GI Pharmacology - Acid Suppressors and Anti-Nausea Agents

Question 1

Gastrin receptor?

Answer 1

• CKK-receptor

Question 2

Acetylcholine receptor?

Answer 2

• M3-receptor (muscarinic)

Question 3

Histamine receptor?

Answer 3

• H2- receptor

Question 4

Prostaglandin receptor?

Answer 4

• PGE-receptor

Question 5

Stimulatory G-protein signalling?

Answer 5

Gastrin, Ach, Histamine

Question 6

Inhibitory G-protein signalling?

Answer 6

Prostaglandin

Question 7

H2-Blocker mechanism of action?

Answer 7

Competitive block of H2-R on parietal cells

Question 8

Common H2-Blockers? (3)

Answer 8

• Cimetidine
• Ranitidine
• Famotidine

Question 9

Therapeutic uses of H2-Blockers? (3)

Answer 9

• Ulcers
• Management of Zollinger-Ellison syndrome (?)
• GERD

Question 10

What type of infection are H2-blockers often associated with?

Answer 10

H. pylori

Question 11

Mechanism of action of anticholinergics?

Answer 11

Block M3-receptors on parietal cells

Question 12

What NT normally acts on M3 receptors? Which nerve releases this NT at the level of the viscera?

Answer 12

Acetylcholine - Vagus nerve

Question 13

Therapeutic uses of anticholinergics?

Answer 13

Ulcers

Question 14

PPI mechanism of action?

Answer 14

H+, K+-ATPase inhibition

Question 15

Specific PPI medications?

Answer 15

• Omeprazole
• Esomeprazole
• Pantoprazole

Question 16

Therapeutic uses of PPIs?

Answer 16

• Ulcers
• GERD
• Management of Zollinger-Ellison syndrome

Question 17

Which do you think would be more effective to manage Zollinger-Ellison syndrome, H2-blockers or PPI’s? Why?

Answer 17

Better with PPI, as inhibits HCl from all stimulatory routes (gastrin, ACH, histamine) and not just via H2 receptors

Question 18

What are prostaglandins considered?

Answer 18

Eicosanoids

Question 19

What are the two structural categories of lipids?

Answer 19

• Triglycerides and phospholipids

Question 20

What specific lipids are most eicosanoids derived from?

Answer 20

Arachodonic acid

Question 21

Mechanism of action of PGE1 analogues? (2)

Answer 21

1. Decreased proton pump activity
2. Increased bicarbonate and mucous secretion

Question 22

PGE1 medication analogue?

Answer 22

Misoprostal

Question 23

Therapeutic use of PGE1 analogues?

Answer 23

Most common = prevention of NSAID-induced ulcer/GI bleed

Question 24

What is the connection between NSAIDs and PGs including the enzymes involved?

Answer 24

NSAIDs block COX, which blocks production of PG’s

Question 25

Why is Misoprostol contraindicated in pregnancy?

Answer 25

Causes uterine contractions

Question 26

Agents that decrease motility?

Answer 26

- Diphenoxylate-atropine (Lomotil) - Loperamide (Imodium)

Question 27

Agents that increase motility?

Answer 27

- Laxatives - Metoclopramide (Maxeran, Reglan) - Domperidone (Motilium)

Question 28

Diphenoxylate-atropine mechanism of action - DIPHENOXYLATE?

Answer 28

- Opioid receptor agonist - Inhibits ACH release in enteric system at low doses

Question 29

What does Ach usually do for gut motility?

Answer 29

Increases gut motility

Question 30

Diphenoxylate-atropine mechanism of action - ATROPINE?

Answer 30

M-blocker = Synergistic effects with diphenoxylate to decrease Ach effects on the gut

Question 31

What are the side effects of anticholinergics? What does this cause?

Answer 31

Dry mouth - low abuse potential

Question 32

Anticholinergic side effects occur before _______ effects are felt?

Answer 32

Euphoric opioid

Question 33

Drug similar to diphenoxylate-atropine, but without the atropine?

Answer 33

Loperamide

Question 34

Why does Loperamide lack CNS effects - therefore having an extremely low abuse potential?

Answer 34

Does not cross BBB

Question 35

Laxative mechanisms? (4)

Answer 35

- Bulking agents - Osmotic laxatives - Chemical stimulants - Stool softeners

Question 36

Examples of Bulking laxatives?

Answer 36

Bran, psyllium

Question 37

Non-absorbed agents that create bulkier stools and draw water into stools?

Answer 37

Bulking laxatives

Question 38

Examples of Osmotic laxatives?

Answer 38

Mg sulfate, Mg hydroxide, lactulose

Question 39

Osmotic laxatives are not well-absorbed from the intestinal tract, what does this cause?

Answer 39

Increase in osmotic pressure leading to retention of water in intestine, lumen extension, and increased bowel action

Question 40

What can low dose of Mg hydroxide do?

Answer 40

Can neutralize stomach acid

Question 41

What is lactulose?

Answer 41

Disaccharide that is not broken down well in the SI => Reaches colon, broken down by bacteria to produce lactic acid

Question 42

Will lactulose increase or decrease excretion of ammonia? Why?

Answer 42

Increase => charged so less likely to be reabsorbed and therefore more likely to be excreted

Question 43

Examples of chemical stimulant laxatives?

Answer 43

Emodin (active ingredient in senna, aloe, cascara)

Question 44

What is the mechanism of action of chemical stimulants?

Answer 44

Irritate the gut to induce peristalsis and increase mucous production

Question 45

Examples of stool softeners?

Answer 45

Mineral oil, sodium docusate

Question 46

What do stool softeners use?

Answer 46

Water or oil to soften stool

Question 47

What does mineral oil do?

Answer 47

Lubricates stools for easier passage

Question 48

What does sodium docusate do?

Answer 48

Detergent that allows water to penetrate stools = prevents hard, dry stools and allows for easier passage

Question 49

Metoclopramide mechanism of action for increased motility?

Answer 49

Block of peripheral D-receptors (dopamine is inhibitory to GIT)

Question 50

What does blocking dopamine result in?

Answer 50

Allows Ach effects to predominate: - Increased peristalsis - Increased tone of LES

Question 51

Metoclopramide mechanism of action for anti-nausea/vomiting?

Answer 51

Antiemetic action comes from block of D2-receptors in medulla (trigger zone from vomiting)

Question 52

Therapeutic uses of Metaclopramide for nausea and vomiting?

Answer 52

- GERD - Diabetic gastric stasis - Nausea and vomiting with chemo

Question 53

What happens when you take the peripheral effects of Metoclopramide too far?

Answer 53

Diarrhea

Question 54

Blocking dopamine causes increased prolactin, which can cause?

Answer 54

Hyperprolactinemia

Question 55

What is similar to metoclopramide, but less likely to cross BBB or into breast milk?

Answer 55

Domperidome

Question 56

How can domperidone stimulate milk production in lactating mothers?

Answer 56

Increased prolactin

Question 57

How do anticholinergics have anti-nausea effects?

Answer 57

Block cholinergic transmissions between vestibular and vomiting centers in the CNS

Question 58

Specific anticholinergic anti-nausea agents?

Answer 58

- Scopolamine (M-receptor) - Promethazine (M-blocker and H1-blocker)