Drugs Affecting Gut Motility Flashcards
What are the types of physiological control of gut motility
Myogenic
Neurological
Hormonal
What is myogenic control of gut motility
Rhythmic contractions of intestinal smooth muscle
Interstitial cells of Cajal act as pacemaker cells
Depolarisations spread through gap junctions
What is neuronal control of gut motility
Enteric Plexus - network of autonomic fibres in intestinal wall
Cholinergic nerves increase force of contraction
Non-adrenergic inhibitory nerves decrease contraction
What is hormonal control of motility
Peptide hormones secreted by endocrine cells in intestinal mucosa
CCK
Secretin
Gastrin
Paracrine - prostaglandin, histamine, somatostatin
What are the steps of vomiting reflex
Contraction of pyloric sphincter
Relaxation of cardia and oesophagus
Contraction of abdominal wall and diaphragm
Expulsion of gastric contents
What are triggers of vomiting reflex
RICP
Vestibular apparatus : rotational movement
Chemoreceptor Trigger Zone: toxins, Drugs, electrolytes
Higher cortical centres: pain, sight, smell
GI tract: stretch, inflammation
What is vomiting centre
Area in medulla responsible for control+coordination of muscles involved in vomiting reflex
What is Area Postrema
Part of vomiting centre containing CTZ
Located in base of 4th ventricle
Thus Outside BBB and exposed to blood vomiting triggers in peripheral circulation
What are neurotransmitters involved in vomiting reflex
Vestibular apparatus: H1 receptor
CTZ: D2, 5HT3
GI: D2
Vomiting centre: ACh, H1, 5HT3
What are types of antiemetic drugs
D2 antagonist 5HT3 antagonist ACh antagonist H1 antagonist Cannabinoids Benzodiazepines
Give examples of D2 antagonists
Domperidone
Metoclopromide
Phenothiazine
What is mechanism of action of D2 antagonists
Antagonise D2 receptor at Area postrema
Antagonise D2 at stomach - slow gastric emptying
What are indications of D2 antagonists
Acute N+V (esp if L-dopa induced)
PONV
What are side effects of D2 antagonists
Galactorrhoea (loss of dopaminergic inhibition of prolactin release)
Dystonia (rare)
What are PK properties of D2 antagonists
Oral, PR
Extensive first pass metabolism
Does not cross BBB
Give examples of 5HT3 antagonists
Ondansetron
Granisetron
What is mechanism of action of 5HT3 antagonists
Antagonise 5HT3 at area postrema
Antagonise 5HT3 receptors of vagus afferent fibres in GIT
What are indications of 5HT3 antagonists
Chemotherapy (1st line)
Radiation sickness
PONV (esp opioid induced)
What are side effects of 5HT3 antagonists
Headache
Constipation
Flushing
How are 5HT3 antagonists administered
IV
Enhanced effect if given with dose of corticosteroids
What is mechanism of action of metoclopramide
Antagonise D2 at area postrema
Antagonise D2 at stomach - slow gastric emptying
Anticholinergic (GI)
Antagonise 5HT3 at vagal afferent fibres of GIT
What are indications of metoclopramide
Acute N+V (first line)
PONV (gastric cause)
How is metoclopramide administered
Oral
TDS - T1/2 4hrs
What are side effects of metoclopramide
Extrapyramidal side effects - CI in PD
Galactorrhoea
Give examples of ACh antagonists
Hyoscine
What is mechanism of action of ACh antagonists
Antagonise mAChR at vestibular apparatus
Anticholinergic at GIT - inhibit gastric secretions
What are indications of ACh antagonists
Motion sickness
N+V in Obstruction
What are side effects of ACh antagonists
Systemic anticholinergic effects
Give examples of H1 antagonists
Cyclizine
Promethiazine
What is mechanism of action if H1 antagonists
Antagonise H1 at vomiting centre
What are indications of H1 antagonists
Acute N+V
What are side effects of H1 antagonists
Sedation
QT prolongation
What are principles of management of constipation
Lifestyle: increase fluids, fibre, exercise
Treat underlying cause: dehydration, DM, PD, opioids, diuretics, anticholinergics
Pharmacological: laxatives
What are the types of laxatives
Stimulant (soft stool) Osmotically active (hard stool) Bulking agent (hard stool) Faecal softeners (hard stool)
Give examples of bulking laxatives
Ispaghula
Cellulose
What is mechanism of action of bulking agents
Insoluble agents draw water in Bowel distension Stimulate stretch receptors Stimulate peristalsis Takes days to take effect
What are indications of bulking agents
Hard stools
What are side effects of bulking agents
Risk of obstruction - CI in adhesions and ulcers
Dehydration
Flatulence
Give examples to faecal softeners
Arachis oil
Glycerol
What is mechanism of action of faecal softeners
Lubricate stool
Assist evacuation of stool
What are indications of faecal softeners
Hard stools
Adhesions
Anal fissure
Haemorrhoids
What are side effects of faecal softeners
Safe
But not effective
Give examples of osmotically active laxatives
Mg, Na salts
Lactulose
Macrogol (Movicol)
What is mechanism of action of osmotically active laxatives
Draw water into lumen
Cause bowel distension
Stimulate stretch receptors in bowel wall
Stimulate peristalsis
What are indications of Mg and Na salts
Urgent relief
Resistant constipation
How is Mg and Na salts administered
PR
What is mechanism of action of lactulose
Broken down by colonic flora into acetic and lactic acid
Acetic and lactic acid are osmotically active
Acetic and lactic acid bind+trap ammonia in gut
What are indications of lactulose
1st line hospital constipation
Liver failure - prevent encephalopathy
Give examples of stimulant laxatives
Senna
Codanthramer
Bisacodyl
What is mechanism of action of stimulant laxatives
Stimulate enteric plexus
Stimulate peristalsis directly
Cause electrolyte and fluid retention, stimulate stretch receptors thus peristalsis
What are indications of stimulant laxatives
Urgent treatment:
Surgical preparation
Impaction
What are side effects of stimulant laxatives
Abdominal cramps Hypokalaemia Colonic atony (chronic use) Melenosis Coli (pigmentation; overuse)
What are principles of management of diarrhoea
Treat cause: infection, IBD, IBS, bile, pancreatic enzymes
Supportive: fluids, electrolyte replacement
Anti-diarrhoea Drugs: for symptom relief
Give examples of anti-motility drugs
Loperamide
What is mechanism of action of loperamide
Opioid analogue Bind to opioid receptors on bowel wall Decreased motility Increased transit time Increased water absorption Increased anal tone
What are indications of loperamide
Chronic diarrhoea
What are side effects of loperamide
Risk of toxic megacolon - CI in IBD
What are types of anti-diarrhoea drugs
Anti-motility
Bulk-forming laxatives
Cholestyramine
Pancreatic enzymes
What is mechanism of action of bulk forming agents for diarrhoea
Absorb water
What are indications of bulk forming agents for diarrhoea
IBS with chronic diarrhoea+constipation
What is mechanism of action of cholestyramine
Bile acid sequestration
What are indications of cholestyramine
Diarrhoea secondary to bile acid malabsorption:
Crohn’s
Ileal resection
Give examples of pancreatic enzymes
Pancreatase
What are indications of pancreatase
Diarrhoea secondary to malabsorption from lack of pancreatic enzymes:
Chronic pancreatitis
Cystic fibrosis
What is IBS
Chronic and relapsing disorder of GI function without physical/biochemical abnormality
What is the diagnostic criteria of IBS
6 months of:
Abdominal pain relieved by defecation
Abdominal bloating
Change in bowel habit: Constipation, diarrhoea
What are principles of management of IBS
Lifestyle: increase fluid, limit fibre, limit caffeine
Diarrhoea: loperamide
Constipation: ispaghul
Pain: peppermint oil, mebeverine
What is mechanism of action of mebeverine
Antispasmodic agent
Anticholinergic effects on gut wall
Relax intestinal smooth muscle
Relieves pain from muscle spasms
