Anti-inflammatories

Question 1

What is inflammation

Answer 1

Physiological:
- a protective response by the body to something harmful:
* injury
* microbial infection
* exposure to noxious stimuli

Pathological:
- inflammation that is appropriate or overexuberent (inflammatory diseases)

Question 2

Describe the key steps of acute inflammation

Answer 2

1. Trigger (bacteria or injury)
2. Recognition by the immune cells (PAMPs released by the pathogen which are recognised by the receptors on sentinel cells)
3. Release of inflammatory mediators e.g. histamine, leukotrienes, cytokines (e.g. TNF-a, IL, chemokines)
4. Vasodilation- inflammatory mediators act on blood vessels and cause vasodilation to increase vascular permeability so fluid can enter the tissues (containing coagulation factors, complement proteins, immune cells)

Cellular component - recruitment of leukotrienes

5. TNF-a acts on endothelium, endothelial cells of blood vessel express adhesion molecules called selectins
6. immune cells in the blood (neutrophils) will attach and pass into the tissue
7. elimination of microbes and dead tissue
8. repair

Question 3

Describe the key steps of the adaptive immune response

Answer 3

1. macrophage/dendritic cells recognise pathogens PAMPs - engulfs, lysosomes inside will digest pathogen and antigens will be presented with MHC on cell surface - this is now an antigen presenting cell
2. APC presents antigen on MHC to t cell
3. CD80/CD86 (B7.1/2) on APC binds to CD28 on t helper cell which is called the co stimulation reaction - this activates the t helper cell and causes proliferation
4. t helper cell releases cytokines which activate cytotoxic t cells and activate B cells
5. to activate B cells the antigen also needs to bind to B cell
6. B cells differentiate into plasma cells which release antibodies and kill the pathogen

Question 4

What is the mechanism of action of NSAIDs

Answer 4

they inhibit cyclooxygenase enzymes (COX1 and COX2)
They can be :
- non-selective e.g. aspirin, ibuprofen
- Coxibs - COX-2 selective

They exert anti-inflammatory, antipyretic and analgesic effects

in chronic diseases they are useful for symptomatic relief

Question 5

What are glucocorticoids used for, and describe the mechanism of action

Answer 5

they are steroids used for acute treatment of inflammatory diseases

They bind to the GR

Then translocate into the nucleus

Alter gene transcription of pro-inflammatory genes

Question 6

Give and example of a glucocorticoid

Answer 6

Cortisone

Question 7

What are 4 side effects of glucocorticoids

Answer 7

1. osteoporosis
2. high blood pressure
3. diabetes
4. cushing’s disease

Question 8

What are 3 types of DMARDs

Answer 8

1. Conventional synthetic DMARDs
2. Biologic DMARDs
3. Targeted synthetic DMARDs

Question 9

What is the MoA of conventional synthetic DMARDs

Answer 9

non specific

Question 10

What are the 2 main pharmacological effects of csDMARDs

Answer 10

• antiproliferative - this can affect activation and proliferation of lymphocytes which can have an immunosuppressive effect
• cytotoxic - can affect other rapidly dividing cells which means they can have side effects

Question 11

What are 2 limitations of csDMARDs

Answer 11

• need regular monitoring
• take time to exert effects (months)

Question 12

How are biologic DMARDs made

Answer 12

recombinant DNA technology

Question 13

What 2 factors made it possible to create bDMARDs

Answer 13

advances in understanding of inflammatory processes

technological advances such a recombinant DNA technology

Question 14

List 3 ways in which biologics are different to conventional DMARDs

Answer 14

• complex to manufacture
• large molecules
• more unstable