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Alimentary therapeutics Flashcards

1
Q

Efferents involved in the vomiting reflex

A

Cranial nerves IX and X

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2
Q

Neural pathway for stimulating vomiting

A

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

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3
Q

Humoral pathway for stimulating vomiting

A

Stimulation of CRTZ by blood borne substances

CRTZ is in dorsal medulla and outside BBB

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4
Q

What are centrally acting anti-emetics?

A

Antagonists of neurotransmitters in CRTZ +/- vomiting centre

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5
Q

Examples of Centrally acting anti-emetics

A

Metoclopramide

Chlorpromazine

Ondansetron

Butorphanol

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6
Q

Metoclopramide

A

Dopamine antagonist
Serotonin antagonist

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7
Q

Chlorpromazine

A

Histamine, cholinergic, and adrenergic antagonist

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8
Q

Ondansetron

A

Serotonin antagonist

Used in man and dogs mainly for cisplatin associated emesis

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9
Q

Butorphanol

A

Opiate mixed agonist/antagonist

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10
Q

Neurotransmitters in CRTZ

A

Dopamine: dogs>cats

Histamine: dogs>cats

Noradrenaline: cats>dogs

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11
Q

Therapy for chemotherapy induced vomiting

A

Maropitant

Give 1hr before chemo

Continue for several days

Consider ondansetron if not effective

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12
Q

Therapy for travel sickness induced vomiting

A

Maropitant - effective and licensed for dogs

4x usual anti-emetic dose 2-10hrs before journey

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13
Q

Maropitant citrate

A

‘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

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14
Q

Metoclopramide

A

‘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

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15
Q

Ondansetron

A

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

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16
Q

Cimetidine

A

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

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17
Q

Phenothiazines

A

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

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18
Q

Indications of emetics

A

Following ingestion of a known toxin and only if recent (within 30-60 mins)

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19
Q

Contraindications of emetics

A

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

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20
Q

Potent stimulator of emesis in cats

A

Xylazine

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21
Q

Potent stimulator of emesis in dogs

A

Apopmorphine (dopamine agonist)

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22
Q

Apomorphine

A

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

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23
Q

Routes of administration of apopmorphine

A

Licensed solution available for S/C administration

Can also give IV, IM, or into conjunctival sac

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24
Q

Xylazine

A

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

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25
Appetite stimulants
Ensure not to overlook underlying disease Useful to help meet resting energy requirements
26
Two main appetite stimulants
Mirtazapine Capromorelin
27
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
28
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
29
Gastroprotectant categories
Acid secretory inhibitiors Drugs which provide physical protection
30
What is the one anti-ulcer medication licensed for use in dogs and cats?
Cimetidine (In horses omeprazole is licensed)
31
What drug is used for protection against non-steroidal induced ulcers or treatment after toxicity?
Misoprostol
32
What stimulates gastric acid secretion by parietal cells?
Anticipation Stomach and SI stretch Protein and amino acids
33
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
34
Gastric mucosal protection
Epithelial tight junctions Rapid epithelial repair Surface mucus layer with bicarbone Mucosal blood supply
35
Prostaglandins and gastric mucosa
Reduces acid secretion Increase blood flow Increase mucus secretion Increase bicarbonate secretion +/- increase epithelial cell turnover
36
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
37
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
38
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
39
Omeprazole vs cimedine
O 10x more potent than C in inhibiting gastric acid secretion and has longer duration of activity
40
What is the drug of choice with an actively bleeding ulcer in dog/cat?
Omeprazole
41
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
42
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
43
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
44
Dosing of cimetidine
Usually given orally 3x a day Can give IV off label but must be slow to prevent hypotension and arrhythmias
45
Dosing of ranitidine
Given IV or orally every 12 hours Give slowly if IV
46
Dosing of famotidine
Only available as oral tablets
47
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
48
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
49
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
50
Antacids
Drugs which neutralise gastric acid Limited efficacy Useful in gastritis and reflux oesophagitis Neutralise HCl, bind bile acids, and reduce pepsin activity
51
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
52
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
53
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.
54
When are prokinetics contraindicated?
Obstructions And dont use to delay decision to provide nutritional support
55
Metoclopramide and ranitidine as prokinetics
Peripheral prokinetic activity - first line Used for delayed gastric emptying in dogs and mega-colon in cats
56
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
57
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
58
Contraindications for metoclopramide
Epilectic patient Patient with CNS disease
59
Normal gastric motility
Vagally mediated stretch during filling Contractions mix/break food Pyloric pump - propulsion, mixing, retropulsion Stomach empty by 10-12 hrs
60
3 phases of interdigestive motility
1. motor quiesence 2. irregular contractions 3. migrating motor complex in the dog or giant contractions in the cat
61
Reflexes for gastric protection
Distension causes gastro-oesophageal sphincter relaxation and pyloric contraction Further distension leads to pyloric opening
62
Delayed gastric emptying
Food vomited >10-12hrs after food Usually no bile in vomit
63
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
64
Prucalopride
5HT4 agonist Prokinetic in canine and feline colon Appears to stimulate gastric empying in the dog
65
Erythromycin
Macrolide antibiotic Also has activity as GI pro-kinetic Vomiting is a common side effect Avoid use in liver disease
66
Sildenafil
Muscle relaxant Improves signs in dogs with congenital megaoesophagus Relaxation of the lower oesophageal sphincter, improving passage of food
67
Bilious vomiting syndrome
Common Thought to result from a reflux of duodenal fluid into the gastric lumen, causing mucosal irritation
68
Classic history of bilious vomiting syndrome
Vomit bile early morning +/- eat grass Otherwise well Often nervous dog
69
Treatment of bilious vomiting syndrome
Dietary modification Frequent feeds or late evening meals Gastroprotectants Prokinetics
70
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
71
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
72
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
73
Parasympatholytics
E.g. propantheline Paralyses the GI tract Avoid: - pre-dispose to paralytic ileus and clostridial overgrowth
74
Opiates
E.g. Diphenoxylate, loperamide Reduce motility of GI tract Preferred Increase segmental contractions Anti-secretory
75
Antibiotic use in diarrhoea
Overused Should be avoided unless specific indication Do not use in uncomplicated diarrhoea
76
Indications for antibiotic use in diarrhoea
Parvo-viral enteritis Signs of systemic involvement G-ve septicaemia Antibiotic responsive diarrhoea granulomatous colitis in Boxers
77
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
78
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
79
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
80
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
81
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
82
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
83
Dietary fibre
Valuable in the treatment of colonic diseases Plant polysaccharides and lignin resistant to hydrolysis by digestive enzymes
84
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
85
Insoluble fibre
Resistant to bacteral degradation and passes through unchanged Stretches colon and encourages normal motility
86
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
87
Categories of laxatives
Osmotic Bulk forming Emollients (stool softeners) Lubricant Stimulants Motility stimulating
88
Osmotic laxatives
Hypertonicity -> increase in faecal water E.g. lactulose, polyethylene glycols, magnesium salts
89
Bulk forming laxatives
Increase faecal bulk -> stimulate motility E.g. cereal grains, wheat bran, and psyllium
90
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
91
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
92
Stimulant laxatives
Increase peristalsis Contraindicated in obstruction E.g. bisacodyl
93
Motility stimulating laxatives
Increase peristalsis Contraindicated in obstruction E.g. cisapride
94
Most commonly used laxatives
Lactulose Polyethylene glycol (Katalax - for hairballs)
95
Most commonly used enemas
Micralax suppositories Instillation of various aqeous solutions

SA Alimentary (37 decks)

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