Prepared By: Anas Jamsa Guided By: Sarika Johari M.

Pharm (Pharmacology) Anand Pharmacy College

Constipation is difficulty in passing stools and infrequent stools. However, patients may describe constipation as Less frequent defecation than is normally observed, Lower stool volume, Difficulty passing stool, Hard or firm stool, The lack of an urge to stool

Lifestyle Factors Inadequate fluid intake Decreased food intake Ignored defecation urge Immobility

Endocrine and Metabolic Hypothyroidism Hypercalcemia

Psychological Depression Eating disorders (e.g., anorexia nervosa) Misconceptions about inner cleanliness Neurologic PD and Multiple sclerosis Spinal lesions Damage to sacral parasympathetic nerves Autonomic neuropathy

Gastrointestinal tract Obstruction Chagas' disease Myopathy Neuropathy Systemic sclerosis Megarectum or Megacolon

Anorectum Anal malformation Hereditary internal anal myopathy Anal stenosis Weak pelvic floor Large rectocele Internal intussusception Anterior mucosal prolapse Solitary rectal ulcer

Medication induced Antacids (e.g., calcium and aluminum-containing) Barium sulfate Bismuth Calcium channel blockers (e.g., verapamil, Diltiazem) Central -adrenergic agonists (e.g., Clonidine, Guanabenz, Guanfacine) Clozapine Diuretics

Ganglion-blocking agents Iron

Laxatives (overuse)
MAO inhibitors Phenothiazines

Resins
Sucralfate Tricyclic antidepressants Vincristine

The normal process of fecal evacuation begins with propulsion of the fecal matter through the colon. High amplitude propagated contractions (HAPCs) that occur several times during the day, an increase in motility of the colon following a meal & the gastrocolic reflex, helps to propel stool along the colon to the rectum, where it is stored until appropriate conditions are present for voluntary evacuation. At the rectum, the mechanism for storage and evacuation of the fecal material is a complex process involving the puborectalis muscle, the detrussor muscles of the rectum and the autonomic and somatic nervous systems.

The puborectalis muscle embraces the rectal neck and forms an angle, the anorectal angle, with the internal and external anal sphincters surrounding the anal canal. This angle, at rest, is 85-105 and supports much of the weight of the fecal mass in the rectum, relieving the sphincters of the bulk of this pressure. Distension of the rectum causes a reflex relaxation of the internal anal sphincter and contraction of the rectal detrussor muscles. If defecation is desired, the puborectalis and levator ani muscles are relaxed, straightening the anorectal angle, increases the intraabdominal pressure and results in evacuation of feces.

Colon & anorectal dysfunction. Disruption of the normal physiology of defecation leads to constipation. Constipation occurs when the colon absorbs too much water or if the colons muscle contractions are slow or sluggish, causing the stool to move through the colon too slowly. As a result, stools can become hard and dry.

Impaired relaxation of the puborectalis muscle Inability to coordinate the abdominal, rectoanal, and pelvic-floor muscles during defecation. Prolonged avoidance of the pain associated with either the passage of a large, hard stool or an anal fissure or hemorrhoid may result in defecatory disorders Abnormal rectal morphology Rectocele: caused by contraction and straining against a closed outlet, rectal muscle gets thinner with age,& anal sphincter injury during childbirth.

Not Enough Fiber in the Diet People who eat a high-fiber diet are less likely to become constipated. The most common causes of constipation are a diet low in fiber or a diet high in fats, such as cheese, eggs, and meats. Fiber - both soluble and insoluble is the part of fruits, vegetables, and grains that the body cannot digest. Soluble fiber dissolves easily in water and takes on a soft, gel-like texture in the intestines. Insoluble fiber passes through the intestines almost unchanged. The bulk and soft texture of fiber help prevent hard, dry stools that are difficult to pass.

Not Enough Liquids Liquids add fluid to the colon and bulk to stools, making bowel movements softer and easier to pass. People who have problems with constipation should try to drink liquids every day in sufficient quantity. It is important to drink fluids that hydrate the body, especially when consuming caffeine containing drinks or alcoholic beverages. Lack of Physical Activity For example, constipation often occurs after an accident or during an illness when one must stay in bed and cannot exercise. Lack of physical activity is thought to be one of the reasons constipation is common in older people.

Changes in Life or Routine During pregnancy, women may be constipated because of hormonal changes or because the uterus compresses the intestine. Aging may also affect bowel regularity, because a slower metabolism results in less intestinal activity and muscle tone. In addition, people often become constipated when traveling, because their normal diet and daily routine are disrupted.

Ignoring the Urge to Have a Bowel Movement People who ignore the urge to have a bowel movement may eventually stop feeling the need to have one, which can lead to constipation. Some people delay having a bowel movement because they do not want to use toilets outside the home. Others ignore the urge because of emotional stress or because they are too busy. Children may postpone having a bowel movement because of stressful toilet training or because they do not want to interrupt their play.

It is important to ascertain whether the patient perceives the problem as infrequent bowel movements, stools of insufficient size, a feeling of fullness, or difficulty and pain on passing stool.

Signs and Symptoms Include: Hard, small or dry stools, Bloated Stomach, Cramping abdominal pain and discomfort, Sensation of blockade, Flatulence & Loss of appetite Lethargy & Depression Fatigue, headache, and nausea and vomiting.

Medical History The doctor may ask a patient to describe his or her constipation, including Duration of symptoms, Frequency of bowel movements, Consistency of stools, Presence of blood in the stool, and Toilet habits

A record of eating habits, medication, and level of physical activity

The clinical definition of constipation is having any two of the following symptoms for at least 12 weeks : Straining during bowel movements Lumpy or hard stool Sensation of incomplete evacuation Sensation of anorectal blockage/obstruction Fewer than three bowel movements per week

Physical Examination Differential diagnosis Rectal examination Colorectal transit study Anorectal function tests Defecography Barium enema x ray Sigmoidoscopy Colonoscopy Other tests to study of rectal evacuation- EMG and pudendal nerve terminal latency(PNTML), balloon proctography, perineometry, scintigraphic

Blood and Thyroid Tests may be necessary to look for thyroid disease and serum calcium or to rule out inflammatory, metabolic, and other disorders.

Rectal examination:

Rectal exam with a gloved, lubricated finger to evaluate the tone of the muscle that closes off the anus- also called anal sphincter- and to detect tenderness, obstruction, or blood.

Colorectal Transit Study: This test shows how well food moves through the colon. The patient swallows capsules containing small markers that are visible on an x ray. The movement of the markers through the colon is monitored by abdominal x rays taken several times 3 to 7 days after the capsule is swallowed. The patient eats a high-fiber diet during the course of this test.

Anorectal Function Tests: These tests diagnose constipation caused by abnormal functioning of the anus or rectum - also called anorectal function. 1. Anorectal manometry- evaluates anal sphincter muscle function. For this test, a catheter or air-filled balloon is inserted into the anus and slowly pulled back through the sphincter muscle to measure muscle tone and contractions.
2.

Balloon expulsion tests- consist of filling a balloon with varying amounts of water after it has been rectally inserted. Then the patient is asked to expel the balloon. The inability to expel a balloon filled with less than 150 ml of water may indicate a decrease in bowel function.

Defecography (Evacuation Proctography) It is an X-Ray of the anorectal area that evaluates completeness of stool elimination, identifies anorectal abnormalities, and evaluates rectal muscle contractions and relaxation. During the exam, the doctor fills the rectum with a soft paste that is the same consistency as stool. The patient sits on a toilet positioned inside an x-ray machine, then relaxes and squeezes the anus to expel the paste. The doctor studies the x rays for anorectal problems that occurred as the paste was expelled.

Barium Enema X-Ray This exam involves viewing the Rectum, Colon, and lower part of the Small Intestine to locate problems. This part of the digestive tract is known as the bowel. This test may show intestinal obstruction and Hirschsprungs disease, which is a lack of nerves within the colon. The night before the test, bowel cleansing, also called bowel prep, is necessary to clear the lower digestive tract. The patient drinks a special liquid to flush out the bowel. A clean bowel is important, because even a small amount of stool in the colon can hide details and result in an incomplete exam.

Because the colon does not show up well on x rays, fills it with barium, a chalky liquid that makes the area visible. Once the mixture coats the inside of the colon and rectum, x rays are taken that show their shape and condition. The patient may feel some abdominal cramping when the barium fills the colon but usually feels little discomfort after the procedure. Stools may be white in color for a few days after the exam.

Sigmoidoscopy An examination of the rectum and lower, or sigmoid, colon is called a Sigmoidoscopy. The person usually has a liquid dinner the night before a Sigmoidoscopy and takes an enema early the next morning. An enema an hour before the test may also be necessary. Long, flexible tube with a light on the end, called a Sigmoidoscope, to view the rectum and lower colon. The patient is lightly sedated before the exam. First, examines the rectum with a gloved, lubricated finger. Then, the Sigmoidoscope is inserted through the anus into the rectum and lower colon.

The procedure may cause abdominal pressure and a mild sensation of wanting to move the bowels. The doctor may fill the colon with air to get a better view. The air can cause mild cramping.

Colonoscopy An examination of the rectum and entire colon is called a colonoscopy. The person usually has a liquid dinner the night before a colonoscopy and takes an enema early the next morning. An enema an hour before the test may also be necessary. A flexible tube with a light on the end, called a colonoscope, to view the entire colon. This tube is longer than a Sigmoidoscope. During the exam, the patient lies on his or her side, to inserts the tube through the anus and rectum into the colon.

If an abnormality is seen, then use the colonoscope to remove a small piece of tissue for examination (biopsy). The patient may feel gassy and bloated after the procedure.

Treatment of Constipation: Life style modification (adequate intake of dietary fiber and fluids, regular physical activity),

Behavioral approaches (habit training, biofeedback),

Pharmacologic treatment (bulk-forming laxatives, Emollient laxatives, hyperosmolar laxatives, saline laxatives, stimulant laxatives & anthraquinones),

Surgical treatment

Diet A diet with enough fiber (20 to 35 grams each day) helps the body form soft, bulky stool. High-fiber foods include beans, whole grains and bran cereals, fresh fruits, and vegetables such as asparagus, brussels sprouts, cabbage, and carrots. For people prone to constipation, limiting foods that have little or no fiber, such as ice cream, cheese, meat, and processed foods, is also important.

Lifestyle Changes Drinking enough water and other liquids, such as fruit and vegetable juices and clear soups, so as not to become dehydrated, Engaging in daily exercise, Reserving enough time to have a bowel movement. In addition, the urge to have a bowel movement should not be ignored.

Laxatives The terms laxatives, cathartics, purgatives, aperients, and evacuants often are used interchangeably. There is a distinction, however, between laxation (the evacuation of formed fecal material from the rectum) and catharsis (the evacuation of unformed, usually watery fecal material from the entire colon). Most of the commonly used agents promote laxation, but some are actually cathartics that act as laxatives at low doses.

 laxation

: the evacuation of formed fecal material from the rectum

Bulk-Forming Laxatives : DRUGS: Bran, Karaya , Malt Soup Extract, Methylcellulose and Sodium CMC, Psyllium Hydrophilic Mucilloid MOA: These agents swell in water, forming an emollient gel that increases bulk in the intestines. Peristalsis is stimulated by the increased fecal mass that decreases the transit time. It is proposed that microflora metabolize polysaccharides to osmotically active metabolites. The metabolites may alter intestinal motility and electrolyte transport.

ADR: Worsening in bloating and abdominal pain. Intestinal and esophageal obstruction may occur if insufficient liquid is administered with the dose. Allergic reactions to Karaya have been noted, characterized by Dermatitis, and Bronchospasm.

Stimulants Laxatives : DRUGS: Diphenylmethane Derivative- Bisacodyl, Phenolphthalein, Anthraquinone Derivative- Senna , Cascara, Aloe Dehydrocholic acid, Castor oil MOA: They are called stimulants because they stimulate peristalsis via mucosal irritation or intramural nerve plexus activity, which results in increased motility. Modify the permeability of the colonic mucosal cells, resulting in intraluminal fluid and electrolyte secretion. Activation of prostaglandin-cyclic AMP and NO-cyclic GMP pathways, platelet-activating factor production , and perhaps inhibition of Na+K+-ATPase.

ADR: Abdominal cramps, nausea, Electrolyte disturbances (e.g. Hypokalemia, Hypocalcemia, metabolic acidosis, or alkalosis), and rectal burning and irritation with suppository use. Anthraquinone derivatives have been noted to cause Melanosis coli, pink or red discoloration of the urine . Hypersensitivity reactions may occur (rarely) with phenolphthalein and Dehydrocholic acid, causing Dermatologic Manifestations (e.g., skin eruptions, rash, pigmentation, pruritus). Phenolphthalein, might increase a persons risk for cancer. Chronic use of stimulant laxatives may produce a Cathartic Colon.

Saline Laxatives : DRUGS: Magnesium citrate, Magnesium hydroxide, Magnesium sulfate, Sodium phosphate, monobasic Sodium phosphate dibasic MOA: Produce an osmotic effect that increases intraluminal volume and stimulates peristalsis. Magnesium may cause Cholecystokinin release from the duodenal mucosa, promoting increased fluid secretion and motility of the small intestine and colon.

ADR: Fluid and electrolyte imbalances & Dehydration hypermagnesemia in patients with renal dysfunction. Caution should be exercised when administering the sodium phosphate salts to patients with congestive heart failure when sodium restriction is necessary. These agents are not recommended for children under 2 years of age because of the potential for hypocalcaemia in this population.

Lubricants Laxatives : DRUG: Mineral oil MOA: Lubrication of the feces , hindrance of water reabsorption in the colon & grease the stool, enabling it to move through the intestine more easily.

ADR: Chronic use of mineral oil to cause impaired absorption of Fat Soluble Vitamins (A, D, E, and K). Aspiration of the product may cause a lipoid pneumonia, so its oral use should be avoided in young children (<6 years), older adults, debilitated patients & at bedtime administration. Foreign-body reactions in the lymphoid tissue of the intestinal tract have resulted from its limited amount of absorption. Seepage of the product from the rectum following highdose oral or rectal administration may cause pruritus, increased infection, and decreased healing of anorectal lesions.

Stool Softeners (Emollient Laxatives): DRUGS: Dioctyl sulfosuccinate (calcium, potassium, sodium) MOA: Docusate salts are anionic surfactants that lower the surface tension of the stool to allow mixing of aqueous and fatty substances, softening the stool and permitting easier defecation. However, these agents also stimulate intestinal fluid and electrolyte secretion (possibly by increasing mucosal cyclic AMP) and alter intestinal mucosal permeability ADR: An electrolyte imbalance, Mild gastrointestinal cramping, Throat irritation

Osmotic Laxatives : DRUGS: PEG 3350, Nonabsorbable sugars Lactulose, sorbitol and Mannitol MOA: Nonabsorbable sugars are hydrolyzed in the colon to short-chain fatty acids, which stimulate colonic propulsive motility by osmotically drawing water into the lumen. Long-chain PEG are poorly absorbed, and PEG solutions are retained in the lumen by virtue of their high osmotic nature.

To avoid net transfer of ions across the intestinal wall, these preparations contain an isotonic mixture of sodium sulfate, sodium bicarbonate, sodium chloride, and potassium chloride (Polyethylene Glycol-Electrolyte Solutions). ADR: Abdominal discomfort or distention and flatulence. A few patients dislike the sweet taste of the preparations; dilution with water or administering the preparation with fruit juice can mask the taste. PEG preparation does not contain electrolytes, so larger volumes may represent a risk for ionic shifts. As with other laxatives, prolonged, frequent, or excessive use may result in dependence or electrolyte imbalance.

Prokinetic and other agents for Constipation Tegaserod Maleate: MOA: It is a 5-HT4, partial receptor agonist. It binds to 5-HT4 receptors, present largely in the gastrointestinal tract, stimulating intestinal peristalsis and secretion. ADR: Diarrhea, abdominal pain, and headaches. Tegaserod is contraindicated in patients with severe renal impairment, moderate to severe hepatic impairment, a history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions.

It should be discontinued if develop rectal bleeding, bloody severe diarrhea, hypotension, syncope, or sudden worsening of abdominal pain occurs.

Cisapride : MOA: Acts as an agonist at presynaptic 5 HT4 receptor. Stimulation of this receptor mediates the release of ACH. facilitates motility of the gut and produce loose stool. Devoid of D2 blocking activity. Not cause extrapyramidal side effects. ADR: Abdominal cramp, loose stools, headache, convulsion, induce serious and often fatal cardiac arrhythmia.

Naloxone: It has been postulated that endogenous opiates regulate colonic propulsive activity. Naloxone (an opiate receptor antagonist) has reversed chronic idiopathic constipation. In addition, naloxone causes acceleration of colonic transit, although it has not been shown to affect the number of bowel movements per 48 hours.

Misoprostol: Synthetic prostaglandin analog, can stimulate colonic contractions, particularly in the descending colon, and this may account for the diarrhea that limits the usefulness of Misoprostol as a Gastroprotectant. On the other hand, this property may be utilized for therapeutic gain in patients with intractable constipation. Another prostaglandin analog, RU-0211, is under development. Colchicine: A microtubule formation inhibitor used for gout also has been shown to be effective in constipation (mechanism unknown), but its toxicity has limited widespread use.

A Novel Biological Agent, Neurotrophin-3 (NT-3): Recently was shown to be effective in improving frequency and stool consistency and decreasing straining, again by an unknown mechanism of action.

OTHER TREATMENTS: Biofeedback : People with chronic constipation caused by anorectal dysfunction can use biofeedback to retrain the muscles that control bowel movements. Biofeedback involves using a sensor to monitor muscle activity, which is displayed on a computer screen, allowing for an accurate assessment of body functions. A health care professional uses this information to help the patient learn how to retrain these muscles.

Chloride Channel Activator: Increase intestinal fluid and motility to help stool pass, thereby reducing the symptoms of constipation. One such agent is Amitiza, which has been shown to be safely used for up to 6 to 12 months

SURGERY: Surgery to correct an anorectal problem such as rectal prolapse, a condition in which the lower portion of the colon turns inside out. Surgical removal of the colon may be an option for people with severe symptoms caused by colonic inertia. However, the benefits of this surgery must be weighed against possible complications, which include abdominal pain and diarrhea. Surgery like : Colectomy with ileosZigmoid anastomosis, Segmental resection of the colon with colo-colonic, colorectal anastomosis, sigmoid resection, rectopexy and patch sacral colpopexy

ENEMAS: Saline solution osmotically active or irritant MOA: Bowel distention by any means will produce an evacuation reflex in most people, to empty the distal colon or rectum of retained solid material. ADR: Repeated enemas with tap water or other hypotonic solutions can cause hyponatremia; repeated enemas with sodium phosphate-containing solution can cause hypocalcaemia. Phosphate-containing enemas also are known to alter the appearance of rectal mucosa.

SUPPOSITORIES : Glycerin MOA: It is a trihydroxy alcohol that is absorbed orally, but acts as a hygroscopic agent and lubricant when given rectally. The resultant water retention stimulates peristalsis and usually produces a bowel movement in less than an hour. ADR: Rectal glycerin may cause local discomfort, burning, or hyperemia and (minimal) bleeding. Some glycerin suppositories contain sodium stearate, which can cause local irritation.

Thank You!!!