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VETM 443 Pharmacology > GI Pharmacology > Flashcards

GI Pharmacology Flashcards

1
Q

What are the basic principles of treating GI disease

A

Identifying the primary cause of the disease.

Provide supportive care like fluids, fasting, diet change

GI drugs

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2
Q

What are the targets that GI drugs act on

A

emesis
motility
mucosal integrity
appetite
fecal consistency
antibiotics

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3
Q

What receptors are involved with emesis

A

They stimulate the vomiting centre in the brain

Receptors:
dopamine
serotonin
muscarinic (M1)
neurokinin
adrenergic (alpha 2)
histamine
cannabinoid

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4
Q

What are the 4 input centers for triggering emesis and their associated stimuli and receptors

A

Afferent inputs in the stomach, esophagus, pharynx that are stimulated by gastric irritation

Cerebral cortex takes stimuli from intellectual input

The chemoreceptor trigger zone can be stimulated by chemicals in the blood as detected by dopamine, serotonin, muscarinic (M1), adrenergic (alpha 2) and neurokinin receptors

The vestibular system has inputs from motion and is detected by histamine (H1) and muscarinic (M1) receptors

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5
Q

What are the 5 neurotransmitters used in the emesis system

A

substance P which binds to neurokinin 1 receptors

Ach which also increases gut motility and secretion

histamine can cause nausea by stimulating the vagus nerve

serotonin and dopamine (D2) act on the 5HT3 receptor in the chemoreceptor trigger zone

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6
Q

List 6 stimuli for the emesis

A

GI - irritation, inflam, obstruction

pharyngeal via the 9th CN (glossopharyngeal)

intracranial from trauma and pressure

vestibular due to motion sickness or vestibulitis

intoxication from drugs or toxins that act on the chemoreceptor trigger zone

neurotransmitters like dopamine, serotonin, muscarinic, and histamine receptor stimulation

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7
Q

Which animals don’t do emesis

A

rabbits and horses

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8
Q

What conditions indicate administration of an emetic

A

If the patient is asymptomatic and have had a recent ingestion of a bad thing or if there is an unknown time since ingestion

Ingested material known to stay in the stomach for aa long time - like chocolate, grape, xylitol

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9
Q

What conditions contraindicate administration of an emetic

A

If the substance ingested is corrosive or a hydrocarbon

If the patient is symptomatic

If the patient has predisposing factors for aspiration pneumonia like megaeseophagus

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10
Q

How is GI motility controlled

A

It is rhythmic depolarization that is controlled by the GI pacemaker

SNS and PSNS systems modulate the enteric system

myenteric plexus controls tone
submucosal plexus controls submucosal function

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11
Q

What neurotransmitters and hormones are used to control motility in GI

A

Neurotransmitters like serotonin, dopamine

excitatory neurotransmitter = Ach

inhibitory neurotransmitter = norepi

hormones like motilin (from M cells) = increase motility

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12
Q

How do opioids influence GI motility?

A

They are anti kinetics

Mu and delta receptors primarily impact motility resulting in an increase or decrease in absorption of fluid, electrolytes, or glucose

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13
Q

How does MDR1 deficiency impact treatment of excess GI motility

A

The antikinetic opiate loperamide should be avoided because it is a p-glycoprotein substrate

It relies on p glycoprotein to remove it from BBB

Can result in CNS toxicity

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14
Q

How does MDR1 deficiency impact treatment of emesis

A

The antiemetic ondansetron should be avoided because it is a p-glycoprotein substrate

It relies on p glycoprotein to remove it from BBB

Can result in CNS toxicity

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15
Q

How is gastric acid stimulated and produced?

A

gastrin release will stimulate increased production of histamine and acid

histamine stimulated H2 receptor migration

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16
Q

What are the drug targets that reduce gastric acid production?

A

H2 receptor blockers

proton pump inhibitors

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17
Q

Provide 3 examples (only one is most important) of H2 receptor blockers

A

*ranitidine

famotidine
cimetidine

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18
Q

Provide 3 examples (only one is most important) of proton pump inhibitor

A

*omeprazole

pantoprazole
esomeprazole

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19
Q

What is the mechanism of ranitidine?

A

It is a competitive histamine receptor antagonist resulting in reduced acid secretion

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20
Q

What is the route of administration of ranitidine and for what species?

A

Used in dogs, cats, horses

via IV or PO

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21
Q

What is the mechanism of action for omeprazole

A

It is an irreversible proton pump inhibitor

It is a weak base and will become ion trapped in the acidic parietal cell secretory canaliculi, therefore the plasma concentration doesn’t predict efficacy

But this process takes time

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22
Q

List 2 types of GI protectants

A

sucralfate
misoprostol

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23
Q

What is the mechanism of sucralfate?

A

It forms a physical barrier because it sticks to mucosal ulcers and is not absorbed by the body

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24
Q

What is the mechanism of misoprostol?

A

It is a synthetic prostaglandin which acts to increase mucosal blood flow and reduce acid secretion

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25
Q

What is the function of adsorbents? Provide some examples (only 1 is relevant)

A

They bind toxins and prevent absorption

*activated charcoal
kaolin-pectin
attapulgite
smectite
bismuth subsalicylate

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26
Q

What is one example of an appetite stimulant?

A

mirtazapine

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27
Q

What is the mechanism of action of mirtazapine

A

pre-synaptic alpha 2 antagonist which antagonizes the negative feedback loop which results in an increase of norepinephrine

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28
Q

What is the function of mirtazapine

A

antinausea
antiemetic
sedative (H1 receptor antagonist)

but the response takes 8-36h for effect

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29
Q

What species is mirtazapine commonly used in

A

cats

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30
Q

What are 3 types of drugs that target the liver

A

lactulose
ursodiol
S-adenosyl-L-methionine (SAMe)

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31
Q

What is lactulose and what is it used for?

A

It is a disaccharide made from galactose and fructose

It is used for hepatic encephalopathy

32
Q

What is the mechanism of action for lactulose?

A

It is not well absorbed and metabolized by colonic bacteria

The colonic bacteria make low molecular weight acid

This increases the osmotic pressure and production of lactic acidifies the colon

Causes a laxative effect because water is pulled into the lumen. It also reduces the blood ammonia because ammonia is also drawn into lumen

33
Q

What is ursodiol used for and why?

A

Cholestasis treatment
- to increase bile flow
- protect hepatocytes from bile acids
- solubilize cholesterol gallstones

34
Q

What is the mechanism of action of ursodiol

A

It reduces hepatic synthesis, secretion, and absorption of cholesterol

It undergoes hepatic recirculation which results in low concentrations in systemic circulation

35
Q

What species is ursodiol used in? What route of administration is used?

A

PO

dogs and cats

NOT hindgut fermenters because it will be toxic

36
Q

What is the use for S-adenosyl-L-methionine?

A

It is a nutraceutical used for hepatocellular dysfunction

37
Q

What is the mechanism of action for S-adenosyl-L-methionine

A

Glutathione is a strong antioxidant and provides exogenous substances for metabolism with minimal side effects

38
Q

Lists 4 antiemetics commonly used

A

phenothiazine tranquilizers - acepromazine

maropitant

odensetron

metaclopramide

39
Q

What is the antiemetic mechanism of action of phenothiazine tranquilizers

A

It is a dopamine receptor antagonist in the chemoreceptor trigger zone

It has some histamine and muscarinic receptor antagonism which affects the vestibular zone

40
Q

What are the additional effects of phenothiazine tranquilizers (other than antiemesis)

A

sedation and hypotension because alpha 1 antagonists result in vasodilation

It may cause paraphimosis (penile protrusion) in horses and cows

NOT analgesia

41
Q

What concerns should you consider when using a phenothiazine tranquilizers

A

It may lower seizure thresholds which may contraindicate in epileptic patients

caution when using in good breeding animals because of the paraphimosis (penile protrusion) because it may be permenant

42
Q

What is the route of administration of phenothiazine tranquilizers

A

IM

43
Q

What is the route of administration of maropitant

A

PO

44
Q

What is the mechanism of action of maropitant

A

It is a neurokinin 1 receptor antagonist and is metabolized in a way similar to NSAIDs and phenobarbital

45
Q

What is the function of maropitant

A

It resolves acute vomiting induced by motion or drugs

It does not prevent nausea

46
Q

What species is maropitant used in

A

dogs and cats

47
Q

What is the route of administration and species ondensetron is used in

A

PO
slow IV q8h
SC
IM

dogs and cats

48
Q

What is the mechanism of action of ondensetron?

A

It is a serotonin (5HT3) receptor antagonist

49
Q

What is the function of ondensetron

A

It reduces vomiting due to irritation

It is the best for reducing nausea

50
Q

What adverse effects are associated with ondensetron? What are contraindications?

A

adverse effects are rare
- reduced GI motility
- increased liver enzyme
- arrhythmia
- hypotension
-headache

caution in
MDR1 deficient dogs
in dogs with hepatic dysfunction because a reduction in the first pass effect will increase the bioavailability and prolonged half life

51
Q

What is the route of administration for metaclopramide and what species is it used in

A

IM or IV

cas and dogs (better in dogs)

52
Q

What is the mechanism of action for metaclopramide

A

It is a dopamine receptor antagonist and at high doses it can be a serotonin receptor antagonist

It has a high first pass effect

53
Q

What is the function of metaclopramide

A

antiemetic

It is a prokinetic - increases gastric and duodenal emptying

It causes behavioural changes like mania and frenzy in adult horses

NOT sedation
NO impact on nausea

54
Q

What would caution the use of metaclopramide?

A

GI obstruction because it is also a prokinetic

55
Q

What are 3 types of emetics

A

apomorphine

alpha 2 agonists - xylazine, dexmedetomidine

hydrogen peroxide

56
Q

What is the route of administration for apomorphine

A

SC
conjunctiva
mucosa

57
Q

What is the mechanism of action for apomorphine

A

dopamine receptor antagonist acting on the chemoreceptor trigger zone

58
Q

What is the effects of apomorphine?

A

emesis

excitement (which can be reversed by naloxone but vomiting wont be reversed)

Motion will increase its effect

59
Q

What species is apomorphine used in

A

dogs (not cats)

60
Q

What is the mechanism of action for alpha 2 agonists (in relation to emesis)

A

It acts on alpha 2 receptors in the chemoreceptor trigger zone

61
Q

What is the effect of alpha 2 agonists

A

emesis
sedation
reduced cardiac output

62
Q

What species is alpha 2 agonists used in for emesis

A

cats

63
Q

What is the route of administration for hydrogen peroxide

A

PO

64
Q

What is the mechanism of action for hydrogen peroxide

A

It causes GI irritation and stimulates an afferent signal

65
Q

What are adverses effects associated with hydrogen peroxide

A

risk of gastritis and esophagitis and/or aspiration

Its effectiveness is also hit or miss

66
Q

What species is hydrogen peroxide used in

A

dogs not cats

67
Q

What are 3 types of prokinetic

A

metaclopramide
cisapride
lidocaine

68
Q

What are 4 types of antikinetics

A

atropine

glycopyrrolate

N-butylscopolammonium bromide/Hyoscine butylbromide

loperamide

69
Q

What is the mechanism of action for metaclopramide

A

it is a dopamine antagonist
it increases the sensitivity of enteric smooth muscle to Ach and it increases Ach release from enteric neurons

At high doses it is a serotonin antagonist

70
Q

What is the effect of metaclopramide

A

increases gastric emptying and duodenal motility

71
Q

What is the mechanism of action of cisapride

A

It targets serotonin receptors
5HT4 receptor agonist which increases Ach release from myenteric plexus

5HT2 receptor agonist on colon muscle

it is also a dopamine antagonist

72
Q

What is the effect of cisapride

A

It increases SI and colon motility and GI secretions

It is better than metoclopramide for colon motilty

73
Q

What is the mechanism of action and route of administration of lidocaine

A

CRI
unknown

74
Q

What are the effects of lidocain

A

reduced pain and inflammation in the gut

75
Q

When is lidocaine commonly usd

A

horse - post colic sx
rabbit - GI stasis

76
Q

What is the mechanism of action for loperamide

A

It targets mu receptors in GI with poor bioavailability resulting in local GI effects (no opioid effects)

77
Q
A

VETM 443 Pharmacology (4 decks)

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