Anti-emetics & Laxatives Flashcards

1
Q

What are the myogenic components of gut motility?

A

Rhythmic contraction via slow waves of depolarisation through smooth muscle

Passive spread of current through gap junctions

Interstitial cells of Cajal act as pacemaker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the hormonal components of gut motility?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the preliminary signs that someone is going to vomit?

A
  • retching
  • increased salivation
  • nausea
  • dilated pupils
  • sweating
  • paleness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the mechanism of vomiting?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the neurological control of vomiting?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Give some examples of states which stimulate the medullary vomiting centre.

A
  • pregnancy
  • drugs, toxins
  • pain
  • irradiation
  • smell
  • touch (gag reflex)
  • rotational movement (vestibular system)
  • raised ICP
  • stomach stretching
  • inflammation of stomach
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the different pharmacological treatments for nausea and vomiting?

A

D2 receptor antagonists

5-HT3 receptor antagonists

ACh antagonists

H1 antagonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

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.

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

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.

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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.

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Give examples of H1 antagonists. Describe the pharmacokinetics of these drugs. When are they indications? Give examples of ADRs associated with their use.

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the general management for constipation?

A

Consider underlying cause:

  • mechanical obstruction
  • cancer
  • diabetes
  • Parkinson’s
  • dehydration
  • pregnancy

Increase fluid intake

High fibre diet

Exercise

Laxatives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the difference between a suppository and an enema?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the different classes of laxatives?

A

Bulk laxatives

Faecal softeners

Osmotically active

Irritant/stimulant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

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.

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give examples of faecal softeners. Describe the mechanism of these drugs. When are they indicated?

A

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

17
Q

Give examples of osmotically active laxatives. Describe their mechanisms of action. When are they indicated?

A

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

18
Q

Give examples of irritant/stimulant laxatives. Describe their mechanism of action. When are they indicated? Give examples of ADRs associated with their use.

A

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

19
Q

Contrast the laxatives indicated when the faeces are soft or hard.

A

Soft faeces = give stimulant laxatives e.g. senna, glycerol

Hard faeces = give osmotic laxatives e.g. Movicol OR bulk-forming laxatives e.g. ispaghula

20
Q

Describe how constipation can lead to hypokalaemia. How can hypokalaemia mimic constipation?

A

“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”

21
Q

What is the general management of diarrhoea?

A

Consider underlying cause

May represent overflow incontinence (constipation)

Fluid/electrolyte management is important

Anti-diarrhoeal drugs treat symptoms, not cause

22
Q

What are the different pharmacological agents used for diarrhoea?

A

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

23
Q

Give examples of anti-motility drugs. Describe their mechanism of action. When are they indicated? Give examples of ADRs associated with their use.

A

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
24
Q

How do bulk-forming laxatives treat diarrhoea? When are they indicated?

A

Retain water —> produces more formed stool

Indications:

  • IBS (constipation and diarrhoea)
  • ileostomy

+ mebeverine also relieves intestinal spasm (useful in IBS)

25
Q

Give an example of a fluid adsorbent. How does it treat diarrhoea? When is it indicated?

A

e.g. kaolin

Absorbs fluid —> produces more formed stool

Little use

26
Q

What is irritable bowel syndrome?

A

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

27
Q

Describe the different reflexes present in the GI tract involved in constipation and diarrhoea.

A

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

28
Q

What are the neural components of gut motility?

A

Post-ganglionic cholinergic enteric nerves —> increase the force of contraction

Non-adrenergic inhibitory nerves —> decrease the force of contraction