1. Constipation Dr Orhan Tarçın Gastroenterology Department Yeditepe University

2. Constipation Epidemiology of Constipation Epidemiology of Constipation Objectives of self-treatment Objectives of self-treatment Nondrug Measures Nondrug Measures OTC medications for the relief of constipation OTC medications for the relief of constipation

3. Constipation Signs and Symptoms include: Signs and Symptoms include: A decrease in the frequency of fecal elimination A decrease in the frequency of fecal elimination Difficult passage of dry hard stools Difficult passage of dry hard stools Straining to have stool Straining to have stool

4. Constipation Common medications that can induce constipation are: Narcotic analgesics Narcotic analgesics Calcium-or aluminum containing antacids Calcium-or aluminum containing antacids Drugs with anticholinergic activity Drugs with anticholinergic activity Tricyclic antidepressants Tricyclic antidepressants Certain calcium channel blockers: ex. Verapamil Certain calcium channel blockers: ex. Verapamil

5. Constipation Can be induced by one of the following diseases: Hypothyroidism Hypothyroidism Megacolon Megacolon Stricture Stricture Diabetes Mellitus Diabetes Mellitus Irritable Bowel Syndrome Irritable Bowel Syndrome

6. A.Ş.K. Ağrı Şişkinlik Kabızlık

7. Irritable bowel syndrome (IBS) IBS is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit, and with features of disordered defecation IBS is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit, and with features of disordered defecation 10-20% adults in world, female predominant 10-20% adults in world, female predominant Come and go over time, overlap with other FGID Come and go over time, overlap with other FGID Poor QoL, high heath care costs Poor QoL, high heath care costs Longstreth GF, et al. Gastroenterology 2006;130:1480-91.

15. Enteric nervous system (ENS)

16. Brain imaging in rectal stimulation (fMR) Normal visceral sensation: 1. Gender difference,  ACC & PFC in females 2. Common FGID in females? 2. Common FGID in females? Grundy D, et al. Gastroenterology 2006;130:1391-1411.

17. IBS in females VS

18. Sex hormones or gender impacts on brain-gut axis Animals Animals Low threshold for visceromotor response in rat proestrus vs estrus phase Low threshold for visceromotor response in rat proestrus vs estrus phase  potency of opiates to  visceromotor response in male rats  potency of opiates to  visceromotor response in male rats Modulation of response in afferent neurons of male GP Modulation of response in afferent neurons of male GP Drugs: estrogen/progesteron on P-450 system Drugs: estrogen/progesteron on P-450 system CYP3A4: women clearing drugs quickly CYP3A4: women clearing drugs quickly Humans Humans Slow GE in women Slow GE in women Women experience greater pain to most stimuli Women experience greater pain to most stimuli Different areas of brain activation: males vs females Different areas of brain activation: males vs females Different polymorphism of 5-HT transporter promoter: males vs females Different polymorphism of 5-HT transporter promoter: males vs females Ouyang A, et al. Am J Gastroenterol 2006;101:S602-9.

19. Diagnostic criteria for IBS, C1 Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following: Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following: Improvement with defecation Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool Onset associated with a change in form (appearance) of stool Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis Discomfort: uncomfortable sensation not described as pain Discomfort: uncomfortable sensation not described as pain Longstreth GF, et al. Gastroenterology 2006;130:1480-91.

20. Diagnostic criteria for IBS Organik sebepleri dışla Organik sebepleri dışla Roma II criteria Roma II criteria Son 12 ayda en az ≥12 hafta olan abdominal ağrı ve huzursuzluk ve dışkılama alışkanlığında değişiklik olacak Son 12 ayda en az ≥12 hafta olan abdominal ağrı ve huzursuzluk ve dışkılama alışkanlığında değişiklik olacak Ve aşağıdakilerden en az ikisi eşlik edecek Ve aşağıdakilerden en az ikisi eşlik edecek defakasyonla rahatlama defakasyonla rahatlama dışkının kıvamında değişiklik dışkının kıvamında değişiklik dışkının şeklinde değişiklik dışkının şeklinde değişiklik Aşağıdaki semptomların bulunması şart değildir, fakat bunlardan ne kadar çoğu mevcutsa, tanı o kadar kesinleşir: Anormal dışkılama sıklığı (>3/gün veya 3/gün veya <3/hafta) Anormal dışkı şekli Anormal dışkı şekli Anormal dışkı pasajı Anormal dışkı pasajı Mukus pasajı Mukus pasajı Şişkinlik veya abdominal distansiyon hissi Şişkinlik veya abdominal distansiyon hissi

21. Sub-typing IBS by predominant stool pattern Subtype (absent use of antidiarrheals or laxatives) Subtype (absent use of antidiarrheals or laxatives) IBS-C (IBS with constipation): hard or lumpy stools >25% and loose (mushy) or watery stools 25% and loose (mushy) or watery stools <25% of BMs IBS-D (IBS with diarrhea): loose (mushy) or watery stools >25% and hard or lumpy stool 25% and hard or lumpy stool <25% of BMs IBS-M (mixed IBS): hard or lump stools >25% and loose (mushy) or watery stools > 25% of BMs IBS-M (mixed IBS): hard or lump stools >25% and loose (mushy) or watery stools > 25% of BMs IBS-U (unsubtyped IBS): insufficient abnormality of stool consistency to meet criteria for IBS-C, D, or M IBS-U (unsubtyped IBS): insufficient abnormality of stool consistency to meet criteria for IBS-C, D, or M Stool form: Bristol scale Stool form: Bristol scale Longstreth GF, et al. Gastroenterology 2006;130:1480-91.

24. Alarm symptoms in IBS diagnosis Age of onset over 50 yrs Age of onset over 50 yrs Progressive or very severe non-fluctuating symptoms Progressive or very severe non-fluctuating symptoms Nocturnal symptoms waking from sleep Nocturnal symptoms waking from sleep Persisted diarrhea, recurrent vomiting Persisted diarrhea, recurrent vomiting Rectal bleeding, anemia Rectal bleeding, anemia Unexplained BW loss Unexplained BW loss Family history of colon cancer Family history of colon cancer Fever Fever Abnormal physical examinations Abnormal physical examinations Talley NJ, et al. Lancet 2002;360:555-564.

26. Patient Assessment Obtain lifestyle and medical history before making any recommendations Obtain lifestyle and medical history before making any recommendations Determine the reason for use of a laxative product Determine the reason for use of a laxative product 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 Inquire about the patient’s current and past use of laxative products

27. Refer When…… Symptoms have persisted for more than 2 weeks Symptoms have persisted for more than 2 weeks Have recurred after previous dietary or lifestyle changes or laxative use Have recurred after previous dietary or lifestyle changes or laxative use Patients who admit to blood in the stool Patients who admit to blood in the stool

28. Objectives for Self Treatment To relieve constipation and restore “normal” bowel functioning using: Dietary and Lifestyle measures Dietary and Lifestyle measures Using OTC medications for the relief of constipation Using OTC medications for the relief of constipation

29. Nondrug Measures include High fiber diet: foods high in wheat grains, oats, or fruits & vegetables High fiber diet: foods high in wheat grains, oats, or fruits & vegetables Adequate fluid intake Adequate fluid intake Exercise Exercise Avoid foods that cause constipation: processed cheeses & concentrated sweets Avoid foods that cause constipation: processed cheeses & concentrated sweets

30. Non Prescription Medications Types of laxatives: Bulk Forming Laxatives Bulk Forming Laxatives Emollient Emollient Lubricant Lubricant Saline Saline Hyperosmotic Hyperosmotic Stimulant Stimulant

31. Bulk Forming Laxatives Derived from agar, or psyllium seed Derived from agar, or psyllium seed Synthetic examples used today are methylcellulose & carboxymethyl cellulose sodium Synthetic examples used today are methylcellulose & carboxymethyl cellulose sodium Dissolve in the intestinal fluid, thus creating emollient gels that increase passage of the intestinal contents Dissolve in the intestinal fluid, thus creating emollient gels that increase passage of the intestinal contents Stimulate peristalsis Stimulate peristalsis No systemic absorption No systemic absorption

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

33. Bulk Forming Laxatives Use caution in patients that are younger than 6 yrs of age Use caution in patients that are younger than 6 yrs of age Avoid in pts with intestinal ulcerations, stenosis Avoid in pts with intestinal ulcerations, stenosis Interact with anticoagulants, digitalis glycosides, and salisylates Interact with anticoagulants, digitalis glycosides, and salisylates Not used for a fast clearing effect before a diagnostic procedure Not used for a fast clearing effect before a diagnostic procedure

34. Emollient Laxatives Are anionic surfactants that eventually lead to the softening of the stool Are anionic surfactants that eventually lead to the softening of the stool Are systemically absorbed (solid) Are systemically absorbed (solid) Onset of action (oral) 24-72hrs Onset of action (oral) 24-72hrs Major use is as a stool softener, & to prevent constipation and maintain regularity Major use is as a stool softener, & to prevent constipation and maintain regularity Example : Docusate sodium Example : Docusate sodium Avoid in pts with who have nausea, vomiting, or undetermined abdominal pain Avoid in pts with who have nausea, vomiting, or undetermined abdominal pain

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

36. Saline Laxatives Nonabsorbable cations & anions that draw water into intestine causing an increase in intraluminal pressure, which stimulates intestinal motility Nonabsorbable cations & anions that draw water into intestine causing an increase in intraluminal pressure, which stimulates intestinal motility Are systemically absorbed Are systemically absorbed Onset of action (oral)30min-3 hrs,(rectal) 2-5min Onset of action (oral)30min-3 hrs,(rectal) 2-5min Used ONLY when fast clearance of the bowel is required Used ONLY when fast clearance of the bowel is required Ex:Citroma, Fleet Ready-to-Use Enema Ex:Citroma, Fleet Ready-to-Use Enema Avoid in pts with CHF, ileostomy, renal function impairment, or younger than 6 yrs old Avoid in pts with CHF, ileostomy, renal function impairment, or younger than 6 yrs old

37. Hyperosmotic Laxatives Combine an osmotic effect with local effect of sodium sterate, which draws water into rectum  bowel movement Combine an osmotic effect with local effect of sodium sterate, which draws water into rectum  bowel movement Onset of action (rectal) 30 min Onset of action (rectal) 30 min Used in suppository form Used in suppository form Minimal side effects Minimal side effects Example: Glycerin suppositories (only) Example: Glycerin suppositories (only) Avoid in pts with rectal irritation Avoid in pts with rectal irritation

38. Stimulant Laxatives Come from 2 classes: anthraquinone (ex:senna) & diphenylmethane ( bisacodyl) Come from 2 classes: anthraquinone (ex:senna) & diphenylmethane ( bisacodyl) Increase the propulsive peristaltic activity of the intestine by local irritation of the mucosa which leads to increased motility Increase the propulsive peristaltic activity of the intestine by local irritation of the mucosa which leads to increased motility Onset of action senna (PO) 8-12 hrs Onset of action senna (PO) 8-12 hrs For Bisacodyl: oral/rectal 15-60min, For Bisacodyl: oral/rectal 15-60min, Are systemically absorbed Are systemically absorbed Major use: for thorough evacuation of the bowel prior to GI surgery or examination Major use: for thorough evacuation of the bowel prior to GI surgery or examination

39. Stimulant Laxatives Examples: Sennakot, Sennakot S (with sodium docusate), Exlax, Dulcolax Examples: Sennakot, Sennakot S (with sodium docusate), Exlax, Dulcolax Interact with H1 blockers, antacids if administered within 1 hr Interact with H1 blockers, antacids if administered within 1 hr Avoid in pregnancy Avoid in pregnancy Pts who are breast feeding & taking senna laxative have reported a brown discoloration of breast milk Pts who are breast feeding & taking senna laxative have reported a brown discoloration of breast milk Adverse effects with regular use are severe cramping, electrolyte & fluid deficiencies, metabolic acidosis/alkalosis, and others Adverse effects with regular use are severe cramping, electrolyte & fluid deficiencies, metabolic acidosis/alkalosis, and others

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