Alimentary therapeutics Flashcards
Efferents involved in the vomiting reflex
Cranial nerves IX and X
Neural pathway for stimulating vomiting
Fro vomiting centre in lateral reticular formation of medulla
Afferents pass to vomiting centre in X (abdomen) and sympathetic nerves (abdomen), IX (pharynx), VIII (vestibular) and in nerves from the chemoreceptor trigger zone (CRTZ) and higher centres
Humoral pathway for stimulating vomiting
Stimulation of CRTZ by blood borne substances
CRTZ is in dorsal medulla and outside BBB
What are centrally acting anti-emetics?
Antagonists of neurotransmitters in CRTZ +/- vomiting centre
Examples of Centrally acting anti-emetics
Metoclopramide
Chlorpromazine
Ondansetron
Butorphanol
Metoclopramide
Dopamine antagonist
Serotonin antagonist
Chlorpromazine
Histamine, cholinergic, and adrenergic antagonist
Ondansetron
Serotonin antagonist
Used in man and dogs mainly for cisplatin associated emesis
Butorphanol
Opiate mixed agonist/antagonist
Neurotransmitters in CRTZ
Dopamine: dogs>cats
Histamine: dogs>cats
Noradrenaline: cats>dogs
Therapy for chemotherapy induced vomiting
Maropitant
Give 1hr before chemo
Continue for several days
Consider ondansetron if not effective
Therapy for travel sickness induced vomiting
Maropitant - effective and licensed for dogs
4x usual anti-emetic dose 2-10hrs before journey
Maropitant citrate
‘Cerenia’ ‘Prevomax’
NK1 (neurokinin-1) receptor antagonist
Strong central and peripheral anti-emetic activity
Very effective for cisplatin induced emesis
Duration of effect is approx 24hrs
Has an anti-nausea effect
Metabolised in liver so needs reduced doses in liver
Used successfully for motion sickness in dogs
Metoclopramide
‘Emeprid’ ‘Vomend’
GI pro-motility drug and a centrally acting antiemetic
Dopamine and serotonin antagonist in the CRTZ
Exerts its effects via serotonin agonism
Anti-emetic with ccentral action
Little activity on the colon
Side effects usually neurological because it crosses the BBB
- Significant depression or excitement
Contraindicated if there is a mechanical gastric outflow obstruction
Ondansetron
Potent serotonin antagonist
Acts on 5HT3 receptors in the CRTZ and peripherally on vagal nerve endings
Mainly indicated fot prevention and treatment of centrally induced emesis due to chemotherapeutic agents
Not effective for motion sickness
Side effects are rare (constipation, extra-pyramidal signs, hypotension)
Good efficacy but expensive
Cimetidine
Licensed for use in dogs but not cats
Symptomatic treatment for the reduction of vomiting associated with chronic gastritis in dogs
Not an anti-emetic but an acid secretory inhibitor
Phenothiazines
Occasionally used as anti-emetics
Role is very limited now
Unlicensed and have undesirable side effects
Blocks CRTZ at low doses, blocks emetic centre at high doses, block H1 receptors
Indications of emetics
Following ingestion of a known toxin and only if recent (within 30-60 mins)
Contraindications of emetics
If patient has ingested caustics, sharp items or petroleum products or if the patient has had recent abdominal surgery, if hernias are present, if there is any concern about the ability to protect the airway, or if the patient is in severe abdominal pain
Potent stimulator of emesis in cats
Xylazine
Potent stimulator of emesis in dogs
Apopmorphine (dopamine agonist)
Apomorphine
Drug of choice for emesis in dogs, do not use in cats
Stimulates CRTZ dopamine D2 receptors
Reflex can only be triggered once
Causes suppression of CNS (respiratory) in most cases
Effective and commonly used but expensive
Routes of administration of apopmorphine
Licensed solution available for S/C administration
Can also give IV, IM, or into conjunctival sac
Xylazine
Drug of choice for emesis in cats
Stimulation of CRTZ accompnied by alpha2 agonist mediated sedation, hypotension, and respiratory depression
Effective in around 40-75% of cats
Much less effective in dogs
Appetite stimulants
Ensure not to overlook underlying disease
Useful to help meet resting energy requirements
Two main appetite stimulants
Mirtazapine
Capromorelin
Mirtazapine
Likely involves antagonism of the 5HT2c receptor
Commonly used in cats
Main side effects are sedation and various behavioural changes
Can be used in patients with liver and renal disease but advised to use lower doses
Transdermal preparation licenced in cats
Capromorelin
Ghrelin receptor agonist for dogs and cats
Increase appetite and weight gain by binding the growth hormone secreatogogue receptor 1a in the pituitary gland
Relatively new but seems well tolerated with diarrhoea, vomiting, increased thirst, hypersalivation
Not yet licensed in the UK
Gastroprotectant categories
Acid secretory inhibitiors
Drugs which provide physical protection
What is the one anti-ulcer medication licensed for use in dogs and cats?
Cimetidine
(In horses omeprazole is licensed)
What drug is used for protection against non-steroidal induced ulcers or treatment after toxicity?
Misoprostol
What stimulates gastric acid secretion by parietal cells?
Anticipation
Stomach and SI stretch
Protein and amino acids
Pathway of gastric acid stimulation by parietal cells
Neural input to ACH receptors
Histamine receptors: paracrine input
Gastrin stimulates acid secretion directly from parietal cells and also causes histamine release
Somatostatin inhibits histamine release
Gastric mucosal protection
Epithelial tight junctions
Rapid epithelial repair
Surface mucus layer with bicarbone
Mucosal blood supply
Prostaglandins and gastric mucosa
Reduces acid secretion
Increase blood flow
Increase mucus secretion
Increase bicarbonate secretion
+/- increase epithelial cell turnover
Causes of gastric ulcers
Relatively common in dogs, horses, and ferrets
Usually due to accidental overdose or poisoning with NSAIDs
Or mast cell tumours
Helicobacter is not considered an important cause
Gastroduodenal ulcer treatment
Aggressive treatment vital
Treat underlying disease
Gastric acid secretory inhibitors
Sucralfate or other coating agent
+/- anti-dote if NSAID induced
Little and often low fat, low fibre, semiliquid diet
DO NOT STARVE
Omeprazole
Not licensed for use in dogs and cats
Potent gastric acid secretory inhibitor
Blocks the H+/K+ ATPase
Most effective drug at reducing acid secretion
Administered as a prodrug that is converted at low pH in parietal cell
Given orally