Gastro-Intestinal Pharmacology Flashcards
What are the different ways for non-specific GI treatment?
Correction of fluids/electrolyte imbalance Resting GI tract Nutritional support Diet modification Pain management
How can electrolyte imbalance occur and how can it be treated?
Severe/chronic vomiting leads to loss of H+ and causes metabolic alkalosis
Obstruction of pylorus leads to loss of HCL into stomach lumen
Treated with parenteral fluid therapy
Why does the GI tract sometimes need to be rested and why?
Reduces gastric secretions for increased time for mucosal healing/enterocyte regeneration
Will sort out most dietary upset disorders
How can a diet be modified?
Bland diet- chicken, lamb and rice, pasta- easy digestion, limits fat
Lactose free diet- damage to mucosal lining results in decrease in lactase
Insoluble fibre- absorbs water, normalises motility for constipation, chronic diarrhoea and colitis
How can pain be treated in the GI tract?
Opioids- morphine, butorphanol- inhibit nociception at spinal or CNS level
NSAIDS- fluxin, dipyrone, phenylbutazone- treatment of colic in horses- can cause gastric ulceration in Small animals
Sedatives- xylazine, detomidine- sedation and alleviation of visceral pain in colic
Anti-spasmodics- hyoscine- inhibits M1 muscarinic acetyl choline receptors in GI tract resulting in smooth muscle relaxation
What is the function of antacids?
To inhibit acid secretion, neutralise existing acids and/or coat duodenal mucosa
What are the three different mechanisms of antacids?
Acid secretion inhibitors
Locally- acting antacids
Gastric protectives
What are the modes of actions of acid secretion inhibitors and examples?
Histamine blockers- cimetidine, ranitidine- blocks H2 stimulation of proton pump
Proton pump inhibitor- omeprazole- irreversibly binds to H+/K+ATPase pump
What are examples of locally acting antacids and how do they work?
Aluminium or magnesium salts
Neutralise luminal acid an inhibit pepsin cleavage, protects mucosa, acts as adsorbent and stimulate prostaglandins
What is an example of gastric protectives and how does it work?
Sucralfate- binds to ulcerated protein protecting from acid/pepsin
How do emetics work?
vomited triggered by vomiting centre
What are the different actions emetics can take?
Centrally or peripherally stimulated:
Chemoreceptor trigger zone via dopaminergic
Chemoreceptor tigger zone and vomiting centre via substance P binding to neurokinin 1 receptor
GI tract via vagal/sympathetic afferent pathways
Vestibular apparatus via cholinergic/histaminergic afferent pathways
Which species lack a vomiting reflex?
Horses, Ruminants, Rodents, Rabbits
When are emetics used?
After ingestion of something toxic or prior to general anaesthesia
What is an example of centrally and peripherally acting emetics?
Centrally- apomorphine
Peripherally- NaCl, Bicarb of soda
Why are anti-emetics used?
Prolonged vomiting leads to electrolyte/acid-base imbalances and dehydration
What are the different types of anti-emetics?
Anti-histamines
Anti-cholinergics
Anti-dopaminergic agents
Neurokinin-1 antagonists
How do anti-histamines and anti-cholinergics act as anti-emetics and name examples?
Anti-histamines:
Block histaminergic and cholinergic afferent pathways from vestibular organs to vomiting centre
Diphenhydramine, promethazine
Anti-cholinergics:
Block cholinergic afferent pathways from GI tract to vomiting centre
Propantheline
What are two examples of anti-doparminergic agents and what are their modes of action?
Phenothiazines- acepromazine, prochlorperazine
Block dopamine receptors in chemo-receptor trigger-zone
Metoclopramide- blocks dopamine receptors in CTZ also stimulates stomach/duodenal motility
How does neurokinin-1 prevent emesis?
Maropitant binds to NK1 receptor in CTZ and blocks binding of substance P
What are laxatives/cathartics used for?
Relief of acute non-dietary constipation
Removal of toxic ingestants
Prevention of tenesmus
Evacuation of bowel prior to surgery/radiography
What do osmotic cathartics and how?
Osmotic cathartics- lactulose, magnesium sulphate- non-absorbable so retain water, lactulose metabolised by colonic bacteria into organic acids which increase osmotic pressure
How do irritant cathartics work and what is an example?
Castor oil- stimulates peristalsis and reduce fluid absorption
Name a bulk laxative and explain how it works?
Ispaghula, sterculia
Contain hydrophilic colloids that absorb water and increase ingesta bulk to stimulate peristalsis
How do surfactants and lubricants work as laxatives?
Lubricants- liquid paraffin- lubricate and soften faeces
Surfactants- docusate- Anionic surfactant that acts in large bowel by hydrating and softening faeces by an emulsifying action
How is diarrhoea treated symptomatically?
Oral rehydration therapy
Protectants/adsorbents
Opiates
Anti-cholinergic agents
How is oral rehydration achieved?
Glucose/amino acids to enhance water absorption via glucose/amino acid co-transporters
Electrolytes to correct imbalance
What are examples of protectants/adsorbents and how do they work?
Kaolin-pectin, bismuth salts
Adsorb toxins and provide protective coating to inflamed mucosa
How do opiates and anti-cholinergic agent help diarrhoea?
Opitates- codeine, loperamide- inhibit acetyl choline release- increase segmental contractions and decreased peristalsis- slow transit increased water absorption
Anti-cholinergic agents- inhibit propulsive and non-propulsive GI motility
Why is anorexia a problem?
Common from disease, malnutrition will exacerbate disease
What non-drugs can be used for treatment of anorexia?
Liquid enteral alimentation- tube feeding
Warm palatable food frequently
What drugs can be used as appetite stimulants and how?
Benzodiazepines- diazepam- increased GABA- anti-serotonergic effect which depresses satiety centre
Cyproheptadine- serotonin and histamine antagonists- suppress satiety centre in hypothalamus
Glucocorticoids- prednisolone, dexamethasone- unkown
What are pro/prebiotics?
Probiotics- sample of normal intestinal microbes
Prebiotics- substrates that promote normal intestinal microbes
Why are pre/probiotics used?
Competitive action to reduce pathogenic microbes
What 4 drugs can be used to treat bowel inflammation?
Sulfasalazine
Osalazine
Tylosin
Metronidazole
What is the mode of action of sulfasalazine and what are its adverse effects?
Cleaved by bacteria to release sulfapyridine and salicylate
Salicylate has anti-inflammatory effect on bowel mucosa
Adverse-
May inhibits prostaglandin synthesis on colonic mucosa
Sulfapyridine may cause keratoconjunctivitis sicca
What is the difference between sulfasalazine and olsalazine?
Olsalazine= 2 salicyclic acid, Sulfasalazine= sulfapyridine and 1 salicyclic acid
Olsalazine is less toxic then sulfapyridine
What is the mode of action of tyrosine and metronidazole?
Tylosin- macrolide antibiotic, surpasses bacterial overgrowth, inhibits protein synthesis in susceptible bacteria
Metronidazole- anti-protozoa, antibacterial, suppressed cell mediated immune reactions
What are the two types of digestants used and why?
Pancreatic enzyme supplements- used in treatment of exocrine pancreatic sufficiency, contains lipases, amylase, proteases, administered with acid inhibitors
Bile acid/salts- stimulate flow of bile- enhance lipid digestion
What is urso-deoxychloid acid used to treat and what is its mode of action?
Cholestatic liver disease bile acids build up in the body, hydrophobic bile acids are toxic to hepato-biliar cell membranes
UCDA is a hydrophilic bile acid- cytoprotective two biliary system, inhibits ileal absorption of hydrophobic bile acids
What is the function of lactulose?
Metabolised by colonic bacteria into organic acids
These trap ammonia as ammonium ions which are digested
Used in patients with hepatic encephalopathy to reduce blood ammonia levels
What are the three hepto-biliary cytoprotective agents?
S-adenosylmethionine
Silymarin
Vitamin E
How does S-adenosylmethionine work?
An anti-oxidant, stabilises membrane function, modulates cytokine expression, anti-apoptotic in normal cells
What is silymarins mode of action?
Reactive oxygen species
Anti-inflammatory
Antifibrotic
Increases hepatic protein synthesis
What are the two features of vitamin E?
Anti-oxidant
Anti-inflammatory
In calves and lambs what needs to be stimulated for successful oral administration of drugs?
Oesophageal groove
What should a rumen pH vary from and to?
5-5.7
How is the rumen innervated extrinsically and intrinsically?
Extrinsically- vagal afferents
Intrisically- enteric nervous system
How can the oesophageal groove be stimulated?
Warm milk, sodium bicarbonate, copper sulphate
How can rumen function be restored?
Cholinergic increase frequency of contractions in rumen
Opiate antagonists stimulate extrinsic contraction when administered parenterally
Rumen fluid transfer of viable luminal bacteria/protozoa
How can incorrect rumen pH be treated?
Rumen antacids- aluminium hydroxide/ calcium carbonate- for mild
Severe acidosis requires parenteral fluid therapy
Rumen acidifiers- vinegar, acetic acid- treat excessive bicarbonate influx from hyper-salivation, used in acute urea poisoning
What is used for treatment of frothy bloat in ruminants?
Viscocity altering agents- mineral/vegetable oil
What medications are used for colics?
Fluids for dehydration
NSAIDs/Opiates for pain
How are spasmodic colics treated?
Small intestinal hyper-motility/ spasms
Anti-spasmodic- butylscopolamine- inhibits M1 receptors
Analgesic- methamzole- NSAIDs
What is a pelvic flexure impaction and how is it treated?
Impaction at narrowing between left ventral and left dorsal colon
Oral fluids for lubrication/softening of impaction
How is flatulent colic treated in horses?
Distension
Pain management- opioids, NSAIDs not usually effective except flunixin
