Gastrointestinal - EMILY Flashcards
What are the targets for pharmaceutical intervention in GI disease?
-Emesis
-Motility
-Mucosal integrity
-Appetite
-Fecal consistency
-Pathogens
Stimulation of the _____ activates the vomiting center?
CRTZ (chemoreceptor trigger zone)
_______ from the vomiting center trigger vomiting
Efferents
What 3 things can stimulate the vomiting center?
- Input from the cerebral cortex
- Afferent input from the stomach, esophagus and pharynx
- Input from the vestibular system
What plays an important role in emesis?
Receptor-drug interactions
What types of receptors are in the vomiting center?
-Dopamine
-Serotonin
-Muscarinic
-Neurokinin
-Histamine
-Adrenergic
-Cannabinoid
Which antiemetics are dopamine receptor antagonists?
-Phenothiazine tranquilizers (acepromazine, chlorpromazine)
-Metoclopramide
Which antiemetic is an anticholinergic?
Atropine
Which antiemetic is a NK-1 (neurokinin-1) receptor antagonist?
Maropitant
Which antiemetics are serotonin (5-HT3) receptor antagonists?
-Mirtazapine
-Metoclopramide
-Ondansetron
What 2 other class of drugs can be antiemetic?
-Glucocorticoids
-Antihistamines
What are the 3 most common emetics used?
- Apomorphine
- Alpha-2 agonists
- Hydrogen peroxide
Which species cant vomit?
Horses and rabbits!!
It’s possible to inhibit vomiting _________ inhibiting nausea
Without
Vomiting usually only removes about _______ of material in stomach (max 80%)
40-60%
When would you want to induce vomiting?
-In toxicity situations when an animal has ingested a non-caustic toxin and the risk of aspiration is low
-Only useful if toxin is in stomach or proximal SI
The antiemetic effect of phenothiazine tranquilizers (acepromazine) is mainly via:
Central dopamine receptor antagonism
-May also have some effects on histamine and muscarinic receptors
What are two possible effects of acepromazine?
- Sedation
- Hypotension (due to alpha-1 antagonism)
Should acepromazine be used in epileptics?
No!! It may lower the seizure threshold
What does maropitant do as a NK-1 receptor antagonist?
Blocks the action of substance P in the CNS which then blocks transmission of the signal for emesis
Maropitant is effective in which species?
Dogs and cats
Does maropitant prevent vomiting without preventing nausea?
Not really
What is the antinausea effect of maropitant dependent on?
Timing of administration relative to nausea-inducing stimulus
What is the best way to give ondansetron to dogs and cats?
Oral or slow IV every 8 hours. Can also be given SQ/IM
What are the primary rare adverse effects of ondansetron?
-Constipation/reduced GI motility
-Increased liver enzymes
-Arrhythmias
-Hypotension
Why do you have to be careful using ondansetron in MDR1 deficient dogs?
It is a p-glycoprotein substrate so it can lead to CNS effects
Why should you be careful using ondansetron in hepatic dysfunction patients?
-Reduced first pass effect can increase bioavailability
-Half-life may be prolonged
At high doses, metoclopramide is also a __________ in addition to being a ____________
Serotonin receptor antagonist; dopamine receptor antagonist
Given metoclopramide increases gastric and duodenal emptying, this means it has _________ effects?
Prokinetic
You should not give metoclopramide if ______________ is suspected
GI obstruction
What are the primary adverse effects of metoclopramide?
-Changes in behaviour/frenzy/mania
Which antiemetic reduced vomiting and nausea the most?
Ondansetron
How can emetics act on the body?
Centrally (CRTZ or vomiting center) or peripherally (GI irritation or on afferent nerves)
What can apomorphine be reversed with?
Naloxone
What is the emetic of choice for DOGS?
Apomorphine
What is the best way to administer apomorphine?
SQ or by application to conjunctival mucosa
Apomorphine is a ________ receptor agonist
Dopamine
What are the best options for inducing emesis in CATS?
-Xylazine
-Dexmedetomidine
Xylazine and dexmedetomidine are _____ agonists and act on receptors in the ______
Alpha-2; CRTZ
What are adverse effects of xylazine and dexmedetomidine?
-Sedation
-Vasoconstriction
-Bradycardia
-Reduced cardiac output
Which drugs could you use to reverse xylazine and dexmedetomidine in cats and why?
-Yohimbine
-Atipamezole
They are both competitive alpha-2 antagonists
Hydrogen peroxide can be used as a peripheral emetic in DOGS. What are some adverse effects, and how does it work?
-Adverse effects include esophagitis and gastritis; aspiration is also a concern
-Acts via GI irritation and afferent signalling to vomiting center
What is motilin and what does it do to the GI tract?
It’s a hormone that’s secreted by M-cells in the stomach and upper duodenum. It stimulates GI motility through the intestinal tract.
What are the 2 types of drugs that affect GI motility?
- Prokinetics (increase motility)
- Antikinetics (decrease motility)
What are the most important prokinetic classes of drugs?
-Cholinergics
-Lidocaine
-Dopamine antagonists
-Serotonergic (5HT4 receptor agonist)
What are the most important antikinetic classes of drugs?
-Anticholinergics
-Opioids
Metoclopramide is a prokinetic that should only be used in dogs and cats. Why?
Can cause crazy excitement in horses
What does metoclopramide do that makes it a prokinetic?
-Increase Ach secretion by enteric neurons
-Increase sensitivity of enteric smooth muscle to Ach
-Increase gastric emptying and stimulates duodenal motility
Cisapride is a _____ receptor agonist on colonic muscle
5-HT4 (serotonin)
What does cisapride do?
-Stimulates SI and colonic motility
-Increases gastric secretions
Which is better for stimulating colon motility: metoclopramide or cisapride?
Cisapride
Why is lidocaine administered as a CRI as a prokinetic?
It only has 20 mins of activation before wearing off
When would lidocaine be indicated as a prokinetic?
-Post-op ileus in horses
-GI stasis in rabbits
How does lidocaine work in the gut?
Works through reducing pain and inflammation associated with damaged gut
What is administration of lidocaine after colic surgery associated with?
Shorter hospitalizations and less gastric reflux during post-op period
What are 3 commonly used anticholinergics (as antikinetics)?
- Atropine
- Glycopyrrolate
- N-butylscopolammonium bromide/Hyoscine butylbromide
What is another effect in the body you would likely see when administering antikinetics?
Increased HR
Which receptors in the GI tract are targets of opioids?
Mu and delta
Opiates can have anti-_________ and anti-_________ actions
secretory; motility
What is loperamide?
A mu opioid receptor agonist (antikinetic)
What is the bioavailability of loperamide in dogs vs humans?
In dogs its 20%, in humans its <0.5%
Why can loperamide be toxic to dogs with the MDR1 mutation?
It’s a p-glycoprotein substrate
What are 3 drugs that are H2 blockers (reduce H+ secretion into the lumen of the GI tract)?
-Ranitidine*
-Famotidine
-Cimetidine
What are general characteristics of H2 blockers?
-Competitive H2 receptor antagonist
-Reduces gastric acid secetion
-Given IV or orally in dogs, cats, and horses
What are 3 proton pump inhibitors?
-Omeprazole*
-Pantoprazole
-Esomeprazole
What are general characteristics of proton pump inhibitors?
-Irreversible inhibitors for the proton pump
-Weak bases that become trapped in acidic environment
-Takes a few days to see full effect since dormant parietal cells become activated
-Increased stomach pH may result in drug-drug PK interactions
What are 2 drugs that are GI protectants?
- Sucralfate
- Misoprostol
How does sucralfate act on the GI tract?
Physical barrier, sticks to ulcerated mucosa
What do adsorbents do?
Bind to toxins in the GI tract and prevent their systemic absorption
What is the most commonly used adsorbent?
Activated charcoal
What is important to remember about adsorbents?
They can have lots of drug interactions and may influence drug absorption
What is the most commonly used appetite stimulant and antiemetic used in CATS?
Mirtazapine
What receptors does mirtazapine act on?
-Presynaptic alpha-2 antagonist (increases NE –> increases appetite)
-Serotonin receptor antagonist (antinausea/antiemetic)
-H1 receptor antagonist (sedative)
Does mirtazapine also work in dogs?
Yes (anecdotally)
What is a pharmaceutical intervention you could use in hepatic encephalopathy?
Lactulose
What is a pharmaceutical intervention you could use in cholestasis?
Urosdiol
What is a pharmaceutical intervention you could use in hepatocellular dysfunction?
S-adenosyl-L-methionine (SAMe)
What species is lactulose used in to treat hepatic encephalopathy or constipation?
Dogs
Cats
Birds
Reptiles
What is lactulose’s mechanism of action on?
Colonic bacteria. Its metabolized to produce low molecular weight acids
Lactulose increases osmotic pressure. What effects does this have on the GI system?
It draws water into the colon and has a laxative effect
Lactulose acidifies colon contents and reduces blood ammonia levels by:
Drawing ammonia into the colon where it is excreted
What does ursodiol do?
-Reduces hepatic synthesis and secretion, and intestinal absorption, of cholesterol
-Improves bile flow
-Protects hepatocytes from toxic bile acids
-Allows solubilization of cholesterol-containing gallstones
What species is ursodiol contraindicated in?
Rabbits and other hind gut fermenters (produces toxic metabolite)
What does SAMe (S-adenosyl-L-methionine) do?
Promotes hepatocellular function and is an essential substrate for many metabolic pathways
SAMe is normally produced by the liver, T or F?
True. A failing liver will under-produce it and it needs to be supplemented
