NSAIDS, IBD, Peptic Ulcers

Question 1

Clinical features of IBD

Answer 1

Cramps
Abdominal pain
Diarrhoea 
Blood in faeces 
Fever
Mouth ulcers
Rashes
Arthritic pain
Uveitis 
Weight loss 
Anaemia

Question 2

Supportive therapies for IBD

Answer 2

• fluid production electrolyte replacement
• blood transfusion/oral iron (anaemia)
• nutritional support (malnutrition)

Question 3

Symptomatic treatment for active and preventative of remission of IBD

Answer 3

• glucocorticoids
• aminosalicylates
• Immunosuppressives

Question 4

Potentially curative treatment for IBD

Answer 4

• Faecal transplant, microbiome manipulation

- Biologic therapies

Question 5

Types of aminosalicylates

Answer 5

• mesalazine (5-ASA)

- Olsalazine (2 5asa molecules linked)

Question 6

How does 5-ASA work?

Answer 6

Binds to PPAR gamma, DRIP, RXR

This complex acts as a TF

Downregulates NFkB and Cox2

Hence decreased TNFa, IL6, IL1b and decreased prostaglandins

Question 7

Why would you use Olsalazine?

Answer 7

It is broken down by colonic flora to 5ASA hence drug action is at the colon which is good if active disease there

Mesalazine is absorbed in the small intestine and colon

Question 8

Advantages of 5-ASA for Ulcerative Collitis

Answer 8

• safe
• good at inducing and maintaining remission
• rectal delivery good for proctitis
• better than glucocorticoids

Question 9

Aminosalicylates and Chrons disease

Answer 9

INEFFECTIVE

Question 10

How do glucocorticoids work in IBD

Answer 10

Immunosuppressive and anti inflammatory

• downregulates inflammatory cytokine production
• downregulates activity of macrophages and T lymphocytes

Question 11

Examples of glucocorticoids used in IBD

Answer 11

Prednisolone
Fluticasone
Budesonide

Question 12

Side effects of glucocorticoids

Answer 12

Cushingoid

Question 13

Why is budesonide safer in IBD?

Answer 13

Has fewer side effects as is not absorbed by the gut hence has all its effects then gets excreted

Question 14

Uses of glucocorticoids in IBD

Answer 14

• oral glucocorticoids better than budesonide at inducing remission of CD but use budesonide if mild
• not useful in UC so use 5ASA
• avoid as maintenance therapy due to side effects

Question 15

How does Azothioprine work?

Answer 15

• prodrug converted into 6-mercaptopurine
• purine antagonist which interferes with DNA and cell replication
• enhances T cell apoptosis
• Inhibits lymphocyte proliferation
• impairs synthesis of antibodies
• impairs mononuclear cell infiltration

Question 16

Azathioprine use

Answer 16

Only used in CD

• not used in active disease
• maintains remission
• takes 3-4 months to work
• last treatment option before biologics

Question 17

Side effects of Azathioprine

Answer 17

• pancreatitis
• bone marrow suppression
• hepatotoxicity
• increased risk of skin cancer
• increased risk of lymphoma

Question 18

Which drug contraindicated azathioprine

Answer 18

Allopurinol as it inhibits Xanthine Oxidase

Question 19

What antiobiotics can be used to treat acute H pylori infection causing peptic ulceration

Answer 19

Amoxicillin
Clathromycin
Metronidazole

Question 20

What antibiotics would you give in a chronic H pylori infection

Answer 20

Quinolone
Tetracycline
Proton pump inhibitors (omeprazole)
Bismuth sucralafate

Question 21

What is omeprazole

Answer 21

H+/K+ ATPase antagonist which reduced acid secretion

Question 22

What is Ranitidine

Answer 22

H2 receptor antagonist hence decreased cAMP hence decreased gastric acid secretion

Question 23

How long would you use a PPI if you had an acute h pylori infection

Answer 23

7 days

Question 24

How long would you use a PPI in a chronic peptic ulcer?

Answer 24

4-8/12 weeks

Question 25

Why should NSAIDS be avoided with asthmatics

Answer 25

Inhibition of COX favours lipo-oxygenase pathway hence leukotrienes produced which cause bronchoconstriction

Question 26

What does aspirin selectively inhibit

Answer 26

COX1 irreversibly Antipyretic, anti inflammatory, analgesic and anti-platelet effects

Question 27

What do the coxibs selectively inhibit

Answer 27

COX2

Question 28

Advantage of celecoxib

Answer 28

Doesn’t cause GI ulceration

Question 29

Disadvantages of NSAIDs other than GI ulceration

Answer 29

Salt and water retention Vasoconstriction This leads to hypertension Hence higher risk of cardiovascular disease

Question 30

How do coxibs have their cardiovascular effects

Answer 30

Decreased PGI2: - increased platelet activation - decreased NO -> endothelial dysfunction - increased salt retention - decreased RBF - reduced protection against oxidative injury-> HF Atherogenesis,hypertension, heart failure

Question 31

Why is it more risky to use NSAIDS as an anti inflammatory?

Answer 31

Use often sustained and at higher dose hence more chance of side effects Occasional use as an analgesic is better due to lower risk of side effects

Question 32

Strategies to limit NSAID side effects

Answer 32

- topical administration - minimise in patients with ulceration history - administer omeprazole too

Question 33

Antiplatelet action of NSAIDS due to?

Answer 33

- COX1 Inhibition suppresses thromboxane production | - platelets cannot resynthesise TXA2 as no nucleus

Question 34

Side effects of Aspirin

Answer 34

- GI irritation - bronchospasm - Prolonged bleeding times - Nephrotoxicity These are more down to the fact that there is IRREVERSIBLE inhibition rather than selectivity for COX1

Question 35

Why isn’t aspirin given to patients under 20 usually?

Answer 35

Reye’s syndrome Damage to mitochondria leading to ammonia production which damages astrocytes, this leads to oedema in the brain.

Question 36

What is paracetamol?

Answer 36

Analgesic, anti pyretic but NOT anti inflammatory Therefore not an NSAID