Session 6

Question 1

What is rheumatoid arthritis?

Answer 1

A chronic, autoimmune, multi-system condition resulting in inflammation of the synovium.

Question 2

What causes inflammation in rheumatoid arthritis?

Answer 2

T-cell activation and production of rheumatic factor, stimulating macrophages via IgG Fc receptors.

Question 3

What is rheumatic factor?

Answer 3

A circulating autoantibody that once bound to the Fc region of the IgG, results in immune complex formation and an inflammatory reaction. Results in persisting synovitis.

Question 4

What is inflamed synovium known as and what can it cause?

Answer 4

A pannus. Can damage underlying cartilage by blocking its route of diffusion, meaning the cartilage becomes thin and the bone exposed.

Question 5

How does rheumatoid arthritis present?

Answer 5

Slowly progressing and symmetrical, with peripheral polyarthritis developing over weeks to months. Pain and stiffness in the hands that is worse in the morning, and improves with gentle activity.

Question 6

What deformities of the hand can be present with RA?

Answer 6

Ulnar deviation, fixed flexion of fixed hyperextension in the PIP.
Swelling and dorsal subluxation of the ulnar styloid process.

Question 7

What are the main drugs used to treat RA?

Answer 7

Disease-modifying anti-rheumatic drugs.

Question 8

What is methotrexate and how does it work?

Answer 8

It is a DMARD and an immunosuppressant. It works as a folic acid antagonist.

Question 9

How does methotrexate differ in malignant and non-malignant disease?

Answer 9

Malignant: allosterically inhibits DHFR, hence inhibits DNA synthesis and subsequent RNA and proteins. Has a greater effect on rapidly dividing cells.

Non-malignant: inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine within the cell. Adenosine reduces activity of T-cells.

Question 10

What is the oral bioavailability of methotrexate and how is it eliminated?

Answer 10

13-76% and it is renally eliminated mainly.

Question 11

Give two examples of ADRs of methotrexate.

Answer 11

Mucositis, bone marrow suppression, hepatitis, cirrhosis and it’s teratogenic.

Question 12

Give two examples of methotrexate DDIs.

Answer 12

Immunosuppressants, anti-cancer drugs and autoimmune drugs.

Question 13

What is sulfasalazine and what is it used for?

Answer 13

A combination of 5-aminosalicylate and sulfapyridine.

Acts in RA to inhibit T-cell proliferation and IL-2 production. Reduces neutrophil chemotaxis and degranulation.

Question 14

What category of drug are anti-TNF agents and B-cell depletors?

Answer 14

Biopharmaceuticals.

Question 15

Give two examples of Anti-TNF agents.

Answer 15

Infliximab and Adalimumab.

Question 16

Name 3 types of immunosuppressants.

Answer 16

1) Corticosteroids
2) Azathioprine
3) Cyclophosphamide
4) Mycophenolate Mofetil
5) Calcineurin inhibitors
6) Methotrexate

Question 17

How do corticosteroids work as immunosuppressants?

Answer 17

Inhibit gene expression. Prevent IL-1 & IL-6 production and inhibit T-cell activation.

Question 18

How does azathioprine work as an immunosuppressant?

Answer 18

Inhibition of purine metabolism, reducing RNA and DNA synthesis.

Question 19

What causes undertreatment when using azathioprine?

Answer 19

High levels of TPMT as this eliminates 6-MP, which is the activated form of azathioprine.

Question 20

How does cyclophosphamide work as an immunosuppressant?

Answer 20

It is a cytotoxic alkylating agent. Forms crosslinks between and within DNA strands, preventing replication.

Question 21

Give 2 ADRs of cyclophosphamide.

Answer 21

Bladder cancer, lymphoma, leukaemia, infertility and teratogenesis.

Question 22

How does Mycophenolate Mofetil work as an immunosuppressant?

Answer 22

Increases oral bioavailability of MPA, which inhibits inosine monophosphate dehydrogenase which is needed for guanine synthesis. Impairs B-cell and T-cell proliferation.

Question 23

How do calcineurin inhibitors work as immunosuppressants?

Answer 23

E.g. ciclosporin and tacrolimus. Prevent the production of IL-2 via calcineurin inhibition.

Question 24

Give two ADRs of calcineurin inhibitors.

Answer 24

Nephotoxicity, hypertension, hyperlipidaemia, nausea, vomiting, diarrhoea and hyperuricaemia.

Question 25

What is asthma?

Answer 25

Inflammatory disease, resulting in airway obstruction and inflammation, caused by bronchoconstriction, mucosal oedema and mucus plugging.

Question 26

What are the two phases of asthma?

Answer 26

Immediate phase: initial response to allergen, causes interaction of mast cells with IgE. Release of histamine and bronchospasm.
Late phase: Leukocytes enter the area, resulting in bronchospasm, thickening of BM, oedema and mucus production.

Question 27

What is bronchial hyperresponsiveness?

Answer 27

Exaggerated bronchoconstrictor response to direct and pharmacological stimuli such as histamine.

Question 28

How do bronchodilators work?

Answer 28

Bind to B2-adrenoceptors in bronchial smooth muscle, resulting in increased cAMP, decrease in intracellular calcium and preventing muscle constriction.

Question 29

What is the ideal size of particles of B2-agonists?

Answer 29

1-5 microns.

Question 30

Give two examples of fast onset bronchodilators.

Answer 30

Short duration = salbutamol and terbutaline.

Long duration = formoterol.

Question 31

Give an example of a slow onset bronchodilator.

Answer 31

Salmeterol.

Question 32

Give two ADRs of bronchodilators.

Answer 32

Tachycardia, tremors, palpitations.

Question 33

How to muscarinic receptor antagonists work to treat asthma?

Answer 33

E.g. Ipatropium. Bind to M3 receptor of bronchial smooth muscle, blocking the constricting effect of ACh and inhibits mucus secretion.

Question 34

What is the role of corticosteroids in the management of asthma?

Answer 34

Anti-inflammatory as supress gene transcription in inflammatory cells. Also increase expression of b2-receptors and anti-inflammatory IL proteins. Reduce number of mast cells in respiratory mucosa.

Question 35

Give an advantage of using combined inhalers.

Answer 35

Easy to use, good compliance, safer and cheaper. E.g. Symbicord (budesonide and Formoterol).

Question 36

Give three signs of good asthmatic control.

Answer 36

• Minimal symptoms during day and night
• Minimal need for reliever inhaler
• No exacerbations
• No limitation of physical activity
• Normal lung function

Question 37

Describe step one and two of the 5-step asthma control.

Answer 37

1) Inhaled short-acting B2-agonist when required.

2) Addition of inhaled steroids.

Question 38

Describe the criteria for initiation of steroids in asthma.

Answer 38

• Using B2-agonists more than 3 times a week
• Symptoms more than 3 times a week
• Waking more than once a week
• Exacerbation requiring oral steroids in the last two years.

Question 39

Describe steps 3, 4 and 5 of the 5-step astha control.

Answer 39

3) Re-check compliance and inhaler technique. Add a long acting B2-agonist.
4) Increase inhaled steroid levels or add a fourth drug.
5) Add an oral steroid tablet or Anti-IgE therapy.

Question 40

What are the four criteria for acute severe asthma in adults?

Answer 40

1) Unable to complete sentences
2) Pulse more than 110 BPM
3) RR over 25.
4) Peak flow 33-50% of best/predicted.

Question 41

How do you treat acute severe asthma?

Answer 41

• Oxygen, high flow
• Nebulised salbutamol
• Oral prednisolone
• Add nebulised ipratropium bromide
• Consider IV aminophylline.