lec 16-17. anti-inflammatories

Question 1

NSAIDs

Answer 1

non-steroidal anti-inflammatory drug

Question 2

properties of NSAIDs

Answer 2

1) anti-inflammatory
2) analgesic
3) antipyretic

decrease production of prostaglandins and thromboxanes

Question 3

aspirin

Answer 3

cox 1 selective NSAID

Question 4

ibuprofen (nurofen)

Answer 4

cox1 selective NSAID

Question 5

paracetamol (acetaminophen)

Answer 5

perhaps cox3 selective NSAID that works in the CNS

not an anti-inflammatory

Question 6

inflammatory mediators

Answer 6

prostaglandins 
PGF (bronchoconstrictor)
PGE2 (hyperalgesic)
PGI2 (hyperalgesic + thrombotic) 
PGD2 (thrombotic

thromboxane
TXA2 (thrombotic, vasoconstrictor)

Question 7

COX

Answer 7

2 subunits each with 2 catalytic site

cox1 - constitutive expression, narrow due to isoleucine, NSAIDS cause anti-thrombotic and gastrotoxicity

cox2 - wider due to valine, NSAIDs cause anti-inflammation, analgesic, and increase blood pressure

cox3 - like cox1, in CNS

Question 8

rofecoxib (vioxx)

Answer 8

a coxib (cox inhibitor)
selective for cox 2
causes CVS problems in pre-existing hypertension

Question 9

NSAID side effects

Answer 9

• damage lining of gut (counter by giving misoprotol)
• paracetamol makes lethal intermediate which harms liver
• prostaglandins mediate renal blood flow -> kidney damage
• skin rashes
• bronchospasm asthma attacks

Question 10

Rheumatoid arthitis

Answer 10

causes swelling of joints, stiffness, pain

onset 40-60 years, 3x more common in women

Question 11

inflammatory mediators in arthitis

Answer 11

activated Th1 cells activate osteoclasts and fibroblasts and produce IL1 and TNFa which promote inflammation, causing erosion of cartilage and bone leading to joint damage

Question 12

DMARDs

Answer 12

disease-modifying anti-rheumatic drugs

they have a slow onset, so need to provide NSAIDs to cover induction

Question 13

methotrexate

Answer 13

DMARD, folic acid antagonist and cytotoxic + immunosuppressant

Question 14

sulfasalazine

Answer 14

scavenges free radicals to decrease the damage produced by neutrophils

Question 15

ciclosporin

Answer 15

inhibits transcription of IL2 (a pro-inflammatory cytokine that activates Th1)

Question 16

biologics

Answer 16

drugs that contain components of living organisms

they are able to target pro-inflammatory cytokines very specifically

Question 17

humanized monoclonal antibodies

Answer 17

biologics - have a high affinity and selectivity for target and because they are humanized they are not recognized as foreign

they neutralize action of pro-inflammatory cytokines

Question 18

Adalimumab (Humira)

Answer 18

a HMA which neutralizes TNF

Question 19

Etanercept

Answer 19

TNF decoy receptor

Question 20

asthma

Answer 20

chronic inflammation of airways, can develop bronchial hypersensitivity

Question 21

salbutamol

Answer 21

small molecule drug that treats asthma by acting as bronchodilators

Question 22

prednisolone

Answer 22

glucocorticoid - anti inflammatory agent that treats asthma

Question 23

omalizumab

Answer 23

anti-IgE antibody - anti inflammatory agent that treats asthma

Question 24

theophylline

Answer 24

treats early phase of asthma - builds up cAMP to relax smooth muscle

Question 25

allergens

Answer 25

exposure to allergens (pollen, dust, fur) and produce IgE antibodies against the allergen which then bind to mast cells which releases histamines, TNF, cytokines, and produces prostaglandins

Question 26

allergic rhinitis (hay fever)

Answer 26

activate mast cells in nasal mucosa and conjunctiva (upper airways)

Question 27

inflammatory mediators in astham

Answer 27

activated Th2 binds to B cells which releases IgE which binds to mast cells which release cytokines