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Pharmacology > Gastrointestinal - EMILY > Flashcards

Gastrointestinal - EMILY Flashcards

1
Q

What are the targets for pharmaceutical intervention in GI disease?

A

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

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2
Q

Stimulation of the _____ activates the vomiting center?

A

CRTZ (chemoreceptor trigger zone)

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3
Q

_______ from the vomiting center trigger vomiting

A

Efferents

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4
Q

What 3 things can stimulate the vomiting center?

A
  1. Input from the cerebral cortex
  2. Afferent input from the stomach, esophagus and pharynx
  3. Input from the vestibular system
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5
Q

What plays an important role in emesis?

A

Receptor-drug interactions

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6
Q

What types of receptors are in the vomiting center?

A

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

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7
Q

Which antiemetics are dopamine receptor antagonists?

A

-Phenothiazine tranquilizers (acepromazine, chlorpromazine)
-Metoclopramide

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8
Q

Which antiemetic is an anticholinergic?

A

Atropine

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9
Q

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

A

Maropitant

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10
Q

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

A

-Mirtazapine
-Metoclopramide
-Ondansetron

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11
Q

What 2 other class of drugs can be antiemetic?

A

-Glucocorticoids
-Antihistamines

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12
Q

What are the 3 most common emetics used?

A
  1. Apomorphine
  2. Alpha-2 agonists
  3. Hydrogen peroxide
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13
Q

Which species cant vomit?

A

Horses and rabbits!!

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14
Q

It’s possible to inhibit vomiting _________ inhibiting nausea

A

Without

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15
Q

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

A

40-60%

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15
Q

When would you want to induce vomiting?

A

-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

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16
Q

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

A

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

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17
Q

What are two possible effects of acepromazine?

A
  1. Sedation
  2. Hypotension (due to alpha-1 antagonism)
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18
Q

Should acepromazine be used in epileptics?

A

No!! It may lower the seizure threshold

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19
Q

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

A

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

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20
Q

Maropitant is effective in which species?

A

Dogs and cats

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21
Q

Does maropitant prevent vomiting without preventing nausea?

A

Not really

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22
Q

What is the antinausea effect of maropitant dependent on?

A

Timing of administration relative to nausea-inducing stimulus

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23
Q

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

A

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

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24
Q

What are the primary rare adverse effects of ondansetron?

A

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

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25
Q

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

A

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

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26
Q

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

A

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

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27
Q

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

A

Serotonin receptor antagonist; dopamine receptor antagonist

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28
Q

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

A

Prokinetic

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29
Q

You should not give metoclopramide if ______________ is suspected

A

GI obstruction

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30
Q

What are the primary adverse effects of metoclopramide?

A

-Changes in behaviour/frenzy/mania

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31
Q

Which antiemetic reduced vomiting and nausea the most?

A

Ondansetron

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32
Q

How can emetics act on the body?

A

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

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33
Q

What can apomorphine be reversed with?

A

Naloxone

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34
Q

What is the emetic of choice for DOGS?

A

Apomorphine

35
Q

What is the best way to administer apomorphine?

A

SQ or by application to conjunctival mucosa

36
Q

Apomorphine is a ________ receptor agonist

A

Dopamine

37
Q

What are the best options for inducing emesis in CATS?

A

-Xylazine
-Dexmedetomidine

38
Q

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

A

Alpha-2; CRTZ

39
Q

What are adverse effects of xylazine and dexmedetomidine?

A

-Sedation
-Vasoconstriction
-Bradycardia
-Reduced cardiac output

40
Q

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

A

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

41
Q

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

A

-Adverse effects include esophagitis and gastritis; aspiration is also a concern

-Acts via GI irritation and afferent signalling to vomiting center

42
Q

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

A

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

43
Q

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

A
  1. Prokinetics (increase motility)
  2. Antikinetics (decrease motility)
44
Q

What are the most important prokinetic classes of drugs?

A

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

45
Q

What are the most important antikinetic classes of drugs?

A

-Anticholinergics
-Opioids

46
Q

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

A

Can cause crazy excitement in horses

47
Q

What does metoclopramide do that makes it a prokinetic?

A

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

48
Q

Cisapride is a _____ receptor agonist on colonic muscle

A

5-HT4 (serotonin)

49
Q

What does cisapride do?

A

-Stimulates SI and colonic motility
-Increases gastric secretions

50
Q

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

A

Cisapride

51
Q

Why is lidocaine administered as a CRI as a prokinetic?

A

It only has 20 mins of activation before wearing off

52
Q

When would lidocaine be indicated as a prokinetic?

A

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

53
Q

How does lidocaine work in the gut?

A

Works through reducing pain and inflammation associated with damaged gut

54
Q

What is administration of lidocaine after colic surgery associated with?

A

Shorter hospitalizations and less gastric reflux during post-op period

55
Q

What are 3 commonly used anticholinergics (as antikinetics)?

A
  1. Atropine
  2. Glycopyrrolate
  3. N-butylscopolammonium bromide/Hyoscine butylbromide
56
Q

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

A

Increased HR

57
Q

Which receptors in the GI tract are targets of opioids?

A

Mu and delta

58
Q

Opiates can have anti-_________ and anti-_________ actions

A

secretory; motility

59
Q

What is loperamide?

A

A mu opioid receptor agonist (antikinetic)

60
Q

What is the bioavailability of loperamide in dogs vs humans?

A

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

61
Q

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

A

It’s a p-glycoprotein substrate

62
Q

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

A

-Ranitidine*
-Famotidine
-Cimetidine

63
Q

What are general characteristics of H2 blockers?

A

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

64
Q

What are 3 proton pump inhibitors?

A

-Omeprazole*
-Pantoprazole
-Esomeprazole

65
Q

What are general characteristics of proton pump inhibitors?

A

-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

66
Q

What are 2 drugs that are GI protectants?

A
  1. Sucralfate
  2. Misoprostol
67
Q

How does sucralfate act on the GI tract?

A

Physical barrier, sticks to ulcerated mucosa

68
Q

What do adsorbents do?

A

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

69
Q

What is the most commonly used adsorbent?

A

Activated charcoal

70
Q

What is important to remember about adsorbents?

A

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

71
Q

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

A

Mirtazapine

72
Q

What receptors does mirtazapine act on?

A

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

73
Q

Does mirtazapine also work in dogs?

A

Yes (anecdotally)

74
Q

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

A

Lactulose

75
Q

What is a pharmaceutical intervention you could use in cholestasis?

A

Urosdiol

76
Q

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

A

S-adenosyl-L-methionine (SAMe)

77
Q

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

A

Dogs
Cats
Birds
Reptiles

78
Q

What is lactulose’s mechanism of action on?

A

Colonic bacteria. Its metabolized to produce low molecular weight acids

79
Q

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

A

It draws water into the colon and has a laxative effect

80
Q

Lactulose acidifies colon contents and reduces blood ammonia levels by:

A

Drawing ammonia into the colon where it is excreted

81
Q

What does ursodiol do?

A

-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

82
Q

What species is ursodiol contraindicated in?

A

Rabbits and other hind gut fermenters (produces toxic metabolite)

83
Q

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

A

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

84
Q

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

A

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

Pharmacology (11 decks)

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