anti-inflammatory drugs

Question 1

examples of inflammatory drugs

Answer 1

• NSAIDs
• SAIDs
• disease modifying anti-rheumatoid drugs (DMARD) but now biological response modifiers (BRMs)

Question 2

what are the pathways for arachidonic acid?

Answer 2

• cyclo-oxygenase producing prostaglandins
• lipo-oxygenase producing leukotrienes
• CYP450 producing EET

Question 3

what is eicosanoids?

Answer 3

antacids

Question 4

what is COX 1?

Answer 4

• control homeostasis production of prostaglandins
• housekeeping genes
• expressed in most tissues

Question 5

what is COX 2?

Answer 5

• increased production of prostaglandin in certain conditions eg: inflammation and cancer

Question 6

what is COX 3?

Answer 6

predominantly found in CNS

Question 7

where is PGE2 (prostanoids) located and its effect?

Answer 7

• in many cell types as inflammatory cells
• contraction and relaxation of smooth muscle
• immunosuppressive and anti-inflammatory
• fever
• gastric secretion and inhibition
• form cancer and promotes metastasize
• promotes angiogenesis

Question 8

where is PGI2 (prostanoids) located and its effect?

Answer 8

• in vascular endothelium
• cause vasodilation
• inhibit platelets aggregation

Question 9

where is PGD2 (prostanoids) located and its effect?

Answer 9

• in mast cells
• cause vasodilation
• inhibit platelets aggregation

Question 10

where is TXA2 (prostanoids) located and its effect?

Answer 10

• in platelets
• cause vasoconstriction
• promotes platelets aggregation

Question 11

what are the main aims for anti-inflammatory drugs?

Answer 11

• relieve pain

- arrest tissue damage

Question 12

what are the 5 major actions in NSAIDs?

Answer 12

1. anti-inflammatory action
2. analgesic effect
3. antipyretic effect
4. anti-platelet effect
5. anti- cancer effect

Question 13

what NSAIDs do in anti-inflammatory action?

Answer 13

decrease in PGE2 and PGI2, reduce vasodilation

Question 14

what NSAIDs do in analgesic action?

Answer 14

decrease PG production results in decrease sensitivity of nerves to inflammatory mediators

Question 15

what NSAIDs do in antipyretic action?

Answer 15

largely inhibition of PG production in hypothalamus

Question 16

what NSAIDs do in anti-platelets action?

Answer 16

• reduction in TXA2
• preventing platelets aggregation
• prolong bleeding time

Question 17

what NSAIDs do in anti-cancer action?

Answer 17

• reduce PGE2 formation
• inhibition of tumour cell proliferation
• enhance tumour cell apoptosis
• inhibition of angiogenesis

Question 18

side effects of NSAIDs in GI (most common)

Answer 18

• GI bleeding
• ulcer disease
• perforation in GI tract
• due to inhibition of PG that protect the mucosa from acidic

Question 19

side effects of NSAIDs in renal

Answer 19

• cause renal insufficiently due to inhibition of PGE and PGI
• neuropathy if chronic use

Question 20

side effects of NSAIDs in blood

Answer 20

• disturbance in platelets function

- increase bleeding time

Question 21

side effects of NSAIDs in liver

Answer 21

failure to excrete drugs

Question 22

side effects of NSAIDs (coxibs) in heart

Answer 22

• MI
• angina
• stroke
• TIA

Question 23

examples of NSAIDs in cox 1 selective

Answer 23

• aspirin
• sulindac
• indomethacin

Question 24

examples of NSAIDs in non-selective cox 1

Answer 24

• ibuprofen

- paracetamol

Question 25

examples of NSAIDs in both selective and non cox 1

Answer 25

- flurbiprofen | - diclofenac

Question 26

examples of NSAIDs in cox 2 selective

Answer 26

- celecoxib | - rofecoxib

Question 27

aspirin?

Answer 27

- oldest NSAIDs | - irreversibly inhibit cox 1 and cox 2

Question 28

side effects of aspirin

Answer 28

- gastric ulcer - asthma - diabetes - gout - hypocoagulation state - reye's syndrome in children

Question 29

drugs interactions with aspirin

Answer 29

- increase warfarin - heparin - increase insulin - increase phenytoin - increase methotrexate

Question 30

ibuprofen?

Answer 30

- competitive inhibitor of cox 1 and cox 2 - better tolerated than aspirin and indomethacin - fewer GI problems

Question 31

indomethacin and sulindac?

Answer 31

1. not normally used as analgesic/ anti-pyretic 2. potent anti-inflammatory agents 3. indomethacin: - less tolerated than aspirin and ibuprofen - high GI problems 4. sulindac: - better tolerated than indomethacin - fewer GI reactions

Question 32

paracetamol?

Answer 32

- suitable for children - effective analgesic and anti-pyretic - weak anti-inflammatory agents - well tolerated - overdose cause hepatotoxicity - max daily dose 4 g

Question 33

what are celecoxib and rofecoxib?

Answer 33

- cox 2 selective inhibitors - competition inhibition of cox 1 - less serious GI reactions

Question 34

side effects of cox 2 inhibitor

Answer 34

- small GI disturbances - dizziness - bronchitis - coughing - pharyngitis - rhinitis - somnolence - insomnia - cardiac problems

Question 35

5-lipoxygenase inhibitors?

Answer 35

- blocks antigen and exercise induced asthma - reduce underlying inflammation - low potency, short half life - eg: zileutin

Question 36

cysteinyl leukotriene antagonists?

Answer 36

- competitive antagonist at LT receptor - prevents aspirin-induced bronchoconstriction - eg: zafirlukast, montelukast, pranlukast

Question 37

dual cox 5-LO inhibitors?

Answer 37

- competitive inhibitor of 5LO and cox 2 - improved tolerability - eg: licofelone

Question 38

indirect inhibitor?

Answer 38

- still under development

Question 39

examples of DMARD

Answer 39

- methotrexate (common use) - leflunomide - chloroquine (treatment of malaria) - sulfasalazine - azathioprine

Question 40

DMARD?

Answer 40

- slow onset of action - mechanism unclear - variable efficacy - many side effects

Question 41

biological response modifiers (BRM)?

Answer 41

- quick onset of action - target specific receptor - fewer side effects

Question 42

examples of TNF inhibitors (BRM)

Answer 42

- etanercept - infliximab (mouse gene) - adalimumab (100% human genes)

Question 43

examples of anti-interleukin therapy (BRM)

Answer 43

- IL-1 anakinra | - IL-6 tocilizumab

Question 44

examples of B-cell depleting theraphy (BRM)

Answer 44

rituximab

Question 45

examples of blocking cell adhesion and migration

Answer 45

- teplizumab | - daclizumab

Question 46

examples of blocking T cell coreceptors

Answer 46

abatacept

Question 47

side effects of TNF inhibitor

Answer 47

- fungal infection - reactivation of myco tuberculosis - malignancy/lymphoma - congestive heart failure - demyelination - autoantibodies - congenital abnormalities