NSAIDS

Question 1

Outline the WHO analgesic ladder

Answer 1

Non-opioid (NSAID, paracaetamol)
+ adjuvant

Mlid-moderate opioid (e.g. codeine phosphate)
+ adjuvant

Moderate-strong opioid (e.g. morphine sulphate)
+adjuvant

Question 2

What is the class of NSAIDs ending in -coxib?

Give an example

• Pros
• Cons

Answer 2

Cox-2 inhibitors

Etoricoxib, celecoxiib

Reduced risk of serious upper GI effects
- Suitable for patients requiring an NSAID but history of GI problems

Not routinely recommended

Question 3

Describe the mechanism of action of NSAIDs

Answer 3

• They exert their clinical effects by inhibiting prostaglandin synthesis
• The primary site of action is the Cox enzyme
• They vary in selectivity for COX1 and COX2

Question 4

What are the normal physiological functions of prostaglandin (4)

Answer 4

• Protect gastric mucosa
• Support renal function
• Support platelet function
• Inflammation and pain

Question 5

Outline the cyclo-oxygenase pathway

Answer 5

Injury/infection/trauma attacks th cell membrane of cells (which contain phospholipids). This causes activation of phospholipase which leads to the production of arachidonic acid

Arachidonic acid is further metabolised by

(1) Cycloexegase pathway–> prostaglandins
(2) Lipooxygenase pathway –> leukotrienes

Question 6

What are the effects of cox -1 inhibition

Answer 6

ANTI PLATELET EFFECT

Blocks the action os thromboxane A2
- This usually causes vasoconstriction and platelet aggregation

GI SIDE EFFECTS
- Prostaglandins (PGE2, PGI2) responsible for gastroprotection

Question 7

What are the effects of cox -2 inhibition

Answer 7

ANTI-INFLAMMATORY

Blocks prostaglandins
- usually responsible for inflammation, pain, fever

Blocks PGI1 (Prostacycline)
- usually responsible for vasodilation, inhibition of platelet aggregation

Question 8

Which of the following drugs can cause gout?

Allopurinol
Amlodipine
Atorvastatin
Bendroflumethiazide
Ramipril

Answer 8

Bendroflumethiazide

• commonly causes hyperuricaemia

Question 9

Which of the following drugs can treat an acute gout attack?

Aspirin
Colchicine
Diclofenac
Febuxostat
Canakinumab
Prednisolone

Answer 9

Acute management of gout

1st line: NSAID + PPI
(NOT ASPIRIN, this can worsen attack; instead, DICLOFENAC, indometacin, ketoprofen, naproxen)

If in HF, or HTN –> Colchicine

Oral corticosteroids can be used as alternative to NSAIDs

Question 10

Key side effect of colchicine?

Answer 10

Diarrhoea

Question 11

State three anti-inflammatory indications for NSAIDs

What else must be given in these conditions?

Answer 11

• Gout
• Sero-negative arthritis (e.g. ank spon)
• RA and SLE

NSAIDs will be used long term in these conditions, important to offer gastro protective agents also

Question 12

Give three indications for which you might prescribe NSAIDs for analgesic purposes orally

Answer 12

• Headache
• Dysmenorrhoea
• Osteoarthritis and RA
• Soft tissue rheumatism and back pain
• Minor injury
• Dental pain

Question 13

Give two indications for which you might prescribe NSAIDs for analgesic purposes paraenterally

Answer 13

• Oeri-and postoperative pain

- Ureteric colic

Question 14

Describe the role of prostaglandins in pyrexia

Answer 14

During an inflammatory reaction IL1 releases prostaglandin in the CNS

Prostaglandins elevate the hypothalamic set point for temperature control

NSAIDs prevent this

Question 15

Which NSAID is predominantly used in CVD? Why?

Give three indications for this use

Answer 15

ASPIRIN

• It exerts antiplatelet effects (the others have a prothrombin tendency due to COX2 selectivity)
• reduces platelet aggregation

ACS: Unstable angina, NSTEMI, STEMI
TIA
Ischaemic stroke
Secondary prevention

Question 16

45yo male with muscular injury to ankle prescribed short course of diclofenac. Which side effect is most common?

Bronchospasm
Erythema multiforma
Gastritis
Renal impairment
Thrombocytopenia

Answer 16

Gastritis is a very common side effect of NSAIDs

Question 17

Why are NSAIDs contraindicated in those with brittle asthma?

Answer 17

NSAIDs can cause bronchospasm

• Due to COX inhibition and shunting of arachidonic acid metabolism through lipooxygenase pathway which results in too much production of leukotrienes

Question 18

State 5 common side effects of NSAIDs

Answer 18

GI discomfort
Nausea
Diarrhoea
Oesophagitis
Gastritis
Renal impairment

Question 19

State 5 less common side effects of NSAIDs

Answer 19

• Upper GI bleed, ulceration
• Renal: fluid retention, interstitial necrosis, papillary necrosis
• increase BP and fluid retention (CCF)
• Hypersensitivity rash (erythema multiforme), angioedema, bronchospasm
• Headache, dizziness
• Blood disorders
• CV events

Question 20

Describe the interaction with NSAIDs for the following drugs

• Anticoagulants
• SSRis and Venlaflaxine

Answer 20

Increased risk of GI bleeding

Question 21

Describe the interaction with NSAIDs for the following drugs

• ACEi
• Antihypertensives
• Diuretics

Answer 21

Antagonism of hypotensive effetc

ACEi
- also increase in renal impairment and hyperkalaemia

Diuretics
- also nephrotoxic

Question 22

Describe the interaction with NSAIDs for the following drugs

• Digoxin

Answer 22

May increase plasma concentration of digoxin, increased risk of HF, decreased renal function

Question 23

Which patient group are at increased risk of GI complications

Answer 23

• Hx of GI complications
• > 65
• concomitant drugs (anticoagulation, steroids, SSRIs)
• on multiple NSAIDs

Question 24

Which patient group are at increased risk of cardiovascular and renal adverse effects

Answer 24

• > 65
• established CVD (HF)
• HTN
• renal and hepatic impairment

Question 25

Are there any other patient groups who are at risk from NSAID use?

Answer 25

• asthma
• hypersensitivity
• coagulation defects
• pregnancy and breast feeding