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Irritable Bowel Syndrome Flashcards

1
Q

What is IBS?

A

A spectrum of disorders
Diarrhoea or constipation or both (mixed)
Diagnosed by first ruling out other conditions

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2
Q

Describe how IBS feels?

A

Recurrent abdominal pain / discomfort
Sensation of incomplete evacuation
Passage of mucus
Bloating and flatulence

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3
Q

What are the non GI symptoms of IBS?

A

Fatigue
Fibromyalgia
Anxiety
Depression
Possibly headaches

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4
Q

What is the characterisation of IBS?

A

Ill defined pattern of dysmotility and altered secretion and sensation through the gut
15% of the western population
Lifelong condition
(often first diagnosed in 20-30 year olds)
Female predominance
Absence of structural or biochemical abnormalities

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5
Q

What are the sub classifications of IBS?

A

IBS-diarrhoea (IBS-D)
IBS-constipation (IBS-C)
IBS-mixed (IBS-M)
IBS-unclassified (IBS-U)

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6
Q

Describe IBS-D

A

> 25% loose or watery stools
<25% hard or lumpy stools
Morning frequency (often with urgency)
Usually accompanied by pain that is often relieved by defecating

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7
Q

Describe IBS-C

A

> 25% hard or lumpy stools
<25% loose or watery stools
Sensation of incomplete evacuation
Associated with passage of mucus

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8
Q

Describe IBS-M

A

> 25% hard or lumpy stools
25% loose or watery stools
Symptoms alternate between constipation and diarrhoea
Hard stools in the morning
Progressively watery stools throughout the day

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9
Q

Describe IBS-U

A

<25% hard or lumpy stools
<25% loose or watery stools
Insufficient abnormality of stool consistency to meet criteria for the other types of

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10
Q

What are some of the causes of IBS?

A

Thought to be multi factorial
IBS symptoms will usually follow an infection
There could be chronic low grade inflammation which activates the immune response
(This is significant enough to trigger symptoms but not major structural changes to the gut)

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11
Q

What are some of the proposed theories of causes for IBS?

A

Altered microbiota
Altered serotonin levels
(Raised in IBS-D but reduced in IBS-C)
Abnormalities in the brain gut axis
Neuroimmune dysregulation

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12
Q

What sort of dietary changes should IBS patients make?

A

Eat regularly and don’t skip meals
(5/6 smaller meals rather than 1/2 larger ones)
Limit certain foods
Increase soluble fibre
Increase fluid intake

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13
Q

What foods should be restricted in IBS?

A

Fresh fruit
Carrots and beans
Honey
Fermentable sugars
Caffeine
Alcohol
Fizzy drinks

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14
Q

What are some treatment methods for IBS?

A

Treatments tend to be very tailored to each individual
Anti diarrhoeals / laxatives
Anti spasmodics for pain relief
Paracetamol for pain relief
Treatment of associated depression and anxiety may help

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15
Q

Why should paracetamol be used to help with pain rather that NSAIDs?

A

NSAIDs inhibit the cyclooxygenase enzyme that produces prostaglandins in the gut
Prostaglandins are important in the regulation of intestinal activity
Therefore blocking this would exacerbate the IBS symptoms not alleviate them
Paracetamol blocks prostaglandin synthesis in the brain and directly blocks the pain pathway

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16
Q

Is IBS psychological or physiological?

A

While treating psychological symptoms is seen to help IBS it has also been seen that 40% of people will actually improve under a placebo treatment calling into question how psychological the disease is

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17
Q

What is tachyphylaxis?

A

The appearance of desensitisation after prolonged use

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18
Q

How useful are anti spasmodics?

A

They do relieve pain and reduce spasms however there can be a great variability in the responses seen from individual patients
Some react better than others

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19
Q

What are the antispasmodic agents available?

A

Muscarinic antagonists
Calcium channel blockers
Otilonium bromide
Mebeverine, alverine and peppermint oil

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20
Q

Name some of the muscarinic antagonists that can be used as anti spasmodics

A

Dicycloverine
Hyoscine
Atropine

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21
Q

How do muscarinic antagonists work?

A

They block the action of ACh at the ACh receptors

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22
Q

Name an example of a calcium channel modulator and explain how it works

A

Nifedipine
They are inhibitory modulators of voltage gated L type calcium channels
Reduces the influx of calcium
Reduces the calcium available for muscle contraction
Relives muscle spasms

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23
Q

Describe otilonium bromide

A

Relatively new but quite successful
Has the advantage of poor systemic absorption
(Minimises systemic side effects)
Acts via the luminal side of the intestine
Mixed pharmacological profile
(Blocks both muscarinic and voltage gated channels to reduce contraction)

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24
Q

What are the direct muscle acting relaxants?

A

Mebeverine
Alverine
Peppermint oil

25
What are the benefits of Mebeverine?
It is found to cause both hyperpolarisation and alternating depolarisation Therefore it is useful to the treat hyper contractility and hyper relaxation that is associated with periodic muscle spasms
26
What are the uses of peppermint oil?
Antimicrobial and anti inflammatory properties Useful for treating IBS
27
What are the side effects of peppermint oil being used for IBS?
Can cause heart burn However this overcome by adding an enteric coating to the peppermint oil formulation Allows the peppermint to pass through the stomach and enter the intestine before it dissociates
28
Name some of the common treatments for IBS
Kolanticon - dicycloverine Buscopan - hyoscine Spasmonal - alverine Colofac IBS - Mebeverine Colpermin and mintec - peppermint oil
29
What is eluxadoline?
Novel treatment for IBS Locally acting mu opioid and kappa opioid agonist
30
What does eluxadoline do?
Mu and kappa: Increases muscle tone Reduces motility Reduces secretion Delta opioid antagonist: Prevents excessive slowing of motility
31
What are the side effects of eluxadoline?
Nausea and vomiting Pain Dizziness Spasm of the sphincter of Oddi (rare) Pancreatitis (rare)
32
When should/ shouldn’t eluxadoline be used?
Reserved for those not responding to established therapies Should not be used in those who have had their gall bladder removed or have had a bile duct obstruction
33
How does serotonin (5-HT3) help treat IBS?
Regulating: GI motility Electrolytes Water secretion
34
Which type of IBS are serotonin antagonists most helpful with?
IBS-D Improves pain as well as the lack of consistency of the stools
35
What are some of the concerns for using serotonin antagonists?
Increased risk of ischaemic colitis and severe constipation Potential cardiac arrhythmia due to prolonged QT interval Access is restricted to severe IBS that isn’t controlled by conventional therapies
36
What do serotonin (5-HT4) receptor agonists do?
Regulate GI motility Electrolytes Water secretion
37
What is tegaserod?
5-HT4 partial agonist Pro kinetic agent for constipation predominant IBS decreases pain and bloating Improves other symptoms
38
What are the side effects of tegaserod?
Stroke and myocardial ischaemia (Prolongation of QT interval) It was withdrawn
39
What caused the prolongation of the QT interval seen when using serotonin agonists?
Thought to be cross reactivity at other 5-HT5 subtypes and hERG channels (Repolarising Ikr currents)
40
What is prucalopride?
An alternative serotonin agonist Better tolerated More selective for 5-HT4 receptors Reduced cardiac risks
41
How do chloride channel activators work?
The movement of chloride into the lumen would be associated with the parallel movement of sodium Water will move into the lumen due to osmosis this will help relieve constipation
42
Give an example of a chloride channel activator
Lubiprostone
43
Name two guanylin receptor guanylate Cyclase activators
Linaclotide Plecanatide
44
How do guanylin receptor guanylate Cyclase activators work?
Increase cGMP Activates protein kinase G Increase chloride Bicarbonate secretion Decreases sodium absorption Increases fluid secretion Increases transit Decreases pain and discomfort
45
When should chloride channel modulators be used?
Patients will chronic constipation who have not responded to other laxatives
46
What is crofelemer?
An inhibitor of the CFTR Chloride channel inhibitor
47
Where does crofelemor come from?
Sap from the bark of croton lechleri (Amazonian rainforest)
48
How does crofelemer help?
For IBS-D Decreases secretion and pain Improves stool conisistencies No effect on motility or urgency
49
Why are peripherally restricted opioid receptors useful?
They cannot enter the systemic circulation or penetrate the BBB Block the opioid receptor activation in the periphery while not affecting the action of the drug in the CNS E.G morphine will still producing pain relieving affects without the side effect of constipation
50
What have the results from clinical trials testing tricyclic antidepressants and SSRIs on IBS found?
Lower doses of serotonin are used to not negatively impact the GI tract They have been shown to help reduce and relieve pain
51
How do cannabinoid agonists help IBS?
CB1 and CB2 receptors are shown to reduce Secretion Motility Hypersensitivity Inflammation
52
What do neurokinin and purinergic P2x antagonists do?
Antagonise the neurokinin receptor and the ATP receptor may target IBS symptoms that are caused by bacterial overgrowth
53
How does rifaximin help IBS?
It is not absorbable therefore it will act locally Used for IBS-D Reduces pain and bloating
54
How do bile acids influence the gut?
Bile acids the intestine may be osmotically active and could draw water into the lumen of the bowel
55
What does colesevelam do?
It is a bile acid sequestrant that impedes absorption in the intestine
56
What is elobixibat?
A bile acid modulator that inhibits the reuptake of of bile acids from the intestine More water is secreted/ less water is reabsorbed
57
What happens during a food allergic reaction?
Histamine is released It dilates post capillary venules Activates the endothelium Increases blood vessel permeability (local oedema, warmth, redness) Attracts other inflammatory cells to site of release Depolarises nerve endings Itch, pain, wheal and flare reaction
58
What are some of the strategies to target histamine to reduce allergic response severity?
Sodium cromoglicate - stabilises mast cells and reduces the release of histamine Phosphodiesterase inhibitors - inhibit the the metabolism of cAMP, elevating cAMP in mast cells is important in stabilising them and inhibiting histamine release Chlorphenamine - antihistamine

Pharmacology (18 decks)

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