Drugs Affecting Gut Motility Flashcards
What happens when a wave of depolarisation occurs in myogenic control in the intestines?
Causes rhythmic contraction of smooth muscle forming
- segmenting seen in small intestine
- haustral shuttling in large intestine
Where does neural control come from?
Intrinsically - enteric plexus
Extrinsically
Effect of the sympathetic and parasympathetic nervous system on gut motility?
Sympathetic - reduces motility via adrenergic receptors
Parasympathetic - increases motility via cholinergic receptors and vagus nerve
Where does the plexus for intrinsic control lie?
Myenteric plexus lies between the circular and longitudinal muscle layers
What is the enteric nervous system? What plexuses is it made up of?
An autonomous collection of nerves within the gut wall
Myenteric - between circular and longitudinal muscle layers
Meissner’s - in submucosa
Henle’s
Cajal’s
What are the reflexes allowing extrinsic control of the gut?
Intestine-inhibitory reflex: distension of one intestinal segment causes complete intestinal inhibition
Anointestinal inhibitory reflex: distension of the anus causes intestinal inhibition
Gastrocolic and duodenocolic reflexes: stimulates motility after material has entered the stomach/duodenum
What are the hormones involved in the control of the gut and where are they secreted from?
Gastric: promotes acid secretion
Secretin: from the duodenum
CCK: from the small intestine
Motilin : from the small intestine
Paracrine: histamine, somatostatin, prostaglandins
Possible causes of constipation?
Diabetes Parkinson's Dehydration Pregnancy Mechanical obstruction Cancer
Which types of drugs are given for soft faeces? Examples?
Stimulant laxatives eg Senna, bisacodyl, glycerol
Which types of drugs are given for hard faeces in constipation? Examples?
Osmotic laxative eg Movicol
Bulk laxative eg Ispaghula
Non-pharmacological interventions for constipation?
Increase fluid intake
High fibre diet
Exercise
What can excessive use of laxatives lead to?
Hypokalaemia due to excessive enteral loss of potassium
This can then itself cause bowel inertia
How do bulk laxatives work?
Insoluble, non-absorbable substances which distend the gut
When can bulk laxatives be used?
To restore normal bowel habit in chronic or simple constipation
- IBS
- pregnancy
ADRs of bulk laxatives (eg Ispaghula)
Flatulence
Adhesions or ulceration that may cause intestinal obstruction
Name some fecal softeners
Arachis oil
Glycerol
How do faecal softeners work?
Lubricate and soften stools - safe but not always effective
Indications for faecal softeners?
Hard stools
Adhesions - no risk of obstruction
Anal fissures
Haemorrhoids
Name some osmotically active laxatives
Magnesium and sodium salts
Lactulose
Macrgols
How do magnesium and sodium salts work?
Cause way retention in the small and large bowel which increases peristalsis
How long does it take for Ispaghula to work?
A couple of days
How long does it take for magnesium and sodium salts to work?
Quickly and are severe
How are magnesium and sodium salts normally administered?
PR
When are magnsrium and sodium salts normally used?
Resistant constipation
If urgent relief is required
Mechanism of action of lactulose?
It is a disaccharide (galactose or fructose)
Cannot be hydrolysed by digestive enzymes
Fermented to lactulose by colon bacteria producing acetic and lactic acid
They have an osmotic effect
How long does it take for lactulose to work?
48 hours
Indications for lactulose?
Liver failure to reduce ammonia production
How do macrogols such as Movicol work?
Osmotic laxative
How is macrogol administered?
A powder dissolved in fluid
How long does macrogol take to work?
Within hours
2-4 days to get full relief
How do irritant/stimulant laxatives work?
Excite sensory nerve endings leading to water and electrolyte retention and therefore peristalsis
Indications for irritant/stimulant laxatives?
Soft faeces
- rapid treatment eg in faecal impaction or surgical prep
- colonic atony
- hypokalaemia
How long do irritant laxatives take to have an effect and when are they given?
6-8 hours
Before bed
Taken orally
Examples of irritant/stimulant laxatives?
Castor oil Bisacodyl Anthraquinones -danthron -Senna -rhubarb roots
Why can anthraquinones not be used in intestinal obstruction?
Cause abdominal cramps
What is docusate sodium?
A faecal softener
-can be combined with danthron to give codanthraner
What can abuse of anthraquinones lead to?
Melanosis coli
Main types of anti-diarrhoeals?
Anti-motility
Bulk-forming - fluid absorbents
Fluid adsorbents
Name some anti-motility drugs
Opiate analgesics eg codeine
Opiate analogues eg loperamide (Imodium)
Mechanism of action of anti-motility drugs?
Act via opioid receptors in the bowel to
- reduce bowel motility - increases time for fluid to reabsorption
- increase anal tone and reduce sensory defacation reflex
Indications for anti-motility drugs?
Chronic diarrhoea
Contra-indications for anti-motility drugs?
IBD due to risk of toxic mega colon
Mechanism of action of bulk-forming drugs in diarrhoea (eg Ispaghula)
Absorb water
Indications for bulk-forming agents?
Patients with IBS - good for constipation and diarrhoea
Ileostomy
Name a fluid adsorbent
Kaolin
How does cholestyramine work?
It is a bike acid sequestration used for bile salt-induced diarrhoea seen in crohn’s or post-vagotomy
What are pancreatic enzymes helpful for?
Diarrhoea
Symptoms of IBS?
Nausea Vomiting Belching Abdominal discomfort Frequent bowel actions Constipation No blood loss
What happens in IBS?
Chronic, re-lapsing condition where abdominal pain is associated with defacation or change in bowel habit
Abnormal smooth muscle activity or visceral hypersensitivity
Treatment of IBS?
Mebeverine - anti spasmodic - anti-muscarinic
- has direct effects on colonic hypermotility
- relieves spasm of intestinal muscle
What is mebeverine normally combined with?
A bulk-forming agent - fybogel mebeverine
What are some other anti-spasmodics?
(Mebeverine)
Hyoscine
What happens in emesis?
Pyloric sphincter closes while the cardia and oesophagus relax
Gastric contents propelled by contraction of abdominal wall and diaphragm
Glottis closes with elevation of the soft palate to prevent entry of vomit into the trachea or nasopharynx
Preliminary signs of vomiting?
Nausea Dilated pupils Increased salivation Sweating Retching Paleness
Where is the vomiting centre?
In the ependymal cells (postrema) on the floor of the fourth ventricle in the brain
What can activate the vomiting centre?
Medications Pregnancy Toxins Pain Irritation Smell Touch (gag) Raised ICP Stomach inflammation Rotation
Neurotransmitters involved in vomiting?
Vestibular apparatus - Ach and histamine (H1)
Medullary centre - Ach, H1, 5-HT
Vomiting centre - dopamine
What drugs are used to prevent vomiting
Dopamine receptor D2 antagonists - eg metoclopramide or domperidone
5-HT3 receptor antagonists eg ondansteron
Anti-muscarinics
H1 receptor antagonists eg cyclizine, promethazine
Others eg cannabinoids, benzodiazepines
Mechanism of action of domperidone?
Acts on postrema on floor of fourth ventricle
Acts on stomach to increase gastric emptying
Antagonises dopamine
Administration of domperidone?
Administered orally
Indications for domperidone?
Acute nausea and vomiting episode
-especially if induced by L-DOPA or dopamine agonists
ADRs of domperidone?
Excessive prolactin release causing galactorrhoea
Occasionally dystonia
When is 5-HT released into the GI tract and from where?
Released when there are poisonous compounds, bacterial toxins, drugs etc
From enterochromaffin cells lining the GI tract
Where does the vomiting centre receive signals from?
5-HT triggering vagal afferents
Vestibular apparatus which receives input from labyrinth
Medullary centre which senses emetic stimuli
Higher cortical centres - pain, sights, smells, emotional factors
Medullary centre also receives input from those three
Mechanism of action of 5-HT antagonists
Effective in the postrema of the fourth ventricle, against vagal afferent nerves in the GI, medullary centre
Indications for 5-HT antagonists?
Radiation therapy
Chemotherapy
Administration of 5-HT antagonists?
IV
IM
Orally
What can enhance the anti-emetic effect of 5-HT antagonists?
A single dose corticosteroid
ADRs of 5-HT antagonists?
Headache
Constipation
Flushing (IV)
Mechanism of action of metoclopramide?
D2 antagonist via fourth ventricle
Has anticholinergic effects (GI tract)
Blocks vagal afferent 5-HT (GI)
Indications for metoclopramide?
GI cause of nausea and vomiting
Migraine
Post-op
Routes of administration of metoclopramide?
Oral
IM
IV
Half-life of metoclopramide?
4 hours
ADRs of metoclopramide?
Extra-pyramidal reactions (dystonia) - so avoid in Parkinson’s
Galactorrhoea due to release of prolactin
Mechanism of action of hyoscine? (Anti-emetic)
Ach antagonist
Indications for hyoscine?
Prevention and treatment of motion sickness
Administration and half life of hyoscine?
Oral or latch
2 hours
ADRs of hyoscine?
Systemic anti-cholinergic effects such as
- bradycardia
- dry mouth
Mechanism of cyclizine?
H1 antagonist
Indications for cyclizine?
Acute nausea and vomiting
Administration of cyclizine?
Oral
IV
IM
ADRs of cyclizine?
Prolonged QT, reducing cardiac index in myocardial ischaemia
Sedative as can cross BBB
What are the pacemaker cells of myogenic control of the gut?
Interstitial cells of cajal act as pacemakers by producing slow waves of depolarisation which travel thought the smooth muscle across gap junctions
