GI pharmacology Flashcards
Describe the layout of the enteric nervous system
Myenteric plexus
Submucosal plexus
Describe the neuronal control of the GIT
Parasympathetic from vagus
- cholinergic and excitatory
Sympathetic fibres are post-ganglionic to:
- BVs
- smooth muscle
- glands
- inhibit acetyl choline release from plexuses
Describe the hormonal control of the GIT
Endocrine - peptides from mucosa (gastrin, CCK)
Paracrine - local regulatory peptides (+ histamine)
What is gastric secretion made up of?
acid
bicarbonate
mucous
In what ways can gastric secretion be modified?
Neutralisation
Mucosal protection
Absorbents
Histamine antagonists
Proton pump inhibitors
Misoprostol
What can be used to neutralise stomach acid?
Weak bases:
- Magnesium hydroxide and trisilicate
- Aluminium hydroxide gel
- Alginates and simeticone
What conditions can be managed by neutralising gastric secretion?
- ruminal acidosis
- gastritis
- oesophagitis
What can be used for mucosal protection in gastric secretion modification - what is the clinical relevance of this?
Sucralfate (disaccharide)
- may prevent uptake of other drugs
What is the function of adding absorbents to gastric secretion?
Coating actions
Bind bacteria and toxins
What absorbents can be added to gastric secretion?
Activated charcoal
Bismuth
Kaolin (aluminium silicate)/pectin
What is the action of adding histamine antagonists in gastric secretion
Inhibits gastrin, histamine and acetylcholine stimulated secretion
Pepsin secretion falls (less volume of fluid)
Get a rebound increase on withdrawal
What histamine antagonists can be added to gastric secretion?
Ranitidine
Cimetidine
what is the action of adding proton pump inhibitors to gastric secretion?
irreversibly bind to ATPase
Inhibits basal and stimulated release
What proton pump inhibitors can be added to gastric secretion?
omeprazole
lansprazole
What is the action of misoprostol when added to gastric secretion?
inhibits acid secretion
increases mucosal blood flow
Increases uterine contraction (don’t use in pregnant animals)
What are the 2 centres that control emetics?
chemo receptor trigger zone (CRTZ)
Vomiting centre in brainstem
what is the function of the chemo receptor trigger zone (CRTZ)?
chemical stimuli
BBB is permeable in area of CRTZ
Gets input from vestibular apparatrus (motion sickness)
Sends impulses to vomiting centre in brainstem
What is the function of the vomiting centre in the brainstem?
coordinates and integrates vomiting
Describe the pathophysiology of vomiting
Impulse to vomiting centre via central, peripheral pathways or vestibular apparatus => substance P (neurotransmitter) binds to NK-1 receptors at cell membrane => signal travels via vagus nerve to abdominal muscles + diaphragm => vomiting
What substances are emetics?
Apomorphine:
- dopamine agonist
Alpha-2 agonists:
- xylazine)
Syrup of Ipecac:
- direct irritant
- causes cardiotoxicity in high doses
what are some dopamine antagonists?
Phenothiazine derivatives e.g., chloropromazine
Metaclopramid
Domperidone
Describe the action of metaclopramide and domperidone
Dopamine antagonists
Short action so need to infuse IV
Metaclopramide - centrally acting (CRTZ)
Domperidone - peripherally acting
Increase gastric emptying and increased motility
Do not use if vomiting due to obstruction (sends obstruction further down GIT)
what are some anti-emetics drugs?
Dopamine antagonists
Cerenia (maropitant)
Anti-histamines
Anticholinergics
Cannabinoids
Describe the action of cerenia (maropitant)
NK-1 antagonist
Competes with substance P
How is diarrhoea managed?
maintenance of fluid balance:
- IV fluid therapy (Hartmann’s solution)
- oral fluids
- anti-infectives e.g., zinc = immune stimulant
why may you want to modify intestinal motility?
reduce pain
increase transit time and re-absorption ‘window’
What are the 2 main classes of spasmolytics (antimotility) drugs?
Opiates e.g., morphine, codeine and loperamide (immodium)
Muscarinic antagonists e.g., atropine, hyoscine (buscopan)
What is the action of morphine as a spasmolytic drug?
increases intestinal contractions but decreases propulsion
increased large intestinal tone
=> constipation
What is the action of muscarinic antagonists as spasmolytic drugs?
neuronal control
inhibit acetylcholine stimulatory effects from vagus nerve
what classes of drugs improve GIT motility?
Prokinetics - cisapride
Laxatives
What are some laxatives?
Saline and hyperosmotic agents
Bulk producing agents
irritants
What is bulk and how does it improve aid intestinal motility
Methylcellulose
Polysaccharide polymers not easily digested => forms hydrated bulk in gut
Holds water and promotes peristalsis
How do osmotic laxatives aid intestinal motility?
Poorly absorbed solutes
Lactulose - broken down to lactic acid => lower pH => traps ammonia and water in gut => softens faeces => eases motility
What is the pharmacological intervention used in idiopathic inflammatory bowel disease?
Anti-inflammatory steroids e.g., prednisolone sulphasalazine
what is a pro-drug?
drug that is broken down into the active substance in the liver
What is the treatment for frothy bloat in ruminants?
antifoaming agents
Surfactants/detergents cause bubbles to break down
what causes frothy bloat in ruminants?
clover
