Gastrointestinal drugs

Question 1

What is the mechanism of action of histamine type 2(H2) blockers? Give examples.

Answer 1

They inhibit H2 receptors in gastric parietal cells, blocking HCl secretion. Ranitidine may also have some prokinetic activity.
Examples: cimetidine, ranitidine, famotidine

Question 2

What are the indications of H2 blockers?

Answer 2

Reflux oesophagitis, gastric ulcers, mast cell tumors, vomiting from liver or renal disease

Question 3

What are some side effects and contraindications of H2 blockers?

Answer 3

Cimetidine is a P450 inhibitor and decreases clearance of may drugs, leading to drug interactions.

Question 4

What is the mechanism of action of pump blockers? Give an example.

Answer 4

Mechanism: Proton pump inhibitor; inhibits NH+/K+ ATPase and inhibits HCl secretion in gastric parietal cells.
Example: omeprazole

Question 5

What are some indications of pump blockers?

Answer 5

Reflux oesophagitis, severe gastric ulcers, mast cell tumors, gastrinoma

Question 6

What are the side effects and contraindications of pump blockers?

Answer 6

Omeprazole is a P450 inhibitor and decreases the clearance of some drugs in people.

Question 7

What is the mechanism of action of gastroprotectants?

Give examples.

Answer 7

Sucralfate, misoprotsol
Sucralfate is an aluminium-containing disaccharide that forms a gel and binds to ulcer beds.
Misoprostol is a prostaglandin E1 (PGE1) analog that ptomotes healing of ulcers caused by nin-steroidal inflammatory drugs(NSAIDs).

Question 8

What are some indications of gastroprotectants?

Answer 8

Sucralfate: Gastric or oesophageal ulceration
Misoprostol: Prevention and treatment of NSAID-induced gastric and duodenal ulcers

Question 9

What are the side effects and contraindications of gastroprotectants?

Answer 9

Sucralfate binds to many drugs and decreases their bioavailability, particularly doxycycline and fluoroquinolones. Should be given at least 2 hours after other drugs
Misoprostol can cause cramping and diarrhea; contraindicated in pregnancy

Question 10

What is the mechanism of action of prokinetic agents? Give examples.

Answer 10

Metoclopramide, cisapride
Metoclopramide increases gastric and intestinal mobility by sensitzing the GI tract to acetylcholine.
Cisapride has a similar mechanism of action, but also improves colonic motility.
Metoclopramide(but not cisapride) is also a central antiemetic via inhibition of dopaminergic receptors.

Question 11

What are some indications of prokinetic agents:

(i) in general
(ii) metoclopramide only
(iii) cisapride only

Answer 11

Gastric atony(lacing muscular tone), ileurs, megaoesophagus(may reduce reflux)
Metoclopramide only: Nausea and vomiting without obstruction
Cisapride only: Constipation and megacolon

Question 12

What are some side effects and contraindications of prokinetic agents?

Answer 12

Prokinetic agents are contraindicated in cases of GI obstruction.
Meclopramide at high doses can cause tremor. Because of renal elimination, the dose should reduced in patients with renal insufficiency.
Cisapride has several drug interactions (e.g with azole antifungals).

Question 13

What are the 3 main categories of anti-emetics?

Answer 13

Phenothiazines
Serotonergic antagonists
Antihistamines

Question 14

Give examples of phenothiazines used as anti-emetics.

Answer 14

Clorpromazine

Prochlorperazine

Question 15

What are the indications of anti-emetics?

Answer 15

Refractory vomiting of defined cause. Use with fluid support.

Question 16

What are some side effects and contraindications of phenothiazines as anti-emetics?

Answer 16

Hypotension, ileus(apinful obstruction of the ileum); masks obstruction. Contraindicated in horses because of ataxia and excitation.

Question 17

Give examples of serotonergic antagonists used as antiemetics. What is their mechanism of action?

Answer 17

Ondansetron, dolasetron

Mechanism of action: 5-Hydroxytryptamine type 3(5-HT3) antagonist; blocks input to emetic center

Question 18

What are some indications of serotonergic antagonists used as antiemetics?

Answer 18

1. Chemotherapy-induced nausea

2. Intractable vomiting and nausea unresponsive to less expensive drugs.

Question 19

What are some side effects and contraindications of serotonergic antagonists used as antiemetics?

Answer 19

Potential to cause CNS signs in collies and other herding dogs with p-glycoprotein defect(p-glycoprotein substrate).

Question 20

Give examples of antihistamines used as antiemetics.

Answer 20

Diphenhydramine (e.g Benadryl), dimenhydrinayte (e.g Dramamine)

Question 21

What is the mechanism of action of antihistamines used as antiemetics?

Answer 21

1. H1 receptors antagonists; block input to emetic center

2. Also have some anticholinergic effects

Question 22

What are some indications of antihistamines used as antiemetics.?

Answer 22

1. Diphenhydramine: Adjunct to prevent chemotherapy-induced nausea
2. Dimenhydrinate: Motion sickness

Question 23

What are some side effects and contraindications of antihistamines used as antiemetics?

Answer 23

Sedation(dogs), excitation or sedation(cats); contraindicated in glaucoma due to anticholinergic effects

Question 24

Give the 3 main drug categories of antidiarrheals?

Answer 24

Adsorbents
Opioids
Anticholinergics