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La terapia medica del colon irritabiledel colon irritabile
Dr.R.Bocchini
Modulo di Fisiopatologia dell’Apparato Digerente, U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileFisiopatologia
Disturbi psichici Disordini psicoaffettivi
Fattori ambientali:stress, stato sociale,supporto affettivo etc
Fisiopatologia
Disordini psicoaffettivi
Fattori predisponenti
supporto affettivo, etcstress di vita, SNC
N. viscerali efferenti
p pgenetici ambientali
SNEN. viscerali afferenti
Ipersensibilità viscerale Disordini motori
Attivazione neuroimmune INTESTINO
Neurotrasmettitori 5HT; Citochine???
INTESTINO
Mild inflammation
Allergie/intolleranze alimentariInfezioni intestinaliMild inflammation
intestinale
Modificata da Drossman, 2005, Farthing, 2004
Alteraz.microflora intestinale
Sindrome del colon irritabileClinica
SintomiDolore/dolenzia addominale e motilitàDolore/dolenzia addominale e motilità
intestinale alterata che si esprime sotto forma di:forma di:- stipsi (forma più frequente)- diarrea
ti i di lt t- stipsi e diarrea alternate
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileClinica
L SII f t t iLe persone con SII frequentemente silamentano di distensione e gonfioreaddominali, di eccessiva flatulenza oeruttazioni, attribuiti ad aumentatae u o , bu d u epresenza di gas (coinvolgimento nell’IBS ditutto il tubo digerente)tutto il tubo digerente)Il 25%-50% dei sofferenti accusa anchedispepsia, pirosi, nausea e vomito
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileClinica
Nelle donne vi può essere un dolore pelvicoda non collegare a patologie ginecologicheda non collegare a patologie ginecologiche(diagnosi differenziale).
i i i i C f i iFrequenti associazioni: Cefalea, insonnia,fibromialgie, disturbi urinari, palpitazioni,disappetenza, dimagrimento, chronicfatigue syndrome, litiasi biliarefatigue syndrome, litiasi biliare
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)( )Condizioni associate e\o diagnosi differenziale
Malattia celiaca Korkut, 2010
Intolleranza o allergia alimentare (“allergiealimentari autodiagnosticate” nel 40% degli adulti ; ilalimentari autodiagnosticate nel 40% degli adulti ; il50% dei pz con SII riferisce intolleranze alimentari;Positività ai test: < 2%)I t ll i di idi ll l iIntolleranza ai disaccaridi: nella popolazionegenerale: 25% (Brandt et al, 2002); H2-BT lattosio positivitàin SII: 27% (Parker et al, 2001). importante non negare le
i tti d i i ti tt l lesperienze soggettive dei pazienti e accettare la loroscelta di evitare il latte/prodotti caseari Talley 2003, Hatlebakk2004
Malattie infiammatorie croniche intestinaliMalattie infiammatorie croniche intestinali
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)( )Condizioni associate e\o diagnosi differenziale
InfezioniS. contaminazione batterica del tenue
i i iDiverticolosi del colonCancro del rettoDiarrea da malassorbimento di acidi biliariDiarrea da malassorbimento di acidi biliariInsufficienza pancreatica 6% Leeds, 2010
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)( )Terapia
M t f IBS i b d ltif t i l hManagement of IBS is based on a multifactorial approachand includes establishment of an effective patient-providerrelationship education reassurance dietary alterationsrelationship, education, reassurance, dietary alterations,pharmacotherapy, behavioral and psychological treatment.Highest efficacy is currently found for peppermint oil ,followed by psychotherapeutic and psychopharmacologicalinterventions and probiotics.
60
70
%
Enck, 2010
Placebo response rates across 40
50
60
spon
se ra
te,
RCTs of pharmacological therapies in IBS were high.
10
20
30Pl
aceb
o re
s
Modulo di Fisiopatologia dell’Apparato Digerente U.O.Gastroenterologia, Cesena
Ford, 2010 Lichstein & Mayer Kasich Wayne Page & Dirnb. Fielding Kruis0
mod n. Thompson 1989
Sindrome del colon irritabilei i f iTerapia: misure non farmacologiche
efficace relazione medico-paziente,p ,counseling,modifiche nello stile di vita (attività fisica,
pattern evacuazione)Correzioni/integrazioni dietetiche (fibre? Caffeina?
Carboidrati non raffinati? Prodotti caseari? Diete dil i ??? ) Al il 60% d i t tt ib i i lesclusione???...). Almeno il 60% dei pts attribuiscono i loro
disturbi a determinati cibipsicoterapia Terapia cognitivo comportamentalepsicoterapia Terapia cognitivo-comportamentale
Ipnoterapia Yoga,
Kuttner 2006, Gunn, 2003
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia: Correzioni/integrazioni dietetiche
Modificazioni stile di vita (stress può esacerbare l’IBS): difficileModificazioni stile di vita (stress può esacerbare l’IBS): difficile da ottenere, efficacia non provata
Eliminazione di cibi producenti gas per ridurre il meteorismo(eruttazioni e flatulenza, distensione addominale) Trattamentoempirico No trials controllatiempirico No trials controllati
Eliminare i cibi che aggravano i sintomi (glutine, specificigg (g , p(latto sio, sorbitolo, fruttosio) Allergie o intolleranze a cibi?raramente provate. Comunque risultati incerti, No trials alungo termine, possibile peggioramento sintomi
Diete ad eliminazione e probiotici
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Drisko,2006
Sindrome del colon irritabileTerapia: Correzioni/integrazioni dietetiche
“t H d (A ti id d li i ) ki if it“two Hayward green (Actinida deliciosa var) kiwifruits perday for 4 weeks significantly decreased (p=0.026) Colontransit time in the IBS/C group ” Ch 2010transit time in the IBS/C group. Chang, 2010
Reduction of short-chain poorly absorbed carbohydrates(FODMAP ) d f i i bl b l d(FODMAPs) reduces symptoms of irritable bowel syndrome(IBS). FODMAPs induce prolonged hydrogen production inthe intestine that is greater in IBS influence the amount ofthe intestine that is greater in IBS, influence the amount ofmethane produced, and induce gastrointestinal and systemicsymptoms experienced by patients with IBS. Ong, 2010sy p o s e pe e ced by p e s w S. g,
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Fibre e Intestino irritabile
Determine predominant symptom pattern
Pain Constipation Diarrhea Bloat/gas/flatus
M tManagement
1st line Increase fiber (or add bulking agent)
Increase fiber (or add bulking agent)
Review diet: removepossible precipitants, increasing fiber may
Review diet: remove possible precipitants, increase fiber very slowly, c eas g be ay
firm up stoolsc ease be e y s o y,
alpha-D galactosidase withvegetable meals
2nd line Antispasmodic Osmotic laxativeor prokinetic
Loperamide Charcoal, simethicone
3 d li P ki i E l d l i Ch l i l A i di ki i3rd line Prokinetic Exclude colonic inertia and pelvic floor dysfunction
Cholestyramine; evaluatefor other causes(secretory or osmoticdiarrhea)
Antispasmodic or prokinetic
Talley NJ: Treatment of Irritable Bowel Syndrome. In: Wolfe MM (eds): Therapy of Digestive Disorders: A comparison to Sleisenger and Fordran’s Gastrointestinal and Liver Disease. W.B. Saunders, 2000, pp. 477-490
Sindrome del colon irritabileTerapia: perchè le fibre nell’Intestino Irritabile
Nella SII vi è motilità intestinale alterata, con ilNella SII vi è motilità intestinale alterata, con ilcorteo di sintomi conseguente (dolore e gonfioreaddominali, stipsi, diarrrea)., p , )Il volume dei contenuti intestinali è noto per essereun riferimento neuro-muscolare essenziale per lapmotilità intestinale.Le fibre sono i componenti alimentari deputati ap pdare volume intraluminale e a trattenere acqua.Nei Paesi “evoluti” vi è documentata carenza difibre introdotte con l’alimentazione
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia: fibre
“therapies by bran and fibers are of no value in IBS”therapies by bran and fibers are of no value in IBSEnck, 2010,Merat, 2010
There is no evidence that bulking agents are effective forThere is no evidence that bulking agents are effective fortreating IBS.
Quartero et al, Cochrane, 2009
limited and conflicting evidence to support the recommendation of psyllium supplementation for symptomatic IBS treatment
Chouinard, 2011
Risultati incerti, No trials a lungo termine, , g ,possibile peggioramento sintomi
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Gonfiore
Sindrome del colon irritabileTerapia farmacologica
Diagnosi positivaper IBSTrattamento
sintomatico
STIPSI DIARREA DOLORE GONFIORELassativi, fibre antiiarroici Antispastici, enzimatic
trattamento centraleAntidepressivi,
psicoterapia
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Gunn, 2003
Sindrome del colon irritabilei f i i iTerapia farmacologica sintomatica
Il trattamento farmacologico ha lo scopo di controllare ilsintomo dominante ed annovera tra i farmaci utilizzati:
Antispastici Anticolinergici, Ca-antagonisti, Carminativiantidiarroici: Loperamide, Difenossilato, Colestiraminaantidiarroici: Loperamide, Difenossilato, Colestiraminaantiflatulenti enzimatici, simeticone, argilla, etcantidepressivi TCA SSRIantidepressivi TCA, SSRIlassativi Agenti formanti massa, Lassativi, Procinetici
Criticità: durata della sindrome, effettilimitati ad un solo aspetto sintomatico.
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica sintomatica: AntispasticiTerapia farmacologica sintomatica: Antispastici
There is enough clinical evidence to recommend the use ofantispasmodics (alone or in combination) , even if traditionalantispasmodic therapy has a moderate efficacy
Enck 2010
There is evidence that antispasmodics are effective for thetreatment of IBS ( cimetropium/dicyclomine, peppermint oil,pinaverium and trimebutine)
Quartero et al, Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group 2009Quartero et al, Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group 2009
Durata?Dolore
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica sintomatica: AntispasticiTerapia farmacologica sintomatica: Antispastici
Otilonium bromide (spasmolytic agent that blocks L-Type Calcium channels). In a placebo-controlled double-blind study shows that otilonium bromide is safe well tolerated and superior to placebo inotilonium bromide is safe, well tolerated and superior to placebo in reducing the frequency of abdominal pain, severity of abdominal bloating and protecting from symptom relapse in IBS.bloating and protecting from symptom relapse in IBS.
Clave, 2011
Patients with IBS and an abdominal pain and discomfort score ofp> or = 3, who may be considered in the active phase of the disease,may derive some benefits from octatropine plus diazepam.
Pace, 2010
DoloreModulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica sintomatica: LassativiTerapia farmacologica sintomatica: Lassativi
Formanti massa costoCruscaPsyllium (Psyllogel) 2 buste al dì 0,94 єIspagula (Fibrolax) 3 bustine al dì 1,35 єp g ( )PHGG (Benefibra) 1 busta al dì (5 gr) 0,96 є
OsmoticiPolietilenglicole (Selg) 17 gr/die 0,75 єPolietilenglicole (Selg) 17 gr/die 0,75 єLattulosio (Laevolac) 30 ml/die 1,33 є
SaliniSolfato di magnesio 15 gr/die
StipsiSolfato di magnesio 15 gr/dieCitrato di magnesio 200 ml/die
StimolantiSenna (Pursennid) 4 cpr/die 0 60 єSenna (Pursennid) 4 cpr/die 0,60 єBisacodile 10 gr/die (Verecolene, Alaxa) 0,50 є
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica sintomatica: Lassativi
Effetto farmacologico
Outcome Effettii indesiderati
Terapia farmacologica sintomatica: Lassativi
farmacologico
Dieta ricca di fibre, S l ti fib
↑Peso feci↑ t it
Miglioramento d ll ti i
Dolore addomina le gonfioreSupplementi fibre
(10-30 g/die), Ispaghula husk
↑ transito della stipsi le,gonfiore
(psyllium)
LassativiOsmotici, Vari Evidenze Dolori addominali, salini, stimolanti,PEG
insufficienti, tranne che per PEG
gonfiore.PEG limitato a 2
settimanesettimane
StipsiModulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica sintomatica: antidiarroiciFarmaci Outcome Effetti indesiderati
p g
Loperamide (4-12 mg/die)
↓ evacuazioni(↓ transito)
Stipsi
DifenossilatoCodeina (15-30 mg
↓ evacuazioni(↓ transito)
Azione centraleDipendenza
x 1-3 volte/die) Sedazione
Colestiramina ↓ evacuazioni nei pz con Stipsi, diarrea, nausea, malassorbimento acidi biliari
vomito, discomfort
Antidepressivi ↓ n. evacuazioni stipsiAntidepressivi triciclici (25-50 mg/die)
↓ n. evacuazioni↓ discomfort↓ distensione add.
stipsi
DiarreaModulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica sintomatica: LassativiTerapia farmacologica sintomatica: Lassativi
Laxatives are useful in the management ofchronic constipation, but there is littlechronic constipation, but there is littleevidence in the management of IBS.Although antiflatulents and antidiarrhealsAlthough, antiflatulents and antidiarrhealsare widely used, there is little informationsupporting its use.
Enck, 2010
StipsiModulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica
Terapia basata sul meccanismo fisiopatologico
IBS as a serotonergic disorder; stimulating intestinalchloride channels; modulation of visceral hypersensitivity;; yp y;altering low-grade intestinal inflammation whichcompromises intestinal permeability; and modulation ofp p y;the gut microbiota
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: probioticiTerapia farmacologica: probiotici
Un episodio acuto di gastroenterite infettiva può indurre losviluppo di sintomi persistenti di IBS fino al 30% dei casisviluppo di sintomi persistenti di IBS fino al 30% dei casi
In almost 20% of the patients, IBS is clearly a post-infectious IBSa new hypothesis for IBS based on alterations in intestinal bacteriala new hypothesis for IBS based on alterations in intestinal bacterial composition Pimentel 2011
Small intestinal bacterial overgrowth observed in a subset of IBSSmall intestinal bacterial overgrowth observed in a subset of IBSpatients describes quantitative changes in the small intestinalmicrobiota. We show that there is evidence for SIBO; that antibioticelimination of the bacteria improves subjects clinically antibioticselimination of the bacteria improves subjects clinically. antibioticsmay be a good choice of therapy Pimentel 2010, Lee 2010
Probiotics may have a role in alleviating some of the symptomsProbiotics may have a role in alleviating some of the symptoms of IBS
Hoveyda, 2009
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: probioticiTerapia farmacologica: probiotici
The mechanisms that cause PI-IBS could include residualinflammation or persistent changes in mucosal immunocytes,enterochromaffin and mast cells, enteric nerves, and thegastrointestinal microbiota 50% IBS patients showed agastrointestinal microbiota. 50% IBS patients showed asignificant 72% increase in mucosal immune cells compared tocont ols (P<0.001) Lee 2010cont ols (P 0.001) Lee 2010
Mucosal mast cell infiltration of IBS patients was significantlyassociated with abdominal bloating frequency (P 0 022) andassociated with abdominal bloating frequency (P=0.022) andwith symptoms of dysmotility-like dyspepsia (P=0.001), but notulcer-like dyspepsia. Adverse psychological factors contributeulcer like dyspepsia. Adverse psychological factors contributeto persistent low-grade inflammation
Spiller, 2009;Cremon, 2009
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: probioticiTerapia farmacologica: probiotici
NSAIDs compromise intestinal permeability in IBS patients to a greater extent than in healthy subjects
Kerckhoffs, 2010
Un trial randomizzato controllato con VSL3 dimostramiglioramento del gonfiore addominale in pz con diarreamiglioramento del gonfiore addominale in pz con diarreapredominanteAlcuni studi hanno evidenziato miglioramento del dolore e dellaAlcuni studi hanno evidenziato miglioramento del dolore e dellastipsi o della consistenza delle feci nelle forme con diarrea
O’Sullivan 2000, Niedzielin 2001 Kim 2003
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia: probioticiTerapia: probiotici
Come modulare la flora batterica?
Lactobacillus rhamnosus GG (significantly reduces the frequencyand severity of abdominal pain in children with IBS; this effect isy p ;sustained and may be secondary to improvement of the gut barrier
Francavilla, 2010 Horvath, 2011
VSL#3 is safe and more effective than placebo in amelioratingsymptoms and improving the quality of life in children affected byIBSIBSBifidobacterium bifidum MIMBb75effectively alleviates globalIBS and improves IBS symptoms simultaneously with anIBS and improves IBS symptoms simultaneously with animprovement of quality of life.
Guandalini, 2010, Guglielmetti, 2011Guandalini, 2010, Guglielmetti, 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: probioticiTerapia farmacologica: probiotici
Come modulare la flora batterica?
Dieta, enzimatici tipo galattosidasi per ridurre meteorismo, trattare condizioni predisponenti (diabete endocrinopatie terapie associate)condizioni predisponenti (diabete, endocrinopatie, terapie associate).
Biointol administration (mixture of beta-glucan, inositol and digesti ve enzymes) has shown to improve some IBS symptoms such asve enzymes) has shown to improve some IBS symptoms, such as bloating, flatulence and abdominal pain, all connected to the presen ce of gas inside the intestinal lumen
Metaanalyses of treatment studies in IBS have shown that
ce of gas inside the intestinal lumenCiacci, 2011
yprobiotics have a high clinical efficacy in IBS, (E.Coli)
Enck, 2011 Moayyedi, 2010Enck, 2011 Moayyedi, 2010
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia: antibioticiTerapia: antibiotici
Come modulare la flora batterica?
Normalization of LBT with neomycin leads to a significant reductionin IBS symptoms The type of gas seen on LBT is also associatedin IBS symptoms. The type of gas seen on LBT is also associatedwith IBS subgroup Pimentel, 2003
Rif i i i IBS f 10 k f hRifaximin improves IBS symptoms for up to 10 weeks after the discontinuation of therapy
Pimentel, 2006
2-week course of rifaximin provided significant relief of IBSsymptoms, as well as bloating and abdominal pain (pts without
400 mg of rifaximin 3
constipation) Schey, 2011,Pimentel 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
times daily for 10 days
Sindrome del colon irritabileTerapia: antibioticiTerapia: antibiotici
Come modulare la flora batterica?
Retreatment with rifaximin for subjects with nonconstipated IBSin a real-world clinical practice was successful up to five timesin a real world clinical practice was successful up to five timeswithout decrease in duration or effect
Pimentel, 2011
Mesalazine 500 mg qid for a period of 28 days was effective in
Agire anche sull’infiammazione?
Mesalazine 500 mg qid for a period of 28 days was effective inreducing several symptoms characteristic of IBS (.pain intensity, painduration, meteorism, stool abnormalities and endoscopic parameters)duration, meteorism, stool abnormalities and endoscopic parameters)It improved cytohistologic parameters of the bowel mucosa
Dorofeyev, 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Dorofeyev, 2011
Sindrome del colon irritabile
i i
Terapia farmacologica: 5HT
5-HT1 antagonisti (sumatriptan, buspirone)
↓ senso di sazietà precoce, ↓ motilità antrale↓ senso di sazietà precoce, ↓ motilità antrale↑ gastric accomodation
5 HT antagonisti ( l t il t d t )5-HT3 antagonisti (alosetron, cilansetron, ondansetron)
Antidiarroici, Antiemetici, Antinocicettivi
5-HT4 agonisti (tegaserod, cisapride)Procinetici, Antinocicettivi ?
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileSindrome del colon irritabileTerapia farmacologica: 5HT
an increase in mucosal 5-HT availability in IBS-Dan increase in mucosal 5-HT availability in IBS-Dincluding a decrease in the serotonin transporter (SERT)which is also seen following acute diverticulitis 5-HT(3)which is also seen following acute diverticulitis. 5-HT(3)receptor antagonists have proved effective in suppressingurgency prolonging small and large bowel transit andurgency, prolonging small and large bowel transit andrelieving symptoms in IBS-D.
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileDiarrea
Terapia farmacologica: 5HT antagonistaalosetron hydrochloride, a selective serotonin type 3 receptoralosetron hydrochloride, a selective serotonin type 3 receptorantagonist, is the only medication approved for the treatmentof severe diarrhea-predominant irritable bowel syndrome(IBS-D) in women who have inadequately responded toconventional therapy. However, rare instances of ischemic
liti d li ti f ti ti h bcolitis and severe complications of constipation have beenreported. Therefore in 2000 alosetron was withdrawn fromthe market but was reintroduced in 2002 with a morethe market but was reintroduced in 2002 with a morerestricted indication and a requirement that clinicians andpatients follow a prescribing program. Serious outcomesassociated with IC and CoC appear to be mitigated sinceintroduction of alosetron under the RMP
L k 2010 Ch 2010Lucak, 2010, Chang, 2010
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: 5HT agonista
Tegaserod appears to improve the overall symptomatology of IBSTegaserod appears to improve the overall symptomatology of IBS, and the frequency of bowel movements in those with chronic consti pation. The clinical importance of these modest improvements is not p p pclear. There are currently few data on its effect on quality of life.
Chang 2004, Talley 2005, Inflammatory Bowel Disease and Functional Bowel Disorders Group 2007
Tegaserod 6 mg given twice daily improved the QOL as well as theTegaserod 6 mg given twice daily improved the QOL as well as the bowel symptoms in Korean female IBS patients with constipation
Kim, 2010
StipsiModulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: nuovi farmaci
5 HT(4) i t i t ti l t ( hl id h l5-HT(4) agonists, intestinal, secretagogues (chloride channelactivators, and guanylate cyclase-C agonists), bile acid modulation,anti-inflammatory agents and visceral analgesics, neurokininanti inflammatory agents and visceral analgesics, neurokininreceptor antagonist,
target cholecystokinin or corticotropin-releasing factor receptors,serve as inhibitors for specific tryptophan hydroxylase iso-enzymes,mod late chloride secretion infl ence imm ne responses ia monomodulate chloride secretion, influence immune responses via monoclonal antibodies or ATP-mediated pathways, and even normalizethe gastrointestinal microflora via supplementation with probioticsthe gastrointestinal microflora via supplementation with probiotics
Camilleri, 2010, Zakko, 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: nuovi farmaci
Prucalopride, the newest European Medicines Agency-approved 5-hydroxytryptamine receptor 4 (5-HT(4)) agonist,is effective in the treatment of chronic constipation withimpro ed cardio asc lar safet relati e to older 5 HT(4)improved cardiovascular safety relative to older 5-HT(4)drugs;Ramosetron, the 5-hydroxytryptamine receptor 3 (5-HT(3))Ramosetron, the 5 hydroxytryptamine receptor 3 (5 HT(3))antagonist, appears efficacious in diarrhea-predominant IBS.
Camilleri, 2010, Zakko, 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: nuovi farmaci
Lubiprostone (Amitiza) approved by FDA for the treatment ofchronic-idiopathic constipation . Oral bicyclic fatty acid thatp p y yselectively activates type 2 chloride channels in the apical membraneof the intestinal epithelial cells, stimulating chloride secretion, alongwith passive secretion of sodium and water, inducing peristalsis andlaxation, without stimulating gastrointestinal smooth muscle. Testedin IBS C and chronic constipationin IBS-C and chronic constipation
Schey, 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: nuovi farmaci
Linaclotide, a minimally absorbed, 14-amino acid peptideLinaclotide, a minimally absorbed, 14 amino acid peptideagonist of guanylate cyclase-C, has shown efficacy in thetreatment of IBS-C, significantly improved symptoms of IBS-C, including abdominal pain and bowel symptoms. Diarrheawas the only dose-dependent adverse event, usually of mild or
d t itmoderate severityJohnston, 2010, Lee, 2011
Sodium chenodeoxycholate accelerates colonic transit and improvesSodium chenodeoxycholate accelerates colonic transit and improvesbowel function in female patients with IBS-C. The rate of bile acidsynthesis influences colonic transit.y
Rao, 2010
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: Farmaci psicotropi
There is good evidence that antidepressants are effective for theg ptreatment of IBS. The subgroup analyses for SSRIs and TCAs areunequivocal and their effectiveness may depend on the individualpatient.
Quartero et al, Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group 2009, Enck, 2010
for the majority of antidepressant medications no evidence existsj y pthat supports their use for the treatment of abdominal pain-relatedFGIDs in children and adolescents. Amitriptyline does not appear toprovide any benefit for the treatment of FGIDs in children andadolescents. Studies in children with depressive disorders haveshown that antidepressants can lead to substantial sometimes lifeshown that antidepressants can lead to substantial, sometimes life-threatening adverse effects
Inflammatory Bowel Disease and Functional Bowel Disorders Group 2011.Inflammatory Bowel Disease and Functional Bowel Disorders Group 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica: Farmaci psicotropi
TCA: amitriptilina, desipramina SSRI: Paroxetina, fluoxetinap , p ,
Rallentano il transito intestinale, effetto analgesico a basso dosaggio Migliorano la sintomatologia globale (↓ discomfort distensioneMigliorano la sintomatologia globale (↓ discomfort, distensione addominale e n. evacuazioni)
Creed 2003, Chial 2003, Tack 2006,, Talley 2008, Creed 2008, Gaman 2009Creed 2003, Chial 2003, Tack 2006,, Talley 2008, Creed 2008, Gaman 2009
The evidence for the benefit of antidepressant treatment in patientswith IBS and comorbid depression was limited and contradictorywith IBS and comorbid depression was limited and contradictory
Friedrich, 2010
Citalopram was not superior to placebo in treating non-depressed IBS patients. Ladabaum, 2010
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabileTerapia farmacologica:psicoterapie
Cognitive behavioural therapy, Interpersonal psychotherapy,Cognitive behavioural therapy, Interpersonal psychotherapy,Relaxation/Stress management Except for a single study, thesetherapies are not superior to placebo and the sustainability of theireffect is questionable
Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group 2009
significant proportion of IBS patients treated with CBT have apositive response within 4 weeks of treatment; these patients arep p ; pmore likely to maintain treatment gains than patients without arapid response.
Lackner, 2010
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)Condizioni associate: defecazione ostruitaCondizioni associate: defecazione ostruita
Riempimento rettale
Distensione rettale
Rilassamento dello SAI e SAE
Aumento dell’angolo anorettale
Passaggio contenutofecale
Modulo di Fisiopatologia dell’Apparato Digerente U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)Condizioni associate: defecazione ostruitaCondizioni associate: defecazione ostruita
Patients with various types of chronic pelvic and perineal pain,especially those seen in urology departments, very often reportp y gy p , y passociated IBS.
The presence of IBS in dyssynergic defecation did not affect theoutcome of biofeedback therapy. In addition, treating dyssynergicdefecation patients with IBS by biofeedback therapy improved bothdefecation patients with IBS by biofeedback therapy improved bothconstipation and IBS symptoms
Watier, 2010, Patcharatrakul, 2011
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)Terapia miscellanea : ipnosiTerapia miscellanea : ipnosi
Gut-directed hypnotherapy is an effective treatment alternative forGut directed hypnotherapy is an effective treatment alternative forpatients with refractory IBS, but the effectiveness is lower when thetherapy is given outside the highly specialized research centers.
Lindfors, 2011
The quality of the included trials was inadequate to allow anyThe quality of the included trials was inadequate to allow anyconclusion about the efficacy of hypnotherapy for irritable bowelsyndromesyndrome..
Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group 2007
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Sindrome del colon irritabile (SII)Terapia miscellanea : agopuntura erbeTerapia miscellanea : agopuntura, erbe
Therefore, it is still inconclusive whether acupuncture is more eff ective than sham acupuncture or other interventions for treating IBSIBS.
Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group 2006
positive findings from less rigorous trials should be interpreted with caution due to inadequate methodology,. Some herbal medicines q gy,deserve further examination in high-quality trials.
C h I fl t B l Di d F ti l B l Di d G 2008Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group, 2008
Placebo!!!
Modulo di Fisiopatologia dell’Apparato Digerente
U.O.Gastroenterologia, Cesena
Grazie per l’attenzione
Modulo di Fisiopatologia dell’Apparato Digerente, U.O.Gastroenterologia, Cesena