Gut motility and emesis

Question 1

List the three types of purgatives.

Answer 1

Laxatives, faecal, stimulant purgatives

Question 2

What are bulk laxatives?

Answer 2

Poorly digested compounds (methylcellulose, psyllium) of plant origin.

Question 3

What is the mechanism of action of bulk laxatives?

Answer 3

Polysaccharide polymers are not broken down by normal digestive processes. Form bulky hydrated mass in GI lumen, promoting peristalsis.

Question 4

What are the side effects of bulk laxatives?

Answer 4

Affect pharmacokinetics of drugs, bloating

Question 5

What are osmotic laxatives?

Answer 5

Poorly absorbed solutes, e.g. salts or sugars

Question 6

What is the mechanism of action of osmotic laxatives?

Answer 6

Increase osmotic pressure in the lumen, driving water into the lumen.
Sugars broken down by bacteria in GIT creating acidic metabolites that attract water.

Question 7

What are side effects of osmotic laxatives?

Answer 7

Abdominal cramps (not significant for PEG)
Systemic effects of salts

Question 8

What are faecal softeners?

Answer 8

Surfactant, reduce surface tension of water, promoting softer faeces.
Weak

Question 9

When are faecal softeners used?

Answer 9

When straining should be avoided.

Question 10

What is the effect of stimulant laxatives?

Answer 10

Increase electrolyte and water secretion by mucosa, increase peristalsis (via enteric nerves)
Bowel can become lazy with use.

Question 11

Which drugs treat constipation without purgation?

Answer 11

D2 receptor antagonists

Question 12

What is the effect of D2 receptor antagonists?

Answer 12

Stimulates cholinergic smooth muscle activation, increases lower oesophageal sphincter pressure, enhancing gastric emptying.
May also block D2 receptors in CTZ.

Question 13

Which agents are antidiarrhoeal?

Answer 13

Opioid derivatives, e.g. loperamide

Muscarinic receptor antagonists

Question 14

What is the mechanism of action of loperamide as an antidiarrhoeal agent?

Answer 14

Selective for GIT
Decreases activity of the myenteric plexus
Decreases tone of longitudinal muscle (peristalsis) and increased tone of circular muscle (segmentation)

Question 15

When is rescue treatment no effective for vomiting?

Answer 15

Post-operative

Question 16

Which two brain structures are important in vomiting?

Answer 16

CTZ: in medulla, lacks BBB, dopamine and tryptamine (5HT) input

Vomiting centre: not a discrete area, inputs from CTZ, GIT, CVS, limbic system, labyrinths via vestibular nuclei, mechano/chemo receptors in GIT (5HT, ACh, histamine, DA, neurokinins)

Question 17

Which antiemetics are best for motion sickness and are prophylactic as well as relieving?

Answer 17

Antimuscarinics

Question 18

What is the mechanism of action of antihistamines in emesis?

Answer 18

H1 receptor antagonists (CTZ, block vestibular communication), some anticholinergic activity.

Question 19

When are H1 receptor antagonists useful for emesis?

Answer 19

Motional sickness, morning sickness, not chemotherapy-induced.

Question 20

What are the side effects of H1 receptor antagonists?

Answer 20

Anti-muscarinic

Question 21

Where do D2 receptor antagonists act?

Answer 21

CTZ and gastric emptying through 5-HT4 agonism.

Question 22

What is the mechanism of action of setrons in emesis?

Answer 22

5HT3 receptor antagonists with central and peripheral action.

Question 23

When are setrons used for emesis?

Answer 23

CINV, PONV, acts at CTZ (GIT and NTS)

Question 24

What are the side effects of setrons?

Answer 24

Constipation due to GIT

Question 25

Which drug is commonly used as an adjuct to antiemetic therapy?

Answer 25

Glucocorticosteroids, potentiate effects of antiemetics, reduce GIT inflammation reducing stimuli to CTZ.

Question 26

List the drugs used for antiemesis.

Answer 26

``` Antimuscarinins H1R antagonists D2R antagonists 5HT3R antagonists Glucocorticosteroids BZNs NK1 receptor antagonists Pyridoxine (vitB6) Ginger Cannabinoids ```

Question 27

Where are NK1 receptors abundant?

Answer 27

GIT, CTZ, CNS

Question 28

When are NK1 receptor antagonists useful for emesis?

Answer 28

Chemotherapy, motion sickness, alcohol.