Pharmacology: Drugs Affecting Gut Motility Flashcards
What is the myogenic control of gut motility?
There are smooth muscle subunits linked by gap junctions
The interstitial cells of Cajal act as pacemaker cells to cause slow action potentials in the smooth muscle cells.
What is the neural control of gut motility?
Intrinsic control: the enteric NS
Extrinsic control:
- distension of the anus causes intestinal inhibition
- the gastrocolic and dueodenalcolic reflexes stimulate motility after material enters the stomach or duodenum
Outline the mechanical mechanism of vomiting
The pyloric sphincter closes and the cardia and the oesophagus relax.
The abdominal wall and diaphragm contract and propel the gastric contents.
The soft palate elevates causing the glottis to close to prevent entry of the vomit into the airways.
What are some causes of vomiting?
- pregnancy
- medications
- toxins
- pain
- irradiation
- smell
- raised ICP
- stretching and inflammation of the stomach
- rotational movement
List the classifications of anti-emesis drugs
- Dopamine (D2) receptor antagonists
- Serotonin receptor antagonists
- anti-muscarinics
- Histamine (H1) receptor antagonists
- Cannabinoids
- Benzodiazepines
How does domperidone (a D2 antagonist) work?
What are its indications?
Acts on the postrema on the floor of the 4th ventricle to inhibit vomiting. Also acts on the stomach to increase the rate of gastric emptying.
It is used for acute nausea and vomiting, esp caused by L-DOPA or dopamine agonists
How does ondansteron (a serotonin antagonist) work?
What are its indications?
5HT in the gut causes vagal stimulation. Works on the postrema on the floor of the 4th ventricle and opposes vagal nerves in the GIT.
It is used in high doses in radiation sickness and chemo. Anti-emetic effects can be enhanced by a single dose of corticosteroid.
How does metoclopramide work?
What are the indications?
Its a D2 antagonist. Also has GI ant-cholinergic effeects and blocks vagal stimulation of the GI tract.
Used for GI causes of N+V, migraine, post-operatively
What is the route of administration of domperidone?
What are some of the ADRs?
Given orally or PR - undergoes extensive first pass metabolism
ADR - stimulates prolactin release so can cause galactorrhoea, dystonia can happen but is rare
What are the routes of administration of ondansteron?
What are the ADRs?
Can be given IM, IV or orally.
ADRs inc headaches, constipation and flushing when given IV
What are the routes of administration of metoclopramide?
What are the ADRs?
Can be given oral, IV or IM. Short half life so given 3x daily
ADRs include extra-pyramidal reactions eg dystonia so must be avoided in parkinsons disease. Can cause galactorrhoea
How does hyoscine work?
When is it used?
It is a direct antagonist of muscarinic cholinergic receptors.
Used to treat motion sickness (half life around 2 hours)
What are the routes of administration of hyoscine?
What are the ADRs?
Usually given as a patch but can be oral if tolerance to transdermal route.
ADRs are systemic anticholinergic effects such as bradycardia
How does cyclizine work?
What are its indications?
A H1 antagonist with additional anti-muscarinic effects
Most common drug used for acute N+V
What are the routes of administration of cyclizine?
What are the ADRs?
Oral, IV or IM
ADRs - can cross the BBB so has a sedative effect. Can cause QT prolongation so contraindicated in myocardial ischaemia
What are the classes of drugs used to treat constipation?
- Bulking agents
- Stool softeners
- Osmotic laxatives
- Irritants / stimulants
What are the non-pharmacological interventions to treat constipation?
Increase fluid intake, high fibre diet, exercise.
Constipation particularly a problem in the elderly and even worse when they are in hospital
How do bulk laxatives work?
What are the indications?
Stretch the bowel to stimulate stretch receptors to cause peristalsis. They take a few days to work.
Used to treat chronic or acute constipation caused by IBS, pregnancy etc
What are the contraindications to bulk laxatives?
What are the ADRs?
Cant be used in people who have adhesions or ulceration due to the risk of intestinal obstruction.
ADR is flatulence.
How do faecal softeners work?
Name examples
Arachis oil which can be used as an enema and glycerol which can be given as a supplement
They act to lubricate and soften the stool.
Unlike bulk laxatives they can be used in adhesions as there is no risk of bowel obstruction.
List some osmotically active laxatives
- Magnesium and sodium salts
- Lactulose
- Macrogols
When are magnesium and sodium salts indicated?
How do they work?
They are quick and severe so are used to clear the bowel before colonoscopy. Also used for constipation where urgent relief is required.
They work by causing water retention in the small and large bowel to increase peristalsis.
How does lactulose work?
When is it indicated?
Lactulose is a disaccharide that cant be digested by enzymes. The lactulose is fermented in the colon producing acetic and lactic acid which causes an osmotic effect.
Used 1st line for constipation - usually takes 48hrs to work. Also a high dose is used in liver failure, reduces production of ammonia (encephalopathy)
How do macrogols work?
Macrogols (such as movicol) are osmotic laxatives. Given in powder form dissolved in water, take 2-4 days to get full relief.
How do irritant /stimulant laxatives work?
When are they indicated?
They cause excitation of the sensory nerve endings in the bowel leading to water and electrolyte retention which stimulates peristalsis.
They are indicated where rapid treatment is needed (6-8hours) such as faecal impaction or surgical prep.
What problems can occur from repeated use of irritant laxatives?
The colon can become atonic and therefore causes constipation.
Hypokalaemia due to excessive losses in the stool
What info do you need to elicit from the Hx to decide the type of laxative?
- Severity
- If there is soft faces then stimulant laxatives should be used such as senna
- If Hx and DRE reveals hard faeces then use osmotic laxatives or bulking agents
What are the key classes of anti-diarrhoeal drugs?
- Anti-motility
- Bulk forming
- Fluid absorbants
Name some anti-motility drugs
How do they work?
What are the contra-indications?
Opiate analgesics such as codeine, opiate analogues such as loperamide (imodium).
Act via opioid receptors in the bowel to reduce bowel motility and therefore more fluid is absorbed. Also increase anal tone and reduce sensory defecation reflex.
Avoid in IBD - risk of rupture of toxic megacolon
Name a bulk forming agent used to treat diarrhoea
How does it work?
Fybogel - more water is absorbed so the stool is more formed.
Useful in pts with IBS
Name a fluid absorbant
Kaolin
