Gastrointestinal - EMILY

Question 1

What are the targets for pharmaceutical intervention in GI disease?

Answer 1

-Emesis
-Motility
-Mucosal integrity
-Appetite
-Fecal consistency
-Pathogens

Question 2

Stimulation of the _____ activates the vomiting center?

Answer 2

CRTZ (chemoreceptor trigger zone)

Question 3

_______ from the vomiting center trigger vomiting

Answer 3

Efferents

Question 4

What 3 things can stimulate the vomiting center?

Answer 4

1. Input from the cerebral cortex
2. Afferent input from the stomach, esophagus and pharynx
3. Input from the vestibular system

Question 5

What plays an important role in emesis?

Answer 5

Receptor-drug interactions

Question 6

What types of receptors are in the vomiting center?

Answer 6

-Dopamine
-Serotonin
-Muscarinic
-Neurokinin
-Histamine
-Adrenergic
-Cannabinoid

Question 7

Which antiemetics are dopamine receptor antagonists?

Answer 7

-Phenothiazine tranquilizers (acepromazine, chlorpromazine)
-Metoclopramide

Question 8

Which antiemetic is an anticholinergic?

Answer 8

Atropine

Question 9

Which antiemetic is a NK-1 (neurokinin-1) receptor antagonist?

Answer 9

Maropitant

Question 10

Which antiemetics are serotonin (5-HT3) receptor antagonists?

Answer 10

-Mirtazapine
-Metoclopramide
-Ondansetron

Question 11

What 2 other class of drugs can be antiemetic?

Answer 11

-Glucocorticoids
-Antihistamines

Question 12

What are the 3 most common emetics used?

Answer 12

1. Apomorphine
2. Alpha-2 agonists
3. Hydrogen peroxide

Question 13

Which species cant vomit?

Answer 13

Horses and rabbits!!

Question 14

It’s possible to inhibit vomiting _________ inhibiting nausea

Answer 14

Without

Question 15

Vomiting usually only removes about _______ of material in stomach (max 80%)

Answer 15

40-60%

Question 15

When would you want to induce vomiting?

Answer 15

-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

Question 16

The antiemetic effect of phenothiazine tranquilizers (acepromazine) is mainly via:

Answer 16

Central dopamine receptor antagonism
-May also have some effects on histamine and muscarinic receptors

Question 17

What are two possible effects of acepromazine?

Answer 17

1. Sedation
2. Hypotension (due to alpha-1 antagonism)

Question 18

Should acepromazine be used in epileptics?

Answer 18

No!! It may lower the seizure threshold

Question 19

What does maropitant do as a NK-1 receptor antagonist?

Answer 19

Blocks the action of substance P in the CNS which then blocks transmission of the signal for emesis

Question 20

Maropitant is effective in which species?

Answer 20

Dogs and cats

Question 21

Does maropitant prevent vomiting without preventing nausea?

Answer 21

Not really

Question 22

What is the antinausea effect of maropitant dependent on?

Answer 22

Timing of administration relative to nausea-inducing stimulus

Question 23

What is the best way to give ondansetron to dogs and cats?

Answer 23

Oral or slow IV every 8 hours. Can also be given SQ/IM

Question 24

What are the primary rare adverse effects of ondansetron?

Answer 24

-Constipation/reduced GI motility -Increased liver enzymes -Arrhythmias -Hypotension

Question 25

Why do you have to be careful using ondansetron in MDR1 deficient dogs?

Answer 25

It is a p-glycoprotein substrate so it can lead to CNS effects

Question 26

Why should you be careful using ondansetron in hepatic dysfunction patients?

Answer 26

-Reduced first pass effect can increase bioavailability -Half-life may be prolonged

Question 27

At high doses, metoclopramide is also a __________ in addition to being a ____________

Answer 27

Serotonin receptor antagonist; dopamine receptor antagonist

Question 28

Given metoclopramide increases gastric and duodenal emptying, this means it has _________ effects?

Answer 28

Prokinetic

Question 29

You should not give metoclopramide if ______________ is suspected

Answer 29

GI obstruction

Question 30

What are the primary adverse effects of metoclopramide?

Answer 30

-Changes in behaviour/frenzy/mania

Question 31

Which antiemetic reduced vomiting and nausea the most?

Answer 31

Ondansetron

Question 32

How can emetics act on the body?

Answer 32

Centrally (CRTZ or vomiting center) or peripherally (GI irritation or on afferent nerves)

Question 33

What can apomorphine be reversed with?

Answer 33

Naloxone

Question 34

What is the emetic of choice for DOGS?

Answer 34

Apomorphine

Question 35

What is the best way to administer apomorphine?

Answer 35

SQ or by application to conjunctival mucosa

Question 36

Apomorphine is a ________ receptor agonist

Answer 36

Dopamine

Question 37

What are the best options for inducing emesis in CATS?

Answer 37

-Xylazine -Dexmedetomidine

Question 38

Xylazine and dexmedetomidine are _____ agonists and act on receptors in the ______

Answer 38

Alpha-2; CRTZ

Question 39

What are adverse effects of xylazine and dexmedetomidine?

Answer 39

-Sedation -Vasoconstriction -Bradycardia -Reduced cardiac output

Question 40

Which drugs could you use to reverse xylazine and dexmedetomidine in cats and why?

Answer 40

-Yohimbine -Atipamezole They are both competitive alpha-2 antagonists

Question 41

Hydrogen peroxide can be used as a peripheral emetic in DOGS. What are some adverse effects, and how does it work?

Answer 41

-Adverse effects include esophagitis and gastritis; aspiration is also a concern -Acts via GI irritation and afferent signalling to vomiting center

Question 42

What is motilin and what does it do to the GI tract?

Answer 42

It's a hormone that's secreted by M-cells in the stomach and upper duodenum. It stimulates GI motility through the intestinal tract.

Question 43

What are the 2 types of drugs that affect GI motility?

Answer 43

1. Prokinetics (increase motility) 2. Antikinetics (decrease motility)

Question 44

What are the most important prokinetic classes of drugs?

Answer 44

-Cholinergics -Lidocaine -Dopamine antagonists -Serotonergic (5HT4 receptor agonist)

Question 45

What are the most important antikinetic classes of drugs?

Answer 45

-Anticholinergics -Opioids

Question 46

Metoclopramide is a prokinetic that should only be used in dogs and cats. Why?

Answer 46

Can cause crazy excitement in horses

Question 47

What does metoclopramide do that makes it a prokinetic?

Answer 47

-Increase Ach secretion by enteric neurons -Increase sensitivity of enteric smooth muscle to Ach -Increase gastric emptying and stimulates duodenal motility

Question 48

Cisapride is a _____ receptor agonist on colonic muscle

Answer 48

5-HT4 (serotonin)

Question 49

What does cisapride do?

Answer 49

-Stimulates SI and colonic motility -Increases gastric secretions

Question 50

Which is better for stimulating colon motility: metoclopramide or cisapride?

Answer 50

Cisapride

Question 51

Why is lidocaine administered as a CRI as a prokinetic?

Answer 51

It only has 20 mins of activation before wearing off

Question 52

When would lidocaine be indicated as a prokinetic?

Answer 52

-Post-op ileus in horses -GI stasis in rabbits

Question 53

How does lidocaine work in the gut?

Answer 53

Works through reducing pain and inflammation associated with damaged gut

Question 54

What is administration of lidocaine after colic surgery associated with?

Answer 54

Shorter hospitalizations and less gastric reflux during post-op period

Question 55

What are 3 commonly used anticholinergics (as antikinetics)?

Answer 55

1. Atropine 2. Glycopyrrolate 3. N-butylscopolammonium bromide/Hyoscine butylbromide

Question 56

What is another effect in the body you would likely see when administering antikinetics?

Answer 56

Increased HR

Question 57

Which receptors in the GI tract are targets of opioids?

Answer 57

Mu and delta

Question 58

Opiates can have anti-_________ and anti-_________ actions

Answer 58

secretory; motility

Question 59

What is loperamide?

Answer 59

A mu opioid receptor agonist (antikinetic)

Question 60

What is the bioavailability of loperamide in dogs vs humans?

Answer 60

In dogs its 20%, in humans its <0.5%

Question 61

Why can loperamide be toxic to dogs with the MDR1 mutation?

Answer 61

It's a p-glycoprotein substrate

Question 62

What are 3 drugs that are H2 blockers (reduce H+ secretion into the lumen of the GI tract)?

Answer 62

-Ranitidine* -Famotidine -Cimetidine

Question 63

What are general characteristics of H2 blockers?

Answer 63

-Competitive H2 receptor antagonist -Reduces gastric acid secetion -Given IV or orally in dogs, cats, and horses

Question 64

What are 3 proton pump inhibitors?

Answer 64

-Omeprazole* -Pantoprazole -Esomeprazole

Question 65

What are general characteristics of proton pump inhibitors?

Answer 65

-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

Question 66

What are 2 drugs that are GI protectants?

Answer 66

1. Sucralfate 2. Misoprostol

Question 67

How does sucralfate act on the GI tract?

Answer 67

Physical barrier, sticks to ulcerated mucosa

Question 68

What do adsorbents do?

Answer 68

Bind to toxins in the GI tract and prevent their systemic absorption

Question 69

What is the most commonly used adsorbent?

Answer 69

Activated charcoal

Question 70

What is important to remember about adsorbents?

Answer 70

They can have lots of drug interactions and may influence drug absorption

Question 71

What is the most commonly used appetite stimulant and antiemetic used in CATS?

Answer 71

Mirtazapine

Question 72

What receptors does mirtazapine act on?

Answer 72

-Presynaptic alpha-2 antagonist (increases NE --> increases appetite) -Serotonin receptor antagonist (antinausea/antiemetic) -H1 receptor antagonist (sedative)

Question 73

Does mirtazapine also work in dogs?

Answer 73

Yes (anecdotally)

Question 74

What is a pharmaceutical intervention you could use in hepatic encephalopathy?

Answer 74

Lactulose

Question 75

What is a pharmaceutical intervention you could use in cholestasis?

Answer 75

Urosdiol

Question 76

What is a pharmaceutical intervention you could use in hepatocellular dysfunction?

Answer 76

S-adenosyl-L-methionine (SAMe)

Question 77

What species is lactulose used in to treat hepatic encephalopathy or constipation?

Answer 77

Dogs Cats Birds Reptiles

Question 78

What is lactulose's mechanism of action on?

Answer 78

Colonic bacteria. Its metabolized to produce low molecular weight acids

Question 79

Lactulose increases osmotic pressure. What effects does this have on the GI system?

Answer 79

It draws water into the colon and has a laxative effect

Question 80

Lactulose acidifies colon contents and reduces blood ammonia levels by:

Answer 80

Drawing ammonia into the colon where it is excreted

Question 81

What does ursodiol do?

Answer 81

-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

Question 82

What species is ursodiol contraindicated in?

Answer 82

Rabbits and other hind gut fermenters (produces toxic metabolite)

Question 83

What does SAMe (S-adenosyl-L-methionine) do?

Answer 83

Promotes hepatocellular function and is an essential substrate for many metabolic pathways

Question 84

SAMe is normally produced by the liver, T or F?

Answer 84

True. A failing liver will under-produce it and it needs to be supplemented