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Laxatives Flashcards

1
Q

What helps regulate gastrointestinal motility?

A

The central nervous system
The enteric nervous system
GI hormones

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2
Q

What are the important mediators that regulate gastrointestinal motility?

A

Serotonin
Tachykinins (substance P and neurokinin A)
Nitric oxide
Prostaglandins
ATP
Peptides (opioids)

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3
Q

What are two reasons for the most common disorders of the GI tract?

A

Enteric neuropathies
Dysfunction of the brain-gut or gut-brain axis

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4
Q

Give an example of how the brain-gut axis can be affected

A

Neuro active drugs like those used in psychiatry are often associated with GI side effects

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5
Q

What is constipation?

A

The passage of small hard stools with excessive straining and less frequently that is normal for that individual

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6
Q

What can influence the consistency of stool?

A

During constipation the stool will remain in the colon longer allowing it to absorb more water. This will result in the stool becoming harder making it more painful to pass

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7
Q

Which part of the GI tract does constipation affect?

A

The large bowel

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8
Q

What are some of the anatomical reasons for constipation?

A

Absence of propagating contractions in the colon or an altered frequency of propagations
Abnormal propulsion generalised or restricted to part of the colon

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9
Q

Who does constipation affect?

A

Seen in roughly 20% of the population
Especially in the elderly population
Higher incidence in women that in men

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10
Q

What are causes of constipation?

A

Diet low in fibre and fluid
Diet high in caffeine
Slow gut transit (higher in women)
Immobility (lack of exercise - seen in elderly people)
Drug induced as a side effect of
Hypotonic colon
Underlying diseases

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11
Q

How does a high caffeine diet affect the chances of constipation?

A

which inhibits the metabolism of cyclic AMP by phosphodiesterase,
cAMP is able to relax the smooth muscle in the intestine
however it is also a diuretic meaning it will cause more water to cross into the lumen thereby exacerbating the constipation

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12
Q

What is hypotonic colon?

A

Seen in the elderly following chronic laxative abuse
The colon smooth muscle is deconditioned so that the contractions become less forceful

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13
Q

What sort of underlying diseases can result in constipation?

A

Colonic cancer
Pelvic floor dysfunction
Endocrine disorders - hypothyroidism or diabetes
Neurological disorders - Parkinson’s, stroke, and psychological disorders

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14
Q

What are the treatment plans for constipation?

A

Improved fibre and fluid up take
Improve mobility and exercise regime
Try and remove any drugs that may be causing the constipation
Treat any underlying issue that may be causing it with drugs that won’t exacerbate it
Only then should you move to laxatives

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15
Q

Why should laxatives be avoided if possible?

A

Abuse might cause hypokalaemia the loss of potassium which can result in arrhythmias
This is more severe in the elderly

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16
Q

What are acceptable circumstances that laxatives are used for?

A

The straining may exacerbate angina attacks
Or cause severe rectal bleeding in someone with haemorrhoids
For relief from drug induced constipation
For the expulsion of parasitic waste after anti helminthic treatment
To clear the bowel for surgery or radiological screening

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17
Q

How many classes of laxative are there?

A

Class 1: bulk forming laxatives
Class 2: osmotic laxatives
Class 3: stimulant contact or irritant laxatives
Class 4: faecal softeners

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18
Q

Give some example of bulk forming laxatives

A

Methyl cellulose
Sterculia gum
Ispaghula husk
Unprocessed bran (oat, wheat)

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19
Q

What are bulk forming laxatives?

A

Non digestible polysaccharide polymers

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20
Q

When should bulk forming laxative be used?

A

For bran intolerant individuals or when fibre (bran) is insufficient in the diet

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21
Q

How do bulk forming laxatives work?

A

They absorb water and swell
This increases faecal mass which will distend the colon
This stimulates colonic mucosal receptors
Increases peristaltic motility
There will be an increased proliferation of colonic bacteria which also increases faecal bulking

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22
Q

What are the benefits / downsides of bulk forming?

A

It normalises the stool texture
But it takes a few days for the full effect to be felt (not immediate)
Can cause bloating, flatulence, abdominal pain, and obstruction

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23
Q

What are two brands that are considered bulk forming?

A

Fybrogel
Regulan

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24
Q

What sort of patients would be given a bulk forming laxative?

A

Colostomy / ileostomy patients
Constipation predominant irritable bowel syndrome
Haemorrhoids
Anal fissure

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25
What are osmotic laxatives?
Poorly absorbed solutes
26
How do osmotic laxative work?
They are poorly absorbed and so will remain in the lumen of the bowel They will increase the fluid volume in the bowel and increase fluid secretion into the lumen Larger volumes will distend the colon The distension will increase peristaltic movement
27
How long does it take osmotic laxatives to work?
Roughly 3 hours
28
Describe the example of lactulose as an osmotic laxative
It is a disaccharide of galactose and fructose It is not absorbed from the intestine It is broken down by colonic bacteria into lactic and acetic acids It prompts osmosis and peristalsis Effective within 2-3 days
29
What are the side effects of osmotic laxatives?
Flatulence Cramps Osmotic diarrhoea of low faecal pH Nausea
30
What are warning associated with lactulose?
Safe for long term use but tolerance may build Avoid in lactose intolerant patients
31
Explain the example of macrogols as an osmotic laxative
They are inert polymers of ethyl glycol They sequester fluid in the bowel lumen Should be given with fluids to avoid a dehydrating effect Relatively safe and effective in the elderly and pediatric populations
32
Give two brand names of osmotic laxatives
Movicol Laxido Both macrogols
33
Which is better lactulose or macrogols?
Macrogols are superior in stool frequency, form and pain relief
34
Explain the example of saline purgatives as osmotic laxatives
Commonly abused Only suitable for occasional use Fluid uptake should be maintained Many are magnesium salts - stimulate a chemical mediator CCK CCK - Important for motility and fluid retention Rapid bowel evacuation
35
Why are saline purgatives less frequently used?
They are associated with heart block Neuromuscular block CNS depression (esp in children and the Renally impaired) Hypertonic solutions can cause emesis (vomiting)
36
What are the three types of saline purgatives?
Magnesium salts Sodium citrate Phosphate enemas - endoscopies
37
What do stimulant contact or irritant laxatives do?
Act within hours Mechanism poorly understood Could be damage to intestinal cell walls which weaken cell junctions May stimulate local reflexes of the myenteric plexus Potentially increases prostaglandins, cAMP, CCK and VIP synthesis To increase the motility, decrease the absorption and increase the secretion of water and electrolytes
38
What are the four examples of irritant laxatives?
Senna Dantron Bisacodyl Sodium picosulphate
39
How does senna work?
It is a plant alkaloid Constituent anthroquinones metabolised by gut bacteria The metabolites stimulate the enteric nervous system Alters the fluid balance across the gut wall Increases pulsatile motility
40
Who is given dantron?
Only for the elderly and the terminally ill Due its potential to be carcinogenic
41
How is bucacodyl taken?
Given rectally for rapid response
42
When is sodium picosulfate used?
Preoperatively before bowel surgery or examination
43
Are irritant laxative safe for long term use?
Although previously though to be unsafe for prolonged use they are now generally considered safe for long term use
44
Why were irritant laxative initially though to be unsafe for long term use?
Abdominal cramping and intestinal obstruction Could lead to diarrhoea and loss of potassium Decreased propagative motility and dilation Increased electrolyte imbalances Exacerbations to underlying issues Potential tolerance developing
45
When are bowel cleansing solutions used?
Before colonic surgeries or endoscopies to ensure bowel is free of solid contents Not meant for constipation
46
What are some examples of bowel cleansing solutions?
Citramag (magnesium carbonate and Citric acid) Klean prep (macrogol and sodium bicarbonate) Picolax (sodium picosulfate and magnesium citrate)
47
What is an example of a faecal softener?
Docusate sodium (detergent)
48
Explain the example of docusate sodium
It is a stimulant laxative and a softening agent Promotes intestinal fluid secretion Stimulates intestinal motility (weakly) It is effective after 1-2 days It is safe in pregnancy
49
What are some other examples of faecal softeners?
Glycerol - suppositories Arachis oil (nut oil) for enemas? Liquid paraffin - may cause anal seepage and interferes with absorption of fat soluble vitamins
50
What is lubiprostone?
A novel therapeutic approach to constipation A prostone metabolite of prostaglandin E1
51
What is the mechanism of action of lubiprostone?
It is an activator of type 2 chloride channels Increases the intestinal fluid secretion Increases passive movement of sodium and water into the lumen Increases transit and spontaneous bowel movements Acts on luminal side not absorbed systemically
52
What are the side effects of of lubiprostone?
Nausea Headache Abdominal pain Diarrhoea
53
What do prokinetic drugs treat?
Motility disorders of the upper GI tract
54
What are the two divisions of pro kinetic drugs?
Parasympathomimetics Dopamine D2 antagonists
55
What do parasympathomimetics do?
They mimic the actions of ACh
56
What are the examples of parasympathomimetics?
Bethanchol (Muscarinic agonist) Neostigmine (AChE inhibitor) Cisapride (5-HT4 agonist)
57
What are the examples of D2 antagonists?
Metoclopramide Domperidone
58
What are some of the details about cisapride?
It is a 5-HT4 agonist Increases release of ACh from the myenteric plexus in the upper GI Effective in disorders of gastric emptying Was withdrawn due to an increased risk of cardiac dysrhythmia
59
How to dopamine antagonists work?
Local action Increase gastric emptying Quicken intestinal transit time Used when giving a barium meal to test a patients gut health
60
What are some of the factors of drug induced constipation or diarrhoea?
Altered Mucosal permeability Transport Metabolism Ion and fluid secretion Enteric nerve activity Propulsive motor activity
61
What should you do if you have drug induced constipation or diarrhoea?
Wait and see if it resolves Side effect may become less severe with time of the drug is essential Switch to a drug with less severe side effects Add a laxative drug for constipation
62
How do opioids cause constipation?
They react with opioid receptors of the intestine as well as those found in the brain for pain relieving effects This causes a reduction in contractility Potentially interferes with absorption and secretion of fluids
63
What are some methods to tackle opioid induced constipation?
The use of opioid receptor antagonist which are poorly absorbed systemically due to high first pass metabolism, these would work to block the receptors in the lumen but not affect those found in the brain The use of peripherally restricted opioid antagonists, again will interact with the intestine but cannot cross the blood brain barrier
64
What are some examples of opioid antagonists to reduce constipation?
Alvimopan Methylnaltrexone Naloxone
65
How is Naloxone improved?
Naloxone can be conjugated with polyethylene glycol to form naloxegol This new compound is 15x less able to cross the blood brain barrier tha Naloxone on its own

Pharmacology (18 decks)

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