IBS

Question 1

Categories of IBS?

Answer 1

• • IBS-Constipation: hard / lumpy stools > 25% BMs
• • IBS-Diarrhea: loose / watery stools >25% BMs
• • Mixed IBS
• • Unsubtyped: insufficient abnormality in stool consistency

Question 2

behavioral changes for IBS

Answer 2

• • education/reassurance
• • exclude gas producing foods, diet low in fermentable saccharides (esp lactose / gluten)
• • increased physical activity

Question 3

ENS and PNS signaling in GI

Answer 3

ENS:

• • ACh @ M3 receptors
• • Serotonin (5-HT) @ 5 HT3 Receptor (6 subtypes)

Question 4

3 Major Components effecting/thought to cause IBS?

Answer 4

1) early life (genetics, environment)
2) psychosocial (stress, coping, social support)
3) Physiology (motility, inflammation, sensation, altered microflora)

**psychosocial component –> SSRIs / TCAs used to relieve symptoms

Question 5

PEG, Psyllum Methyl cellulose polycarbophil

Answer 5

MOA: bulk forming laxatives (IBS-C) –> stimulates stretch receptors / increases Ach activity, little systemic distrobution

Peg – osmotic agent that binds water, retains it in stool;
AEs = infrequent flatulence, nausea, abd pain, bloating

Psyllum – absorbs liquid in GI tract, altering GI fluid/electrolyte transport
AEs = nausea, diarrhea, inc flatulence, pain

Question 6

Linaclotide, lubiprostone

Answer 6

MOA: secretory IBS-C treatment –> inc stretch receptor action / hydration of stool, little systemic distrobution

Linaclotide – activates guanylate cyclase C receptor –> inc cGMP –> stimulates CFTR ion channel –> inc Cl-/H2O in lumen
AEs = contraindicated in neonates/kids activates CIC-2 Cl- channel
AEs = dose related HA, diarrhea, nausea

Question 7

Drugs for IBS-D?

Answer 7

1) Alosetron (5 HT3 receptor antagonist)
2) Loperamide (direct action on circular/longitudinal m)
3) Anticholinergics
4) TCAs (reduce reuptake epinephrine / serotonin)
5) SSRIs (xSer reuptake –> inc 5 HT action) – greater improvement in symptoms compared to TCAs

6) Rifaximin (oral rifampin analog – xRNA polymerase, no systemic bioavailability, tx G+ and G-)

Question 8

Alosetron

Answer 8

MOA: 5 HT3 receptor antagonist @ ENS

AES: BBW! – contraindicated w/ pre existing colitis, severe constipation (physicians enroll in prescribing program), most common SE is constipation,
+GI obstruction/perforation/impaction, toxic megacolon, 2o ischemic colitis, arrhythmia/s-tachycardia

Uses: IBS-D

Question 9

Loperamide

Answer 9

MOA: direct action at longitudinal/circular GI smooth muscle @ ENS

AEs: well tolerated

Uses: IBS-D

Question 10

Main goal/concept in IBS C vs D treatment?

Answer 10

C = increase stretch receptor response by increasing stool volume

D =

1) Block neurotransmitter systems involved in gastric motility (receptors are ubiquitous in ENS of GI wall)
2) Work @ CNS to modulate ENS (TCAs, SSRIs)
3) Antimicrobial to readjust microflora