Therapeutics. Treatment of irritable bowel syndrome (IBS) and constipation. Definition. IBS is an idiopathic chronic relapsing disorder characterized by: Abdominal discomfort (pain), bloating or distension Alteration in bowel habits (diarrhea, constipation or both).
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Treatment of irritable bowel syndrome (IBS) and constipation
IBS is an idiopathic chronic relapsing disorder characterized by:
Aims of treatment:
2) Relieve distension / bloating
Mechanism of action:
Block muscarinic receptors (M₃ on smooth muscles in case of hyoscine or presynaptic M₁ in case of dicyclomine)
Contraindications of anticholinergic drugs
Drug interactions of anticholinergic drugs:
Mechanism of action:
Not known (? calcium channel blocker or ? Direct acting)
Which antispasmodic is preferred in patients with IBS with predominant constipation?
Which antispasmodic is indicated in patients with IBS with glaucoma or prostatic enlargement?
Mechanism of action:
Block synaptic amine uptake (both norepinephrine and serotonin) →↑ presence of serotonin and norepinephrine at their post-synaptic receptors (→ anxiety) followed by down regulation of the receptors →(delayed anxiolytic and antidepressant effect)
Amitriptyline or Desipramine (10 – 50 mg/d) . (N.B. the usual antidepressant dose = 75 – 200 mg)
Patients with cardiac diseases
Mechanism of action:
Selective block of synaptic uptake of serotonin.
Cetalopram (less P450 inhibition → less drug interactions)
Mainly GIT including:
Adequate fluid intake to avoid intestinal obstruction
Abdominal distension (due to fermentation).
Intestinal obstruction when not consumed with sufficient fluid
Contraindications of Mg oxide
Action in the GIT (mediated by binding to opioid receptors)
Mechanism of opioid action:
Inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses
Opioid agonist that has no analgesic properties in standard doses. Higher doses have central opioid actions. Used in combination with a sub-therapeutic dose of atropine (to prevent abuse)
Opioid agonist that does not cross the blood-brain barrier and has no analgesic properties and no potential for addiction
Abdominal pain and distention, constipation, dry mouth, hypersensitivity, and nausea and vomiting.
GIT distension → stimulate EC cells in the mucosa of the intestine → release of 5HT →
Binding of 5HT to
↑ release of
ACH and CGRP
5HT₃R are found on terminals of enteric cholinergic neurons → ↑release of ACh
↑Proximal bowel contraction
↑ Distal bowel relaxation
primary afferent neuron
2nd order enteric cholinergic neuron
→ stimulation of
and abdominal pain
Extrinsic afferent nerve
Action: relieves lower abdominal pain, urgency and diarrhea (no effect on stomach)
Mechanism of action: 5HT₃ receptor antagonist
Uses: Femalepatients with severe IBS with diarrhea with no response to other therapies
Mechanism of action of tegaserod:
Serotonin 5HT₄ partial agonist. Binding to 5HT₄ receptors on the terminals of the 2nd order enteric neuron
→↑ release of Ach and CGRP →
↑gastric emptying and enhance small and large bowel transit (no effect on esophagus)
→↑ Cl secretion from the colon →↑ stool liquidity
Low bioavailability (further reduced by food)→ should be taken before meals
Metabolized in liver (by glucuronidation)
Excreted in feces (unchanged) and in urine (metabolites)
Severe renal or hepatic impairment
Short term treatment (up to 12 weeks) of women with moderate/severe IBS with predominant constipation who have failed to fiber supplementation and laxatives (reduce pain and bloating - ↑ bowel movements and ↓ hardness of stools)
Chronic constipation in patients not responsive or intolerant to other less expensive therapies
Adverse reactions (rare):
A 34-year-old woman presents with a 6-month history of abdominal pain, bloating, distension, decrease in the number of bowel movements per week (<3 times) and difficulty when passing stools. She also states that the abdominal pain and bloating almost occur continuously throughout the day although her symptoms are alleviated by passing stool. She also states that the symptoms are worse when she has midterm or final examinations.
She was taking bran till 3 months ago but could not stand the taste and wasn’t sure how much it was helping. She switched to psyllium powder but she felt that distension increased. She was also treated with sorbitol solution but it has some side effects and she resumed taking psyllium again.
Medical examination and investigations were unremarkable apart from slight abdominal distension and slight tenderness over the lower abdomen.
A case of IBS with:
Psyllium increased abdominal distension because it contain insoluble fiber which is fermented by colonic bacteria.
Side effects of lactulose:
High fiber diet consisting mainly of fruits and vegetables
Bulk-forming laxatives such as methylcellulose with increasing drinking of water
Mebeverine or Hyoscine (Mebeverine is preferred because Hyoscine may increase constipation)
Diet should be low in carbohydrates
The patient had IBS with predominant diarrhea with pain and distension.
Treatment of diarrhea: Loperamide. (why not diphenoxylate?) What can you prescribe if loperamide fails? What are the side effects of the new drug? (see the table)
Treatment of abdominal pain:
Treatment of bloating:
Probiotics. (why tegaserod could not be prescribed in this case?)
If not effective:
Bed ridden, geriatric or chronic constipation patients:
1. First line of treatment is bulk forming laxatives
2. Second line: more potent agents may be required :
Before oral laxatives can be used, the impaction needs to be removed using mechanical methods, including tap-water or saline enemas and digital extraction.
In the hospitalized patient withoutGI disease:
Followed by: 2.
2. Most orally or rectally administered laxatives may be used in these situations.
Irritant laxatives (mentioned in some books)
Evacuation of bowel before surgery or diagnostic procedures involving the GIT as sigmoidoscopy or barium enema:
Oral bisacodyl, sodium picosulfate, cascara or senna (active after 6 -12 h) Given the night before operation or procedure)
Oral castor oil (active after 1-3 h)
Oral Mg hydroxide (active after 2-5h)
Bisacodyl rectal suppository (active after 30 – 60 min)
Rectal Na sulfate enema (active after 30 min)
Polyethylene glycol - electrolyte solution enema
A 35-year-old patient on normal diet and exercise presented with Constipation since 2 weeks. Mention three alternative drugs from different groups that could be used to treat his condition giving the side effect of each.
You have been asked to prescribe a drug for prevention of straining for a hospitalized patient treated from myocardial infarction. Mention 2 drugs from 2 different groups giving their side effects.
A patient will undergo sigmoidoscopy in the next morning. Mention drugs which could be given to evacuate his bowel giving the expected time of action and possible adverse effects.