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Alimentary > Alimentary therapeutics > Flashcards

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
Q

Appetite stimulants

A

Ensure not to overlook underlying disease

Useful to help meet resting energy requirements

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26
Q

Two main appetite stimulants

A

Mirtazapine

Capromorelin

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27
Q

Mirtazapine

A

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

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28
Q

Capromorelin

A

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

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29
Q

Gastroprotectant categories

A

Acid secretory inhibitiors

Drugs which provide physical protection

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30
Q

What is the one anti-ulcer medication licensed for use in dogs and cats?

A

Cimetidine

(In horses omeprazole is licensed)

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31
Q

What drug is used for protection against non-steroidal induced ulcers or treatment after toxicity?

A

Misoprostol

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32
Q

What stimulates gastric acid secretion by parietal cells?

A

Anticipation

Stomach and SI stretch

Protein and amino acids

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33
Q

Pathway of gastric acid stimulation by parietal cells

A

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

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34
Q

Gastric mucosal protection

A

Epithelial tight junctions

Rapid epithelial repair

Surface mucus layer with bicarbone

Mucosal blood supply

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35
Q

Prostaglandins and gastric mucosa

A

Reduces acid secretion

Increase blood flow

Increase mucus secretion

Increase bicarbonate secretion

+/- increase epithelial cell turnover

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36
Q

Causes of gastric ulcers

A

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

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37
Q

Gastroduodenal ulcer treatment

A

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

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38
Q

Omeprazole

A

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

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39
Q

Omeprazole vs cimedine

A

O 10x more potent than C in inhibiting gastric acid secretion and has longer duration of activity

40
Q

What is the drug of choice with an actively bleeding ulcer in dog/cat?

A

Omeprazole

41
Q

Toxicity of omeprazole

A

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
Q

Cimetidine/ranitidine/famotidine

A

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
Q

Ranitidine vs cimetidine

A

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
Q

Dosing of cimetidine

A

Usually given orally 3x a day

Can give IV off label but must be slow to prevent hypotension and arrhythmias

45
Q

Dosing of ranitidine

A

Given IV or orally every 12 hours

Give slowly if IV

46
Q

Dosing of famotidine

A

Only available as oral tablets

47
Q

Sucralfate

A

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
Q

Doseing of sucralfate

A

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
Q

Bismuth salts

A

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
Q

Antacids

A

Drugs which neutralise gastric acid

Limited efficacy

Useful in gastritis and reflux oesophagitis

Neutralise HCl, bind bile acids, and reduce pepsin activity

51
Q

Misprostol

A

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
Q

Prokinetic drugs

A

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
Q

Causes of delayed gastric emptying

A

Infection

Inflammation

Ulcers

Recovery from gastric dilation-volvulus

May be secondary to metabolic/electrolyte disturbances, drugs, acute abdominal inflammation, acute stress.

54
Q

When are prokinetics contraindicated?

A

Obstructions

And dont use to delay decision to provide nutritional support

55
Q

Metoclopramide and ranitidine as prokinetics

A

Peripheral prokinetic activity - first line

Used for delayed gastric emptying in dogs and mega-colon in cats

56
Q

Metoclopramide

A

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
Q

Possible side effects of metoclopramide

A

Changes in mentation or other behavioural changes/movement disorders

May cause splanchnic vasoconstriction
- use in panreatitis controversial
- may reduce renal flow

58
Q

Contraindications for metoclopramide

A

Epilectic patient
Patient with CNS disease

59
Q

Normal gastric motility

A

Vagally mediated stretch during filling

Contractions mix/break food

Pyloric pump - propulsion, mixing, retropulsion

Stomach empty by 10-12 hrs

60
Q

3 phases of interdigestive motility

A
  1. motor quiesence
  2. irregular contractions
  3. migrating motor complex in the dog or giant contractions in the cat
61
Q

Reflexes for gastric protection

A

Distension causes gastro-oesophageal sphincter relaxation and pyloric contraction

Further distension leads to pyloric opening

62
Q

Delayed gastric emptying

A

Food vomited >10-12hrs after food

Usually no bile in vomit

63
Q

Cisapride

A

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
Q

Prucalopride

A

5HT4 agonist

Prokinetic in canine and feline colon

Appears to stimulate gastric empying in the dog

65
Q

Erythromycin

A

Macrolide antibiotic

Also has activity as GI pro-kinetic

Vomiting is a common side effect

Avoid use in liver disease

66
Q

Sildenafil

A

Muscle relaxant

Improves signs in dogs with congenital megaoesophagus

Relaxation of the lower oesophageal sphincter, improving passage of food

67
Q

Bilious vomiting syndrome

A

Common

Thought to result from a reflux of duodenal fluid into the gastric lumen, causing mucosal irritation

68
Q

Classic history of bilious vomiting syndrome

A

Vomit bile early morning

+/- eat grass

Otherwise well

Often nervous dog

69
Q

Treatment of bilious vomiting syndrome

A

Dietary modification

Frequent feeds or late evening meals
Gastroprotectants
Prokinetics

70
Q

Treatment of delayed gastric emptying

A

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
Q

Buscopan

A

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
Q

Drugs used in diarrhoea

A

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
Q

Parasympatholytics

A

E.g. propantheline

Paralyses the GI tract

Avoid:
- pre-dispose to paralytic ileus and clostridial overgrowth

74
Q

Opiates

A

E.g. Diphenoxylate, loperamide

Reduce motility of GI tract

Preferred

Increase segmental contractions

Anti-secretory

75
Q

Antibiotic use in diarrhoea

A

Overused

Should be avoided unless specific indication

Do not use in uncomplicated diarrhoea

76
Q

Indications for antibiotic use in diarrhoea

A

Parvo-viral enteritis

Signs of systemic involvement

G-ve septicaemia

Antibiotic responsive diarrhoea

granulomatous colitis in Boxers

77
Q

Possible problems from indiscriminate use of antibiotics in diarrhoea

A

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
Q

The gut microbiome

A

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
Q

Antibiotic-responsive diarrhoea

A

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
Q

Drug treatment for large intestinal diarrhoea

A

Salicylates - dogs only?

Steroids +/- other immunosuppressives

Probiotics/absorbents?

Metronidazole?
- ofetn used due to concern over slostidial infection but controversial

81
Q

Probiotics

A

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
Q

Pre-biotics

A

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
Q

Dietary fibre

A

Valuable in the treatment of colonic diseases

Plant polysaccharides and lignin resistant to hydrolysis by digestive enzymes

84
Q

Soluble fibre

A

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
Q

Insoluble fibre

A

Resistant to bacteral degradation and passes through unchanged

Stretches colon and encourages normal motility

86
Q

Contraindications and cautions with high fibre diets

A

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
Q

Categories of laxatives

A

Osmotic

Bulk forming

Emollients (stool softeners)

Lubricant

Stimulants

Motility stimulating

88
Q

Osmotic laxatives

A

Hypertonicity -> increase in faecal water

E.g. lactulose, polyethylene glycols, magnesium salts

89
Q

Bulk forming laxatives

A

Increase faecal bulk -> stimulate motility

E.g. cereal grains, wheat bran, and psyllium

90
Q

Emollients (stool softeners)

A

Increases admixture of fat and water to soften faeces

Generally mild effect

Avoid in dehydrated patients

E.g. Dioctyl sodium succinate (DSS), docusate

91
Q

Lubricant luxatives

A

Lubricate faecal surface

Generally not used PO due to limited efficacy and risk of aspiration pneumonia

E.g. liquid paraffin, mineral oil, glycerin

92
Q

Stimulant laxatives

A

Increase peristalsis

Contraindicated in obstruction

E.g. bisacodyl

93
Q

Motility stimulating laxatives

A

Increase peristalsis

Contraindicated in obstruction

E.g. cisapride

94
Q

Most commonly used laxatives

A

Lactulose

Polyethylene glycol

(Katalax - for hairballs)

95
Q

Most commonly used enemas

A

Micralax suppositories

Instillation of various aqeous solutions

Alimentary (22 decks)

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