GI Pharmacology Flashcards by Emma J

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

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What are the targets that GI drugs act on

emesis
motility
mucosal integrity
appetite
fecal consistency
antibiotics

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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

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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

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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

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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

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Which animals don’t do emesis

rabbits and horses

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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

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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

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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

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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

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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

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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

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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

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How is gastric acid stimulated and produced?

gastrin release will stimulate increased production of histamine and acid

histamine stimulated H2 receptor migration

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What are the drug targets that reduce gastric acid production?

H2 receptor blockers

proton pump inhibitors

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

*ranitidine

famotidine
cimetidine

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

*omeprazole

pantoprazole
esomeprazole

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What is the mechanism of ranitidine?

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

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

Used in dogs, cats, horses

via IV or PO

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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

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List 2 types of GI protectants

sucralfate
misoprostol

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What is the mechanism of sucralfate?

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

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What is the mechanism of misoprostol?

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

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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

What is the route of administration of maropitant

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

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)