Skip to main content
SpringerLink
Log in

Gastrointestinal Pharmacology

  • Chapter
  • First Online:
Book cover Gastrointestinal Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 239))

Abstract

There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was beneficial in the treatment of FAPDs in children. There are conflicting data regarding amitriptyline. While one small study found a significant benefit in quality of life compared with placebo, a large multicenter study found no benefit compared with placebo. The antidepressant, citalopram, failed to meet the primary outcomes in intention-to-treat and per-protocol analysis. Rifaximin has been shown to be efficacious in the treatment of adults with IBS. Those findings differ from studies in children where no benefit was found compared to placebo. To date, there are no placebo-controlled trials published on the use of linaclotide or lubiprostone in children. Alpha 2 delta ligands such as gabapentin and pregabalin are sometimes used in the care of this group of children, but no clinical trials are available in children with FAPDs. Similarly, novel drugs that have been approved for the care of irritable bowel with diarrhea in adults such as eluxadoline have yet to be studied in children. Conclusions: Little data support the use of most medications commonly used to treat FAPDs in children. More randomized, placebo-controlled studies are needed to assess the efficacy of pharmacological interventions in the treatment of FAPDs in children.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alajbegovic S, Sanders JW, Atherly DE, Riddle MS (2012) Effectiveness of rifaximin and fluoroquinolones in preventing travelers’ diarrhea (TD): a systematic review and meta-analysis. Syst Rev 1:1

    Article  Google Scholar 

  • Anderson LA, Gross JB (2004) Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea. J Perianesth Nurs 19:29–35

    Article  PubMed  Google Scholar 

  • Arkwright JW, Underhill ID, Dodds KN, Brookes SJ, Costa M, Spencer NJ, Dinning P (2016) A composite fibre optic catheter for monitoring peristaltic transit of an intra-luminal bead. J Biophotonics 9:305–310

    Article  PubMed  Google Scholar 

  • Ashoor A, Nordman JC, Veltri D, Yang KH, Shuba Y, Al Kury L, Sadek B, Howarth FC, Shehu A, Kabbani N, Oz M (2013) Menthol inhibits 5-HT3 receptor-mediated currents. J Pharmacol Exp Ther 347:398–409

    Article  CAS  PubMed  Google Scholar 

  • Bahar RJ, Collins BS, Steinmetz B, Ament ME (2008) Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents. J Pediatr 152:685–689

    Article  CAS  PubMed  Google Scholar 

  • Bharucha AE, Waldman SA (2010) Taking a lesson from microbial diarrheagenesis in the management of chronic constipation. Gastroenterology 138:813

    Article  PubMed  PubMed Central  Google Scholar 

  • Bijvelds MJ, Bot AG, Escher JC, De Jonge HR (2009) Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. Gastroenterology 137:976–985

    Article  CAS  PubMed  Google Scholar 

  • Brandt L, Chey W, Foxx-Orenstein A, Quigley E, Schiller L, Schoenfeld P, Spiegel B, Talley N, Moayyedi P (2009) An evidence-based position statement on the management of irritable bowel syndrome (vol 104, pg S1, 2009). Am J Gastroenterol 104:1072–1072

    Google Scholar 

  • Brawek B, Loffler M, Weyerbrock A, Feuerstein TJ (2009) Effects of gabapentin and pregabalin on K+-evoked 3H-GABA and 3H-glutamate release from human neocortical synaptosomes. Naunyn Schmiedebergs Arch Pharmacol 379:361–369

    Article  CAS  PubMed  Google Scholar 

  • Bryant AP, Busby RW, Bartolini WP, Cordero EA, Hannig G, Kessler MM, Pierce CM, Solinga RM, Tobin JV, Mahajan-Miklos S (2010) Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci 86:760–765

    Article  CAS  PubMed  Google Scholar 

  • Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, Mahajan-Miklos S, Pierce CM, Solinga RM, Sun LJ (2010) Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol 649:328–335

    Article  CAS  PubMed  Google Scholar 

  • Camilleri M, Bharucha AE, Ueno R, Burton D, Thomforde GM, Baxter K, McKinzie S, Zinsmeister AR (2006) Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol 290:G942–G947

    Article  CAS  PubMed  Google Scholar 

  • Cann PA, Read NW, Holdsworth CD, Barends D (1984) Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 29:239–247

    Article  CAS  PubMed  Google Scholar 

  • Castilloux J, Noble A, Faure C (2008) Is visceral hypersensitivity correlated with symptom severity in children with functional gastrointestinal disorders? J Pediatr Gastroenterol Nutr 46:272–278

    Article  PubMed  Google Scholar 

  • Castro VM, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, Erb JL, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH (2013) QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 346:f288

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chang HY, Kelly EC, Lembo AJ (2006) Current gut-directed therapies for irritable bowel syndrome. Curr Treat Options Gastroenterol 9:314–323

    Article  PubMed  Google Scholar 

  • Chao GQ, Zhang S (2013) A meta-analysis of the therapeutic effects of amitriptyline for treating irritable bowel syndrome. Intern Med 52:419–424

    Article  PubMed  Google Scholar 

  • Collins BS, Lin HC (2010) Chronic abdominal pain in children is associated with high prevalence of abnormal microbial fermentation. Dig Dis Sci 55:124–130

    Article  PubMed  Google Scholar 

  • Collins BS, Lin HC (2011) Double-blind, placebo-controlled antibiotic treatment study of small intestinal bacterial overgrowth in children with chronic abdominal pain. J Pediatr Gastroenterol Nutr 52:382–386

    Article  CAS  PubMed  Google Scholar 

  • Croffie JM, Fitzgerald JF, Chong SK (2000) Recurrent abdominal pain in children-a retrospective study of outcome in a group referred to a pediatric gastroenterology practice. Clin Pediatr 39:267–274

    Article  CAS  Google Scholar 

  • Czyzewski DI, Self MM, Williams AE, Weidler EM, Blatz AM, Shulman RJ (2016) Maintenance of pain in children with functional abdominal pain. J Pediatr Gastroenterol Nutr 62:393–398

    Article  PubMed  PubMed Central  Google Scholar 

  • Darvish-Damavandi M, Nikfar S, Abdollahi M (2010) A systematic review of efficacy and tolerability of mebeverine in irritable bowel syndrome. World J Gastroenterol 16:547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J (2015) Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol 55:534–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delvaux M, Wingate D (1997) Trimebutine: mechanism of action, effects on gastrointestinal function and clinical results. J Int Med Res 25:225–246

    Article  CAS  PubMed  Google Scholar 

  • Den Hertog A, Van den Akker J (1987) Modification of α1-receptor-operated channels by mebeverine in smooth muscle cells of guinea-pig taenia caeci. Eur J Pharmacol 138:367–374

    Article  CAS  PubMed  Google Scholar 

  • Devanarayana NM, Adhikari C, Pannala W, Rajindrajith S (2011) Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria. J Trop Pediatr 57:34–39

    Article  PubMed  Google Scholar 

  • Dhroove G, Chogle A, Saps M (2010) A million-dollar work-up for abdominal pain: is it worth it? J Pediatr Gastroenterol Nutr 51:579–583

    Article  PubMed  Google Scholar 

  • Di Lorenzo C, Youssef NN, Sigurdsson L, Scharff L, Griffiths J, Wald A (2001) Visceral hyperalgesia in children with functional abdominal pain. J Pediatr 139:838–843

    Article  CAS  PubMed  Google Scholar 

  • Dickhaus B, Mayer EA, Firooz N, Stains J, Conde F, Olivas TI, Fass R, Chang L, Mayer M, Naliboff BD (2003) Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress. Am J Gastroenterol 98:135–143

    Article  PubMed  Google Scholar 

  • Diederen K, Hoekman D, Hummel T, de Meij T, Koot B, Tabbers M, Vlieger A, Kindermann A, Benninga M (2016) The prevalence of irritable bowel syndrome-type symptoms in paediatric inflammatory bowel disease, and the relationship with biochemical markers of disease activity. Aliment Pharmacol Ther 44(2):181–188

    Article  CAS  PubMed  Google Scholar 

  • Diop L, Raymond F, Fargeau H, Petoux F, Chovet M, Doherty AM (2002) Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat. J Pharmacol Exp Ther 302:1013–1022

    Article  CAS  PubMed  Google Scholar 

  • Dixit RK, Bhargava VK (2002) Neurotransmitter mechanisms in gabapentin antinociception. Pharmacology 65:198–203

    Article  CAS  PubMed  Google Scholar 

  • Dong L, Dingguo L, Xiaoxing X, Hanming L (2005) An epidemiologic study of irritable bowel syndrome in adolescents and children in China: a school-based study. Pediatrics 116:e393–e396

    Article  PubMed  Google Scholar 

  • Dooley DJ, Mieske CA, Borosky SA (2000) Inhibition of K(+)-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin. Neurosci Lett 280:107–110

    Article  CAS  PubMed  Google Scholar 

  • Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS (2013) Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology 145(329–338):e1

    Google Scholar 

  • DuPont H (2016a) Introduction: understanding mechanisms of the actions of rifaximin in selected gastrointestinal diseases. Aliment Pharmacol Ther 43:1–2

    Article  CAS  PubMed  Google Scholar 

  • DuPont H (2016b) Review article: the antimicrobial effects of rifaximin on the gut microbiota. Aliment Pharmacol Ther 43:3–10

    Article  CAS  PubMed  Google Scholar 

  • Efskind PS, Bernklev T, Vatn MH (1996) A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 31:463–468

    Article  CAS  PubMed  Google Scholar 

  • Eisenach JC, Gebhart GF (1995) Intrathecal amitriptyline acts as an N-methyl-D-aspartate receptor antagonist in the presence of inflammatory hyperalgesia in rats. Anesthesiology 83:1046–1054

    Article  CAS  PubMed  Google Scholar 

  • Enna SJ, McCarson KE (2006) The role of GABA in the mediation and perception of pain. Adv Pharmacol 54:1–27

    Article  CAS  PubMed  Google Scholar 

  • Fehrenbacher JC, Taylor CP, Vasko MR (2003) Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 105:133–141

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Cui M, Willis WD (2003) Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology 98:729–733

    Article  CAS  PubMed  Google Scholar 

  • Field MJ, Oles RJ, Lewis AS, McCleary S, Hughes J, Singh L (1997) Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol 121:1513–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ford AC (2012) In irritable bowel syndrome, antispasmodics and antidepressants improve abdominal pain and global assessment and symptom scores, but there is no evidence for the effectiveness of bulking agents. Evid Based Med 17:114–115

    Article  PubMed  Google Scholar 

  • Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P (2008) Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 337:a2313

    Article  PubMed  PubMed Central  Google Scholar 

  • Friesen CA, Rosen JM, Schurman JV (2016) Prevalence of overlap syndromes and symptoms in pediatric functional dyspepsia. BMC Gastroenterol 16:75

    Article  PubMed  PubMed Central  Google Scholar 

  • Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA (2014) Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol 92:448–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gieteling MJ, Bierma-Zeinstra SM, Passchier J, Berger MY (2008) Prognosis of chronic or recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr 47:316–326

    Article  PubMed  Google Scholar 

  • Goerg KJ, Spilker T (2003) Effect of peppermint oil and caraway oil on gastrointestinal motility in healthy volunteers: a pharmacodynamic study using simultaneous determination of gastric and gall-bladder emptying and orocaecal transit time. Aliment Pharmacol Ther 17:445–451

    Article  CAS  PubMed  Google Scholar 

  • Gray AM, Spencer PS, Sewell RD (1998) The involvement of the opioidergic system in the antinociceptive mechanism of action of antidepressant compounds. Br J Pharmacol 124:669–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grigoleit HG, Grigoleit P (2005) Gastrointestinal clinical pharmacology of peppermint oil. Phytomedicine 12:607–611

    Article  CAS  PubMed  Google Scholar 

  • Gulewitsch MD, Enck P, Schwille-Kiuntke J, Weimer K, Schlarb AA (2013) Rome III criteria in parents’ hands: pain-related functional gastrointestinal disorders in community children and associations with somatic complaints and mental health. Eur J Gastroenterol Hepatol 25:1223–1229

    PubMed  Google Scholar 

  • Hawthorn M, Ferrante J, Luchowski E, Rutledge A, Wei XY, Triggle DJ (1988) The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations. Aliment Pharmacol Ther 2:101–118

    Article  CAS  PubMed  Google Scholar 

  • Heimes K, Hauk F, Verspohl EJ (2011) Mode of action of peppermint oil and (−)-menthol with respect to 5-HT3 receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum. Phytother Res 25:702–708

    Article  CAS  PubMed  Google Scholar 

  • Hoekman DR, Rutten JM, Vlieger AM, Benninga MA, Dijkgraaf MG (2015) Annual costs of care for pediatric irritable bowel syndrome, functional abdominal pain, and functional abdominal pain syndrome. J Pediatr 167:1103–1108.e2

    Article  PubMed  Google Scholar 

  • Houghton LA, Fell C, Whorwell PJ, Jones I, Sudworth DP, Gale JD (2007) Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut 56:1218–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang DB, DuPont HL (2005) Rifaximin – a novel antimicrobial for enteric infections. J Infect 50:97–106

    Article  PubMed  Google Scholar 

  • Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M (2016) Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 150:1456–1468.e2

    Article  Google Scholar 

  • Hyman PE, Di Lorenzo C, Prestridge LL, Youssef NN, Ueno R (2014) Lubiprostone for the treatment of functional constipation in children. J Pediatr Gastroenterol Nutr 58:283–291

    Article  CAS  PubMed  Google Scholar 

  • Janssens KA, Zijlema WL, Joustra ML, Rosmalen JG (2015) Mood and anxiety disorders in chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome: results from the LifeLines Cohort Study. Psychosom Med 77:449–457

    Article  PubMed  Google Scholar 

  • Jativa E, Velasco-Benítez CA, Koppen I, Cabezas ZJ, Saps M (2016) Prevalence of functional gastrointestinal disorders in school children in ecuador. J Pediatr Gastroenterol Nutr 63(1):25–28

    Article  PubMed  Google Scholar 

  • Johanson JFGM, Patchen ML, Ueno R (2002) Efficacy and safety of a novel compound, RU-0211, for the treatment of constipation. Gastroenterology 122:A315

    Google Scholar 

  • Johanson JFGA, Holland PC, Patchen ML, Ueno R (2003) Phase III, efficacy and safety of RU-0211 a novel chloride channel activator, for the treatment of constipation. Gastroenterology 124:A48

    Article  Google Scholar 

  • Johanson JFGM, Holland PC, Patchen ML, Ueno R (2004) Phase III, randomized withdrawal study of RU-0211, a novel chloride channel activator for the treatment of constipation. Gastroenterology 126:A100

    Google Scholar 

  • Johnson A, Bickel J, Lebel A (2014) Pediatric migraine prescription patterns at a large academic hospital. Pediatr Neurol 51:706–712

    Article  PubMed  Google Scholar 

  • Kang SB, Marchelletta RR, Penrose H, Docherty MJ, McCole DF (2015) A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa. Pharmacol Res Perspect 3(2):e00128

    Article  PubMed  PubMed Central  Google Scholar 

  • Karabulut GS, Beşer ÖF, Erginöz E, Kutlu T, Çokuğraş FÇ, Erkan T (2013) The incidence of irritable bowel syndrome in children using the Rome III criteria and the effect of trimebutine treatment. J Neurogastroenterol Motil 19(1):90–93

    Article  PubMed  PubMed Central  Google Scholar 

  • Kerckhoffs AP, Samsom M, van der Rest ME, de Vogel J, Knol J, Ben-Amor K, Akkermans LM (2009) Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients. World J Gastroenterol 15:2887–2892

    Article  PubMed  PubMed Central  Google Scholar 

  • Khanna R, MacDonald JK, Levesque BG (2014) Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol 48:505–512

    PubMed  Google Scholar 

  • Kline RM, Kline JJ, Di Palma J, Barbero GJ (2001) Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J Pediatr 138:125–128

    Article  CAS  PubMed  Google Scholar 

  • Korterink JJ, Rutten JM, Venmans L, Benninga MA, Tabbers MM (2015) Pharmacologic treatment in pediatric functional abdominal pain disorders: a systematic review. J Pediatr 166:424–431.e6

    Article  CAS  PubMed  Google Scholar 

  • Kuiken SD, Tytgat GN, Boeckxstaens GE (2003) The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study. Clin Gastroenterol Hepatol 1:219–228

    Article  CAS  PubMed  Google Scholar 

  • Ladabaum U, Sharabidze A, Levin TR, Zhao WK, Chung E, Bacchetti P, Jin C, Grimes B, Pepin CJ (2010) Citalopram provides little or no benefit in nondepressed patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 8(42–48):e1

    Google Scholar 

  • Layer P, Stanghellini V (2014) Review article: linaclotide for the management of irritable bowel syndrome with constipation. Aliment Pharmacol Ther 39:371–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee N, Wald A (2011) The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide. Expert Opin Drug Metab Toxicol 7:651–659

    Article  CAS  PubMed  Google Scholar 

  • Lee KJ, Kim JH, Cho SW (2005) Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 22:981–988

    Article  CAS  PubMed  Google Scholar 

  • Lembo A, Pimentel M, Rao S, Schoenfeld P, Cash B, Weinstock L, Golden P, Paterson C (2014) Efficacy and safety of repeat treatment with rifaximin for diarrhea-predominant irritable bowel syndrome (IBS-D): results of the TARGET 3 study. Am J Gastroenterol 15:1113–1121

    Google Scholar 

  • Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum A (2004) Meta-analysis: the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 20:1253–1269

    Article  CAS  PubMed  Google Scholar 

  • Lewis ML, Palsson OS, Whitehead WE, van Tilburg MA (2016) Prevalence of functional gastrointestinal disorders in children and adolescents. J Pediatr

    Google Scholar 

  • Liang J, Liu X, Pan M, Dai W, Dong Z, Wang X, Liu R, Zheng J, Yu S (2014) Blockade of Nav1.8 currents in nociceptive trigeminal neurons contributes to anti-trigeminovascular nociceptive effect of amitriptyline. Neuromolecular Med 16:308–321

    Article  CAS  PubMed  Google Scholar 

  • Lisman-van Leeuwen Y, Spee LA, Benninga MA, Bierma-Zeinstra SM, Berger MY (2013) Prognosis of abdominal pain in children in primary care – a prospective cohort study. Ann Fam Med 11:238–244

    Article  PubMed  Google Scholar 

  • Liu J, Reid AR, Sawynok J (2013) Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline. Eur J Pharmacol 698:213–219

    Article  CAS  PubMed  Google Scholar 

  • Lu PL, Saps M, Chanis RA, Velasco-Benítez CA (2016) The prevalence of functional gastrointestinal disorders in children in Panama: a school-based study. Acta Paediatr 105:e232–e236

    Article  PubMed  Google Scholar 

  • Lucas KA, Pitari GM, Kazerounian S, Ruiz-Stewart I, Park J, Schulz S, Chepenik KP, Waldman SA (2000) Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 52:375–414

    CAS  PubMed  Google Scholar 

  • Lundberg P (1975) Abdominal migraine-diagnosis and therapy. Headache 15:122–125

    Article  CAS  PubMed  Google Scholar 

  • Madani S, Cortes O, Thomas R (2016) Cyproheptadine use in children with functional gastrointestinal disorders. J Pediatr Gastroenterol Nutr 62:409–413

    Article  CAS  PubMed  Google Scholar 

  • Markman JD, Jensen TS, Semel D, Li C, Parsons B, Behar R, Sadosky AB (2016) Effects of pregabalin in patients with neuropathic pain previously treated with gabapentin: a pooled analysis of parallel-group, randomized, placebo-controlled clinical trials. Pain Pract. doi:10.1111/papr.12516 [Epub ahead of print]

    PubMed  Google Scholar 

  • Martínez-Vázquez M, Vázquez-Elizondo G, González-González J, Gutiérrez-Udave R, Maldonado-Garza H, Bosques-Padilla F (2012) Effect of antispasmodic agents, alone or in combination, in the treatment of irritable bowel syndrome: systematic review and meta-analysis. Rev Gastroenterol Mex 77:82–90

    PubMed  Google Scholar 

  • Masand PS, Pae CU, Krulewicz S, Peindl K, Mannelli P, Varia IM, Patkar AA (2009) A double-blind, randomized, placebo-controlled trial of paroxetine controlled-release in irritable bowel syndrome. Psychosomatics 50:78–86

    Article  CAS  PubMed  Google Scholar 

  • Micklefield GH, Greving I, May B (2000) Effects of peppermint oil and caraway oil on gastroduodenal motility. Phytother Res 14:20–23

    Article  CAS  PubMed  Google Scholar 

  • Million M, Wang L, Adelson DW, Roman F, Diop L, Tache Y (2007) Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats. Gut 56:1482–1484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazawa M, Marumoto S, Takahashi T, Nakahashi H, Haigou R, Nakanishi K (2011) Metabolism of (+)- and (−)-menthols by CYP2A6 in human liver microsomes. J Oleo Sci 60:127–132

    Article  CAS  PubMed  Google Scholar 

  • Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ (2015) Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev CD008242

    Google Scholar 

  • Nozu T, Kudaira M (2009) Altered rectal sensory response induced by balloon distention in patients with functional abdominal pain syndrome. Biopsychosoc Med 3:13

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohashi-Doi K, Gale JD, Kurebayashi Y (2010) Pregabalin inhibits accelerated defecation and decreased colonic nociceptive threshold in sensitized rats. Eur J Pharmacol 643:107–112

    Article  CAS  PubMed  Google Scholar 

  • Ojetti V, Lauritano EC, Barbaro F, Migneco A, Ainora ME, Fontana L, Gabrielli M, Gasbarrini A (2009) Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol 5:675–682

    Article  CAS  PubMed  Google Scholar 

  • Olfson M, Marcus SC, Druss BG (2008) Effects of Food and Drug Administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry 65:94–101

    Article  PubMed  Google Scholar 

  • Otu-Nyarko CG, Gedalia A, Karpinski AC, Kolomensky A, Hyman PE (2015) Disability in children and adolescents with irritable bowel syndrome and/or fibromyalgia. J Pediatr Gastroenterol Nutr 61:558–560

    Article  PubMed  Google Scholar 

  • Pan R, Tian Y, Gao R, Li H, Zhao X, Barrett JE, Hu H (2012) Central mechanisms of menthol-induced analgesia. J Pharmacol Exp Ther 343:661–672

    Article  CAS  PubMed  Google Scholar 

  • Park R, Mikami S, LeClair J, Bollom A, Lembo C, Sethi S, Lembo A, Jones M, Cheng V, Friedlander E (2015) Inpatient burden of childhood functional GI disorders in the USA: an analysis of national trends in the USA from 1997 to 2009. Neurogastroenterol Motil 27:684–692

    Article  CAS  PubMed  Google Scholar 

  • Patel MK, Gonzalez MI, Bramwell S, Pinnock RD, Lee K (2000) Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal cord. Br J Pharmacol 130:1731–1734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel A, Hasak S, Cassell B, Ciorba MA, Vivio EE, Kumar M, Gyawali CP, Sayuk GS (2016) Effects of disturbed sleep on gastrointestinal and somatic pain symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 44:246–258

    Article  CAS  PubMed  Google Scholar 

  • Pimentel M (2016) Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther 43:37–49

    Article  CAS  PubMed  Google Scholar 

  • Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP (2011) Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 364:22–32

    Article  CAS  PubMed  Google Scholar 

  • Posserud I, Stotzer P-O, Björnsson ES, Abrahamsson H, Simrén M (2007) Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut 56:802–808

    Article  PubMed  Google Scholar 

  • Pourmoghaddas Z, Saneian H, Roohafza H, Gholamrezaei A (2014) Mebeverine for pediatric functional abdominal pain: a randomized, placebo-controlled trial. Biomed Res Int 2014:191026

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Powers SW, Kashikar-Zuck SM, Allen JR, LeCates SL, Slater SK, Zafar M, Kabbouche MA, O’Brien HL, Shenk CE, Rausch JR, Hershey AD (2013) Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA 310:2622–2630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M (2012) The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci 57:1321–1329

    Article  PubMed  Google Scholar 

  • Rahimi R, Nikfar S, Rezaie A, Abdollahi M (2009) Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis. World J Gastroenterol 15:1548–1553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahman M, Ahmed D, Mahmuduzzaman M, Rahman M, Chowdhury M, Barua R, Ishaque S (2014) Comparative efficacy and safety of trimebutine versus mebeverine in the treatment of irritable bowel syndrome. Mymensingh Med J 23:105–113

    CAS  PubMed  Google Scholar 

  • Rao SS, Hatfield RA, Suls JM, Chamberlain MJ (1998) Psychological and physical stress induce differential effects on human colonic motility. Am J Gastroenterol 93:985–990

    Article  CAS  PubMed  Google Scholar 

  • Raschi E, De Ponti F (2014) Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome. Expert Opin Drug Metab Toxicol 10:293–305

    Article  CAS  PubMed  Google Scholar 

  • Ravnefjord A, Brusberg M, Larsson H, Lindstrom E, Martinez V (2008) Effects of pregabalin on visceral pain responses and colonic compliance in rats. Br J Pharmacol 155:407–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rico-Villademoros F, Slim M, Calandre EP (2015) Amitriptyline for the treatment of fibromyalgia: a comprehensive review. Expert Rev Neurother 15:1123–1150

    Article  CAS  PubMed  Google Scholar 

  • Rippel SW, Acra S, Correa H, Vaezi M, Di Lorenzo C, Walker LS (2012) Pediatric patients with dyspepsia have chronic symptoms, anxiety, and lower quality of life as adolescents and adults. Gastroenterology 142:754–761

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodriguez L, Diaz J, Nurko S (2013) Safety and efficacy of cyproheptadine for treating dyspeptic symptoms in children. J Pediatr 163:261–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roohafza H, Pourmoghaddas Z, Saneian H, Gholamrezaei A (2014) Citalopram for pediatric functional abdominal pain: a randomized, placebo-controlled trial. Neurogastroenterol Motil 26:1642–1650

    Article  CAS  PubMed  Google Scholar 

  • Rouster AS, Karpinski AC, Silver D, Monagas J, Hyman PE (2016) Functional gastrointestinal disorders dominate pediatric gastroenterology outpatient practice. J Pediatr Gastroenterol Nutr 62:847–851

    Article  PubMed  Google Scholar 

  • Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW (2011) Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev CD003460

    Google Scholar 

  • Saad R, Chey WD (2008) Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation. Expert Rev Gastroenterol Hepatol 2:497–508

    Article  CAS  PubMed  Google Scholar 

  • Sadeghian M, Farahmand F, Fallahi G, Abbasi A (2008) Cyproheptadine for the treatment of functional abdominal pain in childhood: a double-blinded randomized placebo-controlled trial. Minerva Pediatr 60:1367–1374

    CAS  PubMed  Google Scholar 

  • Saps M, Youssef N, Miranda A, Nurko S, Hyman P, Cocjin J, Di Lorenzo C (2009) Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders. Gastroenterology 137:1261–1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saps M, Nichols-Vinueza DX, Rosen JM, Velasco-Benítez CA (2014) Prevalence of functional gastrointestinal disorders in Colombian school children. J Pediatr 164:542–545.e1

    Article  PubMed  Google Scholar 

  • Saps M, Biring HS, Pusatcioglu CK, Mintjens S, Rzeznikiewiz D (2015) A comprehensive review of randomized placebo-controlled pharmacological clinical trials in children with functional abdominal pain disorders. J Pediatr Gastroenterol Nutr 60:645–653

    Article  CAS  PubMed  Google Scholar 

  • Saps M, Tilburg M, Lavigne J, Miranda A, Benninga M, Taminiau J, Di Lorenzo C (2016) Recommendations for pharmacological clinical trials in children with irritable bowel syndrome: the Rome foundation pediatric subcommittee on clinical trials. Neurogastroenterol Motil 28(11):1619–1631

    Article  CAS  PubMed  Google Scholar 

  • Scarpellini E, Giorgio V, Gabrielli M, Filoni S, Vitale G, Tortora A, Ojetti V, Gigante G, Fundarò C, Gasbarrini A (2013) Rifaximin treatment for small intestinal bacterial overgrowth in children with irritable bowel syndrome: a preliminary study. Eur Rev Med Pharmacol Sci 17:1314–1320

    CAS  PubMed  Google Scholar 

  • See MC, Birnbaum AH, Schechter CB, Goldenberg MM, Benkov KJ (2001) Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment. Dig Dis Sci 46:985–92

    Article  CAS  PubMed  Google Scholar 

  • Shannon S, Hollingsworth J, Cook I, Collins S (1989) Effect of trimebutine on postprandial colonic motor activity in healthy subjects and patients with irritable bowel syndrome. Neurogastroenterol Motil 1:9–14

    Article  Google Scholar 

  • Sibelli A, Chalder T, Everitt H, Workman P, Windgassen S, Moss-Morris R (2016) A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset. Psychol Med:1–16

    Google Scholar 

  • Stein DJ, Bruce Lydiard R, Herman BK, Mandel FS (2009) Impact of gastrointestinal symptoms on response to pregabalin in generalized anxiety disorder: results of a six-study combined analysis. Int Clin Psychopharmacol 24:126–132

    Article  PubMed  Google Scholar 

  • Stepanovic-Petrovic RM, Tomic MA, Vuckovic SM, Paranos S, Ugresic ND, Prostran MS, Milovanovic S, Boskovic B (2008) The antinociceptive effects of anticonvulsants in a mouse visceral pain model. Anesth Analg 106:1897–1903

    Article  CAS  PubMed  Google Scholar 

  • Sweetser S, Busciglio IA, Camilleri M, Bharucha AE, Szarka LA, Papathanasopoulos A, Burton DD, Eckert DJ, Zinsmeister AR (2009) Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects. Am J Physiol Gastrointest Liver Physiol 296:G295–G301

    Article  CAS  PubMed  Google Scholar 

  • Tabas G, Beaves M, Wang J, Friday P, Mardini H, Arnold G (2004) Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial. Am J Gastroenterol 99:914–920

    Article  CAS  PubMed  Google Scholar 

  • Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J (2006) A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 55:1095–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talley NJ, Kellow JE, Boyce P, Tennant C, Huskic S, Jones M (2008) Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Dig Dis Sci 53:108–115

    Article  CAS  PubMed  Google Scholar 

  • Tate S (1997) Peppermint oil: a treatment for postoperative nausea. J Adv Nurs 26:543–549

    Article  CAS  PubMed  Google Scholar 

  • Taylor CP (2009) Mechanisms of analgesia by gabapentin and pregabalin--calcium channel alpha2-delta [Cavalpha2-delta] ligands. Pain 142:13–16

    Article  CAS  PubMed  Google Scholar 

  • Taylor CP, Garrido R (2008) Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for calcium channel alpha2-delta (alpha2-delta) type 1 protein. Neuroscience 155:510–521

    Article  CAS  PubMed  Google Scholar 

  • Thoua NM, Murray CD, Winchester WJ, Roy AJ, Pitcher MC, Kamm MA, Emmanuel AV (2009) Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome. Aliment Pharmacol Ther 29:552–560

    Article  CAS  PubMed  Google Scholar 

  • Tzellos TG, Toulis KA, Goulis DG, Papazisis G, Zampeli VA, Vakfari A, Kouvelas D (2010) Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis. J Clin Pharm Ther 35:639–656

    Article  CAS  PubMed  Google Scholar 

  • Udoh E, Devanarayana NM, Rajindrajith S, Meremikwu M, Benninga MA (2016) Abdominal pain-predominant functional gastrointestinal disorders in adolescent nigerians. J Pediatr Gastroenterol Nutr 62:588–593

    Article  PubMed  Google Scholar 

  • Ulbricht C, Costa D, Grimes Serrano JM, Guilford J, Isaac R, Seamon E, Varghese M (2010) An evidence-based systematic review of spearmint by the natural standard research collaboration. J Diet Suppl 7:179–215

    Article  PubMed  Google Scholar 

  • Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R (2005) The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther 22:381–385

    Article  CAS  PubMed  Google Scholar 

  • Valori R, Shannon S, Reddy N, Daniel E, Collins S (1987) The action of trimebutine maleate on gastrointestinal motility is mediated by opiate receptors in human subjects. Gastroenterol Clin Biol 11:102B

    CAS  PubMed  Google Scholar 

  • Van Ginkel R, Voskuijl WP, Benninga MA, Taminiau JA, Boeckxstaens GE (2001) Alterations in rectal sensitivity and motility in childhood irritable bowel syndrome. Gastroenterology 120:31–38

    Article  CAS  PubMed  Google Scholar 

  • Walker LS, Greene JW (1989) Children with recurrent abdominal pain and their parents: more somatic complaints, anxiety, and depression than other patient families? J Pediatr Psychol 14:231–243

    Article  CAS  PubMed  Google Scholar 

  • Warschburger P, Hänig J, Friedt M, Posovszky C, Schier M, Calvano C (2014) Health-related quality of life in children with abdominal pain due to functional or organic gastrointestinal disorders. J Pediatr Psychol 39:45–54

    Article  PubMed  Google Scholar 

  • Watson K, Kim S, Boyle B, Saps M (2016) The prevalence and impact of functional abdominal pain disorders in children with inflammatory bowel diseases (iBD-FGID). J Pediatr Gastroenterol Nutr [Epub ahead of print]

    Google Scholar 

  • Weiss D, Aizenberg D, Hermesh H, Zemishlany Z, Munitz H, Radwan M, Weizman A (1995) Cyproheptadine treatment in neuroleptic-induced akathisia. Br J Psychiatry 167:483–486

    Article  CAS  PubMed  Google Scholar 

  • Worawattanakul M, Rhoads JM, Lichtman SN, Ulshen MH (1999) Abdominal migraine: prophylactic treatment and follow-up. J Pediatr Gastroenterol Nutr 28:37–40

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Niwa S, Iwayama S, Koganei H, S-i F, Takeda T, Kito M, Ono Y, Saitou Y, Takahara A (2006) Discovery, structure–activity relationship study, and oral analgesic efficacy of cyproheptadine derivatives possessing N-type calcium channel inhibitory activity. Bioorg Med Chem 14:5333–5339

    Article  CAS  PubMed  Google Scholar 

  • You HJ, Lei J, Arendt-Nielsen L (2009) Selective inhibitory effects of pregabalin on peripheral C but not A-delta fibers mediated nociception in intact and spinalized rats. Neuroscience 164:1845–1853

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Li D, Cheng G, Fan J, Lu H (2010a) An epidemiologic study of irritable bowel syndrome in adolescents and children in South China: a school-based study. Child 36:781–786

    CAS  Google Scholar 

  • Zhou Q, Fillingim RB, Riley JL 3rd, Malarkey WB, Verne GN (2010b) Central and peripheral hypersensitivity in the irritable bowel syndrome. Pain 148:454–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmerman LA, Srinath AI, Goyal A, Bousvaros A, Ducharme P, Szigethy E, Nurko S (2013) The overlap of functional abdominal pain in pediatric Crohn’s disease. Inflamm Bowel Dis 19(4):826–831

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA

    Miguel Saps

  2. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Wisconsin, Milwaukee, WI, USA

    Adrian Miranda

Authors
  1. Miguel Saps
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adrian Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miguel Saps .

Editor information

Editors and Affiliations

  1. Health Sciences Center, The University of Oklahoma, Oklahoma City, Oklahoma, USA

    Beverley Greenwood-Van Meerveld

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Saps, M., Miranda, A. (2017). Gastrointestinal Pharmacology. In: Greenwood-Van Meerveld, B. (eds) Gastrointestinal Pharmacology . Handbook of Experimental Pharmacology, vol 239. Springer, Cham. https://doi.org/10.1007/164_2016_119

Download citation

Publish with us

Policies and ethics

Search

Navigation