GI Drugs

Question 1

When is antiemetic therapy indicated, give examples?

Answer 1

When vomiting is debilitating or associated with a chronic condition (e.g. pancreatits) where the cause of the vomiting has been determined

To prevent excessive fluid or electrolyte loss. Eg. after eating a toxic substance (as long as are sure the substance has been cleared)

Question 2

What schools of thought are there that are against antiemetic therapy?

Answer 2

When there is an obstruction (increasing gut motility may lead to increased risk of gut perforation)

Infections - may result in longer times for the infection to clear

Toxic substance ingestion - emesis is there to remove toxins.

Question 3

Outline the pathways associated with vomiting.

Which is the key integrator of this system?

Answer 3

The nucleus tractus solitarius is the integrator of the vomiting pathway

Question 4

Which receptors are associated with which system?

Answer 4

NTS - neurokinin 1 (NK1)

CRTZ - D2, M1, 5HT3, H1 & H2

Vestibular - M1 (also linked to CRZT in dogs)

Vomiting Centre - a2, 5HT1a

Peripheral - D2, M2, 5HT3, Motilin

Question 5

What are the classes of antiemetic drugs?

Answer 5

NK1 antagonists

Metaclopramide

Phenothiazines

Antihistamines

5HT3 antagonists

Anticholinergics

Question 6

What is the drug that affects NK1 receptors?

What species is it effective in?

What is it indicated for?

Answer 6

Maropitant

Dogs

Acute gastroenteritis, motion sickness, cytotoxicity induced vomiting (labelled for the last one but not neccessarily that effective for it). It is useful against both peripheral and central causes of vomiting.

Question 7

What should be taken into account when using Maropitant?

Answer 7

It is extremely effective so may mask underlying disease. Ensure correct diagnosis is repeat treatments are needed. Do not use if GI obstruction is suspected.

Question 8

What is the mechanism of action of Metaclopramide?

Answer 8

D2 and 5HT3 antagonist => works on the CRTZ and peripheral receptors.

It also has a pro-cholinergic effect so increases gut motility.

Question 9

How do phenothiazines work?

Answer 9

They antagonise:

• D₂
• a1 & a2
• H1 & H2
• Muscarinic receptors

Therefore they work on all of the centres involved in vomiting apart from the NTS.

Question 10

What are Phenothiazines indicated for? Is there anything that needs to be taken into account?

Answer 10

Any cause of vomiting.

They are not veterinary registered in the UK

Question 11

What can antihistamines be used for?

Answer 11

Causes of vomiting in the CRTZ, only really effective in dogs. Particularly for motion sickness as the CRTZ has a link with the vestibular system.

Cats do not really suffer from motion sickness.

Question 12

Where is the mechanism of action for 5HT₃ antagonists and what are they often used for?

Answer 12

CRTZ and peripherally. They are generally used for cytotoxic drug induced emesis (e.g. cancer therapy).

Question 13

What are the different anticholinergics?

Answer 13

Atropine

Butylscopolamine

Propantheline

Isopromide

Question 14

What is the problem with anticholinergic anti emetics?

Answer 14

Although they act on the M1 receptors in the vestibular system they also act on peripheral M2 receptors which are involved in regulating gut motility, which can cause more problems.

Question 15

What are the different classes of anti-ulcer drugs?

Answer 15

• Systemic antacids
• H₂ receptor antagonists
• Sucralfate
• Misoprostol (synthetic PGE)
• Omeprazole (PPI)

Question 16

Describe the advantages of systemic antacids.

Answer 16

Probably not that effective and need to be used frequently and given orally - poor compliance and not tolerated in vomiting patient. They only treat but DO NOT prevent ulceration. They are cheap.

Question 17

Why are H₂ antagonists considered anti-ulcer drugs rather than anti-emetic drugs?

Answer 17

They ONLY affect the stomach, rather than the CRTZ, which has H₁ receptors.

Question 18

What are some H₂ receptor antagonists, which are available for veterinary use?

Answer 18

Cimetidine, ranitidine & famotidine. Only cimetidine is licenced.

Question 19

What are the H₂ antagonists useful for?

Answer 19

NSAID induced ulceration & ureamia for example.

Question 20

What does the use of H₂ antagonists depend on?

Answer 20

Cost, client conveinience and concurrent drug therapy.

Question 21

Is sucralfate licenced for veterinary use?

Answer 21

No but it is very effective and very safe.

Question 22

What is the main use for Misoprostol and why?

Answer 22

It is mainly used in prevention/treatment of gastric ulcers due to NSAID treatment or in treatment of NSAID toxicity as it is a synthetic PGE_2.

NSAIDs deplete prostaglandins which are essential for proper gut and renal function.

Question 23

What is the main safety concern when using Misoprostol?

Answer 23

It is the morning after pill so needs to be handled with extreme care for some owners.

Question 24

Why is the rationale for using Omeprazole reduced?

What is it used for?

Answer 24

Cinetidine is now licenced so can also use this.

Ulcers/Oesophagitis that are refactory to other treatments. Or Ulcers associated with gastrinomas or MAST cell tumors.

Question 25

What is the rationale for electrolyte solutions?

Answer 25

Enhance fluid absorption from the gut. They do no harm and give the owner something to do.

Question 26

How can hypermotility be treated by drug therapy?

Answer 26

Use Opiods or anticholinergics. These will rarely be indicated as hypermotility is rare and diarrhoea either resolves itself or chronically will not respond to symptomatic treatment.

Question 27

Are adsorbents and protectants useful?

Give an example of one of these, in what species is its use contraindicated?

Answer 27

No, may actually be worse. Gives owner something to do.

Bismuth salicylate - AVOID USE IN CATS

Question 28

What about probiotics?

Answer 28

No proven efficacy in animals

Do no harm - better than using antibiotics for diarrhoea!! Gives owner something to do.