Drugs used in Treatment of constipation & irritable bowel syndrome (IBS) Dr. Asmaa Fady MD., MSC., M.B, B.Ch اسم ورقم المقرر – Course Name and No. 4/17/2019

Learning objectives: By the end of the lecture, the student should: Define constipation. Know the different symptoms of constipation. Know the different lines of treatment of constipation. Identify the different types of laxatives. Discuss the pharmacokinetics, dynamics, side effects and uses of laxatives. Discuss the difference between different treatment including bulk forming laxatives, osmotic laxatives, stimulant laxatives And stool softeners (lubricants). Define irritable bowel syndrome (IBS). Identify the pharmacokinetics, dynamics, side effects and uses of drugs used for IBS اسم ورقم المقرر – Course Name and No. 4/17/2019

Constipation Constipation is infrequent bowel movements or difficult passage of stools that persists for several weeks or longer. It is a symptom not a disease Symptoms: a fewer than three stools/ week hard stools Straining to have bowel movements Feeling of a blockage in the rectum اسم ورقم المقرر – Course Name and No. 4/17/2019

Management of constipation Taking Plenty of vegetables, fruits and milk. Drinking a cup of warm water/ tea/ coffee half an hour before breakfast. Mild exercise for bed ridden patients, patients of old ages are required to improve tone of abdominal muscles. Anxiety and worry to be avoided. Using medications اسم ورقم المقرر – Course Name and No. 4/17/2019

Purgatives These are drugs that promote evacuation of bowels. Generally used to INCREASE the passage of the colonic contents Laxatives: –Milder in action –Produces soft but formed stool. Cathartics: (obsolete due to multiple side effects) –Stronger acting –Produces fluid stool اسم ورقم المقرر – Course Name and No. 4/17/2019

Classification of purgatives Chemical (irritant or stimulant) Mild (castor oil) Moderate (senna & bisacodyl) Physical Bulk: Osmotic or saline Mg sulfate lactulose others Lubricants Paraffin oil Glycerin supp Surface active agents اسم ورقم المقرر – Course Name and No. 4/17/2019

Classification of laxatives or purgatives Chemical (Stimulant Purgatives) : Increase motility and secretion by its action on nervous system in GIT. Physical purgatives: Bulk Purgatives : Increase volume of non-absorbable solid residue. Osmotic Purgatives : Increase water content in large intestine. Lubricants : paraffin oil & glycerin suppository. Surfactants= Surface Active Agents= detergents Stool softeners اسم ورقم المقرر – Course Name and No. 4/17/2019

Taking the medication day or night? Long onset= rapid onset= اسم ورقم المقرر – Course Name and No. 4/17/2019

1. Irritants and stimulants Mechanism of action: act via direct stimulation of enteric system  reflex peristalsis & purgation. Disadvantages & Contraindications of Irritant Purgatives: 1- Colic, diarrhea & dehydration: Add small doses of Atropine or Hyoscine. 2- Absorption of nutrients & drugs due to decreased transit time. 3- Pelvic congestion: Menstruation Dysmenorrhea. ** pregnancy abortion. 4- May be excreted in milk Affect suckling baby, diarrhea (senna). 5- Excreted in urine Red discoloration of alkaline urine (senna). 6- bluish pigmentation of mucosa of large intestine (senna) اسم ورقم المقرر – Course Name and No. 4/17/2019

2. Bisacodyl 3. Castor oil: 1. Senna: Natural origin Taken orally, it causes evacuation of the bowels within 8 to 10 hours (enterohepatic circulation) It causes water and electrolyte secretion into the bowel It is useful in treating opioid-induced constipation. 2. Bisacodyl a potent stimulant of the colon. It acts directly on nerve fibers in the mucosa of the colon. Shorter duration. Effective orally (Purgative) & rectally (Suppository) 3. Castor oil: This agent is broken down in the small intestine (activated by bile) into glycerin & ricinoleic acid, which is very irritating to the stomach and increases peristalsis. Pregnant patients should avoid castor oil because it may stimulate uterine contractions. اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Bulk laxatives High fiber (indigestible vegetables) Mechanism of action: (act on both small & large intestine) Non absorbed hydrophilic colloids  Increase the bulk of intestinal contents by water absorption   mechanical pressure on the walls of intestine  stimulation of stretch receptors   peristalsis. act within 1-3 hrs: taken on morning. They should be cautiously in patients who are immobile because of their potential for causing intestinal obstruction. اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Bulk laxatives 1- Food containing unabsorbed residues e.g. Vegetables & Bran: Bran is suitable & safe for chronic constipation in elderly. 2- Methyl-cellulose Hydrophilic granules. 3- Plantago seeds & Agar Imbibe water. 4- Osmotic laxatives: Saline Purgatives: (Mg sulfate & lactulose) اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Bulk laxatives Osmotic laxatives Water Soluble but non absorbable compounds Increase water content in large intestine. Members 1. Organic (Sugars) : lactulose (semisynthetic disaccharide of fructose and galactose). 2.Non-organic (Saline purgatives) : Magnesium sulphate (Ebsom salt) اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Bulk laxatives Osmotic laxatives (Magnesium sulphate) Mechanism of Action Are poorly absorbed salts. They remain in the bowel and retain water by osmosis thereby increasing the volume of feces   distension   peristalsis  evacuation of watery stool. Rapid effect (within 1-3h ). Magnesium sulfate (Epsom’s salt ). اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Bulk laxatives: Osmotic laxatives: lactulose Synthetic disaccharide (fructose and galactose). Osmotic laxative as Not digested & Not absorbed Retain water in bowel. Splited by Colon bacteria Lactic acid which lower pH of colon: - Formation of soft stool. - Inhibition of proteolytic bacteria Formation of ammonia. Uses: -Constipation. -Hepatic encephalopathy. With neomycin (Aminoglycoside antibiotic: Kill proteolytic bacteria) Side Effects Delayed onset of action (2-3 days) Abdominal cramps and flatulence. Electrolyte disturbance. اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: lubricants: paraffin oil 1- Synthetic mineral oil : Not absorbed orally. 2-Softens & lubricates hard fecal masses & mucosa of large intestine. 3- Onset of action: 8-10 hours. (night) 4- Useful in Chronic Constipation. N.B. Glycerin suppository is another form of lubricants. اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: lubricants: paraffin oil -Disadvantages: a- Bad consistency, so either add fruit juice or use an emulsion. b-Decrease Absorption of fat-soluble vitamins (A, D, E & K). c- Decrease Absorption of other drugs e.g. Oral Contraceptives. d- Uncontrolled leakage from anal sphincter (Pruritis ani. & Anal polyp). e- Delays healing of anorectal operations e.g. piles & fissures. f- If absorbed orally Foreign body reaction in liver. g- If it reaches the lung Lipid pneumonia. اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Surfactants= Surface Active Agents= detergents Docusate sodium (Dioctyl Sodium Sulfosuccinate): 1- Anionic surface active agent Surfactant = Detergent. 2- Lowers surface tension of hard fecal masses facilitate penetration of H2O to stool leading to Wetting & softening of stool. اسم ورقم المقرر – Course Name and No. 4/17/2019

2) Physical agents: Stool softeners Stool softeners include Glycerine suppositories, Paraffin oil & Dioctyl Sodium Sulfosuccinate. Stool softeners may take days to become effective They are used for prophylaxis rather than acute treatment. اسم ورقم المقرر – Course Name and No. 4/17/2019

Therapeutic Uses of Purgatives 1- Constipation: 2- Oral food & drug poisoning. 3- Before operation & X-ray abdomen. 4- Before & after some anti-helminthes e.g. Tinea solium 5- To avoid straining in some patients e.g. hernia & eye operations اسم ورقم المقرر – Course Name and No. 4/17/2019

Laxatives side effects: Bulk forming laxatives cause Bloating, flatulence, distension Caster oil produces sever cramping makes it difficult to tolerate for many including elderly Caster oil shouldn’t be used in pregnancy due to its effect on uterine contractions Mineral oil shouldn’t be used in bedridden patients due to possibility of aspiration all laxatives can cause electrolyte imbalance اسم ورقم المقرر – Course Name and No. 4/17/2019

Irritable bowel syndrome (IBS) This motility disorder of the gut affects approximately 10% of the population symptoms are mostly colonic precipitated by some dietary items, such as alcohol or wheat flour. اسم ورقم المقرر – Course Name and No. 4/17/2019

Subtypes of IBS: Abdominal pain, cramping or bloating that is typically relieved or partially relieved by passing a bowel movement Excess gas Diarrhea or constipation sometimes alternating bouts of diarrhea and constipation Mucus in the stool. Generally, symptoms may be, Diarrhoea predominant. Constipation predominant. Pain predominant. اسم ورقم المقرر – Course Name and No. 4/17/2019

Treatment of IBS: AVOID High-gas foods. such as carbonated and alcoholic beverages, caffeine, raw fruit, and certain vegetables, such as cabbage, broccoli and cauliflower. Gluten. Research shows that some people with IBS report improvement in diarrhea symptoms if they stop eating gluten (wheat, barley and rye). FODMAPs. FODMAPs — fermentable oligo-, di-, and monosaccharides and polyols. FODMAPs are found in certain grains, vegetables, fruits and dairy products. IBS symptoms usually decrease with a strict low-FODMAP diet. اسم ورقم المقرر – Course Name and No. 4/17/2019

Treatment of IBS: allow: Fiber supplements. Taking a supplement such as psyllium (Metamucil) with fluids may help control constipation. Ispaghula husk is one. Drinking plenty of fluids Practicing regular exercise. enough sleep periods. اسم ورقم المقرر – Course Name and No. 4/17/2019

Medications used in treatment of IBS Laxatives: Osmotic laxatives helpful. Stimulant laxatives make symptoms worse. Lactulose may aggravate distension and flatulence Anti-diarrheal medications: lopermide. Pain relieving medications. Others اسم ورقم المقرر – Course Name and No. 4/17/2019

Medications used in treatment of IBS Pain relieving medications: Mebeverine is probably first choice, directly relaxes intestinal smooth muscle without anticholinergic effects. Anticholinergic medications. (Hyosine): helps relieve painful bowel spasms. They are sometimes prescribed for people who have bouts of diarrhea. These medications are generally safe but can cause constipation, dry mouth and blurred vision. Pregabalin (Lyrica) or gabapentin might ease severe pain or bloating. Bloating may be helped by peppermint oil and it relaxes intestinal smooth muscle in an enteric-coated capsule which releases its contents in the distal small bowel. Nausea may require metoclopramide.   اسم ورقم المقرر – Course Name and No. 4/17/2019

Other medications used in treatment of IBS Tricyclic antidepressants. This type of medication can help relieve depression as well as inhibit the activity of neurons that control the intestines to help reduce pain SSRI antidepressants. Selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine. In cases of associated depression. اسم ورقم المقرر – Course Name and No. 4/17/2019

اسم ورقم المقرر – Course Name and No. 4/17/2019