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Pharmacology > Irritable Bowel Syndrome > Flashcards

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
Q

What are the benefits of Mebeverine?

A

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
Q

What are the uses of peppermint oil?

A

Antimicrobial and anti inflammatory properties
Useful for treating IBS

27
Q

What are the side effects of peppermint oil being used for IBS?

A

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
Q

Name some of the common treatments for IBS

A

Kolanticon - dicycloverine
Buscopan - hyoscine
Spasmonal - alverine
Colofac IBS - Mebeverine
Colpermin and mintec - peppermint oil

29
Q

What is eluxadoline?

A

Novel treatment for IBS
Locally acting mu opioid and kappa opioid agonist

30
Q

What does eluxadoline do?

A

Mu and kappa:
Increases muscle tone
Reduces motility
Reduces secretion
Delta opioid antagonist:
Prevents excessive slowing of motility

31
Q

What are the side effects of eluxadoline?

A

Nausea and vomiting
Pain
Dizziness
Spasm of the sphincter of Oddi (rare)
Pancreatitis (rare)

32
Q

When should/ shouldn’t eluxadoline be used?

A

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
Q

How does serotonin (5-HT3) help treat IBS?

A

Regulating:
GI motility
Electrolytes
Water secretion

34
Q

Which type of IBS are serotonin antagonists most helpful with?

A

IBS-D
Improves pain as well as the lack of consistency of the stools

35
Q

What are some of the concerns for using serotonin antagonists?

A

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
Q

What do serotonin (5-HT4) receptor agonists do?

A

Regulate
GI motility
Electrolytes
Water secretion

37
Q

What is tegaserod?

A

5-HT4 partial agonist
Pro kinetic agent for constipation predominant IBS
decreases pain and bloating
Improves other symptoms

38
Q

What are the side effects of tegaserod?

A

Stroke and myocardial ischaemia
(Prolongation of QT interval)
It was withdrawn

39
Q

What caused the prolongation of the QT interval seen when using serotonin agonists?

A

Thought to be cross reactivity at other 5-HT5 subtypes and hERG channels
(Repolarising Ikr currents)

40
Q

What is prucalopride?

A

An alternative serotonin agonist
Better tolerated
More selective for 5-HT4 receptors
Reduced cardiac risks

41
Q

How do chloride channel activators work?

A

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
Q

Give an example of a chloride channel activator

A

Lubiprostone

43
Q

Name two guanylin receptor guanylate Cyclase activators

A

Linaclotide
Plecanatide

44
Q

How do guanylin receptor guanylate Cyclase activators work?

A

Increase cGMP
Activates protein kinase G
Increase chloride
Bicarbonate secretion
Decreases sodium absorption
Increases fluid secretion
Increases transit
Decreases pain and discomfort

45
Q

When should chloride channel modulators be used?

A

Patients will chronic constipation who have not responded to other laxatives

46
Q

What is crofelemer?

A

An inhibitor of the CFTR
Chloride channel inhibitor

47
Q

Where does crofelemor come from?

A

Sap from the bark of croton lechleri
(Amazonian rainforest)

48
Q

How does crofelemer help?

A

For IBS-D
Decreases secretion and pain
Improves stool conisistencies
No effect on motility or urgency

49
Q

Why are peripherally restricted opioid receptors useful?

A

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
Q

What have the results from clinical trials testing tricyclic antidepressants and SSRIs on IBS found?

A

Lower doses of serotonin are used to not negatively impact the GI tract
They have been shown to help reduce and relieve pain

51
Q

How do cannabinoid agonists help IBS?

A

CB1 and CB2 receptors are shown to reduce
Secretion
Motility
Hypersensitivity
Inflammation

52
Q

What do neurokinin and purinergic P2x antagonists do?

A

Antagonise the neurokinin receptor and the ATP receptor may target IBS symptoms that are caused by bacterial overgrowth

53
Q

How does rifaximin help IBS?

A

It is not absorbable therefore it will act locally
Used for IBS-D
Reduces pain and bloating

54
Q

How do bile acids influence the gut?

A

Bile acids the intestine may be osmotically active and could draw water into the lumen of the bowel

55
Q

What does colesevelam do?

A

It is a bile acid sequestrant that impedes absorption in the intestine

56
Q

What is elobixibat?

A

A bile acid modulator that inhibits the reuptake of of bile acids from the intestine
More water is secreted/ less water is reabsorbed

57
Q

What happens during a food allergic reaction?

A

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
Q

What are some of the strategies to target histamine to reduce allergic response severity?

A

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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