National Naval Medical Center Bethesda, MD

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1 Brooks Cash. MD National Naval Medical Center Bethesda, MD

2 Multicomponen nt Approach to Functional GI Disorders Establish therapeutic relations ship Assess patient s medical h istory, personality, and family Assess quality of life an nd level of daily functioning Take psychosocial history Order appropria ate diagnostic testing Make a conf fident diagnosis Explain and reassure In stitute appropriate treatment

3 Suggested Gen neral Measures for Cons stipation Discontinue constip ating medications Correct endocrine di iseases Treat depression Reassure Regular visits to the intake, and exercise toilet, increased fluid

4 Institute Approp priate Treatment Dietary advice Lifestyle advice Judicious i drug treatmen t nt Many in primary care do not need drugs Use when work or soci ial function are impaired Should be evidence-ba ased Target troublesome sym mptoms Prescribe short-term o r as needed Encourage follow-up

5 Dietary Advice No standard FGID diet! Avoid excess s Caffeine, cho ocolate, alcohol Antidiarrheal ls Sorbitol Fatty or junk food Encourage Dietary fiber for hard stools Antireflux me easures for heartburn Allow sufficie ent time and quiet for meals

6 General Measures s for Constipation Constip pating medic ations Address other causes Die etary Lifestyle images

7 Medications Associat ted With Constipation Nonprescription drugs Antacids, especially calcium- containing Calcium supplements Iron supplements Antidiarrheal agents Nonsteroidal antiinflammatory agents Prescription drugs Opioids Anticholinergic agents Tricyclic antidepressants Calcium channel blockers Statin agents Anti-Parkinsonian drugs Sympathomimetics Antipsychotics Diuretics Antihistamines Locke GR III et al. Gastroenterology 2000; 119:1766

8 Fiber Supplem mentation and Bulk Laxatives Classification Wheat bran Whole-grain food produ ucts Soluble-fiber bulk laxati ives Insoluble-fiber bulk laxa atives

9 Wheat Bran and Stool Weight: A Dose Response Increase in stool weight over baseline (g) P<0.01 n-6 0 Stephen AM et al. Br J Nutrition 1986; 56: Wheat fiber (g)

10 Efficacy of F iber in IBS-C 13 randomized clinical trial s Wheat bran, corn fiber, cal lcium polycarbophil, ispaghula, and psyllium Low-intermediate quality studies with small sample sizes Ispaghula (4/5 studies) imp proved global IBS symptoms and ease of stool passage but not pain. Side effects: may increase intestinal gas, bloating and abdominal discomfort Appropriate for constipatio on-predominant symptoms Brandt LJ et al. Am J Gastroenterol 2002;97 suppl:s7-26 Lesbros-Pantoflickova D et al. Aliment Pharmacol Ther 2004;20:1253

11 Fiber/Bulking Agents for IBS: Effect on Glob bal Symptoms Quality Study score (n/n) (n/n) Arthurs 3 29/40 24/38 Cook 4 3/14 4/14 Fowlie /24 Jalihal 2 7/20 2/20 Longstreth 4 20/ Lucey 2 22/28 20/28 Nigam 2 41/84 22/84 Pnor 4 66/80 42/80 Ritchie, /48 23/48 Ritchie, /28 8/28 Snook 4 37/71 38/71 Soltoft /23 Toskes 2 23/48 13/48 Total (05% CI) 344/ /556 Total high-quality 344/ /284 studies (95% CI) Lesbros-Pantoflickova D et al. APT 2004; 20: % CI random Favors placebo Favors fiber

Diphenylmethane derivatives Stimulan nt laxative Absorption

12 Stimulant Laxatives s: Classification and Mechanism of Action Anthraquinones (sennosides) Bisacodyl Castor oil Diphenylmethane derivatives Stimulan nt laxative Absorption Motility Prostaglandins Locke GR III et al. Gastroenterology 2000; 119:1766

13 Stimulant Laxatives s: Classification and Mechanism of Action Anthraquinones (sennosides) Laxative is cleaved by bacteria Bisacodyl Enteric nerves Enteric nerves are stimulated Locke GR II et al. Gastroenterology 2000; 119:1766

14 Efficacy of Stim mulant Laxatives 4 randomized comparative tri ials None placebo-controlled Low-quality study design No difference between stim mulant laxative and control laxative in stool frequency or consistency In 1 study Lactulose was superior to the irritant laxative: 58% vs 42% were passing a no ormal stool by day 7 Insufficient evidence to make a recommendation regarding efficacy Brandt LJ et al. Am J Gastroenterol 2005; 100:S5

15 Osmotic Laxative es: Classification Poorly absorbed mon o- and disaccharides Lactulose Mannitol Sorbitol S l Glycerin supposito ories Saline laxatives Magnesium: citrate e, sulphate, hydroxide Sodium and disodi um phosphate Other Polyethylene glycol (PEG)

16 Osmotic Laxatives: Mo ono- and Disaccharides Laxative Laxatives metabolized by bacteria... Bass P, Dennis S. J Clin Gastroenterol. 1981; 3 (Suppl 1):23 Ramkumar D, Rao SS. Am J Gastroenterol. 2005; 100:936

Osmotic Laxatives: Mo ono- and Disaccharides Laxatives metabolized by bacteria... Laxative... to short-chain fatty acids, increasing the osmotic load and changing the ph Bass P, Dennis S.

17 Osmotic Laxatives: Mo ono- and Disaccharides Laxatives metabolized by bacteria... Laxative... to short-chain fatty acids, increasing the osmotic load and changing the ph Bass P, Dennis S. J Clin Gastroenterol. 1981; 3 (Suppl 1):23 Ramkumar D, Rao SS. Am J Gastroenterol. 2005; 100:936

18 Effectiveness and Safe ety Profile of Lactulose Studies Summary and Adverse Pregnancy Recommendations Events Category 3 RPCTs Improves stool frequency and consistency Nausea Vomiting Bloating Flatulence Intestinal cramps B RPCT = randomized placebo-controlled trial Brandt LJ et al. Am J Gastroenterol. 2005; 100(suppl 1):S5. Physicians Desk Reference Montvale, NJ. Thomson PDR; 2005

19 Osmotic Laxatives s: Saline Laxatives Calcium Potassium Potassium Calcium Electrolyte loss Water is incompletely absorbed Net flux of water, which remains in lumen

20 Effectiveness and Safe ety Profile of PEG 3350 Studies Summary and Adverse Pregnancy Recommendations Events Category 5 RCTs Effective at improving stool frequency and consistency RCTs = randomized controlled trials Nausea Bloating Cramping Caution regarding g electrolyte disturbances C Brandt LJ et al. Am J Gastroenterol. 2005; 100(suppl 1):S5. Tran LC et al. J Clin Gastroenterol. 2005; 39:600 Physicians Desk Reference Montvale, NJ. Thomson PDR; 2005

21 Long-Term Effectiv veness of PEG 3350 in Chronic Constipation Successful treatm ment after 6 months 50 Pla acebo % of 40 patients *P< < * PE EG * 0 All n=304 Elderly l n=75 Dipalma JA et al. Am J Gastroenterol. 2007; 102:1436

22 Chloride Channels in Intestinal Transport H 2 O Na + Cl l - Cl - Enterocytes CFTR channel Ion Transport Cl C2 channel Tight junction K + Na + K + H 2 O Na + Na + 2Cl - K +

23 Effects of Lubipros stone on Number of Spontaneous Bo owel Movements 7 6 P = P = P = P = Mean 4 SBMs per week Baseline Week 1 24 µg lubiprostone bid Placebo n = 242 Intent-to o-treat population Week 2 Week 3 Week 4 SBM = spontaneous bowel movements Johanson JF et al. Am J Gastroenterol. 2008;103:170.

24 Lubiproston ne for IBS-C: Data from 2 Phase III Trials week treatment period Overall responder=monthly responder for at least 2 of 3 months % Overall Responders 25 * P= Monthly responder=at least moderate relief for 4/4 weeks or significant relief for 2/4 weeks Lubiprostone 8 mcg bid n=780 Placebo n=387 Drossman DA et al. Gastroenterology 2007; 132:639f

25 Effect of Linaclotide on Colonic Transit in IBS-C Mean + SEM Ba aseline Po ost treatment * GC Placebo n = 12 Linaclotide 100 mg n = 12 Linaclotide 1000 mg n = 12 *P=0.01 vs placebo GC 48 = geometric center at 48 hours Andresen V et al. Gastroenterology 2007; 133:761

26 Graded Treatm ment Response Multidisciplinary approach Psychological tre eatments Improve function ning + Manage stress Severe Pharmacotherapy + Diet, lifestyle advice Positive diagnosis Explain, reassure Moderate Mild

Constipation an Old Friend. Presented by Dr. Keith Harris

Constipation an Old Friend. Presented by Dr. Keith Harris Constipation an Old Friend Presented by Dr. Keith Harris Irregularity and the Tricks of the Trade." CONSTIPATION What is constipation? INFREQUENT BOWEL MOVEMENTS DIFFICULTY DURING DEFECATION SENSATION