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Basic Pharmacology > Gastrointestinal Pharmacology > Flashcards

Gastrointestinal Pharmacology Flashcards

1
Q

what do gastrointestinal drugs modulate?

A

vomiting
appetite
gastric acidity
gastrointestinal motility
defecation

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2
Q

what is vomiting/emesis?

A

forceful expulsion of stomach contents from mouth

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3
Q

what is the purpose of vomiting/emesis?

A

remove noxious substances or toxins from the gastrointestinal tract and/or release pressure

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4
Q

what controls vomiting?

A

vomiting center

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5
Q

where does input come from for retching and emesis?

A

CRTZ
cerebral cortex
vestibular apparatus
visceral afferent

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6
Q

what receptors play a role in vomiting?

A

emetic center
chemoreceptor trigger zone
peripheral receptors
vestibular input
higher cortical centers

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7
Q

what are indications for emetics?

A

initial treatment of patients who have ingested non-caustic toxicants or foreign material

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8
Q

what are the emetics for dogs?

A

dopamine 2 agonists
apomorphine
ropinirole (Clevor) ophthalmic solution

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9
Q

what are the emetics for cats?

A

alpha-2-adrenergic agonists
xylazine and dexmedetomidine

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10
Q

how do anti-emetics work?

A

inhibit neurotransmission in the emetic center
inhibit neurotransmission in the CRTZ
inhibit stimulation of peripheral 5HT3 receptors

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11
Q

how does metaclopramide work?

A

central action to block dopamine receptors and at higher doses blocks 5HT-3 receptors
peripheral gastrointestinal pro-motility

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12
Q

why is metaclopramide best used IV as a CRI?

A

short half life

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13
Q

how is metaclopramide metabolized?

A

hepatic with some renal excretion unchanged

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14
Q

what are the side effects of metaclopramide?

A

CNS excitement (more often in cats than horses)
sweating in horses

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15
Q

when should you avoid using metaclopramide?

A

obstructive disease

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16
Q

how do serotonin 5HT-3 receptor antagonists work?

A

peripheral receptors in gastrointestinal tract primarily
some action against serotonin receptors in the CRTZ

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17
Q

what drugs are serotonin 5HT-3 receptor antagonists?

A

ondansetron (zofran) and dolesetron (anzemet)

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18
Q

how is ondansetron metabolized?

A

hepatic primarily
substrate for MDR1

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19
Q

what are side effects of serotonin 5HT-3 receptor antagonists?

A

rare
fecal incontinence

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20
Q

what drug is an NK receptor-1 antagonist?

A

maropitant (cerenia)

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21
Q

where are NK-1 receptors present in the body?

A

vomiting center
CRTZ
gastrointestinal tract

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22
Q

how is maropitant metabolized?

A

hepatic and biliary excretion

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23
Q

what are some side effects of maropitant?

A

subcutanous irritation with parenteral formulation
high doses capable of blocking calcium channels and prolonging QT interval

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24
Q

is maropitant highly protein bound?

A

yes

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25
Q

what does maropitant inhibit (other than vomiting)?

A

cytochrome P450 enzymes

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26
Q

what should you think about with oral doses of maropitant?

A

significant hepatic first pass effect: oral dose higher in dog, not in cat
higher dose for motion sickness in dog

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27
Q

what is the mechanism of action of mirtazapine?

A

pre-synaptic alpha-2-adrenergic antagonist increases norepinephrine and serotonin
5HT3 and 5HT2 blocker
weak anti-histamine (H1)

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28
Q

how is mirtazapine metabolized?

A

liver with renal clearance: may accumulate in cats with liver or kidney disease

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29
Q

what are the side effects of mirtazapine?

A

skin irritation
sedation: H1 blocker
serotonin like syndrome

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30
Q

what signs are associated with serotonin like syndrome?

A

altered mentation: agitation, disorientation, excitement, vocalization
with overdose: neuromuscular (tremors, myoclonus, rigidity), autonomic (increased heart rate and respiratory rate, pyrexia, diarrhea)

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31
Q

how do you treat serotonin like syndrome?

A

cyproheptadine (5HT1 and 5HT2 antagonist)

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32
Q

what drugs does mirtazapine interact with?

A

buspirone
monoamine oxidase inhibitors
tri-cyclic antidepressants
SSRI’s

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33
Q

how does capromorelin work?

A

selective ghrelin receptor agonist
binds to ghrelin receptor in the hypothalamus
binds to growth hormone receptor in pituitary

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34
Q

how is capromorelin metabolized?

A

cytochrome P450 in liver, unknown in dogs and cats

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35
Q

what are the side effects of entyce?

A

rarely, increases liver enzymes and hepatic vacuolar change
hypersalivation at high doses

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36
Q

what are the contraindications of elura?

A

diabetic or glucose intolerant in cats
caution with heart disease: decreased heart rate and low blood pressure for up to 4 hours

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37
Q

what are some indications for drugs that modulate gastric acid secretion?

A

acute and chronic gastritis
gastroduodenal ulcer disease
esophagitis
secretagogue producing tumors

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38
Q

what is the gastric mucosal defense and cytoprotection?

A

unstirred layer
surface epithelial cells
cell renewal
alkaline tide
microcirculation
sensory nerves
prostaglandins

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39
Q

what categories of drugs are used to modulate gastric acid secretion?

A

H2 receptor antagonists
proton pump inhibitors
prostaglandin analogues
antacids

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40
Q

what are some H2 receptor antagonists?

A

famotidine
ranitidine (off market)
cimetidine

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41
Q

how are H2 blockers eliminated?

A

hepatic metabolism cytochrome P450 and excretion unchanged in urine

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42
Q

what are some oral proton pump inhibitors?

A

omeprazole
lansoprazole and esomeprazole

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43
Q

what are some IV proton pump inhibitors?

A

pantoprazole
esomeprazole
large animals: omeprazole

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44
Q

what are proton pump inhibitors absorbed as in the small intestine?

A

pro-drug, weak base

45
Q

what do proton pump inhibitors result in?

A

irreversible inhibition of hydrogen/potassium ATPase
apical membrane only

46
Q

what are the drug formulation strategies for proton pump inhibitors?

A

enteric coated tablet
enteric coated granules formulated into a capsule or paste
buffered formulations
rapidly dissolving formulations

47
Q

how long does the pharmacodynamic effect of the proton pump inhibitor last?

A

lifetime of proton pump: 24 hours
half life short

48
Q

what are the side effects of proton pump inhibitors?

A

disruption GI flora: diarrhea, vomiting
inhibition of cytochrome P450: drug interactions

49
Q

how do antacids work?

A

neutralize acid as it’s made
aluminum salts also stimulate prostaglandin release

50
Q

what are the side effects of antacids?

A

we use them more often for these
diarrhea
constipation
hypophosphatemia
hypercalcemia

51
Q

what is misoprostal?

A

synthetic prostaglandin E analogue

52
Q

what does misoprostal do?

A

stimulates blood flow, mucous production, epithelial cell turnover

53
Q

what are the indications for misoprostal?

A

effective in preventing NSAID induced gastric irritation in dogs
treating glandular ulcers in horses

54
Q

what does sucralfate do?

A

binds to damaged mucosa
stimulates prostaglandin release
promotes tissue growth and repair

55
Q

what are the side effects of sucralfate?

A

interferes with drug absorption
constipation

56
Q

what are some indications for drugs that modulate GI motility?

A

diarrhea
constipation
ileus

57
Q

what are some drugs that are excitatory for GI motility?

A

parasympathetic: acetylcholine
serotonin (5HT4)
migrating motor complex: motilin

58
Q

what are some drugs that are inhibitory for GI motility?

A

dopamine (D2)
sympathetic

59
Q

where does metaclopramide work primarily?

A

stomach: enhances emptying

60
Q

where does cisapride work?

A

full length of GI tract

61
Q

how is cisapride metabolized?

A

extensive hepatic metabolism

62
Q

what type of drug is cisapride?

A

5HT4 receptor agonist

63
Q

how does metaclopramide work?

A

5HT4 receptor agonist
dopamine antagonist

64
Q

what is erythromycin?

A

motilin agonist

65
Q

how is erythromycin cleared?

A

hepatic metabolism and hepatic excretion unchanged

66
Q

what is lidocaine used to treat?

A

equine post-operative ileus

67
Q

what is the mechanism of action of lidocaine?

A

possible direct pro-kinetic effect on equine GI smooth muscle
suppress primary afferent neurons, limiting reflex inhibition of intestinal motility
anti-inflammatory

68
Q

where are mu and delta receptors in the GI?

A

submucosal and myenteric plexuses, respectively

69
Q

what do opioids do after activating mu and delta receptors?

A

inhibit calcium channels
activation of potassium channels
decreased neurotransmitter release

70
Q

what are opioids’ pharmacodynamic effects on the GI?

A

inhibit longitudinal muscle
augment circular smooth muscle
increase GI sphincter tone
also inhibit GI secretion

71
Q

why would you want to prescribe a drug that modulates defecation?

A

ease defecation with painfully or partially obstructive colorectal or perineal lesions
reduction of GI impaction
functional colonic motility disorders
cleansing bowel prior to radiographs or endoscopy
elimination of unabsorbed toxins

72
Q

what drugs are osmotic agents?

A

magnesium or sodium salt solutions
sorbitol
polyethylene glycol/electrolyte solutions
lactulose

73
Q

what is the preferred laxative in dogs and cats?

A

lactulose

74
Q

what drugs are lubricating agents?

A

petroleum based products
mineral oil
docusates

75
Q

what is elura labeled for?

A

increase weight gain in cats with CKD

76
Q

what type of enema is deadly in cats and small dogs?

A

sodium phosphate

77
Q

what is the vomiting center?

A

lateral reticular formation in medulla oblongata
afferent sensory co-ordination
efferent signals to initiate vomiting

78
Q

what receptors are part of the emetic center?

A

alpha 2-adrenergic
serotinergic (5HT3)
neurokinin (NK)-1

79
Q

what receptors are part of the chemoreceptor trigger zone?

A

dopaminergic (dogs)
neurokinin (NK)-1
serotinergic (5HT3)
cholinergic
histaminergic

80
Q

what receptors are peripheral receptors that play a role in vomiting?

A

serotinergic (5HT3)
neurokinin (NK)-1

81
Q

what receptors provide vestibular input for dogs for vomiting?

A

cholinergic (M1)
histaminergic (H1)

82
Q

what receptors do NOT provide vestibular input for cats for vomiting?

A

histaminergic

83
Q

what receptors in higher cortical centers play a role in vomiting?

A

opioids?
endocannabinoids

84
Q

how can alpha-2-adrenergic agonists be reversed in cats?

A

alpha-2-adrenergic antagonists
yohimbine
atipamezole

85
Q

what drugs inhibit neurotransmission in the emetic center?

A

dolesetron
ondansetron
maropitant

86
Q

what drugs inhibit neurotransmission in the CRTZ?

A

metoclopramide
maropitant
dolasetron, ondansetron

87
Q

what drugs inhibit stimulation of peripheral 5HT3 receptors?

A

dolesetron, ondansetron
maropitant

88
Q

how is dolasetron metabolized?

A

hepatic metabolism
some renal excretion unchanged

89
Q

__________ is a peptide hormone secreted by the oxyntic glands of the stomach in the fasted state

A

ghrelin

90
Q

what does ghrelin binding to the ghrelin receptor in the hypothalamus do?

A

stimulates appetite

91
Q

how is entyce metabolized in dogs?

A

biliary and renal clearance

92
Q

where is elura metabolized in cats?

A

liver

93
Q

what are some secretagogue producing tumors?

A

mast cell
gastrinoma

94
Q

true/false: cats and dogs may develop a tolerance H2 blockers over a few days

A

true

95
Q

what are the side effects of misoprostol?

A

diarrhea
abdominal discomfort
abortion

96
Q

how does metaclopramide control gastrointestinal motility?

A

5HT4 receptor agonist and dopamine antagonist: enhances acetylcholine release
central anti-emetic action: dopamine antagonist

97
Q

where does erythromycin primarily work in dogs and cats?

A

stomach and proximal small intestine

98
Q

what are the side effects of lidocaine?

A

muscle fasciculations
ataxia
rarely seizures

99
Q

what are some cholinergic agents that increase gastrointestinal motility?

A

bethanechol
neostigmine

100
Q

what is loperamide?

A

opioid: mu agonist
for acute diarrhea in small animals

101
Q

what are the contraindications of loperamide?

A

horses: ileus
acute bacterial diarrhea
chronic diarrhea

102
Q

what are the classes of laxatives and cathartics?

A

contact stimulants
osmotic
lubricants
bulk forming

103
Q

what are two drugs that are contact stimulants?

A

biscodyl
cisapride

104
Q

what are some osmotic agents?

A

magnesium or sodium salt solutions
sorbitol
polyethylene glycol/electrolyte solutions
lactulose

105
Q

what is the preferred laxative in dogs and cats?

A

lactulose

106
Q

what does metabolism of lactulose in the colon lead to?

A

production of free fatty acids that acidify the colon
modulates bacterial population

107
Q

what is sulfasalazine used for?

A

modulate inflammation in the colon

108
Q

what is bismuth subsalicylate used for?

A

inflammation in the stomach and small intestine

Basic Pharmacology (37 decks)

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