruction Colon cancer Benign stricture Rectocele, enterocele, rectal prolapse Megacolon Fissures Metabolic Hypothyroidism Hypercalcemia Hypokalaemia Uraemia Coeliac disease Myopathies Scleroderma Amyloidosis Neuropathies Spinal injury Myelomeningocele Multiple sclerosis Diabetic neuropathy Cerebrovascular disease Parkinson’s disease Complications from surgery or irradiation therapy Depression Cognitive impairment Immobility [/stextbox] Why Does It Happen? Some causes of constipation include Antacid medicines containing calcium or aluminum Changes in your usual diet or activities Colon cancer Eating a lot of dairy products Eating disorders Irritable bowel syndrome Neurological conditions such as Parkinson’s disease or multiple sclerosis Not being active Not enough water or fiber in your diet Overuse of laxatives Pregnancy Problems with the nerves and muscles in the digestive system Resisting the urge to have a bowel movement, which some people do because of hemorrhoids Some medications (especially strong pain drugs such as narcotics, antidepressants, or iron pills) Stress An underactive thyroid (called hypothyroidism) Drugs that Cause constipation prescription drugs that cause constipation include pain relievers like opiates etc. The drug that causes constipation especially among the elderly include Opioid pain relievers like Morphine, Codeine, etc. Anticholinergic agents like Atropine, Trihexyphenidyl Antispasmodics like dicyclomine Tricyclic antidepressants like amitriptyline Calcium channel blockers used in arrhythmias and high blood pressure such as verapamil Anti-Parkinsonian drugs – Parkinson’s disease itself may cause constipation and the drugs used for this condition including Levodopa cause constipation as well Sympathomimetics like ephedrine and terbutaline. Terbutaline is commonly used on bronchial asthma Antipsychotics like clozapine, thioridazine, chlorpromazine used for psychiatric disorders Diuretics for heart failure like furosemide High blood pressure-lowering agents like methyldopa, clonidine, propranolol, etc. Antihistamines like diphenhydramine Antacids especially calcium and aluminum-containing Calcium supplements Iron supplements Antidiarrheal agents (loperamide, attapulgite) Anticonvulsants e.g. phenytoin, clonazepam Pain relievers or NSAIDs (Nonsteroidal anti-inflammatory drugs) like ibuprofen, aspirin, etc. Miscellaneous compounds including Octreotide, polystyrene resins, cholestyramine (for lowering high blood cholesterol) and oral contraceptives Symptoms of constipation Constipation symptoms include Hard, compacted poor that is difficult or painful to pass Straining during bowel movements No bowel movements after 3 days Stomach aches that are relieved by bowel movements Bloody stools due to hard poo, piles (hemorrhoids) and anal fissures Leaks of wet, almost diarrhea-like poo between regular bowel movements Complications of constipation Complications of constipation include: Dry, hard poo collecting in the rectum, called fecal impaction. Leakage of liquid stools called fecal incontinence. Straining on the toilet and constipation leading to piles. Diagnosis of Constipation In addition to a general physical exam and a digital rectal exam, doctors use the following tests and procedures to diagnose chronic constipation and try to find the cause: Blood tests – Your doctor will look for a systemic condition such as low thyroid (hypothyroidism). Examination of the rectum and lower, or sigmoid, colon (sigmoidoscopy) – In this procedure, your doctor inserts a lighted, flexible tube into your anus to examine your rectum and the lower portion of your colon. Examination of the rectum and entire colon (colonoscopy) – This diagnostic procedure allows your doctor to examine the entire colon with a flexible, camera-equipped tube. Evaluation of anal sphincter muscle function (anorectal manometry). In this procedure, your doctor inserts a narrow, flexible tube into your anus and rectum and then inflates a small balloon at the tip of the tube. The device is then pulled back through the sphincter muscle. This procedure allows your doctor to measure the coordination of the muscles you use to move your bowels. Evaluation of anal sphincter muscle speed (balloon expulsion test) – Often used along with anorectal manometry, this test measures the amount of time it takes for you to push out a balloon that has been filled with water and placed in your rectum. Evaluation of how well food moves through the colon (colonic transit study ) – In this procedure, you may swallow a capsule that contains either a radiopaque marker or a wireless recording device. The progress of the capsule through your colon will be recorded over several days and be visible on X-rays. In some cases, you may eat radiocarbon-activated food and a special camera will record its progress (scintigraphy). Your doctor will look for signs of intestinal muscle dysfunction and how well food moves through your colon. An X-ray of the rectum during defecation (defecography). During this procedure, your doctor inserts a soft paste made of barium into your rectum. You then pass the barium paste as you would stool. The barium shows up on X-rays and may reveal a prolapse or problems with muscle function and muscle coordination. MRI defecography. During this procedure, as in barium defecography, a doctor will insert contrast gel into your rectum. You then pass the gel. The MRI scanner can visualize and assess the function of the defecation muscles. This test also can diagnose problems that can cause constipation, such as rectocele or rectal . transit study examination – where you take a short course of special capsules that show up on X-rays; one or more X-rays are taken later on to see how long it takes for the capsules to pass through your digestive system anorectal manometry – where a small device with a balloon at one end is inserted into your rectum and attached to a machine that measures pressure readings from the balloon as you squeeze, relax and push your rectum muscles; this gives an idea of how well the muscles and nerves in and around your rectum are working. Treatment of Constipation Most cases of constipation are easy to treat at home with diet and exercise. Some cases require doctor recommendations, prescription medicine, or a medical procedure. At-home treatment includes Diet – Eating a healthy diet with fiber and drinking plenty of fluids (water is the most helpful) can usually clear up constipation. High fiber foods include beans, dried fruits, fresh fruits and vegetables, whole-grain foods (choose brown rice or whole wheat bread instead of white), flaxseed meal, and powdered products containing psyllium. For example, 3 cups of popped popcorn have a little more than 3 grams of fiber. One cup of oatmeal has 4 grams of fiber. Adding fiber to each meal and snack will help you reach your goal for the day. Fiber supplements are helpful. Processed foods, such as desserts and sugary drinks, only make constipation worse. Men over the age of 50 should get at least 38 grams of fiber per day. Women over 50 should get 25 grams per day. Children ages 1 to 3 should get 19 grams of fiber per day. Children between 4 and 8 years old should get 25 grams per day. Girls between 9 and 18 should get 26 grams of fiber each day. Boys of the same age range should get between 31 and 38 grams of fiber per day. Bowel training – Teach your children to go to the bathroom when they have to. Holding it can lead to constipation. This also may be necessary for your elderly parents, if you are caring for them. Laxatives – This is over-the-counter medicine that helps you have a bowel movement. Laxatives should only be used in rare instances. Do not use them on a regular basis. If you have to use a laxative, bulk-forming laxatives are best. These work naturally to add bulk and water to your stools so they can pass easily. Bulk-forming laxatives can cause some bloating (when your stomach feels full) and gas. [stextbox id=’warning’] Anti- Ulcerant Antiulcer Drugs Brand Name (Generic Name) Possible Common Side Effects Include: Axid (nitzatidine) Diarrhea, headache, nausea and vomiting, sore throat Carafate (sucralfate) Constipation, insomnia, hives, upset stomach, vomiting Cytotec (misoprostol) Cramps, diarrhea, nausea, gas, headache, menstrual disorders (including heavy bleeding and severe cramping) Pepcid (famotidine) Constipation or diarrhea, dizziness, fatigue, fever Prilosec (omeprazole) Nausea and vomiting, headache, diarrhea, abdominal pain Tagamet (cimetidine) Headache, breast development in men, depres- sion and disorientation Zantac (ranitidine hydrochloride) Headache, constipation or diarrhea, joint pain Treatment can be include Type Generic and brand names Forms How fast? Safe to use long-term? Available as a generic? bulk-forming psyllium (Metamucil, Konsyl), calcium polycarbophil (FiberCon), methylcellulose fiber (Citrucel) powder, granules, liquid, tablet, packet, wafer a few days yes yes lubricant mineral oil (Fleet Mineral Oil Enema) enema, oral liquid 6 to 8 hours no yes osmotic magnesium hydroxide (Phillips Milk of Magnesia), magnesium citrate, polyethylene glycol (Miralax), sodium phosphate (Fleet Saline Enema), glycerin (Fleet Glycerin Suppository) enema, suppository, oral liquid 30 minutes or less yes yes stimulant bisacodyl (Dulcolax), senna/sennoside (Senokot) enema, suppository, oral liquid or capsule 6 to 10 hours no yes stool softener docusate (Colace, DulcoEase, Surfak) Enema, suppository, oral tablet, capsule, or liquid 1 to 3 days yes yes [/stextbox] Here are prescription drugs used for the treatment of chronic constipation Linaclotide (Linzess) – This drug is a capsule taken once daily on an empty stomach, at least 30 minutes before the first meal of the day. Linzess helps relieve constipation by helping bowel movements occur more often. It is not approved for use in those aged 17 years and younger. The most common side effect of Linzess is diarrhea. Linaclotide is an agonist of guanylate cyclase-C receptors, which stimulates intestinal fluid secretion and transit. In early studies, it has been found to increase bowel movement frequency and loosen stool consistency.[rx] A recently published dose range-finding study and results from two Phase III trials in 1272 patients with chronic constipation, show that linaclotide significantly improved bowel function (measured as ≥3 complete SBMs (SCBM) per week, with an increase of ≥1 from baseline for ≥9 of 12 weeks) in up to approximately 20% of patients.[rx] The median time to first SBM was 21.9 h (150 μg).[rx]Furthermore, abdominal symptoms, global measures of constipation and quality of life were also significantly improved [rx] and there was no evidence of rebound constipation upon treatment cessation.[rx] The most common AEs were GI-related, of which diarrhea had the highest incidence.[rx]Linaclotide is currently not licensed for use in the EU. Other 5-HT4 agonists – Other enterokinetic agents in development include the 5-HT4 receptor agonists TD-5108 (Phase II),[rx] and ATI-7505 (Phase II).[rx] A number of other prokinetic 5-HT4 receptor agonists have been developed for GI disorders, which are of considerable therapeutic interest but are in the early stages of development. Lactulose (Cephula, Chronulac, Constulose, Duphalac, Enulose) – Lactulose, a prescription laxative with a variety of brand names, draw water into the bowel to soften and loosen the stool. Side effects include gas, diarrhea, upset stomach, and stomach cramps. Lubiprostone (Amitiza) – Amitiza is approved by the FDA for the treatment of chronic constipation from an unknown cause (not constipation due to another condition or treatment). Amitiza softens the stool by increasing its water content, so the stool can pass easily. This medication is taken twice daily with food. Some reported side effects of Amitiza include a headache, nausea, diarrhea, abdominal pain, and vomiting. Plecanatide (Trulance) – Taken once a day, this tablet is a guanylate cyclase-C agonist. It helps stimulate intestinal fluid secretions that help your stool transit through the bowel. It was developed specifically for those suffering from Chronic Idiopathic Constipation. Side effects include diarrhea. It’s not recommended for use in patients younger than 6 years of age because of the dangers of severe dehydration. Polyethylene glycol (Miralax, Glycolax ). This drug is an osmotic laxative and causes water to remain in the stool, which results in softer stools. For those patients who do not tolerate dietary fiber supplements, this medication may be recommended. Prucalopride – Prucalopride is highly selective for the 5-HT4 receptor, unlike cisapride, displaying at least 150-fold selectivity for its therapeutic target receptor.[rx] Early studies demonstrated that it decreased colonic transit time in normal and constipated subjects.[rx] Three large randomized Phase III controlled trials with a total of 1977 patients (1750 female and 227 male) with severe chronic constipation (defined as ≤2 SCBM/week for a minimum of 6 months with either very hard or hard stools, sensation of incomplete evacuation or straining during defecation for at least 25% of the time) confirmed that, averaged over 12 weeks, bowel function (measured as an increase of ≥1 SBM/week) was significantly improved in up to 69% of patients receiving the recommended dose of 2 mg prucalopride, with a median time of 2.5 h to first SBM.[rx] Colchicine – is an alkaloid substance, which is used as an anti-inflammatory agent. It can increase the frequency of bowel movements, where it may be prescribed as a remedy for the treatment of chronic constipation. Alvimopan and methylnaltrexone have been recently suggested as new agents for the treatment of constipation caused by the opioid. Alvimopan – has been recommended for postoperative ileus after surgeries by the Food and Drug Administration (FDA), while FDA indicated that methylnaltrexone could be applied for patients suffering from opioid-induced constipation. However, trials of alvimopan in the confirmed use of methylnaltrexone in in opioid-induced constipation represent seriously dangerous cardiovascular causes with opposite results in terms of efficacy.[rx] In addition, the efficacy of commercially available synbiotic elements has been previously evaluated for the treatment of functional constipation in males.[rx] Mineral oil – Do not use this without your doctor’s recommendation. Your doctor may recommend using it if you recently had surgery and should not strain for a bowel movement. Do not use it regularly. It causes your body to lose important vitamins A, D, E and K. Enema – This is a liquid medicine. It is inserted into your anus to help with constipation. It is often used after a surgery or before some medical procedures. Prescription medicine – Your doctor will prescribe a medicine based on the reason for your constipation. Medical procedures – This is done to help remove stool from the intestine. Surgery – This is rare. It might involve removing a damaged intestine for serious reasons. Opioid antagonists – Three mu-opioid antagonists (naloxone, methylnaltrexone, and alvimopan) are currently under evaluation for the treatment of opiate-induced constipation [rx] and postoperative ileus.[rx] Although endogenous opioids may play a role in modulating GI function,[rx] early reports suggested that opioid antagonists are not effective in idiopathic constipation.[rx] Biofeedback Therapy Previous studies reported that biofeedback therapy could be effectively efficient by using neuromuscular training, visual, and verbal feedback. It has priority over other therapies such as laxative and sham training.[rx] Biofeedback session implicates placing a probe into the anus to give feedback of muscle tension using a computer screen. Biofeedback therapy is an efficient and multidisciplinary approach without the adverse effects of therapy.[rx] It has been observed that more than 70% of patients with gastrointestinal disorders get rid of symptoms by treating biofeedback therapy.[rx] Laxatives [stextbox id=’custom’] Bulk laxatives Dietary fiber, psyllium, polycarbophil, methylcellulose, carboxymethylcellulose Osmotic agents Saline laxatives: Magnesium, sulfate, potassium and phosphate salts Poorly absorbed sugars: Lactulose, sorbitol, mannitol, lactose, glycerine suppositories Polyethylene glycol (PEG): PEG 3350 laxative Stimulant laxatives Surface-active agents: Docusate, bile salts Diphenylmethane derivatives: Phenolphthalein, bisacodyl, sodium picosulfate Ricinoleic acid: Castor oil Anthraquinones: Senna, cascara sagrada, aloe, rhubarb Emollients Mineral oil Neuromuscular agents 5-HT4 Agonists: Cisapride, or cisapride, prucalopride, tegaserod Colchicine Prostaglandin agent – Misoprostol Cholinergic agents – Bethanechol, neostigmine Opiate antagonists – Naloxone, naltrexone Investigational agents Recombinant methionyl human brain-derived neurotrophic factor (r-metHuBDNF), neurotrophin-3 [/stextbox] Bulk Laxatives Fiber Constipation has been associated with a deficiency of dietary fiber in Western society for decades. A correlation between increasing the daily fiber intake and fecal weight, as well as colonic transit time, has been demonstrated.[rx] Dietary fiber appears to be effective in relieving mild to moderate, but not severe constipation. The recommended amount of dietary fiber is 20 to 35 grams per day (g/d) and this can be obtained from whole wheat bread, unrefined cereals, citrus fruits, and vegetables. Insoluble fiber, such as cereal bran, may cause significant abdominal gas and bloating, creating discomfort. In some patients, these agents also delay gastric emptying and depress appetite. To improve the tolerance and adherence you may start with low doses of fiber and increase their dietary fiber intake gradually over the next weeks until ∼20 to 25 g/d. If constipation has not improved, then commercially available fiber supplements should be tried. Patients also must be encouraged to drink water and maintain hydration when increasing fiber intake.[rx] Ispaghula (Psyllium) Ispaghula comes from an Asian plant that has a high water-binding capacity and is fermented in the colon. In an observational study with psyllium, the response to treatment was poor among patients with slow colonic transit, whereas 85% of patients without abnormal physiology improved or became symptom-free. Side effects include delayed gastric emptying and loss of appetite in some patients.[rx] Also, there have been some reports of serious acute allergic reactions, cough, and asthma.[rx] Methylcellulose Methylcellulose[rx] is a synthetic fiber polymer that is methylated. This results in resistance to bacterial fermentation. Mainly, it absorbs water into the colonic lumen, which increases fecal mass promoting motility and reduction in the colonic transit time.[rx] In one study, the patients showed an increase in solid stool mass with 1, 2, and 4 g of methylcellulose per day, but fecal water increased only with the 4-g dose. Despite the fact that bowel frequency was increased, the patients did not report a marked improvement in the consistency or passage of stools.[rx] Calcium Polycarbophil Calcium polycarbophil is a hydrophilic resin that is resistant to bacterial degradation and thus may be less likely to cause gas and bloating. In patients with IBS with features of constipation, calcium polycarbophil seems to improve overall symptoms and passage of stool, but not abdominal pain.[rx] Osmotic Agents In patients unresponsive to bulk agents alone, the addition of other laxatives is often the next step in the management of constipation. There are different forms of laxatives that can be selected based on the patient’s symptoms and preferences.[rx] Poorly Absorbed Ions-H2 Magnesium and Sulfate Magnesium, sulfate, and phosphate ions are poorly absorbed by the gut and thereby create a hyperosmolar intraluminal environment.[rx] Magnesium oxide has been considered safe to use on a regular basis in mildly constipated patients. Standard doses of 40 to 80 mmol of magnesium ion usually provoke a bowel movement within 6 hours. Magnesium sulfate is a more potent laxative that tends to produce a large volume of liquid stool and abdominal distention.[rx]Tas a result of excessive use. Sodium sulfate is a component of some bowel lavage solutions for colon cleansing prior to diagnostic and surgical procedures,[rx] but significant absorption may occur in the jejunum that may cause electrolyte disturbances. Phosphate Phosphate can be absorbed by the small intestine, and a high dose must be ingested to produce an osmotic laxative effect. Complications have been reported with sodium phosphate and OTC use is no longer available in the United States. Some of the complications reported include hyperphosphatemia, especially in patients with renal insufficiency and acute renal injury if used in large amounts as in bowel preparations.[rx] Risk factors include advanced age, dehydration, and the use of angiotensin-converting enzyme inhibitors or nonsteroidal anti-inflammatory drugs. Poorly Absorbed Sugars Lactulose Lactulose is a poorly absorbed synthetic disaccharide of galactose and fructose. This nonabsorbable carbohydrate becomes a substrate for colonic bacterial fermentation that produces hydrogen and methane and lowers fecal pH, carbon dioxide, water, and fatty acids.[rx] These products are osmotic agents that promote intestinal motility and secretion. The recommended dose of lactulose for adults is 15 to 30 mL once or twice daily. The time to onset of action is between 24 to 72 hours, longer than for other osmotic laxatives. Lactulose increases stool frequency in chronically constipated patients and is dose-dependent because it is fermented by colonic bacteria, gas and bloating usually limit its clinical use.[rx] Sorbitol Sorbitol is a poorly absorbed sugar alcohol that may produce effects similar to lactulose if taken in sufficient dosages. Sorbitol is commonly found as an artificial sweetener. It has been shown that as little as 5 g can cause a rise in breath hydrogen from bacterial fermentation, and 20 g produces diarrhea in about half of normal patients. Sorbitol is as effective as lactulose and less expensive. A randomized, double-blind, crossover trial of lactulose (20 g/d) and sorbitol (21 g/d) showed no difference in regards the frequency of bowel movements and patient preference. Patients using lactulose had more nausea compared with sorbitol. Mannitol is another sugar alcohol that can be used as a laxative. Polyethylene Glycol Polyethylene glycol (PEG) is an isosmotic laxative that is metabolically inert, which binds to water and keeps water retention inside the lumen.[rx] PEG is commonly used in solutions for colon cleansing as polyethylene glycol electrolyte lavage solutions (PEG-ELS) and sulfate-free electrolyte lavage solution (SF-ELS).1 These solutions have electrolytes added to avoid side effects from dehydration and electrolyte disturbances and have been shown to be safe for preparation for diagnostic colonoscopy, barium x-ray examinations, and colon surgery.[rx] Most of these solutions have been shown to be dose-dependent, increasing the number of stools with increasing dosage of PEG. Low-dose PEG has been shown in studies to be more effective than lactulose in the treatment of chronic constipation. The most common adverse effects of PEG include abdominal bloating and cramps. However, there are some case reports of severe pulmonary edema that have been reported with the use of PEG.[rx] Stimulant Laxatives Stimulant laxatives – increase intestinal motility and intestinal secretion. They begin working within hours and often are associated with abdominal cramps. Stimulant laxatives include anthraquinones (e.g., cascara, aloe, senna) and diphenylmethanes (e.g., bisacodyl, sodium picosulfate, phenolphthalein). Castor oil – is used less commonly because of its side-effect profile and poor palatability. The effect of stimulant laxatives is dose-dependent. Low doses prevent absorption of water and sodium, whereas high doses stimulate secretion of sodium, followed by water, into the colonic lumen. Stimulant laxatives – sometimes are abused, especially in patients with an eating disorder, even though at high doses they have only a modest effect on calorie absorption. Although a cathartic colon (i.e., a colon with reduced motility) has been attributed to prolonged use of stimulant laxatives, no animal or human data support this effect.[rx] Rather, cathartic colon, as seen on a barium enema examination, is probably a primary motility disorder. Anthraquinones Anthraquinones, such as cascara, senna, aloe, and frangula, are produced by a variety of plants. The compounds are inactive glycosides that when ingested, pass unabsorbed and unchanged down the small intestine and are hydrolyzed by colonic bacterial glycosidases to yield active molecules. These active metabolites increase the transport of electrolytes into the colonic lumen and stimulate myenteric plexuses to increase intestinal motility. The anthraquinones typically induce defecation 6 to 8 hours after oral dosing. Anthraquinones cause apoptosis of colonic epithelial cells, which they are phagocytosed by macrophages and appear as a lipofuscin-like pigment that darkens the colonic mucosa, a condition termed pseudomelanosis coli. Whether anthraquinone laxatives given over the long term cause adverse functional or structural changes in the intestine is controversial. Animal studies have shown neither damage to the myenteric plexus after long-term administration of sennosides nor a functional defect in motility. A case-control study in which multiple colonic mucosal biopsy specimens were examined by electron microscopy showed no differences in the submucosal plexuses between patients taking an anthraquinone laxative regularly for one year and those not taking one. An association between use of anthraquinones and colon cancer or myenteric nerve damage and the development of cathartic colon has not been established.[rx] Diphenylmethane Derivatives Diphenylmethane compounds include bisacodyl, sodium picosulfate, and phenolphthalein. After oral ingestion, bisacodyl and sodium picosulfate are hydrolyzed to the same active metabolite, but the mode of hydrolysis differs. Bisacodyl is hydrolyzed by intestinal enzymes and thus can act in the small and large intestines. Sodium picosulfate is hydrolyzed by colonic bacteria. Like anthraquinones, the action of sodium picosulfate is confined to the colon, and its activity is unpredictable because its activation depends on the bacterial flora.[rx] Like the anthraquinone laxatives, bisacodyl leads to apoptosis of colonic epithelial cells, the remnants of which accumulate in phagocytic macrophages, but these cellular remnants are not pigmented. Aside from these changes, bisacodyl does not appear to cause adverse effects with long-term use.[rx] Phenolphthalein inhibits water absorption in the small intestine and colon by effects on eicosanoids and the Na+/K+-ATPase pump present on the surface of enterocytes. The drug undergoes enterohepatic circulation, which may prolong its effects. It has been removed from the U.S. market because it is teratogenic in animals. Ricinoleic Acid (Bisacodyl and Castor Oil) Castor oil comes from the castor bean. After oral ingestion, it is hydrolyzed by lipase in the small intestine to ricinoleic acid, which inhibits intestinal water absorption and stimulates intestinal motor function by damaging mucosal cells and releasing neurotransmitters. Cramping is a common side effect. Stimulant laxatives, such as bisacodyl and senna exert their primary effects through alteration of electrolyte transport by the intestinal mucosa[rx] and generally work within several hours. In his classification, Schiller refers to this class of drugs as “secretagogues and agents with direct effects on the epithelial, nerve, or smooth muscle cells.”[rx] Following their use, it is not uncommon for patients to report symptoms of abdominal discomfort and cramping.[rx] This grouping includes surface-active agents, diphenylmethane derivatives, ricinoleic acid, and anthraquinones. Although stimulant laxatives may be associated with occasional side effects such as salt overload, hypokalemia, and protein-losing enteropathy, data does not support the theory that they cause a so-called cathartic colon.[rx] Melanosis Coli, pigmentation of the colonic mucosal due to the accumulation of apoptotic epithelial cells phagocytosed by macrophages, may develop in patients who chronically ingest anthraquinone-containing stimulant laxatives.[rx Despite prior theories to the contrary, neither anthracoid laxative use nor macroscopic or microscopic melanosis coli are associated with any significant risk for the development of colorectal adenoma or carcinoma.[rx] Phenolphthalein, no longer marketed in the United States, has been associated with the fixed-drug eruption, protein-losing enteropathy, Stevens-Johnson syndrome, and lupus reactions.[rx]Castor oil, containing ricinoleic acid, alters intestinal water absorption and motor function,[rx] and side effects often include cramping and nutrient malabsorption.[rx] Docusate Sodium Docusate sodium is a widely available stool softener and is a detergent agent that stimulates fluid secretion by the small and large intestine. Like most available OTC agents, conflicting evidence supports its use. One study showed no change in the volume of stool output in patients with ileostomy or weight of stool in normal subjects. A small double-blind crossover study showed improvement in bowel frequency in one-third of the studied patients. Other studies showed docusate to be less effective than psyllium for chronic idiopathic constipation.[rx] Emollients Mineral oil is an indigestible lipid compound which provides lubrication and emulsification of the fecal mass. In addition to being unpalatable, long-term use can cause malabsorption of fat-soluble vitamins, seepage, incontinence, and rarely lipoid aspiration pneumonia. Enemas and Suppositories Enemas general act by causing rectal distention and sometimes irritation of the rectal mucosa. Although generally safe, enemas may cause serious damage to the rectum by misinsertion resulting in trauma to the rectal mucosa. Phosphate Enemas Commercially available sodium phosphate enemas are hypertonic solutions, which cause stimulation and some degree of macro and microscopic irritation of the rectal mucosa. Like most other OTC agents, there is little convincing evidence of their efficacy, mostly because of the lack of well-designed trials. Saline, Tap Water, and Soapsuds Enemas Saline, tap water, and soapsuds enemas also cause rectal distention, prompting an evacuation. As a group, they are less irritating to the rectal mucosa if used in small volumes. With larger volumes, water intoxication has been reported with tap water enemas. Similarly, electrolyte disturbances have also been reported with larger volume soapsuds enemas. Saline enemas have been proposed as a survival technique in situations without pure freshwater. Stimulant Suppositories and Enemas Glycerin and bisacodyl are available without a prescription as suppositories for use in constipation. Glycerin appears to work by stimulating an osmotic effect in the rectum. Bisacodyl exerts its action on neurons in the rectum, prompting defecation. Few if any clinical trials support their use. Prokinetic Agents (5-HT4 Agonists) Prokinetic agents induce contractions in the gastrointestinal tract. Recently, most attention in the development of prokinetic agents has focused on the 5-HT4 serotonin receptor, given prior toxicities of drugs with other targets (metoclopramide and cisapride in particular). Tegaserod showed particular promise in the treatment of chronic constipation, but was withdrawn from the U. S. market due to observed cardiovascular toxicities; however, it remains available in other parts of the world. Newer 5-HT4 agonists are under development and appear promising as treatments for chronic constipation.[,rx] Unfortunately, prucalopride is not yet available in the United States.[rx] TD-5108, also known as velusetrag, is also a full 5-HT4 agonist. It has shown promise in phase II studies as an agent for chronic constipation. Despite positive results of early studies published around 2007, no phase III studies have been published and there may be issues with tachyphylaxis that may limit its utility for chronic constipation.[rx] Peripheral µ-Opioid Antagonists Methylnaltrexone Methylnaltrexone is a peripheral µ-opioid receptor antagonist that was U.S. Food & Drug Administration- (FDA-) approved in 2008 for opioid-induced constipation in patients with late-stage illness who receive opioids on a continuous basis. Most patients in clinical trials had limited life expectancy. Results are usually brisk, with almost half of patients having a bowel movement within 4 hours of the first dose. In the clinical trials, methylnaltrexone did not appear to precipitate opioid withdrawal.[rx] Alvimopan Alvimopan is FDA approved to hasten bowel recovery after surgery. Like methylnaltrexone, it is also a µ-opioid receptor antagonist. It may also be useful in opioid-induced constipation.[rx] Other Agents Clostridium Botulinum Toxin Type A (Botox) Clostridium botulinum toxin has been used to relieve outlet dysfunction defecatory disorders. Usually, it is injected into the puborectalis muscle. Controlled trials are lacking and it is not FDA approved for this indication. Bethanechol Cholinergic agents have been used in the treatment of constipation. Bethanechol appears to be beneficial in patients whose constipation results from tricyclic antidepressants. Use outside of this setting lacks evidence of efficacy. Neostigmine is clearly beneficial in colonic pseudo-obstruction, but given the severity of side effects, its use in chronic constipation would likely be problematic or intolerable. Colchicine Colchicine is commonly used for constipation in practice. Again though, there is limited evidence in the form of quality clinical trials to support its use. One study did demonstrate increased bowel movement frequency, but patients treated with colchicine had more abdominal pain than controls. Misoprostol is also used in treating chronic constipation, but given that its mechanism is probably similar to lubiprostone and its toxicities are likely greater, its regular clinical use is probably not warranted. Newer Agents Linaclotide Linaclotide targets the guanylate cyclase C protein and is minimally absorbed. In clinical trials, it has been shown to be safe, well-tolerated, decrease abdominal pain, accelerate colon transit, and improve bowel function and CSBM. Despite recent high-profile publications demonstrating its efficacy, it is unclear when or if FDA approval will occur.[rx] R-Manhunt-3 Another promising approach in the management of chronic constipation is targeting neurotrophins, a family of proteins that may induce nerve growth, nerve transmission, and consequently improve colonic and/or GI tract transit times. Thus far, the only agent studied is R-metHuNT-3 (recombinant human neurotrophic factor 3). It appears to offer improvement in gut transit but suffers from some significant toxicities (injection site reactions and paresthesias).[rx] Alternative Treatment Defecation Training Defecation training may be helpful, but few specially trained instructors are available. The process involves teaching and supportive listening as well as the encouragement of progress in follow-up sessions. The basics are teaching patients not to suppress the urge to defecate, setting aside time for regular bowel habits, and correct body positioning while defecating (including raising the feet above the floor when using Western-style toilets). Anorectal Biofeedback Anorectal biofeedback can be similarly beneficial, but finding qualified therapists may be challenging. The process usually involves several sessions performed with either surface electromyogram (EMG) electrodes or an anorectal manometry catheter. Patients are taught coordinated movements to promote successful defecation. The process is usually beneficial—a pooled analysis estimated about two-thirds of patients improved, but insurance coverage usually is an obstacle to its use. Home Remedies For Constipation Triphala powder or churna This consists of three fruits – amla or Indian gooseberry, haritaki (Chebulic Myrobalan) and vibhitaki (Bellirica Myrobalan). It is a great laxative and helps to regulate digestion and bowel movements. How to use You can either have one teaspoon with warm water or. Mix the powder with honey either before going to bed or early in the morning on an empty stomach. Raisins (kishmish) They are packed with fiber and act as great natural laxatives. This remedy also works wonders for pregnant women, without the side-effects of medication. Here are more reasons to eat raisins. How to use Soak a handful in water overnight. Have them first thing in the morning on an empty stomach. Guavas (abroad or Peru) They have soluble fiber in the pulp and insoluble fiber content in the seeds. They also help with the mucus production in the anus and with peristalsis (a series of contractions within the intestinal lining that helps the passage of food in the stomach). Don’t forget about these health benefits of guavas. Lemon (nimbu) juice It acts as a cleansing agent for the intestines, the salt content helps in quick and easy passage of stool. This juice also is a great way to detox your body. Here are more reasons to add lemons to your diet. How to use All you need to do is mix one teaspoon of lemon juice in a glass of warm water. Add a pinch of salt to the solution. Drink this juice on an empty stomach to relieve constipation. Figs (Anjeer) Either dried or ripe, figs are packed with fiber and act as a great natural laxative. How to use For relief from constipation, boil a few figs in a glass of milk, drink this mixture at night before bed. Make sure the mixture is warm when you drink it. Using a whole fruit for this purpose is much better as compared to syrups that are available commercially. Flaxseeds (Alsi) They are known for their fiber content, and can very well help you when it comes to constipation. How to use You can mix flaxseeds in your cereal every morning. Or just have a handful with warm water early in the morning. More reasons they are great for health. Castor oil (Arandi ka tel) This has been used for centuries as a sure shot remedy for constipation and has properties that can kill intestinal worms. How to use If drinking a spoon of castor oil alone is not something you’d like to do, you could add a tablespoon of it in a warm glass of milk. Have this mixture at night before bed to relieve constipation. Did you know castor oil is great for your skin too? Spinach (Palak) This has properties that cleanse, rebuild and renew the intestinal tract. You can also reap in these 10 amazing health benefits of palak. How to use You can have about 100 ml of spinach juice mixed with an equal quantity of water twice daily. This home remedy is the most effective method to cure even the most stubborn cases of constipation. Oranges They are not only a great source of vitamin C but also have a large amount of fiber content. How to use Eating two oranges every day, once in the morning and once in the evening can provide great relief from constipation. Eat them without peeling off the white threads for added effect. Here’s how oranges keep you healthy. Seed Mixtures This is a great source of fiber and can help relieve constipation. This mixture not only provides the necessary fiber content to relieve constipation but it also helps in rejuvenating the intestinal walls. How to use -2-3 sunflower seeds, a few flaxseeds, til or sesame seeds and almonds ground together to a fine powder can help relieve constipation. -Have one tablespoon of this mixture every day, for a week. -You can add it to your salad or cereal every morning. Diet tips to avoid constipation In order to avoid and cure constipation, it is essential that you maintain healthy food habits. Here are a few changes you could make in your diet to cure constipation: Avoid foods that contain white flour-like maida, white sugar, and other processed foods. Eat light regular meals, and make sure you eat at least 3-4 hours before you go to bed. Regular meals not only keep constipation at bay. Include fruits and vegetables into your daily diet. Adding condiments like jeera, Haldi, and ajwain in your food while cooking it is a great way to help digestion. Drink at least eight glasses of water every day. Make sure you have a glass of warm water every morning and before you go to bed. Constipation is an entirely curable and manageable condition, all you need to do is keep some of these home remedies in mind and you should be well on your way to a happy morning. Can constipation be prevented or avoided? There are things you can do to reduce constipation. This includes: Add more fiber to your diet – Adults should eat between 20-35 grams of fiber each day. Foods, such as beans, whole grains, fruits, and vegetables are high in fiber. Drink more water – Being dehydrated causes your stool to dry out. This makes having a bowel movement more difficult and painful. Don’t wait – When you have the urge to have a bowel movement, don’t hold it in. This causes the stool to build up. Get physical – exercise is helpful in keeping your bowel movements regular. Beware of medicines – Certain prescription medicines (especially pain medicines) can slow your digestive system. This causes constipation. Talk to your doctor about how to prepare for this if you need these medicines. Try warm liquids, especially in the morning. Add fruits and vegetables to your diet. Eat prunes and bran cereal. If needed, use a very mild over-the-counter stool softener like docusate or a laxative like magnesium hydroxide. Don’t use laxatives for more than 2 weeks without calling your doctor. If you overdo it, your symptoms may get worse. Talk to your doctor if you are being treated for certain diseases that are related to constipation. He or she may have additional guidance for lowering your risks. [stextbox id=’info’] Laxatives to avoid or use with caution for elderly patients LAXATIVE PRECAUTIONS Docusate • Lacks evidence for prevention and treatment of constipation (ie, no harm, but ineffective) Magnesium • Avoid in individuals with cardiac or renal dysfunction Mineral oil • Oral mineral oil should be avoided for older adults owing to concerns about aspiration (safer alternatives are available) Soapsuds enema • Risk of colonic mucosa irritation Sodium phosphate enema • As a purgative, avoid owing to serious electrolyte, renal, cardiovascular, and neurological concerns • As a laxative, avoid in individuals with dehydration, renal impairment, cardiac dysfunction, or electrolyte disturbances picosulfate, magnesium oxide, and citric acid • Risk of electrolyte imbalance • Avoid for patients with renal impairment (creatinine clearance < 30 mL/min) Polyethylene glycol 3350 with electrolytes • Avoid if the patient has impaired gag reflex, is prone to aspiration or regurgitation, is semiconscious, has a risk of electrolyte imbalance, has severe renal dysfunction (creatinine clearance < 30 mL/min), or has congestive heart failure [/stextbox] References https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206558/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446139/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170709/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976340/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348737/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217654/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641855/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291444/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544045/ Show More