Lesson 21: Gastrointestinal Motility & Chronic Bowel Disease PDF

Lesson 21 Gastrointestinal Motility 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  1. Drugs altering the GI tract motility Purgatives, which accelerate the passage of food through the intestine Agents that increase the motility of the GI smooth...

Lesson 21 Gastrointestinal Motility 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  1. Drugs altering the GI tract motility Purgatives, which accelerate the passage of food through the intestine Agents that increase the motility of the GI smooth muscle without causing purgation (prokinetic drugs). Antidiarrhoeal drugs, which decrease motility Antispasmodic drugs, which decrease smooth muscle tone (spasmolytic drugs) 2. Laxative agents Purgatives or laxative agents include: 1. Bulk laxatives (e.g. ispaghula husk , first choice for slow action) 2. Osmotic laxatives (e.g. lactulose ) 3. Faecal softeners (e.g. docusate ) 4. Stimulant purgatives (e.g. senna )  2. Laxative agents 1. BULK LAXATIVES METHYLCELLULOSE and certain plant extracts (e.g: ispaghula husk) Mechanism of action Water-attracting polymers: form a bulky hydrated mass, improving faecal volume and consistency , producing peristalsis in the gut. Takes several days to work (1-3 days) First choice in chronic constipation and long-term treatment ADRs: Flatulences and abdominal distension May produce obstruction in patients with intestinal pathologies  2. Laxative agents 2. OSMOTIC LAXATIVES LACTULOSE, Mg2+ and Na+ SALTS Mechanism of action Poorly absorbed in the intestinal wall producing an osmotic load. Their osmotic action retains a large volume of fluid in the intestine, speeding up the transit of contents. This increased volume reaches the colon, causing its distension and leading to a purgative effectwithin about an hour. Effect within 1 hour ADRs: Abdominal cramps can occur Low systemic absorption but avoid Mg salt small children and in patients with poor renal function (electrolyte alterations)  2. Laxative agents 3. FAECAL SOFTENERS DOCUSATE SODIUM, ARACHIS OILS AND GLYCERIN (rectal administration) Mechanism of action They act in the gastrointestinal tract in a similar way to a detergent, promoting the production of soft stools and also a laxative with weak stimulant activity. ADRs: Causes impaired absorption of liposoluble vitamins (A,D,E)  2. Laxative agents 4. STIMULANT LAXATIVES BISACODYL, SODIUM PICOSULFATE Mechanism of action Increase electrolyte and hence water secretion by the mucosa Increase peristalsis through stimulation of enteric nerves Bisacodyl may be given orally but is often given by suppository: stimulates the rectal mucosa, inducing defecation in 15–30 min Indications: temporal constipation  2. Laxative agents 4. STIMULANT LAXATIVES SENNA and DANTRON (Anthraquinone derivatives) Mechanism of action They directly stimulates the myenteric plexus, resulting in increased peristalsis and thus defecation. Senna alexandrina Indications: Special patients: bedridden patients, patients where defecation effort is It acts as an irritant purgative and manifests carcinogenic effects ( its administration is restricted to the terminally ill). contraidicated, with mental disorders In preparation for digestive assestments and prior to surgery Contraindications Obstruction of the bowel ---> Overuse can lead to an atonic colon (dependence) Abdominal cramping may be experienced as a side effect with almost any of these drugs.  3. Prokinetic drugs Mechanism of action Stimulate and improve intestinal transit by increasing the GI cholinergic activation thus: ✓ Increase the stomach emptying rate ✓ Increase peristaltism and transit rate in the gut SEROTONIN increases cholinergic activity SEROTONINERGIC AGONISTS DOPAMINE decreases cholinergic activity ANTIDOPAMINERGICS AGONIST OF 5-HT 4 RECEPTOR: PRUCALOPRIDE used when other laxative treatments have failed TEGASEROD is used to treat symptoms of constipation in patient with irritable bowel syndrome (IBS)  3. Prokinetic drugs D2 ANTAGONISTS (AGONIST-5-HT 4 /ANTAGONIST D2/ANTAGONIST 5-HT 3) DOMPERIDONE It is primarily used as an antiemetic (in patients that takes L-Dopa), but it also increases GI motility with a indirect mechanism. Doesn’t cross the BBB! METOCLOPRAMIDE (also an antiemetic) stimulates gastric motility, causing a marked acceleration of gastric emptying. It is useful in gastro-oesophageal reflux and in disorders of gastric emptying but is ineffective in paralytic ileus. It crosses BBB (acts on the CTZ) ADRs: D2 blocking at the CNS: hyperprolactinemia, extrapyramidal symptoms  3. Prokinetic drugs OTHER AGENTS LUBIPROSTONE Chloride channel-2 activator that acts on cells in the apical membrane of the small intestine to promote chloride and fluid secretion into the lumen, with associated improvements in gut motility and softer stool. Indications: constipation due to opioids, in IBS and in patients who have failed to respond to non-drug treatment of constipation. NALOXEGOL It is a μ opioid-receptor antagonist that is similar to naloxone, but with the addition of a pegylated portion to prevent penetration into the CNS. Indications: counteracts the reduced GI motility and hypertonicity that is seen in opioid-induced constipation, but without exerting any adverse effect on the analgesic properties of opioid agonists centrally. METHYLNALTREXONE is a peripheral opioid-receptor antagonist that is licensed for opioid- induced constipation  4. Antidiarrhoeal Agents DIARRHOEA Increase in the motility of the GI tract Increased secretion, coupled with a decreased absorption, of fluid. This leads to a loss of electrolytes (particularly Na + ) and water Treatment severe acute diarrhoea Maintenance of fluid and electrolyte balance (isotonic solutions of NaCl plus glucose and starch-based cereal (important in infants) Use of anti-infective agents Use of spasmolytic or other antidiarrhoeal agents. Drugs that reduce GI motility are also useful in IBS and diverticular disease *IBS: irritable bowel syndrome  4. Antidiarrhoeal Agents 1. INHIBITORS OF INTESTINAL MOTILITY OPIOIDS LOPERAMIDE Selective and local action in the GI tract Undergoes significant enterohepatic cycling. Reduces the frequency of abdominal cramps, decreases the passage of faeces and shortens the duration of the illness First choice for the treatment of traveller’s diarrhoea ADRs: Constipation, abdominal cramps, drowsiness and dizziness Complete loss of intestinal motility (paralytic ileus) can also occur. They should not be used in young (