NSAIDs

Question 1

Describe the WHO analgesic ladder

Answer 1

Step 1 - non opioid analgesic +/- adjuvant analgesic

Step 2 - opioid analgesic for mild to moderate pain +/- non opioid analgesic +/- adjuvant analgesic

Step 3 - opioid analgesic for moderate to severe pain +/- non opioid analgesic +/- adjuvant analgesic

Question 2

Name some non opioid anlagesics

Answer 2

NSAIDs

Paracetamol

Question 3

Name an opioid analgesic for mild to moderate pain

Answer 3

Codeine phosphate

Question 4

Name an opioid analgesic for moderate to severe pain

Answer 4

Morphine sulfate

Question 5

Where is aspirin derived from?

Answer 5

Willow trees

Question 6

Where is Ibuprofen derived from?

Answer 6

Propionic acid

Question 7

Name some NSAIDs

Answer 7

Naproxen
Diclofenac
Ibuprofen
Aspirin (salicylate) 
Indomethacin
Phenylbutazone 
Meloxicam 
Ketoprofen
Etoricoxib

Question 8

What does the term NSAID stand for?

Answer 8

Non steroidal anti inflammatory drug

Question 9

Describe the mechanism of action of all NSAIDs

Answer 9

Exert effects on inhibition of prostaglandin synthesis

Question 10

What is the primary site of action of NSAIDs?

Answer 10

Cyclooxygenase enzyme - COX1 and COX2

Question 11

What is the role of prostaglandins?

Answer 11

Modulate components of inflammation
Control of body temperature - fever
Platelet aggregation - thromboxane A2
Pain transmission 
Support renal function

Question 12

Describe the storage and release of prostaglandins

Answer 12

They are not stored. They are produced and released on demand

Question 13

How long is the half life of prostaglandins?

Answer 13

minutes

Question 14

What does COX catalyse?

Answer 14

Conversion of arachidonic acid to prostaglandins and endoperoxide

Question 15

What does constitutively mean?

Answer 15

Produced at a steady rate regardless of physiological demand

Question 16

Where is COX 1 expressed?

Answer 16

Most tissues

Question 17

What is the function of COX 1?

Answer 17

Protects the gastric mucosa

Question 18

Where is COX 2 expressed?

Answer 18

Brain and kidney, is induced in sites of inflammation

Question 19

Which COX is present in platelets?

Answer 19

COX 1

Question 20

What do older NSAIDs block?

Answer 20

Both COX isoforms

Question 21

What NSAID blocks both COX isoforms

Answer 21

Ibuprofen

Question 22

Blocking which COX isoform is undesirable and why?

Answer 22

COX 1

Stomach (PGE2,PGI2), intestine, kidney (PGE2, PGI2), platelet (thromboxane A2)

Question 23

Which NSAID works on blocking thromboxane A2?

Answer 23

Aspirin

Question 24

What do glucocorticoids do?

Answer 24

Block mRNA expression of COX2

Question 25

How does celecoxib act?

Answer 25

Blocks COX2 - blocks the inflammatory effect of macrophages

Question 26

Describe the metabolism of arachidonic acid

Answer 26

Arachidonic acid is metabolised by either COX1/2 to PGG2 and then PGH2 which is then converted to thromboxane A2 and prostaglandins (PGE2 and PGI2) (BY COX 1) or Prostacyclin (PGI2) and prostaglandins (inflammation, pain and fever)

Question 27

Describe the action of thromboxane A2

Answer 27

Vasoconstriction | Stimulates platelet aggregation

Question 28

Describe the action of PGI2

Answer 28

Vasodilation | Inhibits platelet aggregation

Question 29

Name some COX 2 inhibitors

Answer 29

Etoricoxib and celecoxib

Question 30

Why are COX 2 inhibitors more preferable as NSAIDs in patients with a history of GI bleeds

Answer 30

Reduced risk of serous upper GI bleed | Do not inhibit platelet aggregation

Question 31

What is the first line treatment of gout

Answer 31

NSIADs

Question 32

What drug is given to someone with out who can not tolerate NSAIDs

Answer 32

Colchicine

Question 33

How long can the anti-inflammatory effect take to show in NSAIDs

Answer 33

3 weeks

Question 34

What conditions are NSAIDs used for their anti-inflammatory properties?

Answer 34

Gout Sero negative arthritis Rheumatoid arthritis SLE

Question 35

What must be prescribed in addition to NSAIDs for long term use?

Answer 35

Gastroprotective drugs

Question 36

Describe when the effect should be present for NSAIDs used as analgesics

Answer 36

Effect after first dose, full affect takes up to 1 week

Question 37

Give the indications for using NSAIDs as analgesics

Answer 37

``` Osteoarthritis Rheumatoid arthritis Soft tissue rheumatism and back pain Minor trauma Soft tissue injury and sports injury Headache Dysmenohrrhea Oeri-/post- operatively Ureteric colic ```

Question 38

Describe the mechanism of pyrexia

Answer 38

During inflammation Interleukin 1 releases prostaglandins into the CNS Prostaglandins elevate the hypothalamic set point for temperature control

Question 39

Describe how NSAIDs have anti pyrexic properties

Answer 39

Prevent prostaglandins synthesis so prevent hypothalamic set point of temp control from being raised

Question 40

Name an NSAID indicated in cardiovascular disease

Answer 40

Aspirin

Question 41

Describe the action of aspirin

Answer 41

Reduces platelet aggregation and therefore reduces the bloods ability to clot

Question 42

Give some indications of aspirin

Answer 42

``` Unstable angina STEMI NSTEMI TIA Ischaemic stroke Secondary prevention ```

Question 43

Describe the cyclo oxygenase pathway

Answer 43

Injury/infection/trauma Attacks the cell membrane of the cell Cell membrane contains phospholipids Activation of phospholipase occurs It causes formation of arachidonic acid Arachidonic acid is further metabolised by cyclooxygenase pathway to produce prostaglandins and the lipoxygenase pathway to produce leukotrienes

Question 44

List some common side effects of NSAIDs

Answer 44

GI discomfort - nausea, diarrhoea, oesophagitis, gastritis | Renal impairment

Question 45

List some less common side effects of NSAIDs

Answer 45

Upper GI - bleeding and Peptic ulceration Renal - fluid retention, papillary necrosis, interstitial nephritis Increased BP and fluid retention - CCF Hypersensitivity rashes - erythema multiforme, angioedema and bronchospasm Headache, dizziness Blood disorders Cardiovascular events

Question 46

Describe how NSAIDs can sometimes cause bronchospasm

Answer 46

COX inhibition and shunting of arachiodonic acid metabolism across the lipoxygenase pathway with resultant production of asthmogenic cysteinyl leukotreines

Question 47

Describe the steroid and NSAID drug interaction

Answer 47

Increased risk of GI bleeding

Question 48

Describe the anticoagulant and NSAID drug interaction

Answer 48

Increased risk of GI bleeding | Increased anticoagulant effect

Question 49

Describe the ACE inhibitor and NSAID drug interaction

Answer 49

Increased risk of renal impairment, hyperkalaemia and antagonism of hypotensive effect

Question 50

Describe the digoxin and NSAID drug interaction

Answer 50

May increase plasma digoxin concentrations Increase risk of heart failure Decrease renal function

Question 51

Describe the interaction between NSAIDs and sulfonylureas

Answer 51

Enhances sulfonylureas effect

Question 52

Describe the interaction between NSAIDs and quinolone antibiotics

Answer 52

Increased risk of seizures

Question 53

Describe the interaction between NSAIDs and phenytoin

Answer 53

Increased risk of phenytoin toxicity

Question 54

Describe the interaction between NSAIDs and SSRIs and venlafaxine

Answer 54

Increased risk of bleeding

Question 55

Describe the interaction between NSAIDs and diuretics

Answer 55

Increased nephrotoxicity risk

Question 56

Which patient groups are at risk of GI bleeding with NSAIDs

Answer 56

History of GI ulceration Age >65 Concomitant drugs - anticoagulants, SSRIS, Steroids Multiple NSAIDs

Question 57

Which patients are at risk of cardiovascular or renal side effects of NSAIDs

Answer 57

Patients aged over 65 Established CVD Hypertension Renal and hepatic impairment

Question 58

What groups of patients should be cautious of using NSAIDs

Answer 58

``` Pregnant Breast feeding Asthmatics Hypersensitivity Coagulation defects ```