Pharm of Emesis and GI Motility Disorders

Question 1

What is the enteric nervous system and what is its function?

Answer 1

Highly regulated neuronal network located in Auerbach’s myenteric plexus and submucosal plexus

Controls motor and secretory activity of the GI

Question 2

What are neurons in the intrinsic network called? What is the main neurotransmitter?

Answer 2

Neurons called iPANS (intrinsic primary afferent nerves)

Main neurotransmitter is serotonin

Question 3

Where are 5HT3 receptors located? What do they induce?

Answer 3

On extrinsic afferent nerves to induce nausea and abdominal pain

Question 4

Where are 5HT1P receptors located? What do they induce?

Answer 4

On iPANS; release Ach and calcitonin gene related peptide (CGRP) into the myenteric plexus interneurons to increase motility and regulate peristalsis

Question 5

Where are 5HT4 receptors located? What do they induce?

Answer 5

On presynaptic terminals of iPANS; enhance release of ACh and CGRP to increase motility and regulate peristalsis

Question 6

What does dopamine do in GI?

Answer 6

Binds to D2 receptors to reduce cholinergic effects (inhibitory) and decreases esophageal and gastric motility

Question 7

What does Ach do in GI?

Answer 7

Binds to muscarinic receptors to stimulate intestinal motility

Question 8

What does epinephrine do in GI?

Answer 8

Binds to adrenergic receptors to stimulate motility (only nominally effect though)

Question 9

What are the three phases of emesis?

Answer 9

Pre-ejection (gastric relaxation and retro-peristalsis)

Retching (rhythmic contraction of muscles)

Ejection (intense contraction of muscles and relaxation of UES)

Question 10

Where is the vomiting center located?

Answer 10

Reticular formation of the medulla next to the chemo receptor trigger zone (CTZ) at the base of 4th ventricle

Question 11

What receptors does CTZ have a high concentration of?

Answer 11

Histamine, 5Ht3, dopamine, neurokinin

Question 12

What are the pharmacological approaches to emesis

Answer 12

Antihistamines (H1 receptor antagonist)

5HT3 receptor antagonism

D2 antagonism

M1 antagonism

CB1 agonism

Neurokin antagonism

Question 13

What does histamine do in GI?

Answer 13

Mediates nausea, allergy and inflammatory response

Question 14

How do antihistamines work as antiemetics?

Answer 14

Reversible H1 antagonists with no effects on other H receptors

Question 15

Are antihistamines “dirty” or “clean”

Answer 15

Dirty. Have significant antimuscarinic and sedative effects

Question 16

What is the first line treatment for motion sickness and vertigo?

Answer 16

H1 receptor blockers with antimuscarinic effects

Question 17

What does serotonin do in the GI tract?

Answer 17

Vasoconstrictor and intestinal smooth muscle

Question 18

Are 5HT3 Receptor Antagonists “dirty” or “clean”

Answer 18

Clean! No antagonism of other receptors or extra-pyramidal side effects

Question 19

What is the first line/prophylactic treatment for chemo induced nausea/vomiting?

Answer 19

5HT3 Receptor antagonists

Ondansetron and Granisetron

Question 20

Are D2 Receptor Antagonists “dirty” or “clean”

Answer 20

Very dirty. Frequently antagonize other receptor types including 5HT3 and histamine receptors

Have a lot of side effects

Question 21

What is the most common use of muscarinic receptor antagonists?

Answer 21

transdermal patch attached to behind the ear for motion sickness (Scopolamine)

Question 22

How do NK1 receptor antagonists work against emesis ?

Answer 22

Central blockade of chemoreceptor trigger zone (CTZ)

Question 23

Are NK1 Receptor Antagonists “dirty” or “clean”

Answer 23

Clean

Question 24

How do CB1 agonists work against emesis?

Answer 24

Activate cannabinoid receptors close to CTZ

Used in combination with other anti-emetics and as an appetite stimulant

Question 25

What receptors are involved in GI motility? How specifically?

Answer 25

D2 receptors - decrease
5HT receptors - increase
Muscarinic (M3) receptors - increase

Question 26

What are therapeutic approaches to constipation?

Answer 26

Laxatives
Receptor mediated therapy
Chloride channel mediated

Question 27

How are emollient laxatives different from lubricant laxatives?

Answer 27

Emollient laxatives increase water secretion into the small intestine and lubricant laxatives just coat the bowel and reduce H20 absorption

Question 28

What are therapeutic approaches to Diarrhea? How do they work?

Answer 28

Supportive often suffices

Antisecretory agents

Opiod agonists - inhibit cholinergic input into plexi

Anticholinergics - inhibit M3 receptors

5HT3 Receptor antagonists –decreases gI afferent sensation, reduces colonic motility