SA GI Drugs Flashcards
What is the goal of antiemetic therapy?
Why should it be used with caution
As a symptomatic therapy - treating the clinical signs, not the underlying problem.
COULD MASK A SERIOUS PROBLEM
What receptors associated with eyes is are found in the nucleus tractus solitarius?
NK1
Where are serotonin receptors found in relation to emesis?
Vomiting centre in the medulla,
Chemoreceptor trigger zone
Vomiting centre
What are the classes of antiemetic drugs?
NK1 antagonists Metaclopramide Phenothiazines Antihistamines (motion sickness) Serotonin antagonists
Where are H1 and H2 histamine receptors found in relation to emesis?
The CRTZ
What is the most effective vet licensed anti-emetic for dogs and cats?
Maropitant (Cerenia)
How does maropitant work?
NK1 receptor antagonist
Inhibits nucleus tractus solitarius
Therefore inhibits final common pathway involved in activating the vomiting reflex in the CNS.
Effective against emesis induced by both peripheral and central stimuli
In what clinical context may maropitant be used?
Acute gastroenteritis
Cytotoxic-induced vomiting
Motion sickness (higher dose required)
Also:
Pancreatitis, liver disease etc which will RESOLVE
What is a limitation of maropitant?
Why?
Effective antiemetic BUT
NOT VERY EFFECTIVE ANTI-NAUSEA DRUG
Nausea has a different mechanism - therefore animal will stop vomiting but my still not want to eat
What is the ligand for the NK1 receptor?
Substance P
Why are the oral and injectable doses of maropitant different?
Oral dose is much higher than injectable dose due to significant first pass metabolism in LIVER
This reduces the amount of blood that reaches the blood stream.
When should you NOT give maropitant?
If GI obstruction is suspected
What would you do if vomiting returned after the first course of maropitant?
INVESTIGATE THE CAUSE
Don’t repeat unless you know what is causing the vomiting
Where are D2 receptors found in relation to emesis?
The chemoreceptor tigger zone
Peripheral receptors
How does metaclopramide work?
Antagonises d2 dopaminergic receptors
Antagonises serotonin receptors
Has a peripheral PRO-cholinergic effect
How can the peripheral pro cholinergic effect of metoclopramide be beneficial?
Increases GIT motility
When is metoclopramide indicated?
Various emesis inducing disorders which involve central or peripheral activation of vomiting
Cancer chemotherapy
Gastroesophageal Reflux
Decreased gastric emptying
When might you choose metaclopramide over maropitant ?
Where a patient has decreased gut motility
When there is decreased gastric emptying
What could cause decreased gastric emptying?
Inflammatory GI disorders gastric ulcers gastric neoplasia Autonomic neuropathy (diabetes mellitus) Pyloric stenosis(thickening) Postoperative gastric volvulus patient Hypokalaemia Abnormal gastric motility
Where are alpha adrenergic receptors found in relation to emesis?
The vomiting centre in the medulla
Where are muscarinic cholinergic receptors found in relation to emesis?
In the vestibular system
CRTZ
How do Phenothiazines act?
Antagonists of:
alpha 1+2 adrenergic receptors
D2 dopaminergic receptors
H1 and H2 histaminergic receptors
Muscarinic cholinergic receptors
What ‘areas’ of emesis do phenothiazines effect?
Vestibular system (M2) Vomiting centre (a2) CRTZ (D2,M1, H1+2) Peripheral receptors (D2)
What are phenothiazines indicated for?
Why might another drug be favoured?
Any central or peripheral cause of vomiting
NOT licensed for veterinary use in the UK
What MUST you do when giving off label drugs to patients?
Get informed consent from owner
Are antihistamines effective for all small animals?
Why?
Antihistamines effective for DOGS not cats.
Histamine receptors in CRTZ involved in motion sickness in dogs
What are the most effective anti-emetic and anti-nausea drugs?
Serotonin antagonists
E.g. Dolasetron and ondansatron (Zofran)
Efficacy as antiemetic orders of magnitude above metaclopramide !!!!!
When are serotonin antagonists indicated?
To control cytotoxic drug induced emesis (chemo e.g. cisplatin)
What is the typical combination/progression of antiemetics in practice?
Usually start with maropitant then progress onto ODANSATRON (serotonin antagonist)
Why are anti cholinergics NOT used as antiemetics?
affect peripheral M2 receptors resulting in potential for delayed gastric emptying and ileus
Why would anti cholinergics be effective against motion sickness (even though there would be side effects)?
Antagonism of M1 receptors in vestibular apparatus
What is the species difference in the importance of dopamine receptors in emesis?
D2 receptors in CRTZ mor important in DOG
How is the species difference in the difference in the importance of D2 receptors clinically relevant?
APOMORPHINE - a D2 agonist, is a potent EMETIC agent in the DOG but not the cat
What receptors may be more important in cat emesis?
How is this clinically relevant
Alpha 2 adrenergic receptors
Xylazine more potent emetic in cats
Prochloperazine (a2 blocker) might be more useful that’s metaclopramide (dopamine antagonist)
What is the species difference in cytotoxic drug induced emesis?
In cats - mediated by serotonin receptors in CRTZ
In dogs - visceral and vagal afferent serotonin receptors
What are some anti-ulcer drugs ?
Nonsystemic antacids H2 receptor antagonists Sucralfate Misoprostol Omeprazol
How does omeprazole act as an anti-ulcer drug?
Blocks proton pump for HCl production
Licensed for horses, not cats or dogs (but increasingly being used off licence)
How does sucralfate act as an anti-ulcer drug?
When is it indicated?
Sticks to lesion like a plaster
Symptomatic treatment of gastric ulcers - can be useful for chronic ulcers
When are anti-ulcer drugs indicated?
Treatment of confirmed gastric ulceration
Management of diseases where gastric ulceration is a risk
To prevent secondary oesophagitis in severe vomiting
Are anti-ulcer drugs indicated for every case of vomiting?
No
Gastritis does not mean gastric ulceration
(Ulceration goes through to the mucosa)
Discuss the pros and cons of non-systemic antacids.
Inexpensive
Oral administration - problem for vomiting patients
Frequent administration required - poor owner compliance
Doesn’t treat problem, only symptoms
Describe the action of Cimetidine, ranitidine and famotidine
H2 receptor antagonists - prevents gastric acid production
Effective in TREATING gastric ulcers
When are H2 receptor antagonists indicated?
NSAIDs, uraemia
Discuss the pros and cons of Cimetidine (Zitac)?
Only veterinary licensed product
Has the highest frequency of dosing therefore limitied client compliance
What would be the best H2 receptor antagonist to use?
Ranitidine (Zantac)
Also has prokinetic activity (especially in upper GI tract)
Less frequent dosing required for efficacy - enough justification to use off label
When might electrolyte solutions be indicated?
Large animal - calves with diarrhoea
Small animal - not so much - gives owner something to do
When might motility enhancing drugs be indicated?
Rabbits - ileus
Cats - megacolon
What are the key motility enhancing drugs (in order of efficacy)?
Cisapride
Ranitidine
Metaclopramide
Why might ranitidine be used over cisapride?
Reduced availability of cisapride
What is the effect of opioids on gut transit?
PROLONG intestinal transit time
Increase segmental contractions in gut, fluid stays in for longer to be absorbed
HARDLY USED
When might opioids be indicated?
RARELY
More important to treat underlying cause
When might anticholinergics be indicated?
Used in management of spasmodic colic in horses
Why are drugs which reduce gut motility rarely indicated?
Most patients have hypomotile rather than hypermotile gut
Reduction in peristalsis can result in delayed gastric emptying and ileus
May be justified for short term relief from pain associated with large bowel inflammatory disease
When might probiotics be indicated?
Little confirmed efficacy BUT
Do no harm and give owners something to do
STOPS PRESSURE TO PRESCRIBE ANTIBIOTICS for acute self resolving diarrhoea
When MIGHT antibiotics be indicated for GI disease?
IBD - metronidazole
Symptomatic treatment of colitis - sulphasalazine
Histiocytic colitis (in boxers and related breeds) - fluoroquinolones
Vomiting - ONLY if infectious cause suspected
