Anti-Inflammatories

Question 1

How do NSAIDs work?

Answer 1

They decrease prostaglandin and thromboxane production

Question 2

What are the three properties of NSAIDs?

Answer 2

Anti-Inflammatory - decrease vasodilation and in turn oedema, they’re ineffective against mediators that contribute to tissue damage associated with chronic inflammatory conditions
Analgesic - decrease production of prostaglandins in inflammed tissue which sensitises nociceptiors to inflammatory mediators
Thermostat in hypothalamus activated via IL-1 induced COX production of PDE

Question 3

What is the structure of COX?

Answer 3

Two identical subunits, each with two catalytic sites

Question 4

What are the two isoforms of COX and how do they differ?

Answer 4

COX1 - constitutive expression

COX2 - inducible expression

Question 5

Where is COX1 present?

Answer 5

Platelet, stomach, kidneys, most tissue

Question 6

Where is COX2 present?

Answer 6

Most cells, especially imflammatory cells after stimulation with cytokines, growth factors or tumour promoters

Question 7

How do NSAIDs exert their action?

Answer 7

They block COX channels

Question 8

What are some side effects of NSAIDs?

Answer 8

Diarrhoea, nausea, vomiting (PGs normally inhibit acid secretion and protect muscosa)
Renal failure (PGs maintain renal blood flow)
Liver damage
Bronchospasm asthma attacks
Skin rashes

Question 9

What are the advantages and disadvantages of COX1 selective NSAIDs?

Answer 9

Advantages:
Antithrombotic
Disadvantages:
Gastrotoxicity

Question 10

What are the advantages and disadvantages of COX2 selective NSAIDs?

Answer 10

Advantages:
Anti-inflammatory, analgesic
Disadvantages:
Increase BP, salt retention, prothrombotic

Question 11

How does Aspirin prevent the action of arachnoid acid?

Answer 11

Aspirin binds covalently to a Ser residue in COX preventing arachnoid acid reaching the cyclooxygenase site

Question 12

Aspirin vs Paracetamol

Answer 12

Aspirin:
Reduced risk of Alzheimer’s, reduced risk of colonic and rectal cancer, anti-platelet action, weak acid, rapid and efficient absorption in the ileum, suicide inhibitor
Paracetamol:
Analgesic-antipyretic, weak anti-inflammatory, well absorbed, metabolised in the liver, N-acetyl-p-quinoneimine is heptotoxic in unconjugated form, competitive inhibitor

Question 13

Which drugs are used to treat rheumatoid joint damage?

Answer 13

Methotrexate and sulfasalazine

Question 14

What is methotrexate?

Answer 14

A folic acid antagonist, has cytotoxic and immunosuppressant activity

Question 15

What is sulfasalazine?

Answer 15

A sulfa drug used for chronic inflammatory bowel disease

Question 16

What do bacteria in the colon produce that may act as a free radical scavenger?

Answer 16

5-aminosalycylic acid, decreased damage produced by neutrophils

Question 17

How do immunosuppressant drugs decrease the inflammatory response?

Answer 17

They inhibit the induction phase of the inflammatory response

Question 18

How do ciclosporin and glucocorticoids reduce the inflammatory response?

Answer 18

They inhibit the transcription of proinflammatory cytokines

Question 19

What are the advantages of humanised monoclonal antibodies?

Answer 19

They have high affinity and selectivity for the target
They neutralise action of membrane bound or soluble proinflammatory cytokines
They have a long half life

Question 20

What happens during type-I hypersensitivity?

Answer 20

Mast cells have IgE Fc receptors
IgE antibodies produced against the allergen bind to the Fc receptors
Allergen binds to IgE antibodies and leads to crosslinking which leads to degranulation
Degranulation leads to smooth muscle contraction, increased vascular permeability, mucous secretion, platelet activation, stimulation of nerve endings, recruitment and activation of eosinophils

Question 21

What causes allergic rhinitis?

Answer 21

The allergen activates mast cells in the nasal mucous and conjuntivae
Hayfever

Question 22

What is allergic asthma?

Answer 22

Allergen activates mast cells in lower respiratory tract

Question 23

What happens during early and late phase asthma?

Answer 23

Early - reversible airway obstruction, inflammation. Increased number of mast cells in bronchi mediate these effects
Late - cytokine to leukocyte infiltration

Question 24

What is asthma associated with?

Answer 24

Over activity of TH2 cells, leads to increased IgE antibodies

Question 25

Which molecules cause a late phase asthma attack?

Answer 25

Cytokines and chemokines released during the immediate phase

Question 26

What are some new therapies for treating asthma?

Answer 26

Humanised antibodies and soluble receptors to IgE, cytokines and chemokines
PGD2R antagonists