Anti-inflammatories

Question 1

What does COX do?

Answer 1

Acts on Arachidonic acid and creates an intermediate which is further acted on by different prostaglandins

Question 2

What does prostaglandin B2 do?

Answer 2

Platelet aggregation

Question 3

How does blood temperature increase?

Answer 3

IL-1 which induces COX enzyme in hypothalamus to produce prostaglandin which raised blood temperature

Question 4

What does TxA2 do?

Answer 4

Endothelium vasoconstriction

Question 5

What does PGE2 do?

Answer 5

Inflammation, bronchoconstriction, vasodilation

Question 6

What are the 2 sites on COX?

Answer 6

Cycloxygenate site and then peroxidase

Question 7

Where is COX docked?

Answer 7

The ER

Question 8

Where do drugs bind to COX?

Answer 8

To the active site

Question 9

Where does aspirin bind to COX?

Answer 9

Serine residue

Question 10

What is aspirins duration?

Answer 10

10-20 minutes to be absorbed, 4 hours to go

Question 11

What do amino acid to NSAIDs interact with on COX1 and COX2?

Answer 11

COX1-iosleucine, COX2-Valine

Question 12

What does Dicholenic show some selectivity towards?

Answer 12

COX2- for musculoskeletal pain

Question 13

What does ibuprofen show some selectivity towards?

Answer 13

COX1

Question 14

What are side effects of NSAIDs?

Answer 14

Renal function, gut problems, bronchospasm, liver damage, skin rashes

Question 15

Why do NSAIDs cause kidney function problems?

Answer 15

Prostaglandins normally maintain renal blood flow

Question 16

Why do NSAIDs cause liver damage?

Answer 16

Toxic intermediates

Question 17

What are the advantages and disadvantages for NSAIDs selective for COX1?

Answer 17

Advantages- reduce strokes due to involvement in platelet aggregation
Disadvantages- bad for gut

Question 18

What are the advantages and disadvantages for NSAIDs selective for COX2?

Answer 18

Advantages- anti inflammatory and analgesics

Disadvantages- kidney - salt retention so raised bp

Question 19

What are novel therapeutic uses for NSAIDs?

Answer 19

Parkinsons, HIV, Alzheimers

Question 20

What is the occurrence of Rheumatoid arthritis?

Answer 20

Half a million in UK, 3x more common in females than males

Question 21

What is the cause of arthritis?

Answer 21

Tk1 cells autoimmune disease

Question 22

What is the pathway leading to joint damage in arthritis?

Answer 22

TCD4-TH0-activated Th1 - osteoclast, fibroblast= joint damage, Th1- macrophages which activates Il-1/TNFa (cytokines) - increase osteoclast and fibroblast and also the influx of other inflammatory cells leading to joint damage

Question 23

What is methotrexate?

Answer 23

Immunosuppressant, folic acid antagonist which slows down the conversion of TH0 to Th1 so limits cytokines

Question 24

What is the key treatment for arthiritus?

Answer 24

Disease Modifying Anti Rheumatic Drugs DMARDs

Question 25

What is Sulfasalazine?

Answer 25

A DMARD, also used to treat chronic inflammatory bowel disease

Question 26

Give example of DMARDs.

Answer 26

Sulfasalzine, Pencilllaminine

Question 27

What do anti-TNF agents act through?

Answer 27

IL-1, TNF

Question 28

How does cyclosporine work?

Answer 28

In activation stage of T cells- rise in calcium - activation of Caloneurin phosphatase- target TF NFkappa- IL-1 and others. Cyclosporine inhibits Coloneurin

Question 29

What do humanised monoclonal antibodies do?

Answer 29

Mimic soluble receptors of TNF - highly specific and effective, recognise TNFa/ its receptor, so neutralises action of soluble or membrane bound pro inflammatory cytokines

Question 30

What are all the possible treatments for arthritis?

Answer 30

Methotrexate, DMARDs, Cyclosporine, antiTNF, monoclonal antibodies

Question 31

What is an allergy?

Answer 31

Disease following an immune response to innocuous antigen, mostly IgE mediated

Question 32

What are hypersensitivity reactions?

Answer 32

Inappropriate or exaggerated immune responses that cause inflammation

Question 33

What is the response for Wheal and Flare syndrome?

Answer 33

Local increase in blood flow, vascular permeability

Question 34

What is the response to hay fever?

Answer 34

Irritation of nasal mucosa, oedema of nasal mucosa

Question 35

What is the response to a food allergy?

Answer 35

vomititing, diarrhoea, pruitis, anaphylaxis, urticarial

Question 36

What happens to the skin on allergy/

Answer 36

Angiodema, hibes

Question 37

What are activated in chronic allergy reactions?

Answer 37

Eosinophils

Question 38

What causes hay fever (allergic Rhinitis)?

Answer 38

Allergen activates mast cells in nasal mucosa

Question 39

What is allergic asthma caused by?

Answer 39

Allergen activates mast cells in lower respiratory tract

Question 40

What is early phase allergic asthma?

Answer 40

Reversible obstruction of airway, inflammation- many mast cells in bronchi

Question 41

What is late phase allergic asthma?

Answer 41

Activation of transcription factor such as NFkappaB leading to producing of cytokines which cause leukocyte infiltration

Question 42

What is allergic asthma associated with?

Answer 42

Overactivity of Th2, produce IL-4, produces IgE antibodies

Question 43

What environmental factors increase susceptibility to allergen?

Answer 43

Level of allergen, nutrition, pollutants, family size

Question 44

What do inflammatory mediators do?

Answer 44

Smooth muscle contraction, increased vascular permeability, mucous secretion, platelet activation, stimulation of nerve endings, recruitment and activation of eosinophils

Question 45

What are new therapies for treating asthma?

Answer 45

Humanised antibodies and soluble receptors to IgE, PGD-12 antagonists- inhibits immune cell and mast cell signalling