GI Pharmacology Flashcards
What are the basic principles of treating GI disease
Identifying the primary cause of the disease.
Provide supportive care like fluids, fasting, diet change
GI drugs
What are the targets that GI drugs act on
emesis
motility
mucosal integrity
appetite
fecal consistency
antibiotics
What receptors are involved with emesis
They stimulate the vomiting centre in the brain
Receptors:
dopamine
serotonin
muscarinic (M1)
neurokinin
adrenergic (alpha 2)
histamine
cannabinoid
What are the 4 input centers for triggering emesis and their associated stimuli and receptors
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
What are the 5 neurotransmitters used in the emesis system
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
List 6 stimuli for the emesis
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
Which animals don’t do emesis
rabbits and horses
What conditions indicate administration of an emetic
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
What conditions contraindicate administration of an emetic
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
How is GI motility controlled
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
What neurotransmitters and hormones are used to control motility in GI
Neurotransmitters like serotonin, dopamine
excitatory neurotransmitter = Ach
inhibitory neurotransmitter = norepi
hormones like motilin (from M cells) = increase motility
How do opioids influence GI motility?
They are anti kinetics
Mu and delta receptors primarily impact motility resulting in an increase or decrease in absorption of fluid, electrolytes, or glucose
How does MDR1 deficiency impact treatment of excess GI motility
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
How does MDR1 deficiency impact treatment of emesis
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
How is gastric acid stimulated and produced?
gastrin release will stimulate increased production of histamine and acid
histamine stimulated H2 receptor migration
What are the drug targets that reduce gastric acid production?
H2 receptor blockers
proton pump inhibitors
Provide 3 examples (only one is most important) of H2 receptor blockers
*ranitidine
famotidine
cimetidine
Provide 3 examples (only one is most important) of proton pump inhibitor
*omeprazole
pantoprazole
esomeprazole
What is the mechanism of ranitidine?
It is a competitive histamine receptor antagonist resulting in reduced acid secretion
What is the route of administration of ranitidine and for what species?
Used in dogs, cats, horses
via IV or PO
What is the mechanism of action for omeprazole
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
List 2 types of GI protectants
sucralfate
misoprostol
What is the mechanism of sucralfate?
It forms a physical barrier because it sticks to mucosal ulcers and is not absorbed by the body
What is the mechanism of misoprostol?
It is a synthetic prostaglandin which acts to increase mucosal blood flow and reduce acid secretion
What is the function of adsorbents? Provide some examples (only 1 is relevant)
They bind toxins and prevent absorption
*activated charcoal
kaolin-pectin
attapulgite
smectite
bismuth subsalicylate
What is one example of an appetite stimulant?
mirtazapine
What is the mechanism of action of mirtazapine
pre-synaptic alpha 2 antagonist which antagonizes the negative feedback loop which results in an increase of norepinephrine
What is the function of mirtazapine
antinausea
antiemetic
sedative (H1 receptor antagonist)
but the response takes 8-36h for effect
What species is mirtazapine commonly used in
cats
What are 3 types of drugs that target the liver
lactulose
ursodiol
S-adenosyl-L-methionine (SAMe)
What is lactulose and what is it used for?
It is a disaccharide made from galactose and fructose
It is used for hepatic encephalopathy
What is the mechanism of action for lactulose?
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
What is ursodiol used for and why?
Cholestasis treatment
- to increase bile flow
- protect hepatocytes from bile acids
- solubilize cholesterol gallstones
What is the mechanism of action of ursodiol
It reduces hepatic synthesis, secretion, and absorption of cholesterol
It undergoes hepatic recirculation which results in low concentrations in systemic circulation
What species is ursodiol used in? What route of administration is used?
PO
dogs and cats
NOT hindgut fermenters because it will be toxic
What is the use for S-adenosyl-L-methionine?
It is a nutraceutical used for hepatocellular dysfunction
What is the mechanism of action for S-adenosyl-L-methionine
Glutathione is a strong antioxidant and provides exogenous substances for metabolism with minimal side effects
Lists 4 antiemetics commonly used
phenothiazine tranquilizers - acepromazine
maropitant
odensetron
metaclopramide
What is the antiemetic mechanism of action of phenothiazine tranquilizers
It is a dopamine receptor antagonist in the chemoreceptor trigger zone
It has some histamine and muscarinic receptor antagonism which affects the vestibular zone
What are the additional effects of phenothiazine tranquilizers (other than antiemesis)
sedation and hypotension because alpha 1 antagonists result in vasodilation
It may cause paraphimosis (penile protrusion) in horses and cows
NOT analgesia
What concerns should you consider when using a phenothiazine tranquilizers
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
What is the route of administration of phenothiazine tranquilizers
IM
What is the route of administration of maropitant
PO
What is the mechanism of action of maropitant
It is a neurokinin 1 receptor antagonist and is metabolized in a way similar to NSAIDs and phenobarbital
What is the function of maropitant
It resolves acute vomiting induced by motion or drugs
It does not prevent nausea
What species is maropitant used in
dogs and cats
What is the route of administration and species ondensetron is used in
PO
slow IV q8h
SC
IM
dogs and cats
What is the mechanism of action of ondensetron?
It is a serotonin (5HT3) receptor antagonist
What is the function of ondensetron
It reduces vomiting due to irritation
It is the best for reducing nausea
What adverse effects are associated with ondensetron? What are contraindications?
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
What is the route of administration for metaclopramide and what species is it used in
IM or IV
cas and dogs (better in dogs)
What is the mechanism of action for metaclopramide
It is a dopamine receptor antagonist and at high doses it can be a serotonin receptor antagonist
It has a high first pass effect
What is the function of metaclopramide
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
What would caution the use of metaclopramide?
GI obstruction because it is also a prokinetic
What are 3 types of emetics
apomorphine
alpha 2 agonists - xylazine, dexmedetomidine
hydrogen peroxide
What is the route of administration for apomorphine
SC
conjunctiva
mucosa
What is the mechanism of action for apomorphine
dopamine receptor agonist acting on the chemoreceptor trigger zone
What is the effects of apomorphine?
emesis
excitement (which can be reversed by naloxone but vomiting wont be reversed)
Motion will increase its effect
What species is apomorphine used in
dogs (not cats)
What is the mechanism of action for alpha 2 agonists (in relation to emesis)
It acts on alpha 2 receptors in the chemoreceptor trigger zone
What is the effect of alpha 2 agonists
emesis
sedation
reduced cardiac output
What species is alpha 2 agonists used in for emesis
cats
What is the route of administration for hydrogen peroxide
PO
What is the mechanism of action for hydrogen peroxide
It causes GI irritation and stimulates an afferent signal
What are adverses effects associated with hydrogen peroxide
risk of gastritis and esophagitis and/or aspiration
Its effectiveness is also hit or miss
What species is hydrogen peroxide used in
dogs not cats
What are 3 types of prokinetic
metaclopramide
cisapride
lidocaine
What are 4 types of antikinetics
atropine
glycopyrrolate
N-butylscopolammonium bromide/Hyoscine butylbromide
loperamide
What is the mechanism of action for metaclopramide
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
What is the effect of metaclopramide
increases gastric emptying and duodenal motility
What is the mechanism of action of cisapride
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
What is the effect of cisapride
It increases SI and colon motility and GI secretions
It is better than metoclopramide for colon motilty
What is the mechanism of action and route of administration of lidocaine
CRI
unknown
What are the effects of lidocain
reduced pain and inflammation in the gut
When is lidocaine commonly usd
horse - post colic sx
rabbit - GI stasis
What is the mechanism of action for loperamide
It targets mu receptors in GI with poor bioavailability resulting in local GI effects (no opioid effects)
