Gastroenterology: Pharmacology - Laxatives

Question 1

7 classes of laxatives with example(s)

Answer 1

1. Bulk-forming: psyllium, methylcellulose, polycarbophil
2. Stool softeners: docusate, glycerin suppository, mineral oil
3. Osmotic: magnesium hydroxide (milk of magnesia), sorbitol, lactulose, combination purgatives, PEG
4. Stimulant: senna, aloe, cascara, bisacodyl
5. Chloride secretion activators: lubiprostone, linaclotide, plecanatide
6. Opioid receptor antagonists: methylnaltrexone, alvimopan
7. 5HT-4 agonists: cisapride, prucalopride, tegaserod

Question 2

Mechanism of action of bulk-forming laxatives

Answer 2

Indigestible hydrophilic colloids that absorb water and distend the colon to promote peristalsis

Question 3

Adverse effect of bulk-forming laxatives

Answer 3

Increased bloating and flatus

Question 4

Mechanism of action of stool softeners

Answer 4

Soften stool material to allow water and lipids to penetrate
May also impair water and lipid absorption from stool

Question 5

Adverse effects of mineral oil as stool softener

Answer 5

1. Aspiration causes severe lipid pneumonitis
2. Long-term use inhibits fat-soluble vitamin absorption

Question 6

Mechanism of action of osmotic laxatives

Answer 6

Soluble but nonabsorbable compounds which increase faecal fluid

Question 7

Adverse effect of milk of magnesia

Answer 7

Hypermagnesaemia in patients with renal insufficiency

Question 8

Adverse effects of sorbitol and lactulose

Answer 8

Sugars are metabolised by colonic bacteria -> flatus, cramps

Question 9

Adverse effect of sodium phosphate (used as osmotic laxative)

Answer 9

Electrolyte derangement (hyperphosphataemia, hypocalcaemia, hypernatraemia, hypokalaemia) leading to increased risk of cardiac arrhythmias or nephrocalcinosis-induced AKI

Question 10

Adverse effects of anthraquinone derivatives (aloe, senna, cascara)

Answer 10

Brown pigmentation of the colon (“melanosis coli”)

Question 11

Mechanism of action of lubiprostone, linaclotide, plecanatide

Answer 11

Stimulates type 2 chloride channel CIC-2 in small intestine, increasing intestinal motility

Question 12

Mechanism of action of methylnaltrexone, alvimopan

Answer 12

Selective mu-opioid receptor antagonists

Question 13

Which opioid receptors are responsible opioid-induced constipation?

Answer 13

Mu receptors

Question 14

Mechanism of action of tegaserod, cisapride, prucalopride

Answer 14

5HT-4 receptor agonists

Question 15

How do 5HT-4 agonists exert their laxative effects?

Answer 15

Stimulation of 5HT-4 receptors results in activation of enteric neurons promoting peristalsis

Question 16

Mechanism of action of loperamide, diphenoxylate, eluxadoline. What is special about eluxadoline?

Answer 16

Opioid agonists
Eluxadoline has high affinity for mu-opioid receptor

Question 17

Contraindications to eluxadoline

Answer 17

Can induce sphincter of Oddi spasm: should not be used in patients with a history of pancreatitis, alcoholism, or known sphincter of Oddi disease (and with caution in patients with prior cholecystectomy)

Question 18

How does bismuth salicylate exert its antidiarrhoeal effects?

Answer 18

Inhibits intestinal prostaglandin and chloride secretion

Question 19

What medications can be used to treat colonic secretory diarrhoea secondary to bile salt malabsorption?

Answer 19

Bile salt-binding resins (cholestyramine, colestipol, colesevelam)

Question 20

Five physiologic effects of somatostatin

Answer 20

1. Inhibits numerous GI hormones and transmitters (gastrin, CCK, glucagon, GH, insulin, secretin, VIP, 5HT)
2. Reduces intestinal and pancreatic secretions
3. Slows GI motility and inhibits gall bladder contraction
4. Reduces portal and splanchnic blood flow
5. Inhibits secretion of some anterior pituitary hormones

Question 21

What is octreotide?

Answer 21

Synthetic octapeptide with actions similar to endogenous somatostatin

Question 22

Four clinical uses of octreotide

Answer 22

1. Inhibition of neuroendocrine tumour effects (carcinoid, VIPoma)
2. Antidiarrhoeal
3. Treatment of pituitary tumours (e.g. treatment of acromegaly)
4. UGIB in setting of portal HTN (reduce portal blood flow and variceal pressures)