Gastrointestinal Pharmacology Flashcards
1
Q
what do gastrointestinal drugs modulate?
A
vomiting
appetite
gastric acidity
gastrointestinal motility
defecation
2
Q
what is vomiting/emesis?
A
forceful expulsion of stomach contents from mouth
3
Q
what is the purpose of vomiting/emesis?
A
remove noxious substances or toxins from the gastrointestinal tract and/or release pressure
4
Q
what controls vomiting?
A
vomiting center
5
Q
where does input come from for retching and emesis?
A
CRTZ
cerebral cortex
vestibular apparatus
visceral afferent
6
Q
what receptors play a role in vomiting?
A
emetic center
chemoreceptor trigger zone
peripheral receptors
vestibular input
higher cortical centers
7
Q
what are indications for emetics?
A
initial treatment of patients who have ingested non-caustic toxicants or foreign material
8
Q
what are the emetics for dogs?
A
dopamine 2 agonists
apomorphine
ropinirole (Clevor) ophthalmic solution
9
Q
what are the emetics for cats?
A
alpha-2-adrenergic agonists
xylazine and dexmedetomidine
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
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
12
Q
why is metaclopramide best used IV as a CRI?
A
short half life
13
Q
how is metaclopramide metabolized?
A
hepatic with some renal excretion unchanged
14
Q
what are the side effects of metaclopramide?
A
CNS excitement (more often in cats than horses)
sweating in horses
15
Q
when should you avoid using metaclopramide?
A
obstructive disease
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
17
Q
what drugs are serotonin 5HT-3 receptor antagonists?
A
ondansetron (zofran) and dolesetron (anzemet)
18
Q
how is ondansetron metabolized?
A
hepatic primarily
substrate for MDR1
19
Q
what are side effects of serotonin 5HT-3 receptor antagonists?
A
rare
fecal incontinence
20
Q
what drug is an NK receptor-1 antagonist?
A
maropitant (cerenia)
21
Q
where are NK-1 receptors present in the body?
A
vomiting center
CRTZ
gastrointestinal tract
22
Q
how is maropitant metabolized?
A
hepatic and biliary excretion
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
24
Q
is maropitant highly protein bound?
A
yes
25
what does maropitant inhibit (other than vomiting)?
cytochrome P450 enzymes
26
what should you think about with oral doses of maropitant?
significant hepatic first pass effect: oral dose higher in dog, not in cat
higher dose for motion sickness in dog
27
what is the mechanism of action of mirtazapine?
pre-synaptic alpha-2-adrenergic antagonist increases norepinephrine and serotonin
5HT3 and 5HT2 blocker
weak anti-histamine (H1)
28
how is mirtazapine metabolized?
liver with renal clearance: may accumulate in cats with liver or kidney disease
29
what are the side effects of mirtazapine?
skin irritation
sedation: H1 blocker
serotonin like syndrome
30
what signs are associated with serotonin like syndrome?
altered mentation: agitation, disorientation, excitement, vocalization
with overdose: neuromuscular (tremors, myoclonus, rigidity), autonomic (increased heart rate and respiratory rate, pyrexia, diarrhea)
31
how do you treat serotonin like syndrome?
cyproheptadine (5HT1 and 5HT2 antagonist)
32
what drugs does mirtazapine interact with?
buspirone
monoamine oxidase inhibitors
tri-cyclic antidepressants
SSRI's
33
how does capromorelin work?
selective ghrelin receptor agonist
binds to ghrelin receptor in the hypothalamus
binds to growth hormone receptor in pituitary
34
how is capromorelin metabolized?
cytochrome P450 in liver, unknown in dogs and cats
35
what are the side effects of entyce?
rarely, increases liver enzymes and hepatic vacuolar change
hypersalivation at high doses
36
what are the contraindications of elura?
diabetic or glucose intolerant in cats
caution with heart disease: decreased heart rate and low blood pressure for up to 4 hours
37
what are some indications for drugs that modulate gastric acid secretion?
acute and chronic gastritis
gastroduodenal ulcer disease
esophagitis
secretagogue producing tumors
38
what is the gastric mucosal defense and cytoprotection?
unstirred layer
surface epithelial cells
cell renewal
alkaline tide
microcirculation
sensory nerves
prostaglandins
39
what categories of drugs are used to modulate gastric acid secretion?
H2 receptor antagonists
proton pump inhibitors
prostaglandin analogues
antacids
40
what are some H2 receptor antagonists?
famotidine
ranitidine (off market)
cimetidine
41
how are H2 blockers eliminated?
hepatic metabolism cytochrome P450 and excretion unchanged in urine
42
what are some oral proton pump inhibitors?
omeprazole
lansoprazole and esomeprazole
43
what are some IV proton pump inhibitors?
pantoprazole
esomeprazole
large animals: omeprazole
44
what are proton pump inhibitors absorbed as in the small intestine?
pro-drug, weak base
45
what do proton pump inhibitors result in?
irreversible inhibition of hydrogen/potassium ATPase
apical membrane only
46
what are the drug formulation strategies for proton pump inhibitors?
enteric coated tablet
enteric coated granules formulated into a capsule or paste
buffered formulations
rapidly dissolving formulations
47
how long does the pharmacodynamic effect of the proton pump inhibitor last?
lifetime of proton pump: 24 hours
half life short
48
what are the side effects of proton pump inhibitors?
disruption GI flora: diarrhea, vomiting
inhibition of cytochrome P450: drug interactions
49
how do antacids work?
neutralize acid as it's made
aluminum salts also stimulate prostaglandin release
50
what are the side effects of antacids?
we use them more often for these
diarrhea
constipation
hypophosphatemia
hypercalcemia
51
what is misoprostal?
synthetic prostaglandin E analogue
52
what does misoprostal do?
stimulates blood flow, mucous production, epithelial cell turnover
53
what are the indications for misoprostal?
effective in preventing NSAID induced gastric irritation in dogs
treating glandular ulcers in horses
54
what does sucralfate do?
binds to damaged mucosa
stimulates prostaglandin release
promotes tissue growth and repair
55
what are the side effects of sucralfate?
interferes with drug absorption
constipation
56
what are some indications for drugs that modulate GI motility?
diarrhea
constipation
ileus
57
what are some drugs that are excitatory for GI motility?
parasympathetic: acetylcholine
serotonin (5HT4)
migrating motor complex: motilin
58
what are some drugs that are inhibitory for GI motility?
dopamine (D2)
sympathetic
59
where does metaclopramide work primarily?
stomach: enhances emptying
60
where does cisapride work?
full length of GI tract
61
how is cisapride metabolized?
extensive hepatic metabolism
62
what type of drug is cisapride?
5HT4 receptor agonist
63
how does metaclopramide work?
5HT4 receptor agonist
dopamine antagonist
64
what is erythromycin?
motilin agonist
65
how is erythromycin cleared?
hepatic metabolism and hepatic excretion unchanged
66
what is lidocaine used to treat?
equine post-operative ileus
67
what is the mechanism of action of lidocaine?
possible direct pro-kinetic effect on equine GI smooth muscle
suppress primary afferent neurons, limiting reflex inhibition of intestinal motility
anti-inflammatory
68
where are mu and delta receptors in the GI?
submucosal and myenteric plexuses, respectively
69
what do opioids do after activating mu and delta receptors?
inhibit calcium channels
activation of potassium channels
decreased neurotransmitter release
70
what are opioids' pharmacodynamic effects on the GI?
inhibit longitudinal muscle
augment circular smooth muscle
increase GI sphincter tone
also inhibit GI secretion
71
why would you want to prescribe a drug that modulates defecation?
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
what drugs are osmotic agents?
magnesium or sodium salt solutions
sorbitol
polyethylene glycol/electrolyte solutions
lactulose
73
what is the preferred laxative in dogs and cats?
lactulose
74
what drugs are lubricating agents?
petroleum based products
mineral oil
docusates
75
what is elura labeled for?
increase weight gain in cats with CKD
76
what type of enema is deadly in cats and small dogs?
sodium phosphate
77
what is the vomiting center?
lateral reticular formation in medulla oblongata
afferent sensory co-ordination
efferent signals to initiate vomiting
78
what receptors are part of the emetic center?
alpha 2-adrenergic
serotinergic (5HT3)
neurokinin (NK)-1
79
what receptors are part of the chemoreceptor trigger zone?
dopaminergic (dogs)
neurokinin (NK)-1
serotinergic (5HT3)
cholinergic
histaminergic
80
what receptors are peripheral receptors that play a role in vomiting?
serotinergic (5HT3)
neurokinin (NK)-1
81
what receptors provide vestibular input for dogs for vomiting?
cholinergic (M1)
histaminergic (H1)
82
what receptors do NOT provide vestibular input for cats for vomiting?
histaminergic
83
what receptors in higher cortical centers play a role in vomiting?
opioids?
endocannabinoids
84
how can alpha-2-adrenergic agonists be reversed in cats?
alpha-2-adrenergic antagonists
yohimbine
atipamezole
85
what drugs inhibit neurotransmission in the emetic center?
dolesetron
ondansetron
maropitant
86
what drugs inhibit neurotransmission in the CRTZ?
metoclopramide
maropitant
dolasetron, ondansetron
87
what drugs inhibit stimulation of peripheral 5HT3 receptors?
dolesetron, ondansetron
maropitant
88
how is dolasetron metabolized?
hepatic metabolism
some renal excretion unchanged
89
__________ is a peptide hormone secreted by the oxyntic glands of the stomach in the fasted state
ghrelin
90
what does ghrelin binding to the ghrelin receptor in the hypothalamus do?
stimulates appetite
91
how is entyce metabolized in dogs?
biliary and renal clearance
92
where is elura metabolized in cats?
liver
93
what are some secretagogue producing tumors?
mast cell
gastrinoma
94
true/false: cats and dogs may develop a tolerance H2 blockers over a few days
true
95
what are the side effects of misoprostol?
diarrhea
abdominal discomfort
abortion
96
how does metaclopramide control gastrointestinal motility?
5HT4 receptor agonist and dopamine antagonist: enhances acetylcholine release
central anti-emetic action: dopamine antagonist
97
where does erythromycin primarily work in dogs and cats?
stomach and proximal small intestine
98
what are the side effects of lidocaine?
muscle fasciculations
ataxia
rarely seizures
99
what are some cholinergic agents that increase gastrointestinal motility?
bethanechol
neostigmine
100
what is loperamide?
opioid: mu agonist
for acute diarrhea in small animals
101
what are the contraindications of loperamide?
horses: ileus
acute bacterial diarrhea
chronic diarrhea
102
what are the classes of laxatives and cathartics?
contact stimulants
osmotic
lubricants
bulk forming
103
what are two drugs that are contact stimulants?
biscodyl
cisapride
104
what are some osmotic agents?
magnesium or sodium salt solutions
sorbitol
polyethylene glycol/electrolyte solutions
lactulose
105
what is the preferred laxative in dogs and cats?
lactulose
106
what does metabolism of lactulose in the colon lead to?
production of free fatty acids that acidify the colon
modulates bacterial population
107
what is sulfasalazine used for?
modulate inflammation in the colon
108
what is bismuth subsalicylate used for?
inflammation in the stomach and small intestine
