II - GI Small Animal Flashcards
In what clinical situations would administering appetite stimulants be most effective?
- feeding tube cannot be placed
- underlying cause of anorexia/Hyporexia has been removed but patient is still not eating
- short term during diagnostic phase
- secondary to behavioral or environmental factors
- overcome food aversion
- chronically ill or palliative cases when a feeding tube cannot be placed
List five appetite stimulants.
- Cyproheptadine
- Mirtazapine
- Capromorelin (Entyce - dog, Elura - cat)
- Benzodiazepines: Diazepam
- Glucocorticoids
MOA: 5-HT3 (serotonin) antagonist
- Hypothalamus secretes opiates which stimulate appetite, and serotonin inhibits opiate release
Cyproheptadine
This appetite stimulant shows some efficacy in cats as they are more sensitive to serotonin changes.
Cyproheptadine
Adverse effects of Cyproheptadine (4)
Sedation
Paradoxical CNS stimulation/aggression
Anticholinergic effects
Dry mucous membranes
MOA:
5HT3 (serotonin) antagonist - anti nausea, increased app.
Alpha adrenergic receptor antagonist - increased norepinephrine leads to increased app.
Histamine receptor antagonist - sedation
Mirtazapine
Adverse effects of Mirtazapine (5)
Sedation
Focalization
Behavior changes
GI upset
Irritation of pinna
Mirtazapine is an effective appetite stimulant for _______.
Dogs and cats
MOA: Ghrelin receptor agonist - directly signals hypothalamus and increases growth hormone excretion from the pituitary
Capromorelin - Entyce (dogs), Elura (cats)
Appetite stimulant
Adverse effects of this appetite stimulant identified so far are increased salivation after dosing and GI upset.
Capromorelin - Entyce (dogs), Elura (cats)
Capromorelin is FDA approved for which species?
Dogs (Entyce) and cats (Elura)
MOA: GABAminergic inhibition of satiety center
Benzodiazepines: Diazepam
As an appetite stimulant, diazepam is most effective in _______.
Cats
This appetite stimulant is administered IV and has a short half-life.
Diazepam
_________ cause polyphagia in dogs but are not recommended as an appetite stimulant due to side effects such as catabolic muscle loss.
Glucocorticoids
- Also poor effects on appetite in cats
Name three receptors found in the Emetic/Vomiting Center
Neurokinergic - NK1
Serotonergic - 5HT3
Adrenergic - a2
Name six receptors found in the Chemoreceptor Trigger Zone (CRTZ)
Neurokinergic - NK1
Serotonergic - 5HT3
Adrenergic - a2
Dopaminergic - D2
Cholinergic - M1
Histaminergic - H1
CRTZ in cats:
Poorly developed ______ receptors.
Absence of ______ receptors.
Higher number of _______ receptors.
Dopaminergic - D2
Histaminergic - H1
Adrenergic - a2
CRTZ in dogs:
Well developed ________ and ________ receptors
Lower number of ________ receptors
Dopaminergic - D1 and Histaminergic - H1
Adrenergic - a2
Inducing emesis is most productive when performed within what time period?
Within 2-3 hours of ingestion
List five emetics used in small animal medicine.
- Apomorphine
- Ropinerole (Clevor)
- Xylazine
- Dexmedetomidine
- Hydrogen peroxide 3%
MOA: Stimulates dopamine D2 receptors in CRTZ to cause vomiting in dogs
Two drugs
Apomorphine
Ropinerole (Clevor)
Three adverse effects of apomorphine
Ocular irritation
Lethargy
Protracted nausea/vomiting
This drug is the emetic of choice in dogs.
Apomorphine
Apomorphine can be given ________.
IV (preferred) or conjunctival (tablet)
MOA: Alpha-2 agonist
Two drugs for inducing emesis.
Xylazine
Dexmedetomidine
In addition to ocular irritation and protracted vomiting, this drug inhibits prolactin and should not be used during pregnancy or lactation (staff should also be cautious when handling).
Ropinerole (Clevor)
How would you treat protracted nausea/vomiting brought about by Ropinerole and apomorphine?
Dopamine antagonists such as metoclopramide
Two drugs used to induce emesis in cats
Xylazine
Dexmedetomidine
IM or IV
How do you reverse Xylazine and Dexmedetomidine?
Xylazine - yohimbine
Dexmedetomidine - atipamezole
Depending on the dose used, sedation is a possible side effect for ______________ and _______________.
Xylazine and Dexmedetomidine
MOA: generates water and gas, foam expands the stomach, irritation stimulates GI nerve endings to induce emesis
Hydrogen peroxide
Why isn’t hydrogen peroxide recommended for inducing emesis in cats?
Low efficacy and increased risk of adverse effects
Adverse effects of hydrogen peroxide for inducing emesis
Gastritis
Esophagitis
GI ulceration
Air embolus
*particularly if overdosed or wrong concentration used
Name four antiemetics.
- Metoclopramide (Reglan)
- Maropitant (Cerenia)
- Ondansetron (Zofran)
- Dolasetron (Anzemet)
MOA: Serotonin antagonist and antidopaminergic; also a pro-motility agent
Metoclopramide (Reglan)
Which antiemetic works better in dogs than in cats?
Metoclopramide (Reglan)
Which antiemetic has a very short half-life and must be a CRI if given IV?
Metoclopramide (Reglan)
Adverse effects of metoclopramide (Reglan) - 3
Change in mentation/behavior
Disorientation
Constipation
MOA: Neurokinin-1 receptor antagonist; inhibits substance P - a key neurotransmitter involved in vomiting; works directly at the emetic center
Maropitant (Cerenia)
This antiemetic is used in dogs and cats
Maropitant (Cerenia)
Adverse effect of maropitant (Cerenia) - 1
Pain at site of injection (esp. SQ)
*refrigeration may reduce pain
MOA: serotonin antagonists
Ondansetron (Zofran)
Dolasetron (Anzemet)
Which antiemetics are often used for chemotherapy induced nausea?
Ondansetron (Zofran)
Dolasetron (Anzemet)
Maropitant (Cerenia)
Ondansetron can be given _______.
IV or PO
Dolasetron can be given ________.
PO, IV, SQ
Possible side effect for Ondansetron and Dolasetron - 1
P-glycoprotein substrates may cause neurological toxicity in herding breed dogs with the MDR1 mutation
Risk factors for GI ulceration
- Drugs: NSAIDS, corticosteroids
- Stress
- Compromised mucosal blood supply: anesthesia, dehydration, hypoadrenocorticism
- Inflammatory bowel disease
- Gastronomy, adenocarcinoma
- Helicobacter?
Risk factors for esophagitis and reflux
Gastroesophageal reflux
Esophageal dysmotility
Foreign body
Toxins
Caustic substances
Causes of gastroesophageal reflux
Primary idiopathic
Anesthesia associated
Secondary (inflammatory, neoplastic)
Hiatal hernia, brachycephalic syndrome
Many more
Causes of esophageal dysmotility
Megaesophagus
Myopathies/neuropathies
Neoplasia
Etc.
List three antacids found OTC and give their MOA.
Aluminum hydroxide (Mylanta)
Magnesium hydroxide (Milk of magnesia)
Calcium carbonate (Tums)
MOA: neutralize acid (don’t decrease production)
- Insufficient evidence to recommend as treatment for ulceration or reflux in SA med; longer acting and more effective treatments are available
List four H2 antagonists used to reduce gastric secretions.
Famotidine (Pepcid)
Ranitidine
Cimetidine (Tagamet)
Nizatidine
MOA: reversible, competitive antagonist at histamine H2 receptor in parietal cells; reduce gastric acid secretion; some have prokinetic effects
Histamine H2 Antagonists
- Famotidine (Pepcid)
- Ranitidine
- Cimetidine (Tagamet)
- Nizatidine
H2 antagonists are classically used for:
Uremic patients and mast cell tumors
Which H2 antagonist has the most drug interactions?
Cimetidine (Tagamet) - inhibits CYP 450
Name the two proton pump inhibitors used in small animal medicine.
Omeprazole (Prilosec) - PO
Pantoprazole (Protonix) - IV
MOA: inhibit the gastric hydrogen-potassium-ATpase proton pump; reduces gastric secretion
Omeprazole (Prilosec)
Pantoprazole (Protonix)
How often should PPIs be given?
Twice daily
What is considered to be the most effective treatment for increasing gastric pH and treatment of ulceration?
Proton pump inhibitors
- omprazole (Prilosec)
- Pantoprazole (Protonix)
When should PPIs be tapered in dogs and cats?
After prolonged use > 3-4 weeks
Which PPI inhibits CYP 450?
Omeprazole (Prilosec)
Which PPI takes effect more rapidly?
Pantoprazole (Protonix)
Name two mucosal protectants used in small animal medicine.
Misoprostal
Sucralfate
MOA: Prostaglandin E1 analog; inhibits gastric acid secretion; increases bicarbonate secretion; increase mucus secretion; increase gastric blood flow
Mucosal protectant
- Misoprostal
Clinical indications for misoprostal
Treatment and prevention of aspirin (and maybe other NSAID) induced ulcers
No indication of efficacy for treating glucocorticoid induced ulcers
Adverse effects of misoprostal
GI distress
Uterine contractions, vaginal bleeding, induction of parturition - risk to women, handle with care
MOA: When combined with acid forms sucrose octasulfate and aluminum hydroxide; binds to exposed epithelial cell membranes and not normal mucosa; protects mucosa against HCl, bile, pepsin; possibly stimulates local prostaglandin production
Sucralfate
Drug interactions with Sucralfate
Affects oral absorption of drugs
Is Sucralfate helpful in preventing/treating esophageal injury?
No
Which drugs are superior for treatment of ulceration?
Proton Pump Inhibitors
- Omeprazole
- Pantoprazole
A dog’s esophagus is essentially all ________.
Skeletal muscle
The lower esophageal sphincter is made of ______.
Smooth muscle
The cat’s esophagus is ________ the cranial 2/3 and ________ the distal 1/3.
Skeletal muscle
Smooth muscle
Which receptors are sympathetic?
Adrenergic
- inhibit motility
- fight or flight
Which receptors are parasympathetic?
Cholinergic
- enhance motility
- rest and digest
List six prokinetic drugs used in small animal medicine.
Metoclopramide
Cisapride
Ranitidine (no longer on the market)
Nizatidine
Erythromycin
Bethanechol
The clinical uses of this drug include ileus, GDV - post op, delayed gastric emptying, gastroesophageal reflux (increases LES tone).
Metoclopramide
This drug’s site of action is mainly the proximal GI tract as the distal GI tract is less responsive.
Metoclopramide
MOA: serotonin antagonist and antidopaminergic
Promotility MOA: sensitizes GI smooth muscle to effects of acetylcholine
Metoclopramide
MOA: enhances acetylcholine from intrinsic cholinergic neurons; not antidopaminergic
Cisapride
The site of action of this drug is smooth muscle from esophagus through to the colon.
Cisapride
This prokinetic is metabolized by CYP 450, so it is affected by drugs that inhibit this enzyme.
Cisapride
This prokinetic has minimal side effects that can include vomiting, diarrhea, and abdominal discomfort.
Cisapride
Clinical uses for this drug include megaesophagus in cats, mega colon in cats, gastroesophageal reflux, delayed gastric emptying, and ileus.
Cisapride
*does not work in megaesophagus in dogs as their esophagus is all skeletal muscle
Two prokinetics with MOA: H2 receptor blocker, inhibition of acetylcholinesterase activity
Ranitidine (no longer on the market)
Nizatidine
Clinical uses for this drug include delayed gastric emptying, constipation, pseudo-obstruction of the intestines, and gastroesophageal reflux
Nizatidine
What is the site of action of Nizatidine?
GI
What is the site of action of Ranitidine?
GI, especially stomach
MOA: macrolide antibiotic with motilin-like activity
Erythromycin
Why is ertythromycin less effective in the distal GI tract and diseased GI tract?
Lack of motilin receptors
This drug is used for decreased colonic motility in dogs only.
Erythromycin
This prokinetic inhibits CYP 450 (and interacts with Cisapride)
Erythromycin
Possible adverse reaction of erythromycin.
Possible reactions with MDR1 mutations
Drug interaction - inhibition of CYP 450
Cholinergic / prokinetic mainly used to improve bladder contractility but has potential use in megaesophagus
Bethanechol
Adverse effects of this drug include SLUD, bradycardia, increased gastric acid secretion, and increased pancreatic secretions
Bethanechol
What is the primary indication for drugs that suppress motility?
Diarrhea
*may be contraindicated for infectious causes of diarrhea
List the motility modifiers / anti-diarrheals - 6
Diphenoxylate (Lomotil)
Loperamide (Imodium)
Kaolin/Pectin
Bismuth salts, charcoal
Metronidazole (Flagyl)
Tyrosine (Tylan)
These two motility modifiers are not recommended for use in cats due to excitatory behavior.
Diphenoxylate and loperamide
These motility modifiers cause constipation, bloat and sedation in dogs.
Diphenoxylate, loperamide
Which motility modifers do not require a prescription?
Loperamide (Imodium)
- Bismuth salts, charcoal (Pepto-Bismol) - efficacy unknown; can make stool black - don’t confuse with Melina; give with food due to GI upset
Which motility modifier causes reactions in dogs with the MDR1 mutation?
Loperamide (Imodium)
Motility modifier that binds enteric opioid receptors; direct inhibition of GI motility (2)
Diphenoxylate
Loperamide (Imodium)
MOA: demulcent / protectant; relieves irritation by lining mucosal surface; absorbs some potential toxicants
Kaolin/Pectin
Efficacy as tx for diarrhea unknown
GI upset - give with food
MOA: Synthetic nitroimidazole compound; disrupts bacterial DNA synthesis; effective against certain protozoal species and anaerobic bacteria
Metronidazole (Flagyl)
This motility modifier has a wide range of doses, with increased risk of adverse effects at higher doses and extensive hepatic metabolism.
Metronidazole (Flagyl)
Clinical uses for this drug include altering GI microbes, chronic enteropathy, EPI, and hepatic encephalopathy; Giardia, clostridium, anaerobic infections.
Metronidazole (Flagyl)
Adverse effects of this drug include GI upset, hepatotoxicity, neurotoxicosis, and reduced olfactory function (hyposmia) in dogs.
Metronidazole (Flagyl)
This drug does not improve outcome in dog with acute hemorrhagic diarrhea.
Metronidazole (Flagyl)
MOA: Macrolide antibiotic; inhibits 50s subunit of bacterial ribosomes to inhibit protein synthesis, mainly bacteriostatic
Tylosin (Tylan)
Adverse effects for this drug are considered minimal and uncommon but include potential hypersensitivity.
Tylosin (Tylan)
Clinical uses for this drug include alteration of GI microbes, treatment of antibiotic responsive diarrhea or GI dysbiosis, chronic enteropathy, and EPI.
Tylosin (Tylan)
This motility modifier can be given chronically but has a bitter taste so may need to be flavored or put in a capsule.
Tylosin (Tylan)
Three treatments for constipation
Laxatives - Psyllium, wheat dextrin, pumpkin; preferred tx due to safety, tolerance, and efficacy
Osmotic - lactulose effective and commonly used
Lubricants - not generally advised due to risk of aspiration
Megacolon is most commonly seen in _____.
Cats
Treatment for megacolon includes diet modification, fiber, enemas, and surgery plus what two drugs?
Lactulose (laxative)
Cisapride
Secondary esophagitis in megaesophagus is treated with ____ and ____.
Omeprazole
Sucralfate
Are metoclopramide, Cisapride, and Bethanacol (promotility drugs) effective in treating megaesophagus in dogs?
No - dogs have no smooth muscle in the esophagus
These drugs only work on smooth muscle
This drug is used in megaesophagus in dogs and cats as it is thought to allow for better esophageal clearance of ingest into the stomach, which can reduce regurgitation and improve weight gain.
Sildenafil (Viagra, Revatio)
MOA: Phosphodiesterase-5 inhibitor that relaxes smooth muscle causing vasodilation; relaxes smooth muscle of lower esophageal sphincter for a short time
Sildenafil (Viagra, Revatio)
This drug is effective in treating both dogs and cats with megaesophagus.
Sildenafil (Viagra, Revatio)
Treatment options for EPI
Replacement pancreatic enzymes - viokase, pancreazyme
Dried extracts of bovine or porcine pancreas
Powdered form preferred
Cobalamin supplementation - vitamin B12
EPI, chronic enteropathy, and pancreatitis (esp. cats) may need supplementation with ____.
Cobalamin - vitamin B12
Chronic enteropathy is classified as responsive to these four things:
Diet
Fiber
Antibiotics - metronidazole or tylosin
Immunosuppressants
- steroids, cyclosporine, Mycophenolate, Chlorambucil, leflunomide, azathioprine (dogs only!)
Denamarin, Denosyl, SAMe, and silymarin (milk thistle) are ______.
Hepatoprotectants
MOA: decreases hepatic synthesis/secretion of cholesterol and intestinal absorption of cholesterol; allows solubilization of cholesterol-containing gallstones; increases bile flow; reduces hepatotoxic effects of bile salts; may reduce hepatocellular inflammatory changes and fibrosis
Ursodiol
Clinical uses for this drug include cholestasis, gallbladder sludge, and mucoceles.
Ursodiol
Ursodeoxycholic acid
Two drugs used to treat hepatic encephalopathy
Lactulose
Neomycin (or amoxicillin, metronidazole)
Hepatic encephalopathy is seen with severe liver failure (>70% loss) and _____.
Portosystemic shunts
MOA: once reaching the colon, increases osmotic pressure drawing water into the bowel - laxative effect; metabolized by bacteria into acid metabolites; acidifies colonic contents; causes NH3 ammonia to migrate from blood into colon where it is trapped as NH4 ammonium and expelled with feces
Lactulose - nonabsorbable disaccharide
MOA: given orally has minimal systemic absorption; local effects in the GI tract to reduce the number of ammonia producing bacteria
Aminoglycoside antibiotic
- Neomycin