DIARRHEA AND CONSTIPATION

DIARRHEA AND CONSTIPATION
Andrew N. Schmelz, PharmD Post-Doctoral Teaching Fellow Dept Pharmacy Practice, Purdue University April 27, 2009 Not a topic on mortality, but much like physical therapy, can have a significant effect on morbidity

Objectives List 4 causes of diarrhea and constipation
Identify the names of drugs commonly used to treat diarrhea and constipation Explain the general mechanism of action of drugs used to treat diarrhea and constipation List major side effects and drug interactions with common drugs used to treat diarrhea and constipation Explain how diarrhea, constipation, and the agents to treat these conditions impact the practice of physical therapy

DIARRHEA

Epidemiology Average person in America has an episode of diarrhea about 4 times per year. Up to 20% of persons receiving antibiotics in the US get diarrhea Approx 272,000,000 episodes per year or 517 episodes per minute About 707,000 deaths due to diarrheal diseases in Africa in 2002 vs. 57,000 deaths in the Americas 20% from antibiotics is from Mayo clinic data (8 episodes per second!) Deaths data = World Health Report from WHO in 2004. Approx 7-9L of fluid enter the GI tract daily in a fasting state (just from internal secretions)

Introduction Clinical Definition Acute vs. Chronic Diarrhea
An increased frequency of bowel movements Decreased consistency of fecal discharge compared to an individual’s normal bowel pattern Acute vs. Chronic Diarrhea 4 Types of Diarrhea: Secretory Osmotic Exudative Altered intestinal transit -Literature is extremely variable on definition of diarrhea and stats are even more difficult to accurately obtain because MDs and healthcare professionals don’t usually report diarrhea unless it is unusual or due to a known pathogen (people don’t report every episode of diarrhea to their doctor) -Most bouts of diarrhea begin abruptly and subside within 1 to 2 days without treatment. -Normal bowel pattern different per individual and per individual’s diet (Western diet vs. Asian diet, sedentary vs. active/athletic, etc) -Acute vs. chronic = acute episodes subside within 72 hrs of onset vs. chronic which involves frequent attacks over an extended time period Secretory = occurs when a stimulating substance either increases secretion or decreases absorption of large amts of water and electrolytes (such as unabsorbed dietary fat in steatorrhea, hormones, laxatives, bacterial toxins, etc) Clinically recognized by large stool volumes that is not altered by a fasting state. Osmotic = d/t poorly absorbed substances that retain intestinal fluids or d/t malabsorption syndromes, many dietary causes such as lactose intolerance, go into further later Exudative = d/t inflammatory diseases of the intestine that result in increased discharge of mucus, serum proteins, and blood into the gut. Assoc. with large stool volumes and is usually secondary to larger disease processes occuring in the body Altered intestinal transit = d/t 3 mechanisms: decreased intestinal contact time (increase peristalsis), premature emptying of the colon, and bacterial overgrowth

Etiology Infection Diet Medications Gastrointestinal diseases
Infection = viral or bacterial  refer to MD! GI diseases = IBD, Crohn’s, ulcerative colitis, etc. = Not going into Make sure not having an intolerance to any medications or food

Infectious Causes Viral Bacterial Superinfection Shigella Salmonella
E. coli Campylobacter Superinfection Common viral: Influenza Bacterial causes mostly food-bourne illnesses d/t eating undercooked meat or d/t poor sanitary conditions Superinfection usually d/t antibiotic use: Clostridium difficile

Dietary Causes Lactose intolerance Excessive dietary fiber
Large amounts of salty drinks/foods Consumption of poorly soluble carbohydrates Unabsorbed dietary fat Pooly soluble carbs = very sugary things such as lactulose As a poorly soluble solute is transported, the gut adjusts the osmolality to that of plasma; in so doing, water and electrolytes flux into the lumen. (osmotic)

Medication Causes Laxatives NSAIDs Antacids Misc Antibiotics
Broad spectrum Augmentin Erythromycin Clindamycin Antihypertensives Atenolol Methyldopa Chemotherapy Laxatives NSAIDs Antacids Misc Colchicine Digoxin Potassium Quinidine And many many more  almost every drug that is approved! Augmentin up to 25% causes diarrhea, most PIs report 10-20% occurrence rate

GASTROINTESTINAL DISEASES
Inflammatory Bowel Disease Thyrotoxicosis

Diarrhea Treatment Options
Adsorbents Antisecretory Bismuth subsalicylate Enzymes (lactase) Antimotility Loperamide Diphenoxylate Opioids Misc Agents Octreotide #1) Nonpharm: Dietary management – D/C use of solid foods and dairy products for at least 24 hrs then progress to a bland diet with electrolyte replacement fluids if controlled. If not, continue water and electrolyte replacement strategies until diarrhea episode ends then progress – may need anti-N/V meds to help if have SSx Most of these drugs are not curative – only treat symptoms. Must treat underlying cause to get rid of diarrhea – NOT everyone will require antidiarrheals. Diarrhea can be the body’s defense mechanism to rid itself of toxins (ie food poisoning) and therefore should be allowed to run its course. Our goal is to minimize the potential secondary effects of diarrhea such as dehydration. Small frequent meals encouraging hydration. BRAT diet = bananas, rice, applesauce, toast. Avoid foods with artificial sweeteners like sorbitol! Adsorbents – not going into…not recommended anymore with newer, safer, more effective medications Opioids – Not used anymore – d/t abuse potential and better agents for diarrhea

Bismuth Subsalicylate
MOA Inhibits intestinal secretions Increases stool consistency Adsorbs bacteria Antimicrobial properties Adverse Effects Nausea Vomiting Constipation Discoloration of feces and tongue Tinnitus (OTC) indications for indigestion, relieving abdominal cramps, and controlling diarrhea including traveler’s diarrhea Can reduce the number of diarrheal stools by 50% Antimicrobial properties against E coli and other common GI pathogens ADRs- can induce gout attacks. Tinnitus – dose related related to the salicylate content Discoloration due to bismuth salts reacting with hydrogen sulfide produced by bacteria in mouth and colon to form bismuth sulfide = black discoloration Contraindicated in nursing/pregnant pts

Bismuth Subsalicylate
Warnings Contains salicylate Can overdose Drug Interactions Tetracyclines & Quinolones Methotrexate Warfarin Valproic Acid Usual Dosage: 2 tablets or 30mL q30min to 1 hr up to 8 doses/day Can increase effects of warfarin and valproic acid by significantly decreasing the protein binding of these drugs. Increases levels of MTX by decreasing its renal clearance. Bismuth is a trivalent cation and decreases absorption of tetracyclines and quinolones

Lactobacillus MOA Adverse Effects Drug Interactions
Replaces normal intestinal bacteria Inhibit growth of pathogenic bacteria Enhanced immune response Adverse Effects Flatulence Drug Interactions None known Lactobacillus acidophilus – used to help prevent episodes of acute diarrhea usually; not FDA approved so not officially recommended. Probiotic = live organisms that when ingested, produce some therapeutic or preventative health benefit. MOA not really known but theorized these three; suppresses…by competing with them for intestinal mucosal binding sites.

Lactobacillus Warnings Toxicity Allergy to milk or lactose None known
Can also take lactaid enzyme – various products for lactose intolerance  enzyme required for carb digestion (lack thereof causes an osmotic diarrhea)

Loperamide MOA Adverse Effects
Inhibits peristalsis via stimulation of μ-opiod receptor Antisecretory activity Adverse Effects Dizziness – Anorexia Abdominal pain – Nausea Vomiting – Fatigue Dry mouth Mu receptors located on intestinal circular muscles Inhibition of peristalsis  slows motility  allows for absorption of electrolytes and water thru the intestine 50x more potent than morphine and 2-3x more potent than diphenoxylate in its effects on GI motility. ADRs- penetrates CNS poorly so low risk of CNS side effects Yellow = usual SE at normal doses

Loperamide Drug Interactions Warnings Usual Dosage None known
Caution in children < 6 years Usual Dosage 4mg initially then 2mg after each loose stool Max dose = 16mg/ 24hrs

Diphenoxylate & Atropine
MOA Inhibits peristalsis Results seen in minutes Drug Interactions Anticholinergic Agents Usual Dosage 5mg (2 tablets) up to 4 times daily PRN Max dose: 20mg/ 24hrs Diphenoxylate is a controlled substance (schedule V); Atropine added to discourage abuse (anticholinergic) *If not response in 48hrs of cont therapy – this is likely to be ineffective and should be D/C’d Controlled substance = can cause psychological and physical dependence

Adverse Effects Nausea Vomiting Abdominal pain Constipation Dizziness Drowsiness Headache Nervousness Miosis Respiratory depression Tachycardia Urinary retention Anticholinergic SE

Drug Interactions Monoamine Oxidase Inhibitors (MAOIs) Tolerance/Dependence Controlled substance (Schedule V) Physical and psychological dependence

Octreotide MOA Usual Dosage
Blocks release of serotonin and other active peptides involved in controlling diarrhea Inhibitory effects on intestinal secretion Promotes intestinal absorption Usual Dosage 50mcg SQ initially then titrate dose based on indication up to 600mcg SQ daily in 2-4 divided doses Somatostatin analog Indications: FDA – control of symptoms with metastatic carcinoid and vasoactive intestinal peptide-secreting tumors. nonFDA – AIDS-assoc. secretory diarrhea; control of bleeding of esophageal varices, breast cancer, cryptosporidoiosis, Cushing’s syndrome, insulinomas, small bowel fistulas, pancreatic tumors, gastrinomas, chemo-induced diarrhea, graft-vs. host disease, congenital hyperinsulinism, hypothalamic obesity.

Octreotide Adverse Effects Flatulence (38%) Bradycardia (25%)
Chest Pain (20%) Hyperglycemia (27%) Diarrhea (58%) Abdominal discomfort (61%) Upper Respiratory infection (20%) Backache (20%) Flatulence (38%) Nausea (61%) Cholelithiasis (27%) Vomiting (21%) Injection site pain (50%) Dyspnea (20%) Flu Symptoms (20%) Conduction abnormalities (10%) Gallbladder/biliary tract complications such as cholelithiasis with prolonged use. Injection site rxn = 8% of patients Steatorrhea bc with high doses octreotide may reduce dietary fat absorption. Can also cause fecal discoloration. Drug interactions – may enhance effects of other QTc prolonging agents.

Complementary Therapies for Diarrhea
Acerola Aletris Chamomile Chinese Rhubarb Meadowsweet Nutmeg Oak Bark Podophyllum Pulsatilla Quince Tormentil Veratrum Arsenicum album Mercurius corrosives Sulfur FYI only none are FDA approved; none have been proven safe or effective for treatment of diarrhea and cannot be recommended.

PRODUCTS USED FOR DIARRHEA AND CONSTIPATION

Bulk-Forming Laxatives
Examples: Metamucil® Miralax® Citrucel® MOA Adds bulk to stool Activates peristalsis Absorbs water – antidiarrheal Get results in hrs but important to drink lots of water with these to avoid obstruction! Creates a viscous liquid that shortens GI transit time and promotes peristalsis Because these most closely approximate the physiologic mechanism in promoting defecation, these products are the recommended choice as initial therapy for most forms of constipation!

Adverse Effects Flatulence Abdominal cramping Obstruction Drug Interactions Warfarin Digoxin Tetracyclines Nitrofurantoin DIs- decreased absorption of other medications  decreased effect of the above medications – should separate admin times by at least 2 hrs.

Adverse Effects Diarrhea Excessive fluid loss Obstruction

Polyethylene Glycol MOA Usual Dosage Draws water into stool
Increases stool frequency and consistency Results seen in 2 to 4 days Usual Dosage 17gms (1 heaping Tablespoonful) in 8 ounces water daily Should not be used OTC for >2 weeks

Polyethylene Glycol Adverse Effects Drug Interactions
Nausea – Diarrhea Abdominal distention – Flatulence Abdominal cramping – Obstruction Vomiting Drug Interactions Separate from other meds by at least 1 hour

CONSTIPATION

Epidemiology Most common GI complaint in the US
Causes ~2 million doctor visits per year Most commonly afflicts women (pregnancy), children, and elderly >65yo US has the highest estimated prevalence of constipation than any other country (>4.4 million people) Doctor visits – only those that are reported. Most people treat constipation on their themselves without seeking help. Elderly obsessed with BM!

Constipation Clinical Definition Rome Criteria
<3 stools/week (women) <5 stools/week (men) ≥3 days without a BM Straining at defecation >25% of the time Rome Criteria Hard stools >25% of the time Sensation of incomplete bowel evacuation >25% of the time ≤2 BMs/week Many definitions and depends highly on baseline habits and diet! Very difficult to characterize! Rome criteria = ≥2 of the following SSx for ≥3 consecutive months

ROME CRITERIA  2 of the following symptoms for  3 months:
Straining at defecation ~ 25% of the time Lumpy and/or hard stools ~25% of the time A sensation of incomplete bowel evacuation ~25% of the time 2 or fewer bowel movements a week

Etiology Dietary Sedentary lifestyle Pregnancy Colorectal disorders
Neurological disorders Metabolic disorders Medications Constipation is NOT a disease but a symptom of an underlying disease or process. Tx should be targeted at correcting the problem. Dietary = lack of fiber and water/liquids Pregnancy = depressed gut motility, increased fluid absorption from colon, decreased physical activity, dietary changes, use of iron MVIs Colorectal disorders – hernias, hemorrhoids, diverticulitis, others Neurological disorders – Trauma, spinal cord injury, CNS diseases Metabolic disorders – diabetes and neuropathy (gastroparesis), hypothyroidism, hypercalcemia, others Meds – Bowels = last organ to ‘wake up’ after anesthesia

Drug-Induced Constipation
Cholestyramine Sodium polystyrene sulfonate Opiates Morphine Oxycodone Iron NSAIDs Diuretics Clonidine Antacids Aluminum Calcium Anticholinergics Antihistamines Anti-parkinson’s Tricyclic Antidepressants Antidiarrheals CCBs Basically listed in PI of all drugs!

Laxative Abuse Long term use
Inability to have a bowel movement without taking Clinical features: Severe watery diarrhea frequently occurring at night Abdominal pain, weight loss, nausea, vomiting Electrolyte imbalances Steatorrhea, cathartic colon, liver disease Similar to sleeping meds; use only as needed when indicated and use bulk-forming or softener/lubricant when can Can affect anyone- elderly or younger adolescents and college-aged adults Electrolyte imbalances= mostly potassium and calcium and magnesium Must try to wean pt off before permanent damage occurs such as loss of intrinis innervation to colon or atrophy of smooth muscle in gut (loss of gut fxn)

Constipation Treatment Options
Treat underlying cause Nonpharmacologic treatment Increase fiber, fluids, and exercise Remove potential offending agent Drug Therapy Stool Softener/Lubricants (Docusate, Mineral Oil) Stimulant Laxatives (Bisacodyl, Anthraquinones) Osmotic Laxatives (Sorbitol, Lactulose, Polyethylene Glycol, Glycerin) Saline Laxatives (Magnesium Citrate, MOM) Misc Agents (Erythromycin) Robust physical assessment – diet changes, changes in exercise American Dietetic Assoc recommends an adult daily dietary fiber intake of 20 to 30g consisting of both soluble and insoluble fiber.

Docusate Sodium MOA Adverse Effects Usual Dosage
Increases penetration of fluid into stool Softens stools to facilitate passage Adverse Effects Abdominal cramping Diarrhea Usual Dosage 50 to 360mg / day divided up to 4 times daily Emollient laxative  stool softener Results seen in hours Not significantly absorbed from GI tract and doesn’t affect absorption of other nutrients Pt should drink plenty of fluids to facilitate these drugs

ADVERSE EFFECTS Cramping Nausea Diarrhea

DRUG INTERACTIONS Mineral Oil
Docusate may increase absorption of mineral oil causing inflammation

Mineral Oil MOA Adverse Effects Usual Dosage
Coats and lubricates stools Results seen in 6 – 8 hours Adverse Effects Incontinence Lipid pneumonia Impaired absorption of fat-soluble vitamins Usual Dosage 15 to 45mL / day Lubricant laxative Routine use not indicated ADRs assoc with prolonged use Lipid pneumonia from aspiration of mineral oil (do not give at bedtime if aspiration risk)

Mineral Oil Drug Interactions
May impair absorption of vitamins A,D,E, and K Indirectly impair absorption of calcium and phosphates Do not give with meals (delays gastric emptying) Avoid use in pregnancy Warfarin Oral contraceptives Digoxin Docusate Indirectly impair  via impairing vit D absorption Pregnancy  can impair vitamin K absorption and decrease its availability to fetus May increase or decrease effect of warfarin by impaired absorption of vit. K or by impairing absorption of warfarin May impair absorption of OCs and dig May be absorbed if given with docusate

Bisacodyl (Dulcolax) MOA Adverse Effects Usual Dosage
Causes peristalsis Adverse Effects Abdominal pain / cramping Diarrhea Hypokalemia Malabsorption Usual Dosage 5-15mg (PO) as a single dose Max dose 30mg 10mg (PR) as a single dose Stimulant laxative  should not be used >1 week! Response = dose dependent Results seen in 15min to 1hr after rectal admin and 6-12h after PO ADR- can cause laxative dependence

Bisacodyl Drug Interactions Antacids Cimetidine Famotidine Ranitidine
Milk Proton Pump Inhibitors Should not be given within 1 hr of these products which increase gastric pH and erode off enteric coating therefore causing gastric or duodenal irritation. Tablets should not be broken, crushed, or chewed.

ADVERSE EFFECTS/DIs Adverse Effects Drug Interactions None known
Abdominal cramps Diarrhea Irritation Drug Interactions None known

Senokot (Sennosides) MOA Adverse Effects Usual Dosage
Increases colonic motility Results in 6 – 24 hours Adverse Effects Abdominal pain / cramping Nausea Discoloration of urine Usual Dosage 15mg Daily Max Dose 50mg BID (Sennosides  “all natural” from vegetable sources) – anthraquinone laxative May be used in combo with stool softeners Discolors urine pink to red, red to violet or red to brown

ADVERSE EFFECTS/DIs Adverse Effects Drug Interactions Abdominal pain
Cramping Diarrhea Nausea Discoloration of urine Drug Interactions None known

Castor Oil MOA Adverse Effects Usual Dosage Induces peristalsis
Hypotension Dizziness Nausea Vomiting Abdominal pain / cramping Usual Dosage 15-60mL as a single dose Results seen in 2-6 hrs

Sorbitol MOA Adverse Effects Usual Dosage Draws water into stool
Stimulates evacuation Adverse Effects Nausea Hyperglycemia Electrolyte disturbances Abdominal cramps Usual Dosage 30-150mL as a single dose Hyperosmotic laxative Results seen in as little as 1 hr Can also be given as a rectal enema

ADVERSE EFFECTS Diarrhea Nausea Vomiting Abdominal cramps Flatulence
Electrolyte disturbances

Lactulose MOA Adverse Effects Usual Dosage
Acidifies fecal contents and softens stool Causes abdominal distention Promotes peristalsis Adverse Effects Flatulence / Diarrhea Abdominal distension / cramping Usual Dosage 10-20gms / day (15-30mL) Max dose 60mL in 1-2 divided doses Results seen in hrs Drug interactions – neomycin, antacids, and other laxatives may reduce effects of lactulose (significance?) Also used for encephalopathy  causes diffusion of NH3 (ammonia) from blood to gut (given PR too)

ADVERSE EFFECTS Flatulence Abdominal distension Abdominal discomfort
Belching Cramping Diarrhea

DRUG INTERACTIONS Neomycin May reduce effects of lactulose Drug Inter

Lactulose Toxicity Cramping Dehydration Lactic acidosis Hypernatremia
Nausea Vomiting Diarrhea Flatulence Abdominal pain Cramping Dehydration Lactic acidosis Hypernatremia

Glycerin MOA Adverse Effects Usual Dosage
Draws fluid into the rectum to induce a bowel movement Induces peristalsis Adverse Effects Rectal irritation Usual Dosage 1 suppository PR 1-2 times / day PRN 5-15mL PR daily PRN as an enema Hyperosmotic laxative Results in 15 minutes to 1 hr

DIs/TOXICITY Drug Interactions None known Toxicity Diarrhea

Saline Laxatives MOA Adverse Effects Increases colonic volume
Stimulates intestinal motility Results in 30 min to 3 hrs (PO) or 5 min (PR) Adverse Effects Nausea Vomiting Electrolyte disturbances Flatulence Bloating Abdominal cramping Diuresis Dehydration Increases colonic volume by drawing fluid into colon and aids in colonic transit Indicated for use only when acute evacuation of the bowel is required (bowel prep for a procedure) Up to 20% of a PO dose can be absorbed

ADVERSE EFFECTS Dizziness Fainting Palpitations Weakness Diarrhea
Nausea Vomiting Abdominal cramping Bloating Flatulence

Saline Laxatives Drug Interactions Aspirin Iron Atenolol Azoles
Bismuth subsalicylate Cefpodoxime Fluroquinolones Hyoscyamine Digoxin Iron Azoles Sucralfate Tetracyclines Ticlopidine Zalcitabine Warfarin Contraindicated in pts with an ileostomy or colostomy, renal impairment, or CHF

Saline Laxatives Toxicity Hypernatremia Hyperphosphatemia Hypocalcemia
Nausea Vomiting Abdominal pain Diarrhea

Complementary Therapies for Constipation
Aloe vera Buckthorn Butternut Cascara sagrada bark Chicory Dandelion Dong quai Feverfew Flaxseed Fo-ti Licorice Plantago ovata seed Rhubarb Rose hips Sarsaparilla Senna leaves Sunflower Yellow dock FYI only

IMPLICATIONS FOR PHYSICAL THERAPISTS

Disease State Considerations
Drugs used do not directly influence rehabilitation Diarrhea and constipation common in nursing home and elderly patients Constipation is a known adverse effect of pain medications Frequent use of laxatives in hospitalized patients Elderly preoccupation with bowel habits Social considerations social = embarrassment

Common Adverse Effects of Diarrhea and Constipation
Cramping Bloating Flatulence Diarrhea Constipation Fatigue Dehydration

Effects on Physical Therapy
Positive effects Very treatable conditions Medications available OTC Most medications = cheap Symptom control - PRN Areas for concern Embarrassment Scheduling of session Dehydration Obstruction Very treatable conditions – been recognized as a problem for a loooooong time and there are drugs with decades of experience of use to treat conditions with Medications relatively cheap – been out for a long time Dehydration – affect cognition Overall affects mood and motivation to participate in therapy

QUESTIONS?

DIARRHEA AND CONSTIPATION

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