Anti-emetics & Laxatives Flashcards
What are the myogenic components of gut motility?
Rhythmic contraction via slow waves of depolarisation through smooth muscle
Passive spread of current through gap junctions
Interstitial cells of Cajal act as pacemaker
What are the hormonal components of gut motility?
Local hormones (produced in endocrine cells in mucosa)
Paracrine:
- histamine —> reduce pH
- somatostatin —> reduce acid secretion
- prostaglandins —> reduce acid secretion and increase mucus secretion
- gastrin —> increase acid secretion
- secretin (duodenum) —> decrease acid secretion and increase HCO3- production
- cholecystokinin (small intestine) —> gall bladder contraction and pancreatic enzyme secretion
- motilin (small intestine) —> increase peristalsis in small intestine and increase pepsin production
What are the preliminary signs that someone is going to vomit?
- retching
- increased salivation
- nausea
- dilated pupils
- sweating
- paleness
What is the mechanism of vomiting?
Medullary vomiting centre stimulated
- pyloric sphincter closes
- duodenal contraction
- abdominal muscle contraction
- diaphragm contraction
- GOJ open
- cardia and oesophagus relax
- glottis closure
- soft palate elevation
- fixed respiration
What is the neurological control of vomiting?
Medullary vomiting centre:
- ACh
- Histamine (H1)
- 5-HT3
Stimulated by vestibular apparatus:
- ACh
- Histamine (H1)
Stimulated by dopamine released from the postrema on the floor of the 4th ventricle
Give some examples of states which stimulate the medullary vomiting centre.
- pregnancy
- drugs, toxins
- pain
- irradiation
- smell
- touch (gag reflex)
- rotational movement (vestibular system)
- raised ICP
- stomach stretching
- inflammation of stomach
What are the different pharmacological treatments for nausea and vomiting?
D2 receptor antagonists
5-HT3 receptor antagonists
ACh antagonists
H1 antagonists
Give some examples of D2 receptor antagonists. Describe their pharmacokinetics and pharmacodynamics. When are they indicated? Give some examples of ADRs associated with their use.
e.g. domperidone, metoclopramide (+ anti-cholinergic effects)
Pharmacokinetics:
- act on postrema on floor of 4th ventricle
- act on stomach to increase the rate of gastric emptying
- metoclopramide also has anti-cholinergic effects and blocks vagal afferent 5-HT3 receptors in GI
- domperidone is PO or PR, metoclopramide is PO, IM, IV
- metoclompramide has t1/2= ~4hrs
Pharmacodynamics:
- domperidone has extensive first pass metabolism
- domperidone does not cross blood-brain barrier
Indications:
- domperidone = mild acute N&V (esp. when induced by L-dopa/dopamine agonists)
- metoclopramide = GI causes of N&V, migraine, post-op
ADRs: DOMPERIDONE: - dry mouth - increased prolactin release ---> galactorrhoea - dystonia (rare) METOCLOPRAMIDE: - extra-pyramidal reactions (dystonia) in 1% (contraindicated in Parkinson's) - galactorrhoea
Give examples of 5-HT3 receptor antagonists. Describe the pharmacokinetics of these drugs. When are they indicated? Give some examples of ADRs associated with their use.
e.g. ondansteron, granisteron
Pharmacokinetics:
- 5-HT released into gut causes vagal stimulation
- acts on floor of 4th ventricle and vagal afferent nerves in gut
- IV, IM, oral
- anti-emetic effect can be enhanced by a single dose of corticosteroid
Indications:
- radiation sickness (high dose)
- chemotherapy
- post-op
ADRs:
- headache
- constipation
- flushing (IV)
Give an example of a ACh antagonist. Describe the pharmacokinetics of this drug. When are they indicated? Give examples of ADRs associated with its use.
e.g. hyoscine (scopolamine)
Pharmacokinetics:
- direct antagonist of muscarinic cholinergic receptors
- oral (30min before and 6hrs after situation) or transdermal (tolerance can build up over time)
- t1/2 = ~2hrs
Indications:
- motion sickness
- palliative care
ADRs:
- systemic anti-cholinergic effects e.g. dry mouth, blurred vision, constipation, drowsiness, etc.
- bradycardia (at low doses; transient)
Give examples of H1 antagonists. Describe the pharmacokinetics of these drugs. When are they indications? Give examples of ADRs associated with their use.
e.g. cyclizine, promethazine (phenothiazine)
Pharmacokinetics:
- antagonise H1 receptor AND have additional anti-muscarinic effects
- oral, IV, IM
Indications:
- acute N&V
- phenothiazine may suppress nausea following surgery/gastric irritation/opioid-induced nausea
- phenothiazine is useful if sedation is required
ADRs:
- sedation (crosses blood-brain barrier)
- QT lengthening (contraindicated in myocardial ischaemia)
What is the general management for constipation?
Consider underlying cause:
- mechanical obstruction
- cancer
- diabetes
- Parkinson’s
- dehydration
- pregnancy
Increase fluid intake
High fibre diet
Exercise
Laxatives
What is the difference between a suppository and an enema?
SUPPOSITORY = solid drug placed into rectum/vagina to dissolve
ENEMA = liquid/gas injected into rectum to expel its contents/introduce drugs/permit X-ray imaging
What are the different classes of laxatives?
Bulk laxatives
Faecal softeners
Osmotically active
Irritant/stimulant
Give examples of bulk laxatives. Describe the mechanism of action of these drugs. When are they indicated? Give examples of ADRs associated with their use.
e.g. fybogel, ispaghula
Insoluble and non-absorbable substances —> distend the gut ——–> increase gut motility
- take a few days to work
- normal fluid intake
- ideally should increase dietary fibre
Indications (re-establish normal bowel habit):
- simple/chronic constipation related to IBS
- pregnancy
ADRs:
- flatulence
- abdominal distension
- GI obstruction/impaction (contraindicated when adhesions/ulceration is present)
Give examples of faecal softeners. Describe the mechanism of these drugs. When are they indicated?
e.g. glycerol (also acts as stimulant), arachis oil
Lubricates and softens stool
- glycerol is a suppository
- arachis oil is an enema
Indications (re-establish normal bowel habit):
- simple/chronic constipation related to IBS
- pregnancy
ADRs:
- no risk of obstruction with adhesions; can also be used with anal fissures/haemorrhoids
Give examples of osmotically active laxatives. Describe their mechanisms of action. When are they indicated?
Magnesium/sodium salts (phosphate enema):
- water retention in small/large intestine —> increase peristalsis
- quick action (hrs)
- PR
- reserved for “resistant” constipation or if urgent relief is required
Lactulose:
- insoluble; colon bacteria ferment —> production of acetic acid and lactic acid —> osmotic effect
- oral
- 48hrs to work
- indicated in liver failure (reduced production of ammonia)
Macrogols e.g. Movicol (polyethylene glycol)
- powder (given orally with fluid; therefore may prevent dehydration)
- initial effect within hrs, 2-4 days to get full relief
All osmotically active laxatives should be used with caution to prevent intestinal obstruction
Give examples of irritant/stimulant laxatives. Describe their mechanism of action. When are they indicated? Give examples of ADRs associated with their use.
e.g. castor oil (watery discharge), senna (anthraquinone), sodium picosulfate,
(+ glycerol)
Excitation of sensory nerve endings —> water and electrolyte retention —> peristalsis
- oral
- duration of 6-8hrs (taken just before bed)
Indications (rapid treatment required):
- faecal impaction
- surgical preparation
ADRs (repeated use):
- colonic atony —> constipation
- hypokalaemia
- melanosis coli (pigmentation of colon wall; indicates laxative abuse in order to lose weight)
Contra-indicated in intestinal obstruction
Contrast the laxatives indicated when the faeces are soft or hard.
Soft faeces = give stimulant laxatives e.g. senna, glycerol
Hard faeces = give osmotic laxatives e.g. Movicol OR bulk-forming laxatives e.g. ispaghula
Describe how constipation can lead to hypokalaemia. How can hypokalaemia mimic constipation?
“Constipation” —> laxatives given
- –> enteral loss of K+ —> hypokalaemia
- –> Na+ and water loss —> increased aldosterone —> renal retention of Na+ and water —> renal loss of K+ —> hypokalaemia
Hypokalaemia —> bowel inertia —> “constipation”
What is the general management of diarrhoea?
Consider underlying cause
May represent overflow incontinence (constipation)
Fluid/electrolyte management is important
Anti-diarrhoeal drugs treat symptoms, not cause
What are the different pharmacological agents used for diarrhoea?
Anti-motility
Bulk-forming
Fluid adsorbents
Cholestyramine = bile acid sequestrant used for bile salt induced diarrhoea (e.g. Crohn’s, post-vagotomy)
Pancreatic enzymes if diarrhoea is due to pancreatic malabsorption
Give examples of anti-motility drugs. Describe their mechanism of action. When are they indicated? Give examples of ADRs associated with their use.
e.g. codeine, loperamide (Immodium; opiate analogue)
Act on opioid receptors in the bowel
- reduce motility —> increase time for fluid to be reabsorbed
- increase anal tone
- reduce sensory defecation reflex
Indicated for chronic diarrhoea
Contra-indicated in IBD (risk of toxic megacolon)
ADRs:
- nausea
- flatulence
- headache
- dizziness
How do bulk-forming laxatives treat diarrhoea? When are they indicated?
Retain water —> produces more formed stool
Indications:
- IBS (constipation and diarrhoea)
- ileostomy
+ mebeverine also relieves intestinal spasm (useful in IBS)
Give an example of a fluid adsorbent. How does it treat diarrhoea? When is it indicated?
e.g. kaolin
Absorbs fluid —> produces more formed stool
Little use
What is irritable bowel syndrome?
Abdominal pain/bloating/discomfort associated with alteration in bowel habit in the absence of an organic cause
Symptoms caused by abnormal muscular contractions in intestine and increase sensitivity to stimuli e.g. stretching, distension
Associated with stress/anxiety
May occur following severe infection of the intestine
Describe the different reflexes present in the GI tract involved in constipation and diarrhoea.
Intestino-intestinal inhibitory reflex = distension of one intestinal segment causes complete intestinal inhibition
Anointestinal inhibitory reflex = distension of anus causes intestinal inhibition
Gastrocolic and duodenocolic reflexes = stimulates motility after material has entered the stomach or duodenum
What are the neural components of gut motility?
Post-ganglionic cholinergic enteric nerves —> increase the force of contraction
Non-adrenergic inhibitory nerves —> decrease the force of contraction
