Vomiting: Clinical Pharmacology in Practice

What are four potential general categories of causes of vomiting?

Gastrointestinal inflammation

Gastrointestinal obstruction

Extra-alimentary tract disease

Motion sickness

*What are four inputs/pathways to the emetic center that a drug might target?

CRTZ

Vestibular

Peripheral Sensory

(Cerebral Cortex - anxiety)

What are two components that play a role in acting on the emetic center?

Humoral (in the blood)

Neural

Humoral - things in the blood - pathway that may act on the emetic center via the CRTZ are either __________ or __________

Endogenous (like hepatotoxins) or Exogenous (like a drug)

Neural pathways to the emetic center include what inputs?

vagal, sympathetic

CRTZ

Vestibular

(Cerebrocortical)

*What is the difference between dogs and cats when it comes to the motion sickness pathway to the emetic center?

In cats: the vestibular pathway directly targets (synapses with) the emetic center

In dogs: the vestibular system must synapse on the CRTZ, before the signal reaches the emetic center

*What is an example of a situation where we would want to induce vomiting? What are a couple instances where we would NOT want to induce vomiting?

Want to induce vomiting: foreign body swallowed that's still potential in stomach and is non-noxious

NOT want to induce: if they swallowed a toxic/noxious substance. If the animal does not have control of their airway

*What location might we want to target with a drug, like apomorphine, in a dog with motion sickness?

CRTZ

*What is an emesis agent commonly used in dogs? Where are these receptors that these drugs are targeting located ?

Apomorphine

CRTZ

*What is apomorphine used for?

as an emesis agent in dogs

*What are two emesis agents commonly used in cats? Where are the receptors that these drugs are targeting located?

xylazine

dexmedetomidine

they target the emetic center directly

Apomorphine is a ____________ receptor agonist.

dopamine

*What drug should not be used in dogs that do not have control of their airway?

apomorphine

*What are potential adverse effects of apomorphine?

CNS depression

respiratory failure

protracted vomiting

What is xylazine used for?

as an emesis agent in cats

What is dexmedetomidine used for?

as an emesis agent in cats

Xylazine and Dexmedetomidine are _______ receptor agonists

alpha-2

*What are potential adverse effects of Xylazine and Dexmedetomidine?

bradycardia

dose should be noted

Metoclopramide is an antagonist to what receptor in the CRTZ?

D-2 Dopaminergic

Metoclopramide is a D2 Dopaminergic ______________

antagonist

What is metoclopramide used for?

an anti-emetic in cats

Ondansetron & Metoclopramide are antagonists to what receptor in the CRTZ?

5-HT3 Serotonergic

Why might a dopamine antagonist, like metoclopramide, not be super effective in preventing vomiting in cats?

Well, dopamine agonists don't do much to activate vomiting in the cat because they target receptors in the CRTZ, not the emetic center, which is not the required pathway to induce vomiting in a cat. (cats go from vestibular system straight to emetic center)

*What are three considerations for metoclopramide as an anti-emetic?

it has a short half-life

it's adverse effects: CNS signs

Contraindications

*What is a contraindication of metoclopramide?

it's more so used for it's prokinetic properties - to increase GI motility

would not want to use in an animal with an obstruction

Ondansetron is a ____________ antagonist. What specific receptor is it antagonist to?

serotonin

5-HT3

What are the sites of action of Ondansetron?

CRTZ and Peripheral vagal afferents

*What are the main clinical uses of Ondansetron?

Cancer chemotherapy

short half-life: might see used in an in-hospital IV situation

*What are two adverse effects/considerations for ondansetron?

Sedation

Not effective for motion sickness

Maropitant targets what emetic center receptor?

Neurokinin-1

*Why is maropitant special when it comes to it's mechanism of action/what's unique about it?

it is labeled specifically for animals! (not hoomans)

is a neurokinin-1 antagonist - that's special

What drugs have we learned about that directly target receptors in the emetic center? What receptor in the emetic center are they targeting? What is their function (i.e. an emesis agent or anti-emetic)?

Xylazine, alpha-2 receptor, emesis agent

Dexmedetomidine, alpha-2 receptor, emesis agent

Maropitant, neurokinin-1, anti-emetic

What drugs have we learned about that directly target receptors in the CRTZ? What receptor in the CRTZ are they targeting? What is their function (i.e. an emesis agent or anti-emetic)?

Apomorphine: dopamine, emesis agent

Metaclopramide: dopamine & 5-HT3 serotonergic, anti-emetic

Maropitant: neurokinin-1, anti-emetic

Ondansetron: 5-HT3 serotonergic, anti-emetic

Maropitant is a neurokinin-1 _____________(agonist/antagonits)

antagonist

Is maropitant an emesis agent or anti-emetic?

as an anti-emetic

What are the sites of action of Maropitant?

CRTZ, Emetic Center, Peripheral - in the gi tract itself, Vestibular system (motion sickness causes)

*What caution should be applied with the use of Maropitant?

should adjust the overall dose in animals with liver disease

What makes maropitant such an effective anti-emetic?

it has multiple sites of action, including targeting the final pathway (substance p neurokinin complex) for vomiting reflex

*Metoclopramide is a ________ serotonergic agonist. What action does this have?

5-HT4

prokinetic effect: increases gut motility

Metoclopramide is a 5HT4 serotonergic receptor agonist - where is this receptor located that it targets?

In the efferent neurons

*____________ is a 5HT-3 antagonist (can be more than one drug)

Ondansetron

Metaclopramide

*____________ is a neurokinin-1 antagonist. (can be more than one drug)

Maropitant

___________ is an alpha-2 receptor agonist. (can be more than one drug)

Xylazine & Dexmedetomidine

_____________ is a dopamine receptor agonist (can be more than one drug).

Apomorphine

____________ is a D-2 dopaminergic antagonist (can be more than one drug).

Metoclopramide

Should NSAIDS and corticosteroids ever be co-administered in small animal patients?

NO

What are 4 kinds of conditions can lead to a significant gastric ulcer?

Primary gastrointestinal disease

Drugs

Gastric hyperacidity

Systemic disease

What are examples of primary gastrointestinal diseases that may lead to a gastric ulcer?

• Neoplasia

• Inflammatory bowel disease

What are examples of drugs that may lead to a gastric ulcer?

NSAIDs & Corticosteroids

*What are examples of gastric hyperacidity conditions that may lead to a gastric ulcer?

mast cell tumor

gastrinoma

*What are examples of systemic disease that may lead to a gastric ulcer?

• Shock

• Hypoadrenocorticism

• Hepatic disease

*What are some defense mechanisms (protective of gastric mucosa) against gastric ulcer formation present?

apical cell membranes

tight junction

bicarbonate secretion

mucus production

rich blood supply

active cell renewal

surface active phospholipids

endogenous prostaglandins

Review phys from last semester about decreasing acidity in the stomach

in a quizlet

*Famotidine and Ranitidine are both _______ receptor antagonists

H2

*______________ is a/are H2 receptor antagonist(s). (can be more than one drug)

Famotidine and Ranitidine

*_____________ is a proton pump inhibitor.

Omeprazole

*Omeprazole is a __________ inhibitor

Proton-pump

*____________ is a prostaglandin analogue.

Misoprostol

*___________ is a chemical diffusion barrier.

sucralfate

*What are the two clinical uses of famotidine?

gastric ulcers

gastroesophageal reflux

Famotidine is metabolized in the _________ and excreted via the ________.

liver

kidney

*When it comes to managing gastric ulcers, is famotidine or omeprazole more effective? Why?

Omeprazole big time!

it targets the proton pump directly, which will greatly suppress acid in stomach

*___________ is used for treatment of gastric ulcers, particularly in the horse.

Ranitidine

*How does ranitidine affect motility?

promotes motility by prolonging the effect of acetylcholine, with its anticholinesterase activity

*What is a potential adverse effect of ranitidine?

potentially renal impairment

*Describe the mechanism of action of Omeprazole.

• Final common pathway (of acid production): proton pump

• Binds active proton pumps

• Irreversible

*What are the clinical uses of Omeprazole?

Gastric, duodenal ulcers

Hypersecretory conditions

*What drug intereactions should be considered with Omeprazole?

if administering a drug that may rely on the acidity in the stomach in order to take effect, the omeprazole may decrease chances of said drug being metabolized.

*Misoprostol is a prostaglandin analogue, what is it's function?

in mucosal defense

bicarbonate production

*Misoprostol has been shown to be effective with preventing ________-related gastric ulcers, but not _____________ related ones.

NSAID

Corticosteroid

*What are conditions, whose adverse effects should be considered with the administration with misoprostol?

GI distress

In pregnant animals --> abortion (because it's a prostaglandin analogue)

*What must be present in order for cytoprotective agents, like Sucralfate, to take affect?

an actual gastric ulcer

- it is not effective in preventing ulcers

*Sulcralfate is a ____________ agent.

cytoprotective

What should we keep in mind as far as sucralfate and drug interactions?

that there are a lot and you can look em up

don't gotta put that info in your noggin' right now

What are potential adverse effects of Sucralfate?

it's fairly safe

not fun to administer

When considering which drugs that function in gastric protection, what clinical conclusions should be determined before administering the drug?

What are the differential diagnosis?

Concurrent medications?

Therapeutic goals?

*Which of the drugs we've discussed effects the parietal cell's production of acid?

Famotidine & Ranitidine (H2 histamine antagonists)

Misoprostol (prostaglandin analogue)

Omeprazole (proton pump inhibitor)