1. Cengiz Pata Gastroenterology Department Yeditepe University
Constipation
Cengiz Pata
Gastroenterology Department Yeditepe University

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

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

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

5. Constipation Can be induced by one of the following diseases:
Hypothoroidism
Megacolon
Stricture
Diabetes Mellitus
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
10-20% adults in world, female predominant
Come and go over time, overlap with other FGID
Poor QoL, high heath care costs
Longstreth GF, et al. Gastroenterology 2006;130:

13. Serotonin is involved at just about every level of the communication between gut and brain, both going from gut to brain and then from brain to gut. One appealing therapeutic avenue is to focus on the site where most of the 5-HT is being released and try to affect outcome and symptoms by modulating symptoms at the level of the gut trying to avoid the possible side effects that may come with more central modulation of serotoninergic pathways.

14. This may be further demonstrated in the sense that there is increased circulating 5-HT in patients with diarrhea-dominant IBS and increased EC cell population in the gut, whereas in some subgroup of patients with chronic constipation, there appears to be a decreased number of EC cells suggesting that, if we stimulate serotoninergic pathways, we might be able to improve symptoms in these patients.

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?
Grundy D, et al. Gastroenterology 2006;130:

17. VS
IBS in females

18. Sex hormones or gender impacts on brain-gut axis
Animals
Low threshold for visceromotor response in rat proestrus vs estrus phase
 potency of opiates to  visceromotor response in male rats
Modulation of response in afferent neurons of male GP
Drugs: estrogen/progesteron on P-450 system
CYP3A4: women clearing drugs quickly
Humans
Slow GE in women
Women experience greater pain to most stimuli
Different areas of brain activation: 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:
Improvement with defecation
Onset associated with a change in frequency 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
Discomfort: uncomfortable sensation not described as pain
Longstreth GF, et al. Gastroenterology 2006;130:

20. Diagnostic criteria for IBS
Organik sebepleri dışla
Roma II criteria
Son 12 ayda en az ≥12 hafta olan abdominal ağrı ve huzursuzluk ve dışkılama alışkanlığında değişiklik olacak
Ve aşağıdakilerden en az ikisi eşlik edecek
defakasyonla rahatlama
dışkının kıvamında 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/hafta)
Anormal dışkı şekli
Anormal dışkı pasajı
Mukus pasajı
Şişkinlik veya abdominal distansiyon hissi

21. Sub-typing IBS by predominant stool pattern
Subtype (absent use of antidiarrheals or laxatives)
IBS-C (IBS with constipation): hard or lumpy 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% 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
Stool form: Bristol scale
Longstreth GF, et al. Gastroenterology 2006;130:

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

24. Patient Assessment
Obtain lifestyle and medical history before making any recommendations
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

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

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

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

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

29. Bulk Forming Laxatives
Derived from agar, or psyllium seed
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
Stimulate peristalsis
No systemic absorption

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

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

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

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

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

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

36. Stimulant Laxatives
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
Onset of action senna (PO) 8-12 hrs
For Bisacodyl: oral/rectal 15-60min,
Are systemically absorbed
Major use: for thorough evacuation of the bowel prior to GI surgery or examination

37. Stimulant Laxatives
Examples: Sennakot, Sennakot S (with sodium docusate), Exlax, Dulcolax
Interact with H1 blockers, antacids if administered within 1 hr
Avoid in pregnancy
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

38. 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