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
Omeprazole vs cimedine
O 10x more potent than C in inhibiting gastric acid secretion and has longer duration of activity
What is the drug of choice with an actively bleeding ulcer in dog/cat?
Omeprazole
Toxicity of omeprazole
Well tolerated acutely
Some P450 enzyme inhibition
Dose for limited time only
Chronic dosing could cause rebound increase in gastrin with subsequent gastric mucosal hyperplasia
Cimetidine/ranitidine/famotidine
H2 blockers (competitive, reversible)
Cimetidine licensed for use in dogs so should be picked
H2 blockers are less effective at reducing gastric pH than proton pump inhibitors
Ranitidine vs cimetidine
Ranitidine good for vomiting cats - prokinetic
R has longer half life in dogs so only needs to be dosed twice a day
R has less of an effect on the cytochrome P450 system so would be a wiser choice in dogs
C crosses into the CSF
C should be considered first as it is licensed but not good for patients with liver disease
Dosing of cimetidine
Usually given orally 3x a day
Can give IV off label but must be slow to prevent hypotension and arrhythmias
Dosing of ranitidine
Given IV or orally every 12 hours
Give slowly if IV
Dosing of famotidine
Only available as oral tablets
Sucralfate
Complex of aluminium hydroxide and sulphated sucrose
Useful in gastroduodenal ulceration and oesophagitis
Adheres to ulcer base and barrier to acid and enzymes
Absorbs refluxed bile acids
Stimulates PG synthesis
Stimulates epithelial repair
Doseing of sucralfate
Use liquid form if treating oesophagitis
Tablet may not dissolve effectively in dogs so best crushed
Can be given at the same time as gastric secretory inhibitors
Bismuth salts
Coat the mucosa
Peptobismol has been used in cats and dogs as part of triple therapy for helicobacter
Can be used for oesophagitis as a replacement for sucralfate
Antacids
Drugs which neutralise gastric acid
Limited efficacy
Useful in gastritis and reflux oesophagitis
Neutralise HCl, bind bile acids, and reduce pepsin activity
Misprostol
Prostaglandin E1 analogue
Used to prevent and heal NSAID induced gastric +/- duodenal ulceration
Increases gastric mucus and bicarbonate secretion and blood flow and decreases gastric acid secretion
Also stabilises gastric mucosal mast cells
NB: abortogenic
Prokinetic drugs
Generally work most effectvely at the beginning and of the GI tract due to the greater importance of the intrinsic nervous system
Used to enhance gastric emptying and to encourage normal colonic motility - esp cats with megacolon
Causes of delayed gastric emptying
Infection
Inflammation
Ulcers
Recovery from gastric dilation-volvulus
May be secondary to metabolic/electrolyte disturbances, drugs, acute abdominal inflammation, acute stress.
When are prokinetics contraindicated?
Obstructions
And dont use to delay decision to provide nutritional support
Metoclopramide and ranitidine as prokinetics
Peripheral prokinetic activity - first line
Used for delayed gastric emptying in dogs and mega-colon in cats
Metoclopramide
Weak prokinetic activity via serotonin (5-HT4) agonism and Dopamine (D2) agonism
Best as coordinating gastro-duodenal motility
Useful anti-emetic
Useful fot bilious vomiting syndrome in dogs
Generally well tolerated
Possible side effects of metoclopramide
Changes in mentation or other behavioural changes/movement disorders
May cause splanchnic vasoconstriction
- use in panreatitis controversial
- may reduce renal flow
Contraindications for metoclopramide
Epilectic patient
Patient with CNS disease
Normal gastric motility
Vagally mediated stretch during filling
Contractions mix/break food
Pyloric pump - propulsion, mixing, retropulsion
Stomach empty by 10-12 hrs
3 phases of interdigestive motility
- motor quiesence
- irregular contractions
- migrating motor complex in the dog or giant contractions in the cat
Reflexes for gastric protection
Distension causes gastro-oesophageal sphincter relaxation and pyloric contraction
Further distension leads to pyloric opening
Delayed gastric emptying
Food vomited >10-12hrs after food
Usually no bile in vomit
Cisapride
5-HT4 agonist
Promotes acetylcholine release via GI serotinergic agonism
prokinetic agen for delayed gastric emptying in dogs and in the feline colon
Not licensed for dogs and cats
Active throughout whole gut
no central action so no neuro side effects
Prucalopride
5HT4 agonist
Prokinetic in canine and feline colon
Appears to stimulate gastric empying in the dog
Erythromycin
Macrolide antibiotic
Also has activity as GI pro-kinetic
Vomiting is a common side effect
Avoid use in liver disease
Sildenafil
Muscle relaxant
Improves signs in dogs with congenital megaoesophagus
Relaxation of the lower oesophageal sphincter, improving passage of food
Bilious vomiting syndrome
Common
Thought to result from a reflux of duodenal fluid into the gastric lumen, causing mucosal irritation
Classic history of bilious vomiting syndrome
Vomit bile early morning
+/- eat grass
Otherwise well
Often nervous dog
Treatment of bilious vomiting syndrome
Dietary modification
Frequent feeds or late evening meals
Gastroprotectants
Prokinetics
Treatment of delayed gastric emptying
Treat underlying cause if possible
Little and often low fat, low fibre, liquid food may be enough
Pro-kinetic agent
- metoclopramide
- cisapride
- ranitidine
- erythromycin
Buscopan
Anti-spasmodic
Butylscopolamine bromide (hyoscine)
Licensed in dogs, horses, cattle for IV/IM administration
ACh muscarinic M1 receptor antagonist
Similar to atropine
Poorly absorbed after oral administration
Licensed for treatment of colic, GI, and urinary spasm, gastroenteritis
Very rarely usedin dogs and cats
Drugs used in diarrhoea
Anti-diarrhoeal drugs have limited use in SAs
Shouldn’t be suppressed with motility modifiers (parasympatholytics and opiates)
Pro-biotics or pre-biotics and absorbents are widely used and generally harmless
Parasympatholytics
E.g. propantheline
Paralyses the GI tract
Avoid:
- pre-dispose to paralytic ileus and clostridial overgrowth
Opiates
E.g. Diphenoxylate, loperamide
Reduce motility of GI tract
Preferred
Increase segmental contractions
Anti-secretory
Antibiotic use in diarrhoea
Overused
Should be avoided unless specific indication
Do not use in uncomplicated diarrhoea
Indications for antibiotic use in diarrhoea
Parvo-viral enteritis
Signs of systemic involvement
G-ve septicaemia
Antibiotic responsive diarrhoea
granulomatous colitis in Boxers
Possible problems from indiscriminate use of antibiotics in diarrhoea
Suppression of normal bowel flora
Use with salmonella may prolong carrier state
Significant GI side effects
Interferes with action of pancreatic lipase and reduced bile acid resporption
The gut microbiome
Small intestinal bacteria - relatively fewer numbers but stable
Large intestine - large population of bacteria, more anaerobes, a mini rumen
Important for gut health
Important for self-tolerance - probably have a role in the pathogenesis of IBD
Antibiotic-responsive diarrhoea
Primary (e.g. young GSDs with mucosal immunodeficiency) or secodnary (e.g. to EPI)
May cause increased folate and low B12 but not sensitive or specific
Based on response to exclusion of other causes and definitive response to antibiosis (4-6 week trial of metronidazole, tylosin, oxytetracycline)
May relapse following discontinuation
Drug treatment for large intestinal diarrhoea
Salicylates - dogs only?
Steroids +/- other immunosuppressives
Probiotics/absorbents?
Metronidazole?
- ofetn used due to concern over slostidial infection but controversial
Probiotics
Diarrhoea is associated with a change in SI microflora with a decrease in lactobacillus spp and an increase in bacteroides and enterobacteria
Limited evidence
Pre-biotics may have a part to play
Pre-biotics
Soluble fibre suorces e.g. fructo-oligosaccharides
Act as a food source for bacteria and may encourage the growth of more beneficial small intestinal bacteria
Dietary fibre
Valuable in the treatment of colonic diseases
Plant polysaccharides and lignin resistant to hydrolysis by digestive enzymes
Soluble fibre
Fermented by large intestinal bacteria to short chain fatty acids (SCFAs)
Butyrate provides 50% of calorie requirements for colonocytes
SCFAs lower colonic pH, promoting beneficial bacteria
Binds water
Binds bile acids
Insoluble fibre
Resistant to bacteral degradation and passes through unchanged
Stretches colon and encourages normal motility
Contraindications and cautions with high fibre diets
SI diarrhoea as impairs nutrient absorption and brush border enzyme activity
Pancreatic disease (EPI and pancreatitis) - interferes with pancreatic enzyme function and stretch stomach
Gastritis - delays gastric emptying
Feed with plenty of fluids
Binds minerals so potential for deficiency
Categories of laxatives
Osmotic
Bulk forming
Emollients (stool softeners)
Lubricant
Stimulants
Motility stimulating
Osmotic laxatives
Hypertonicity -> increase in faecal water
E.g. lactulose, polyethylene glycols, magnesium salts
Bulk forming laxatives
Increase faecal bulk -> stimulate motility
E.g. cereal grains, wheat bran, and psyllium
Emollients (stool softeners)
Increases admixture of fat and water to soften faeces
Generally mild effect
Avoid in dehydrated patients
E.g. Dioctyl sodium succinate (DSS), docusate
Lubricant luxatives
Lubricate faecal surface
Generally not used PO due to limited efficacy and risk of aspiration pneumonia
E.g. liquid paraffin, mineral oil, glycerin
Stimulant laxatives
Increase peristalsis
Contraindicated in obstruction
E.g. bisacodyl
Motility stimulating laxatives
Increase peristalsis
Contraindicated in obstruction
E.g. cisapride
Most commonly used laxatives
Lactulose
Polyethylene glycol
(Katalax - for hairballs)
Most commonly used enemas
Micralax suppositories
Instillation of various aqeous solutions
