Drugs to Treat Inflammation

Question 1

What do glucocorticoids inhibit?

Answer 1

Arachidonic acid release and metabolism

Question 2

What do NSAIDs inhibit?

Answer 2

Cyclo-oxygenases

Question 3

What do cysteinyl leukotriene 1 receptor antagonists inhibit?

Answer 3

LTD4 and LTD5 actions

Question 4

Why are prostaglandins not commonly used as a drug?

Answer 4

Too unstable and expensive

Question 5

What prostaglandin is used in pulmonary hypertension?

Answer 5

Epoprostenol PGI2 analogue

Question 6

What are the effects of NSAIDs?

Answer 6

Anti-inflammatory = palliative for manifestations of inflammation
Analgesic - limit hyperalgesic effects of prostaglandins
Anti-pyretic

Question 7

What are the indications for NSAIDs as an anti-inflammatory?

Answer 7

Acute and chronic conditions

• Rheumatoid arthritis
• Gout > NOT aspirin

Question 8

Why is aspirin not used in gout?

Answer 8

Competes with uric acid for transporter > makes condition worse

Question 9

When are NSAIDs indicated as an analgesic?

Answer 9

Headache
Menstrual pain
Musculoskeletal pain

Question 10

Are NSAIDs curative?

Answer 10

No, palliative

Question 11

What are the gastro-protective roles of PGE2?

Answer 11

Increases mucus secretion
Reduces gastric acid secretion
Promotes blood flow
Promotes angiogenesis

Question 12

How do NSAIDs cause cause gastrointestinal adverse effects?

Answer 12

Inhibit mucosal synthesis of PGI2 and PGE2

Question 13

How do NSAIDs increase bleeding time?

Answer 13

Decrease TXA2 synthesis > impaired platelet aggregation

Question 14

How do NSAIDs cause renal and vascular adverse effects?

Answer 14

Compromise renal blood flow
- Decrease prostacyclin dilation
Increase blood pressure
- Decrease PGE2 natriuresis

Question 15

When may NSAIDs cause renal failure?

Answer 15

Hypovolaemic
Underlying renal disease
Heart failure

Question 16

In which demographic is renal failure caused by NSAIDs more common?

Answer 16

Elderly

Question 17

What is aspirin-sensitive asthma?

Answer 17

Respond to NSAIDs with bronchospasm

Question 18

What proportion of people with asthma are affected with aspirin-sensitive asthma?

Answer 18

10%

Question 19

How does asprin resolve inflammation?

Answer 19

Suppression of pro-inflammatory compounds

Promotion of substances that resolve inflammation

Question 20

Why is aspirin use contra-indicated in children?

Answer 20

Reye’s syndrome

- Liver toxicity, particularly associated with viral infection in children under 12

Question 21

How are aspirin-triggered lipoxins formed?

Answer 21

Acetylated COX2

Question 22

What are aspirin-triggered lipoxins?

Answer 22

Inflammation-resolving lipids

Aren’t usually made

Question 23

How does the use of aspirin in cardiovascular disease work?

Answer 23

Increases ratio of PGI2/TXA2 in blood vessels, via loss of COX activity in platelets, which
- Selectively reduces thromboxane
- Prostacyclin preserved
Dilates vessels
Diminishes platelet reactivity

Question 24

What are the effects of paracetamol?

Answer 24

Analgesic

Anti-pyretic

Question 25

Which demographic is paracetamol especially used in?

Answer 25

Children

Question 26

Does paracetamol have anti-inflammatory effects?

Answer 26

No

Question 27

What is the mechanism of action of paracetamol?

Answer 27

Still uncertain

Question 28

What does paracetamol cause in overdose?

Answer 28

Irreversible liver failure

Question 29

What are the differences between different structural classes of NSAIDs?

Answer 29

Potency Half lives Make them more or less helpful in different applications

Question 30

What are the indications for glucocorticoids?

Answer 30

``` Physiological replacement; eg: Addison's disease Anti-inflammatory - Asthma - Topical - Hypersensitivity states - Rheumatoid arthritis ```

Question 31

What is the mechanism of action of glucocorticoids?

Answer 31

Gene regulatory effects > anti-inflammatory effects - Transactivation - Transrepression

Question 32

What is transactivation in terms of glucocorticoid action?

Answer 32

Transcription factors interact with promoter regions of target genes

Question 33

What is transrepression in terms of glucocorticoid action?

Answer 33

Protein-protein interaction | Glucocorticoid receptor binds to pro-inflammatory transcription factors > blocks their effects

Question 34

What is neutralisation of TNF-alpha used as a treatment in?

Answer 34

Rheumatoid arthritis

Question 35

What are the adverse effects of neutralisation of TNF-alpha?

Answer 35

Reactivation of latent TB | Other developing infections need aggressive antibiotic treatment