GI Motility / Nausea and Vomiting Flashcards
what drugs are there to control GI motility and vomiting?
- motility stimulants
- antispasmodics
- laxatives
- antidiarrhoeals
where is the myenteric plexus and what is it?
major nerve supply to GI tract to control motility
between circular and submucosal muscles
where is the submucosal plexus and what is it?
nerves derived from the myenteric plexus
controls the movement of the mucosa
what is the mesentry and what is it used for?
holds the gut together
used as a pharmacological base
what is a perfusion pump used for
used to inject drugs, e.g. vasoconstriction drugs
describe the autonomic control of the GI tract
parasympathetic = excitatory - releases ACh at ganglia
nicotonic
sympathetic = inhibitory - releases NA at the ganglia which affects ACh
ACh released on the smooth muscle
what are motility stimulants and what are they used to treat?
increase GI motility without a laxative effect
treats:
- GORD
- Gastroparesis
- Gastric stasis
what is an example of a muscarinic agonist?
bethanechol
what is bethanechol used to treat?
- post-op gastric distension
- post-op ileus
- post-op atony
- can’t use ACh- not selective enough
- resistant to AChE
- to expel gas from the intestine prior to x-ray examination and to reduce transit time of barium
how does bethanechol work?
cholinergic- stimulate ACh receptors directly
how else can ACh be increased, apart from stimulating the release of ACh?
anticholinesterases to prevent ACh from being broken down
what is dopamine?
inhibitory
decrease oesophageal sphincter
decrease intragastric pressure
what are examples of dopamine antagonists?
metaclopramide and domperidone
what do dopamine antagonists do?
stimulate gastric motility and gastric empyting
block D2 receptors -decrease the inhibition of DA and ACh release
stimulates 5-HT receptors
what is the mechanism of action of dopamine normally?
dopamine normally inhibits ACh release at ganglia via D2 receptors
what is the mechanism of action of dopamine agonists?
block D2 receptors to reduce how much ACh release is inhibited
what are the features of serotonin?
important role in normal motor and secretory function of the GI tract
most is produced by enterochromaffin cells in the mucosa
serotonin released in response to chemical and mechanical stimulation = stimulation of peristalsis
found in neurones of myenteric plexus
stimulates smooth muscle, ganglion cells and sensory nerve endings
what is the synthesis and metabolism of serotonin?
tryptophan (from diet) -> 5-hydroxytryptophan VIA TRYPTOPHAN HYDROXYLASE
5-hydroxytryptophan -> 5-HT VIA NON-SPECIFIC DECARBOXYLASE
5-HT -> 5-HIAA VIA MAO
-> excretion
what is an example of a 5-HT4 receptor agonist?
tegaserod - partial agonist at 5-HT4 recepotrs
what is tegaserod used for?
initially for constipation in IBS
now for gastroparesis
how does tegaserod work?
promote peristaltic activity by acting on presynaptic 5-HT to enhance release of ACh
what is an alternative drug to tegaserod?
prucalopride
what is an example of a motilin agonist?
erythromycin
what does erythromycin do?
stimulate motilin receptors on GI smooth muscle
promote peristalsis
tolerance quickly develops
what is the migrating motor complex?
every 80-90-100 mins 3 phases 1) quiet period 2) irregular contraction 3) peristaltic rush - starting in stomach. increased gastric pancreatic and biliary secretion
what are antispasmodics? drug type example?
muscarinic antagonists
what are the features of muscarinic antagonists and what are they used to treat?
reduce GI motility tract
IBS (reduce spasm)
non-ulcer dyspepsia
diverticular disease
what is an example of a muscarinic antagonist?
dicyclomine - direct effect on smooth muscle
what is constipation caused by?
poor diet
low fluid intake
improper bowel movements
loss of rhythm surgery pregnancy diabetes hypothyroidism kidney dialysis constipating drugs laxative abuse ageing-reduces bowel movement lack of abdominal muscle movements
what do osmotic laxatives do in the lumen?
increase intestinal fluid secretion
what do stimulant laxatives do?
stimulate enteric NS
what do bulk laxatives do?
swells and distends colon
what is an example of a bulk laxative?
methylcellulose, bran
what are the features of bulk laxatives?
increase volume of faecal material
distends smooth muscle of GIT - promoting refelx peristalsis
act within days
what is an example of an osmotic laxative?
lactulose, magnesium hydroxide/sulphate
what are the features of osmotic laxatives?
poorly absorbed
increase osmotic pressure of intestinal contents
draws water into the lumen of the GIT
increased faecal volume
distends smooth muscle - promoting reflex peristalsis
what is an example of a faecal softener laxative?
docusate sodium
what are the features of faecal softener laxatives?
detergent action reduces surface tension of luminal contents
softens faeces
weak laxative stimulant action
what is an example of a stimulant laxative?
(6-12 hours)
senna
bisacodyl
sodium picosulphate
what are the features of stimulant laxatives?
senna - contains anthracene derivatives which have a direct stimulant effect on the myenteric plexus
bisacodyl - usually suppository - stimulates rectal muscosa
sodium picosulphate - similar to bisacodyl but given orally prior to intestinal surgery
what are the causes of diarrhoea?
change in diet lactose intolerance stress/emotional disturbance toxins drugs infection that irritates/damages GI mucosa
what are the 3 approches to anti-diarrhoeal?
correct fluid and electrolyte balance
antimicrobial agents
anti motility agents and adsorbents
what opiod anti-motilities are there?
morphine, codeine etc.
what do opiod anti-motilitiesdo?
inhibit GI activity by stimulating u-opiod receptors
increase segmentation receptors but reduce peristalsis
forward movement is slowed and absorption of water is increased = increased viscocity of GI contents
what is loperamide?
anti-motility
synthetic opiod
cant cross BBB - low abuse potential
what are the two main centres involved in nausea and vomiting?
- chemoreceptor trigger zone (CTZ)
- vomiting centre in the medulla
what stimulates CTZ?
drugs, toxins, vestibular centre
what stimulates the vomiting centre?
CTZ
what neuronal pathways act on the vomiting centre?
higher cortical centres
chemoreceptor trigger zones
stomach small intestine
labyrinths
what happens when the vomiting centre is stimulated?
contraction of diaphragm, anterior abdominal muscles and stomach
closure of the glottis
abdominal wall moves upwards
vomiting occurs
what neurotransmitters are involved in the vomiting reflex?
acetylcholine
dopamine
histamine
serotonin
what are the drug targets for vomiting?
M1- decrease vestibular centre and impact of CTZ on vomiting centre
H1- decrease vestibular centre and impact of CTZ on vomiting centre
D2- decrease CTZ impact on vomiting centre
5-HT3- decrease CTZ impact on vomiting centre
what is an example of antihistamines?
cinnarizine,
what is an example of muscarinic receptor antagnonist?
hyocine
what is an example of 5HT3 receptor antagonist?
graniestron
what is an example of dopamine antagonist?
metaclopramide,
what is an example of cannabinoids?
nabilone
CB1 GIT
what is an example of NK1 receptor antagonists?
aprepritant
what is an example of glucocorticoids?
dexamethasone
