Constipation Pharmacotherapy Rastegarpanah Clinical pharmacy Department Shariati GI Research Center Tehran university of medical sciences

DEFINITION A Disturbance In Bowel Function. Stools Too Hard Or Too Small, Defecation Too Difficult Or Infrequent. “Normal” 3 Times / Day To 3 Times / Week A Stool Frequency Of Less Than Three Per Week

EPIDEMIOLOGY Prevalence 12-19% Prevalence Chronic Constipation Rises With Age, (65 Years Of Age Or Older). In Old Age, 26% Of Men & 34% Of Women Common In Pregnancy.

Digestion period Stomach: 3hours Small intestine: 4 – 6 hours Large intestine: 12 – 72 hours

Small intestine Duodenum 25-30cm Jejunum 2 metres Ileum 3 metres

Large intestine Ascending colon Transverse colon Descending colon Sigmoid colon

Peristalsis

Excretion Muscles work together to propel waste matter (Peristalsis) substances not absorbed by the body becomes faeces Faeces arrives in rectum to be expelled

What affects the bowel? Poor diet Lack of fluid Low Mobility Medications Surgery

PATHOPHYSIOLOGY  Constipation = disordered movement of stool through colon or rectum Slowing of colonic transit idiopathic or: Due to diseases Side effect of drugs

Etiology: Disease-Induced: Irritable bowel syndrome Metabolic disorders (diabetes), Endocrine disorders (hypothyroidism), Neurogenic disorders (Diabetes mellitus, Multiple sclerosis , Spinal cord injury). Drug-Induced Psychogenic causes Life-style factors Old age Children

Drugs associated with constipation

Constipation in Elderly Constipation Is Common: Improper Diets (Low In Fiber And Liquids) Diminished Abdominal Wall Muscular Strength Possibly Diminished Physical Activity Frequency Of Bowel Movements Is Not Decreased With Aging. Diseases Such As Colon Cancer And Diverticulitis, Drugs In Elderly: Anticholinergics, Aspirin, Furosemide, Nitroglycerin, Amitriptyline

Signs and Symptoms : Decrease in frequency of fecal elimination Difficult passage of dry hard stools Straining to have stool

Diagnostic Criteria Diagnosis Based On Presence Of Following For At Least Three Months (With Symptom Onset At Least Six Months Prior To Diagnosis).

Diagnostic Criteria Must Have Two Or More Of Following: Hard Stools In 25% Of Defecations Sensation Of Incomplete Evacuation For At Least 25% Of Defecations Sensation Of Anorectal Obstruction / Blockage For At Least 25% Of Defecations Fewer Than Three Defecations Per Week

Ten markers daily for six days CONSTIPATION Diagnostic Studies: Colonic Transit Time (CTT): radio-opaque markers & day 4 X-ray. Ten markers daily for six days No laxative and drugs

CTT In Evaluating Patients With Chronic Idiopathic Constipation. It Is Available And Has No Complication. No Surgical Intervention Without Colonic Transit Study Is Recommended .

Patient Assessment Obtain Lifestyle And Medical History Before Making Any Recommendations Determine Reason For Use Of A Laxative 1. To Relieve Constipation 2. To Evacuate The Bowel Prior To An Upcoming Radiologic Or Endoscopic Examination Inquire About The Patient’s Current And Past Use Of Laxative Products

Treatment If Underlying Disease Is Recognized, Cause Should Be Correct It. GI Cancer Removed Via Surgery. Endocrine And Metabolic Dz Corrected. If Hypo-thyroidism, Thyroid-replacement Therapy .

Refer to M.D. When…… Symptoms Have Persisted For More Than 2 Weeks Recurred After Previous Dietary Or Lifestyle Changes Or Laxative Use Patients With Blood In The Stool

Management Dietary Modification. Increase In Daily Fiber. Exercise (Even By Walking After Dinner) Bowel Habits, Regular & Adequate Time To Respond To Urge To Defecate. Increase Fluid Intake.

Non-drug Treatment High Fiber Food: Wheat Grains, Oats, Or Fruits & Vegetables Adequate Fluid Intake Exercise Avoid Foods That Cause Constipation: (Cheeses & Sweets)

NON-PHARMACOLOGIC THERAPY Fiber Increases Stool Bulk, Retention Stool Water & Increases Rate Transit Increase Frequency Of Defecation Fruits, vegetables, cereals have highest fiber Bran, a by-product of milling of wheat, Trial of dietary high-fiber should be for at least 1 month before effects on bowel function are determined

Non Prescription Medications Over The Counter (OTC) Types of laxatives: Bulk Forming Emollient Lubricant Saline Hyper-osmotic Stimulant

DRUG CLASSES Most Induce Bowel Evacuation By: Active Electrolyte Secretion Decreased Water And Electrolyte Absorption Increased Intraluminal Osmolarity Increased Hydrostatic Pressure In The Gut

Semifluid Stool In 6 To 12 Hours (Bisacodyl); Three Classifications: Softening Of Feces In 1 To 3 Days (Bulk-forming Laxatives, And Lactulose) Semifluid Stool In 6 To 12 Hours (Bisacodyl); Evacuation In 1 To 6 Hours (Magnesium Hydroxide, Castor Oil, And Polyethylene Glycol-electrolyte Solution).

Dosage Recommendations for Laxatives and Cathartics

Bulk Forming Laxatives Derived From Agar, Or Psyllium Seed Synthetic, Methylcellulose & Carboxymethyl Cellulose Sodium Dissolve In Intestinal Fluid, Thus Creating Emollient Gels That Increase Passage Of Intestinal Contents Stimulate Peristalsis No Systemic Absorption

Bulk Forming Laxatives Onset of action is 12-24hrs physiologic in promoting evacuation FIRST choice for constipation Examples are: Citrucel powder, Metamucil, Mitrolan Chewable Tablets

Bulk Forming Laxatives Caution In Younger Than 6 Yrs Of Age Avoid In Intestinal Ulcerations, Stenosis Interact With Anticoagulants, Digitalis Glycosides, And Salisylates Not Used For A Fast Clearing Effect Before A Diagnostic Procedure Used Daily And Continued In Most Patients, With Chronic Constipation.

Emollient Laxatives Anionic Surfactants, Softening Of Stool Systemically Absorbed (Solid) Onset Of Action (Oral) 24-72hrs As A Stool Softener, & To Prevent Constipation And Maintain Regularity Example : Docusate Sodium Avoid In Pts Who Have Nausea, Vomiting, Or Undetermined Abdominal Pain

Saline Laxatives Non-absorbable Cations & Anions - Draw Water Into Intestine - Increase In Intra-luminal Pressure, Stimulates Intestinal Motility Onset Of Action (Oral) 30min-3 Hrs, (Rectal) 2-5min ONLY When Fast Clearance Of The Bowel Is Required Ex: Fleet Phospho-soda Avoid In Pts With CHF, Ileostomy, Renal Function Impairment, Or Younger Than 6 Yrs Old

SALINE CATHARTICS Saline Cathartics Poorly Absorbed Ions Magnesium Sulfate Effects By Osmotic Action In Retaining Fluid In GI. Magnesium Stimulates The Secretion Of Chole-cystokinin, A Hormone That Causes Stimulation Of Bowel Motility And Fluid Secretion.

M.O.M May Be Given Orally Or Rectally. Bowel Movement Within A Few Hours After Oral Doses And In 1 Hour Or Less After Rectal May Cause Fluid And Electrolyte Depletion. Magnesium Or Sodium Accumulation In Patients With Renal Dysfunction

Hyper-Osmotic Laxatives Combine An Osmotic & Local Effect Of Sodium Stearate, Draws Water Into Rectum  bowel Movement Onset Of Action (Rectal) 30 Min Suppository Form Minimal Side Effects Example: Glycerin Suppositories Avoid In Pts With Rectal Irritation

GLYCERIN Glycerin as a 1 & 3 g suppository and exerts its effect by osmotic action in the rectum. onset of action is less than 30 minutes. Glycerin is very safe infants, children. Its use is acceptable on for constipation, in children.

Lubricant Laxatives Prevent colonic absorption of fecal water, thus soften the stool minimally absorbed Onset of action (oral)6-8 hrs, (rectal) 5-15 min Avoid prolonged use cause mal-absorption of fat-soluble vitamins Example: Mineral oil

LUBRICANTS Mineral oil (Paraffin) only lubricant laxative Mechanism from petroleum, coating stool and allowing for easier passage inhibits colonic absorption of water, increasing stool weight and decreasing stool transit time

Dose and ADR Mineral Oil Orally Or Rectally In A Dose Of 15 To 45 Ml Effect On Bowel After 2 Or 3 Days Of Use. In Debilitated Or Recumbent Patients, May Aspirated, Lipoid-pneumonia ADR: Decrease Absorption Of Fat-soluble Vitamins (A, D, E, And K) With Chronic Use Even Orally, May Leak From The Anal Sphincter, Causing Soiling Of Clothing.

LACTULOSE Lactulose - Disaccharide, used Orally Or Rectally Metabolized By Colonic Bacteria To Low-molecular-weight Acids, Result In Osmotic Effect = Fluid Is Retained In The Colon. The Fluid Retained In The Colon Lowers The Ph And Increases Colonic Peristalsis

LACTULOSE Not First-line, Not More Effective Than Sorbitol Or Milk Of Magnesia Alternative For Acute Constipation, Useful In Elderly Patients Lactulose May Result Flatulence, Cramps, Diarrhea, And Electrolyte Abnormality.

Lactulose Dose Initial Dose 5 To 30 Ml Daily PO In A Single Dose Or In 2 Divided Doses; Doses Up To 45 Ml Daily Dose Is Adjusted To Patient's Needs Children 5 To 10 Years Initial Doses Of 10 Ml Twice Daily 1 To 5 Years, 5 Ml Twice Daily Under 1 Year, 2.5 Ml Twice Daily.

Sorbitol A Monosaccharide, Osmotic Action, Primary Agent In Functional Constipation As Effective As Lactulose, Less Expensive. Sorbitol By Mouth Or Rectally As An Osmotic Laxative; Doses Of 20 To 50 G.

Stimulant Laxatives 2 Classes: - Diphenylmethane (Bisacodyl) - Anthraquinone (Senna) Increases Propulsive Peristaltic Activity By Local Irritation Of Mucosa Onset Of Action: Senna (PO) 8-12 Hrs Bisacodyl: Oral/Rectal 15-60min, Systemically Absorbed Major Use: For Evacuation Of Bowel Prior To GI Surgery Or Examination

Bisacodyl Stimulating Mucosal Nerve Plexus Of Colon Significant Inter-patient Variability Exists With Dosing A Dose That Causes No Effect In One Patient May Result In Excessive Cramping And Fluid Evacuation In Others. Not Recommended For Regular Daily Use.

Bisacodyl Acceptable Intermittently (Every Few Weeks) To Treat Constipation Or As A Bowel Preparation Cause Abdominal Cramping Significant Fluid And Electrolyte Imbalances With Chronic Use. Should Not Use In Appendicitis Is A Possibility (Perforation Of The Appendix May Result) Or During Pregnancy Or Lactation

ANTHRAQUINONE Cascara, Sennosides, And Casanthrol. Gut Bacteria Metabolizes These Agents To Their Active Compounds, Exact Mechanisms Of Action Not Understood. Effects Are Limited To The Colon, Use Of These Agents Are Similar To Those For The Diphenylmethane Derivatives. Intermittent Use Is Acceptable; Daily Use Discouraged

Stimulant Laxatives Sennakot, Sennakot S (With Sodium Docusate), Exlax, Dulcolax, Fijan Syrup (5.85 Mg Sennoside/5 Ml) Interact With H1 Blockers, Antacids If Administered Within 1 Hr Avoid In Pregnancy Breast Feeding: Senna Laxative Reported Brown Discoloration Of Breast Milk Adverse Effects: Severe Cramping, Electrolyte & Fluid Deficiencies, Metabolic Acidosis/Alkalosis

CASTOR OIL Castor Oil Metabolized In GI To Active Compound, Ricinoleic Acid, Stimulates Secretory Processes, Decreases Glucose Absorption, And Promotes Intestinal Motility, In Small Intestine. Castor Oil Results In A Bowel Movement 1 To 3 Hours. Because Strong Purgative Action, Should Not Used For Routine Treatment Of Constipation.

Polyethylene Glycol PEG Become Popular For Colon Cleansing Before Diagnostic Procedures Or Colorectal Operations. Four Liters Of This Solution Is Administered Over 3 Hours Not Recommended For Routine Treatment Of Constipation And Should Be Avoided In Patients With Intestinal Obstruction.

Acute Constipation infrequent use (less than every few weeks) of laxative is acceptable. Relieved by use of a tap-water enema or a glycerin suppository; if ineffective, use of oral sorbitol, low doses of diphenylmethane or anthraquinone laxatives, or saline laxative (e.g., milk of magnesia) If laxative is required for longer than 1 week, consult a physician

Bedridden or Geriatric patients For some bedridden or geriatric patients, or with chronic constipation, bulk-forming laxatives first line of treatment, Use of laxatives may be required frequently. Lowest effective dose and infrequently as possible to maintain regular bowel function (more than three stools per week). Milk of magnesia, and sorbitol or lactulose. Mineral oil should be avoided

Patient Counseling Laxative use to treat constipation should be only on a temporary measure If laxatives are not effective after 1 week, a physician should be consulted

Management 1-Management of chronic constipation due to slow transit including: patient education behavior modification dietary changes drug therapy

2-Management of defecation involves: biofeedback sensory training relaxation exercises suppository programs

Patient education: reassurance explanation of normal bowel habits reduce use of laxatives and cathartics increase fluid and fiber intake use normal postprandial increases in colonic motility by instructing patients to defecate after meals important in the morning when colonic motor activity is highest

What Can You Do? Become more physically active A 30 minute walk every day may help keep you more regular As we said earlier, too much inactivity like sitting and watching TV, riding in a car, or on an airplane can contribute to constipation. Make an effort to walk 30 minutes every day. You can space it out into 10-15 minutes sessions several times a day. Other good activities include swimming or bicycling. If you have difficulty walking or can’t swim, there are armchair videos available to help increase your physical activity while sitting in a chair.

What Can You Do? Eat more fiber More beans, whole grains and bran cereals, fresh fruits, vegetables Limit foods with no fiber (cheese, meat, sweets, processed foods) There are several things you can do to prevent and treat constipation. Eat more fiber (both soluble and insoluble). Americans eat too many refined and processed foods in which the natural fiber has been removed. Choose breakfast cereals with more than 4 grams of dietary fiber per serving such as All-Bran, All-Bran with Extra Fiber, Bran Buds, Bran Flakes, and Raisin Bran. If you add bran to your diet, be sure to do it slowly so your system gets used to it. This can help prevent a lot of gas and bloating. Eat more fresh fruits and vegetables. Add fresh fruit to your cereal and as snacks and dessert. Dried fruit such as apricots, prunes, and figs are especially high in fiber. Eat more salads and cooked vegetables. A good goal is to eat at least 2 vegetables or fruits at each meal.

What Can You Do? Fiber supplements are best choice Absorb water and make stool softer Safe to use everyday Be sure to drink at least 8 to 10 glasses of water everyday Add to diet slowly to prevent problems with gas Brand names of fiber supplements include Metamucil, Citrucel, Fiberall, Konsyl. Fiber supplements can interfere with absorption of some medicines, so be sure to check with your doctor about using these.

What Can You Do? Drink more water and other liquids (8 eight-ounce glasses a day) Liquid helps keep the stool soft Avoid caffeine or alcohol which can dehydrate you Make a special effort to drink more water, vegetable juices, clear broth, and fruit juices. Use decaffeinated beverages instead of those that contain caffeine like coffee, tea, and colas. They, like, alcohol, can have the opposite effect - they can dehydrate you.

Treatment algorithm for normal transit constipation

Treatment algorithm for slow-transit constipation

Thank you for your attention

Constipation in Infants & children Constipation common. neurologic, metabolic, or anatomic abnormalities. Management: Dietary modification with high-fiber foods

Magnesium Hydroxide (Milk of magnesium MOM)240cc 8% Susp Drugs for Constipation: Fluid & High fibers Laxatives -osmotic: Polyethylene glycol (70 g powder)   Lactulose (10g/15 ml syrup)     Sorbitol (5g powder) Glycerin Laxatives - stimulant: Bisacodyl (Dulcolax, Correctol) 5 mg tab;5,10 mg supp.   Castor oil Senna Figan syrup (5.85 mg sennoside B/5 ml) Magnesium Hydroxide (Milk of magnesium MOM)240cc 8% Susp

Thank you for your attention Rastegarpanah