Gastrointestinal Flashcards
What can cause physiochemical injury to the GI tract lining?
Some NSAIDs, caustics
What can cause hyperacidity in the GI tract?
Histamine release from MCTs
Cholinergic stimulation
Glucocorticoid therapy
What causes impaired cytoprotection in the GI tract?
NSAID therpay
What causes inflmmation in the GI tract?
Ulcerative colitis
What is understood about the role of stress and infection in causing gastric ulcers?
Once believed that stress prevented ulcers from being removed. This turned out to not be the case. Doesn’t play a role in animals that we know of
Pig and horses are a potential exception.If you had to say one species that is predisposed to stress induced ulcers, it would be the horse
In man, helicobacter is a major predisposing factor to gastric ulcers. Doesn’t play a role in animals
Dogs and cats can culture positive for helicobacter in the ulcer, but normal dogs and cats also culture positive for helicobacter in the stomach
Infectious: granulomatous colitis of Boxers (histiocytic ulcerative colitis)
What is the site of action of H2 receptor antagonists?
H2 receptors
What is the site of action and mechanism of PPIs?
H+/K+ ATPase
Blocks the generation of the hydrogen ion such that is not produced regardless of stimuli from receptors
What is the site of action and mechanism of misoprostol?
PG receptors
A synthetic PGE analog, it replaces the PG decreased by NSAID therapy to reestablish the cytoprotective mucus
What is the site of action and mechanism of sucralfate?
Binds to the surface of the ulcer
Forms a coating over the ulcer, acts locally, prefers an acid environment for optimal effect
What is an oral and injectable PPI?
Oral: Omeprazole
Injectable: Pantoprazole
Why is sodium bicarb no longer used as a routine oral antacid?
Rebound hyperacidity
Why do common human OTC antacids contain a combination of aluminum hydroxide and magnesium hydroxide rather than only one or the other?
Aluminum hydroxide can be constipating so it is often combined with MgOH which acts as a laxative
Why may oral antacid therapy for abomasal ulcers be of use in cattle while oral antacids are frowned upon for use in small animals and horses?
In cattle, the rumen meters out the compound producing long-term antacid effects. In SA and horses, you have to give po q 2hrs for it to be effective- that’s just not feasible
What are the effects of cimetidine as an enzyme inhibitor and a prokinetic?
Potent P450 enzyme inhibitor; drug interactions
No effect on GI motility
What are the effects of ranitidine as an enzyme inhibitor and a prokinetic?
Mild P450 inhibition; less prone to drug interactions
Prokinetic GI activity
What are the effects of famotidine as an enzyme inhibitor and a prokinetic?
Not a P450 inhibitor
No prokinetic GI activity
What rule of thumb is used regarding the timing of sucralfate administration relative to when other oral drugs or food is given?
Give at least 2 hours before or 2 hours after other oral medication or food
What is the merit of using a sucralfate suspension versus its use as a tablet?
Tablet may not dissolve and disperse adequately in small animals
Historically to treat/prevent GI ulcers in small animals it was common to place patients simultaneously on an H2 blocker and a proton pump inhibitor. What was the basis for this simultaneous use, what evidence supports it, and is it still warranted?
Recent research indicated acid suppression occurred in the dog as fast with proton pump inhibitors (PPI) as with H2 blockers. While some clinicians still prefer to begin with an H2 blocker, the majority now go straight to PPIs
How can you manage NSAID-induced ulcers?
Misoprostol is most effective
Omeparzole is also very useful
H2 blockers least effective
How can you manage steroid-induced ulcers?
H2 blockers
Omeprazole is also very useful
Misoprostol is least effective for gastric ulcers
What receptors involved in vomiting are in the chemo-receptor trigger zone?
5-HT3 D2 M NK1 δ α2
What receptors involved in vomiting are in the solitary tract nucleus?
5-HT3
D2
M
H1
What receptors involved in vomiting are in the stomach/SI?
5-HT3
D2
What receptors involved in vomiting are in the BBB between the inner ear and cerebellum?
H1
M
What receptors involved in vomiting are between higher centers and emetic center/medulla?
M
What species are not capable of vomiting?
Rodents Rabbits Most birds Horses Ruminants
Why should you not cause emesis in small animals after ingestion of caustics (strong acids or bases), petroleum distillates, or oils? What should be done instead?
Oils that are thrown up can have high risk of aspiration
Caustic agents will irritate and damage esophagus on the way back up
Do a gastric lavage instead
How do 3% hydrogen peroxide and apomorphine cause vomiting in the dog? What concerns exist about their use in cats?
Apomorphine works on chemo-receptor trigger zone which goes to the emetic center in the medulla and causes your pet to up chuck
Cats have had esophagitis and gastritis from H2O2 administration
How do xylazine and dexmedetomidine cause vomiting in the cat? How does route of administration affect their efficacy as emetics?
As a blood emetic, it causes vomiting by working on the chemo-receptor trigger zone which goes to emetic center
Unfortunately, the IV route is less likely to cause emesis in cats
The drug meclizine typically is only useful for what type of vomiting and on what receptor does it work?
Motion sickness
Works on H1 receptors
Which antiemetics have both central and peripheral antiemetic effects?
Metoclopramide
Serotonin 5-HT3 receptor antagonists (Ondansetron and dolasetron)
Extra-pyramidal side-effects can occur with an overdose of what two types of antiemetics? What mechanism of action do they share? What signs are associated with such side-effects?
Metoclopramide and Phenothiazine tranquilizers (acepromazine)
These are both central antidopaminergic antiemetics
Cause alpha 1 blockade –> vasodilation, risk of hypotension and hypothermia
PCV is lowered by ace
Do not use metoclopramide if GI obstruction exists because it is a prokinetic and you risk rupture
What antiemetics work on H1 receptors?
Diphenhydramine
Dimenhydronate
Meclizine
Promethazine
What antiemetics work on muscarinic receptors?
Scopolamine (in man)
Aminopentamide
What antiemetics work on dopamine-2 receptors?
Metoclopramide Phenothiazine tranquilizers Trimethobenzamide Glucocorticoids Butorphanol
What antiemetics work on NK1 receptors?
Maropitant citrate
What antiemetics work on serotonin 5-HT3 receptors?
Ondansetron
Dolasetron
Which antiemetics are efficacious enough to block cisplatin emesis?
Maropitant citrate (Cerenia) Ondansetron (Zofran) and dolasetron (Anzemet)
Though not considered antiemetics, what common drugs are often used in cancer chemotherapy protocols to limit vomiting?
Glucocorticoids and butorphanol
For some drugs rectal administration, as either a suppository or retention enema, results in higher bioavailability that oral dosing. Why?
Distal rectal venous return significantly bypasses the liver therefore decreasing first-pass effect for some drugs
Bioavailability can vary because of the amount of feces (anywhere form 30-100%)
Why are most lubricant laxatives intended for cats flavored?
Necessary to prevent aspiration pneumonia
What classes of laxatives should not be used if GI obstruction or ileus is present?
Stimulant, osmotic, or bulk (soluble fiber) laxatives
What classes of laxatives can be used if GI obstruction or ileus is present?
Lubricant laxatives
Surfactants
What are examples of osmotic laxatives?
Polyethylene glycol
Lactulose
Saline laxatives: Magnesium hydroxide
What are examples of bulk (soluble fiber) laxatives?
Psylliuum husk (Metamucil)
What are examples of lubricant laxatives?
Mineral oil
Flavored gels in cats (CatLax, Laxaire)
What are examples of surfactants?
Docusate (dioctyl sodium (calcium) sulfosuccinate), Colace, and Surfak
What GI prokinetic has primary effects on the urinary detrusor muscle?
Bethanicol
What older GI prokinetic is still sometimes used in horses to treat disorders of the lower GI tract: ileum, cecum, and right ventral colon and in cattle for rumen stasis? (Also used to treat myasthenia gravis.)
Neostigmine
What is the only prokinetic with effects on both anterior and posterior GI tracts?
Cisapride
Name three uses of lidocaine other than as a local anesthetic.
Blocks some effects of endotoxin
Restores intestinal coordination
Decreasing inflammation
Explain how loperamide and diphenoxylate act as antidiarrheals.
They are opioid receptor agonists
Stimulation of the opioid (mu) receptor in the myenteric plexus causes increase contraction of the intestinal circular smooth muscle, This increase in segmentation decreases GI transit time allowing for greater absorption of water
Why are parasympatholytic drugs (such as methylscopolamine or atropine) no longer used as antidiarrheals?
They interfere with normal peristalsis and predispose to ileus
Name the H2 blocker(s) that are prokinetics as well as suppressing stomach acid production.
Ranitidine
Which species is most prone to adverse reactions from metoclopramide administration?
Horses
Which antibiotic can be used as a prokinetics and which formulation is used?
Erythromycin
Erythromycin lactobionate injection and probably erythromycin glucepate
Discuss the pros and cons of bismuth subsalicylate as an antidiarrheal in the dog and cat
In cats, there is a risk of salicylate poisoning
Turns stool black; r/o melena
Pro is that it limits diarrhea due to secretory mechanisms
Name three oral toxin adsorbents that can be used as antidiarrheals.
Activated charcoal
Activated attpulgite
Di-tri-octahedral smectite (Bio Sponge)
What drug used in GI conditions can cause CNS toxicity in dogs with the ABCB1-1Δ (MDR1) gene mutation?
Loperamide
Identify the top three dog breeds that have the ABCB1-1Δ (MDR1) gene mutation.
Collie (70%)
Long-haired Whippet (65%)
Australian Shepherd and Mini Australian Shepherd (50%)
What are the limitations of glucocorticoids, anabolic steroids, progestogens, and B vitamins as primary appetite stimulants?
Glucocorticoids, anabolic steroids, progestogens: May cause an increase in appetite in many patients. They are not consistent in anorexic animals and other agents are preferred
B vitamins: have no effect on appetite unless the animal has a deficiency
What is the onset benzodiazepines?
Immediate onset IV
Minutes IM
What is the onset of cyproheptadine?
Slower onset of a few days
What is the onset of mirtazapine?
Within a few hours
Why appetite stimulant is effective in dogs?
Mirtazapine
Contrast the side-effects seen with overdose of mirtazapine in dogs versus cats
Dogs are less prone to side-effects in an overdose
Cats have marked vocalization, severe hyperactivity, and agitation
What is Entyce® (capromorelin) used for and how does it work in dogs?
A selective ghrelin receptor agonist
Ghrelin is a peptide hormone produced in the GI tract which functions as a neuropeptide in the CNS to regulate appetite and energy use
For what is dirlotapide (Slentrol®) used in dogs and what is its major adverse effect? Can it be used in other species
Indicated for the management of obesity in dogs
Its major adverse is effect is vomiting. As well as diarrhea and lethargy
It cannot be used in cats or humans
Explain how ursodiol is beneficial for both gallbladder mucoceles medical management as well as in cholistatic liver disease.
a. Management of gallbladder mucoceles in dogs because ursodial is choleretic meaning it increases bile flow by decreasing cholesterol content of bile and thinning biliary secretions.
Cholistatic disease: in cholestasis, the impaired biliary secretion of toxic bile acids causes their accumulation in the liver parenchyma and may contribute to subsequent hepatic failure. Ursodiol is a hepatoprotectant and competes with other bile acids for absorption in the ileum and shifts the bile acid profile in favor of less toxic hydrophilic forms.
What are the proposed mechanism of actions for silymarin and S-adenosyl-L-methionine (SAMe) as hepatoprotectants? How much evidence supports this use?
SAMe is a metabolic intermediate, sold as a nutraceutical, that is an indirect precursor of the antioxidant glutathione. It is commonly used in hepatic disease, and though it seems well tolerated, the evidence is scant
Silymarin works as an antioxidant and IV it may have some benefit in protection of dogs in tetrachloromethane-induced liver disease. Little evidence. A study in India also suggested that it is protected against oxytetracycline-induced liver damage in dogs
Why is oral neomycin and/or oral metronidazole used to medically manage hepatoencephalopathy?
Antibiotics to decrease colonic bacterial production
Why is lactulose used to medically manage hepatoencephalopathy?
Nonabsorbable disaccharide cleave by colonic bacteria into organic acids. It acidifies into the gut to cause ion trapping of ammonia ion
What effect do benzodiazepines have in an animal with hepatoencephalopathy and why is flumazenil sometime of use even if a benzodiazepine has not been given?
Benzos worsen encephalopathy
Flumazenil helps improve CNS signs and is supportive of diagnosis of heptaoencephalopathy
Why are D-penicillamine and zinc acetate used in copper storage diseases?
D-penicillamine is a chelator of copper. So give D-penicillamine first and then put them on long term zinc acetate because it binds intestinal copper and prevents its absorption
For what familial disease in dogs is colchicine used?
Shar Pei fever
Explain the current thinking on the cause of Granulomatous Colitis of Boxers (Histiocytic Ulcerative Colitis). What antibiotic(s) is it responsive to?
Evidence suggests a new “adherent and invasive E. coli” of colonic mucosal macrophages
Responds to antibiotics against E. coli that penetrate intracellularly
Fluoroquinolones seem to be the drug of choice
What is the treatment of choice perianal fistulas?
Cyclosporine often with ketoconazole
Why is ketoconazole often given with cyclosporine even though no fungal disease exists?
To decrease the dose and cost of cyclosporine
How does poloxalene work in frothy bloat in cattle?
It is a surfactant that breaks the surface tension on the foam and the foam breaks apart. The foam is eliminated as the animal will have gas
For which type of bloat do ionophores, such as monensin, have a benefit and how?
Gas-cap bloat
They change the rumen flora so that they produce less methane
For exocrine pancreatic insufficiency which product containing pancreatic enzymes is viewed as more effective, tablets or powder?
Powder sprinkled on food is viewed as more effective then tablets
For what type(s) of equine colic is N-butylscopolammonium (Buscopan®) approved as a treatment?
Spasmodic colic
Flatulent colic
Simple impactions
What is the mechanism of action of N-butylscopolammonium (Buscopan®)?
It is an antimuscarinic that stops intestinal spasms and controls abdominal pain
What are the side effect and contraindications of N-butylscopolammonium (Buscopan®)?
Short (30 min) tachycardia and dilated pupils
Contraindicated in GI ileus and glaucoma
Name one GI and one respiratory extra-label use of N-butylscopolammonium (Buscopan®)
GI: relax rectum prior to palpation
Resp: diagnostic test for COPD (chronic obstructive pulmonary dz)
What compound is commonly used both as an antacid and as a laxative in cattle?
Magnesium hydroxide
