Laxatives and Emetics

Question 1

What is constipation?

How does it happen?

Answer 1

Less frequent bowel emptying compared to a patients normal pattern

Excessive water reabsorption and inadequate peristalsis (hard, dry and painful on passing)

• Occurs often in elderly patients with fibre deficient diets
• Can be drug induced (opioids, CCB’s, antidepressants)

Question 2

What treatments are available for constipation?

Answer 2

Laxatives

1) Bulk-forming agents (swells, bulk triggers peristalsis)
2) Stimulant laxatives (triggers)
3) Osmotic agents (attract water)
4) Lubricant/stool softeners
5) Secretagogues (newer agents)

Question 3

Bulk-forming agents

role, examples and side effects

Answer 3

Indigestible vegetable material attracts water and swells in colon causing increase peristalsis and a softer stool

• hydrophilic colloids
• takes several days to begin working, no s/e

Ispaghula husk
Methylcellulose, high fibre diets (bran)
- can cause flatulence and abdominal swelling
Sterculia

Question 4

Osmotic laxatives (5)
(role, examples and side effects)

Answer 4

Attract water to soften stools

1) Lactulose
- synthetic non-absorbable disaccharide
- acts 24 - 48 hours
- suitable for chronic constipation
- s/e: cramps, flatulence, diarrhoea, electrolyte disturbance, tolerance

2) Macrogols
- inert polymers of ethylene glycol
- superior to lactulose

4) Magnesium salts (epsom salts)
- acts 2-4 hours

5) Sodium citrate or phosphate enemas
- rectal use prior to endoscopy/surgery

Question 5

Stimulant laxatives

role, examples and side effects

Answer 5

Induces propagated colonic contractions, forcing bolus down colonic region
- single dose

1) Bisacodyl
- Works in 8 hours (administered night before)
- Stimulates enteric nerves
- can cause cramping

2) Senna
- anthraquinone
- stimulates myenteric plexus

3) Glycerol suppositories
- mild stimulant

4) Dantron
- terminally ill patients with constipation
- often used for opioid-induced constipation
- proven carcinogenic in rodents and is a skin irritant

Question 6

Lubricant laxatives

role, examples and side effects

Answer 6

Stool softeners/emollients (increases fluid contents)

• useful for haemorrhoids and anal fissures
• s/e: pneumonia

1) Docusate sodium
- surface active agent acts like detergent and used as stool softener

2) Arachis
- peanut/nut oil used as enema

3) Liquid paraffin no longer used

Question 7

Secretagogues

role, examples and side effects

Answer 7

Modulation of electrolyte secretion and motility

1) Prucalopride
- 5HT4 antagonist
- for chronic constipation unresponsive to conventional laxatives
- increases colon transit by stimulating 5HT4 receptors and enteric nerves involved in peristalsis

2) Lubiprostone
- PGE1-like and CFTR (Cl-) activator
- enhances fluid and mucosal Cl- secretion
- colonic motility
NB: can directly open CFTR itself or can act on epithelial lining for cAMP mechanism to open CFTR

Question 8

Where and how does Prucalopride act?

Answer 8

5HT4 receptors found on ECL cells

• release 5HT
• acts on enteric sensory nerves on epithelia
• acts across nerves found in submucosal plexus and myenteric plexus

Mucosal secretion is coordinated with contraction of smooth muscle (pro-secretion coincides with pro-motility)

Question 9

What is diarrhoea?

Answer 9

Increased frequency (>3), fluidity and volume of stools

Question 10

How does diarrhoea occur?

Answer 10

Hypermotility (quick transit time through colon)
Failure of colonic water reabsorption

Often transient, but serious/chronic requires intervention, such as fluid replacement

Question 11

What causes diarrhoea? (8)

Answer 11

1 Diarrhoea diseases e.g. rotavirus, cholera
2 Large parasites (worms, amoebic dysentery)
3 Viral Gastroenteritis
4 Irritant drugs and poisons
5 Allergic reactions
6 Chronic inflammatory bowel diseases
7 Irritable bowel syndrome
8 Bacterial (food poison, travellers diarrhoea)

Question 12

What is irritable bowel syndrome?

Answer 12

Abnormal bowel activity with alternative episodes of diarrhoea and constipation
- associated with colic pain (comes and goes)

Question 13

How is irritable bowel syndrome treated?

Answer 13

Symptomatic

1) Anxiolytics
2) Direct acting anti-spasmodics (mebeverine)
3) Anti-motility drugs (loperamide)
4) Dietary improvement

Question 14

Main piece of lifestyle advice can be given for diarrhoea?

Answer 14

Plenty of fluid intake to prevent dehydration

Question 15

Treatments for diarrhoea? (5)

Answer 15

1) Oral rehydration therapy
2) Narcotic anti-diarrhoeal (loperamide, co-phenotope)
3) Kaolin or charcoal (adsorb toxins)
4) Racedotril (enkephalinase inhibitor: prevents degradation of enkephalins that are pro-absorptive)
5) Ciprofloxacin (occasional antibiotic)

Question 16

What is ORT?

Answer 16

Oral rehydration therapy (oral or IV)

• replacing electrolytes and water to prevent dehydration and electrolyte disturbance
• Glucose: enhances intestinal absorption of salts and water
• NaHCO3: alkalinising agent to counter acidosis

Question 17

What benefits is there for dietary improvements?

Answer 17

Increased indigestible vegetable fibre promotes regular bowel movement

• enhances mechanical efficiency (provides ‘bulk)
• increases transit time
• absorbs water

Question 18

What is term encompasses nausea and vomiting?

What causes this?

Answer 18

Emesis

• common feature of disease and drug toxicity
• vomiting: activation of chemoreceptor trigger zone in brain stem

Question 19

Treatment for emesis

Answer 19

1) Hyoscine: muscarinic antagonist
- blocks cholinergic input into vomiting centre
- motion sickness

2) Promethazine
- H1 antagonist

3) Aprepitant
- NK1 receptor blocker (neurokinin, substance P initiating emesis)

4) 5HT3 antagonists (ondansetron)

5) D2 antagonists (domperidone, metoclopramide)
- block CTZ (indirect mechanism)

Question 20

What natural substance causes emesis?

When is it used?

Answer 20

Ipecacuanha

• suspected poisoning e.g. pesticides
• triggers CTZ for emesis and stimulates vomiting reflex

Question 21

What is often used for pregnancy associated sickness?

Answer 21

Promethazine

Question 22

What is used to treat radiation and cytotoxic drug emesis?

Answer 22

Ondansetron (5HT)
Aprepitant
Nabilone (synthetic cannabinoid) 
Dexamethasone (anti-emetic corticosteroid)
Domperidone