GI drugs Flashcards
What type of therapy should anti-emetics be considered as?
Symptomatic, NOT therapeutic (may encourage eating, minimise damage due to physical damage)
- always need to resolve the underlying problem
Give 3 situations where anti-emetic therapy would be contra-indicated
- GI infection: prolong infection esp bacterial
- GI obstruction: some anti-emetics ^motility -> perforation
- GI toxicity: antiemetics may prevent the patient from eliminating the toxin (though usually they have already eliminated in 1st couple of vomits by the time they present - at this stage you are treating the secondary inflammation and damage caused by the substance)
Give 6 inputs to the vomiting centre?
- CRTZ (area within brain with no BBB)
- higher CNS (smell, fear, pain)
- vestibular (motion sickness, inner ear infection)
- Peripheral receptors (gut esp duodenum - inflam, toxic damage, abdo organs, peritoneum)
- toxins
- nucleus tractus solitarius (integrating centre)
What is the vomiting centre?
series of nuclei in medulla
Where does the most common (first vet licensced) anti-emetic drug act?
Nucleus tractus solitarius NK1-Rs (final common pathway)
- Maropitant
How do cats and dogs differ in importance of receptors in emesis?
- D2-Rs in CRTZ more important in dogs
> apomorphine [not a morphine derivative] D2 ag is a potent EMETIC in the dog but not the cat.
> Metclopramide (DA-ag) more effective in dogs
> Histamine is a potent emetic in the dog but not the cat - A2-Rs in CRTZ more important in cats
> xylazine more potent emetic in cats (side effect of sedative_
> prochlorperazine (a2 blocker) more effective in cats
When are emetics indicated?
Poison ingestion (providing not caustic)
Do all animals have a vomiting centre?
NO
some may not have the anatomical features to vomit as well, separate reason
What is the “shock organ” in the cat v the dog? ie. how do severe allergic reactions manifest?
Cat: respiratory signs
Dog: liver -> GI signs, vomiting
Give 6 classes of anti-emetic drugs
- NK1 antagonists
- metoclopramide (multiple Rs)
- phenothiazines
- antihistamines
- 5HT3 antagonists
- anticholinergics (have issues)
What was the first anti-emetic to be licensed for vet use? What is its trade name? What is it indicated for?
Maropitant - Cerenia Indicated for > acute gastroenteritis > cytotoxic induced vomiting > motion sickness (higher dose required)
What is the mechanism of action of maropitan?
Selective antagonist of supbstance P at NK1-R
- final common pathway involved in activating vomiting reflex in CNS
- effective against stimulation from peripheral and central stimuli
What is the mechanism of action of metoclopramide?
- D2 antagonist
- 5HT3 antagonist
> Acts on CRTZ and peripheral receptors
Peripheral pro-cholinergic effect (^GI motility)
What is metoclopramide indicated for?
- Various emesis-inducing disorders which involve central/peripheral actiation of vomiting
- cancer chemotherapy (not as effective as maropitan)
- gastroesophageal reflux (endoscopy etc)
- decreased gastric emptying (inflam GI disorders, ulcers, neoplasia, autonomic neuropathy with diabetes mellitis, pyloric stenosis, postop gastric volvulus patients, hypokaleamia, abnormal gastric motility)
What is the action of the phenothiazines?
Antagonise
- a1 a2 (vomiting centre)
- D2 (CRTZ and peripheral Rs)
- H1 H2 (CRTZ)
- muscarinic cholinergic (CRTZ)
What does a1 antagonism cause as a side effect?
Dramatic blood pressure decrease
Give an example of a phenothiazine
Acepromazine (ACP) - sedative/tranq
What are phenothiazines indicated for use in?
Central or peripheral causes of vomiting BUT not vet registered so should use maropitan/metoclopramide
Give two examples of antihistamines and their main uses
Diphenhydrinate (Dramamine) - motion sickness [possible because CRTZ has links with vestibular system]
Diphenhydramine (Benedryl) - allergy
In which species are antihistamines effective against motion sickness? Why? Are they used on label?
Dogs because histamine Rs in CRTZ are involved in vomiting. Used off label.
What are ondansetron (zofran) and dolasetron (anzemet) examples of? What is their potency like?
5HT3 antagonists (CRTZ and periphery) Very powerful - much more effective than metoclopramide, may be better than maropitan
What are 5HT3 antagonists indicated for use in?
- usually to control cytotoxic drug induced emesis eg. cisplatin
NB: EXPENSIVE!
Give 4 examples of anticholinergics
- atropine [used to be used as premed]
- butylscopolamine (hyoscine)
- propantheline
- isopropamide
What is the mechanism of action of anticholinergics? When are they indicated?
M1-R ant in vestibular apparatus -> good for motion sickness BUT also have effects on M2 -> potential for delayed gastric emptying and ileus due to v gut motility SO DO NOT USE AS AN ANTIEMETIC
Is gastric ulceration a disease?
NO it is a clinical sign resulting from 1* or 2*(renal/hepatic/pancreatitis/gastrinoma) GI disease
> underlying problem always needs to be treated
When are anti-ulcer drugs indicated?
When ulcers are present OR as standard vomiting therapy protocol even if ulcers are not present
Which anti-ulcer drug is only licensed in horses?
Omeprazole (Gastroguard)
Give 5 examples of anti-ulcer drugs
- Nonsystemic antacids
- H2 receptor antagonists
- Sucralfate
- Misoprostol
- Omeprazole
Why are non-systemic antacids used regularly? What is the downside?
- cheap
> oral administration difficult with V+
> frequent dosing necesssary -> poor owner compliance
> treat but DO NOT PREVENT
Which histamine receptors are involved in allergy? What is the function of other H-Rs?
H1 allergy
H2 gastric acid secretion (only found in gut)
Give examples of H2-R ants. Which are licensed for veterinary use?
- Cimetidine (Zitac) - only registered recently so others stil in wide use
- Ranitidine (Zantac)
- Famotidine (Pepcid)
What are H2-R ants effective in treating?
- gastric ulceration caused by variety of disorders including NSAIDs and uraemia
What is the potency of ranitidine, cimetidine and famotidine? What does this mean? How should the drug choice be made?
> The potencies differ, but they are equally effective at promoting ulcer healing (just require different dosages)
- choose based on cost, client convenience, concurrent drug therapy and drug cascade (usually cimetidine wins!)
Is sucralfate used on label? How is it administered?
No BUT very safe!
Enterally
What is sucralfate indicated for use in? How effective is it?
- Symptomatic treatment of gastric ulceration from variety of causes
- In humans = equally effective as antacids or H2 antagonists (though these can be given IV -> Better?)
What is misoprostol? What is its trade name?
- Trade name: cytotec
- Synthetic PGE1
What is misoprostol indicated for use in? What is the data on it like?
Management or prevention of NSAID toxicity - replenishes PGEs lost
- in humans as effective/more effective than H2 antagonists
Why should care be taken when prescribing misoprostol?
It is the morning after pill -> causes abortion
What is the mechanism of action of omeprazole?
Proton pump inhibitor
What is the efficacy of omeprazole (based on human studies)
Slightly greater efficacy than H2 antagonists
- But more expensive
What is omeprazole often used for? Is this on label?
- Increasingly commonly used
- Ulcers/oesophagitis refractory to other anti-ulcer meds
- ulcers associated with gastinomas or mast cell tumour
> off label! (And rational for using it usually quite weak)
How can electrolyte solutions assist in ulcer healing? Hoe effective are they?
- enhance fluid absorption from gut (glucose and aminoacetic acid), directly linked with sodium and water movement
- not much evidence for them
- but do not harm
- gives owners something to do!
> may v incidence of AB prescription for vomiting which is GOOD!
How do opioids function to affect GI? What are these indicated for use in?
- ^ segmental contractions (keep food in gut for longer)
- Prolong intestinal transit time
- Allow greater time for fluid absorption
- v feacal output
- relieve abdominal pain and tenesmus
> rarely used as acute diarrhoea is self limiting (with appropriate symptomatic treatment) and chronic diarrhoea requires a definitive diagnosis and does not respond to symptomatic therapy
How do anticholinergics affect the gut? What are these indicated for use in?
> Decrease peristalsis
- This is BAD - little use in SA diarrhoea management as most animals have hyPOmotile gut anyway. May lead to v gastric emptying and ileus.
- BUT indicated for use in spasmodic colic in horses
- or short term relief of tenesmus associated with large bowel inflamatory disease
What is the evidence for/against absorbants and protectants? Are these advocated?
- little evidence for them (no evidence they v GI fluid/electrolyte loss)
- Kaolin may ^ feacal Na loss
- Messy to administer
> gives owner something to do!!
Give an example of an adsorbant/protectant. What is its mechanism of action? Which species should avoid this?
Bismuth salicylate - may inhibit action of PGs - may v GI secretion in acute secretory diarrhoea - proven efficacy is questionable > avoid in cats
Give an example of a neutroceutical. Has efficacy of this product been demonstrated?
Probiotics - efficacy demonstrated in humans - little evidence in pets - but evidence of activity at cellular level in gut > does no harm > gives owner something to do!!
