NSAIDS Flashcards
Outline the WHO analgesic ladder
Non-opioid (NSAID, paracaetamol)
+ adjuvant
Mlid-moderate opioid (e.g. codeine phosphate)
+ adjuvant
Moderate-strong opioid (e.g. morphine sulphate)
+adjuvant
What is the class of NSAIDs ending in -coxib?
Give an example
- Pros
- Cons
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
Describe the mechanism of action of NSAIDs
- 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
What are the normal physiological functions of prostaglandin (4)
- Protect gastric mucosa
- Support renal function
- Support platelet function
- Inflammation and pain
Outline the cyclo-oxygenase pathway
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
What are the effects of cox -1 inhibition
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
What are the effects of cox -2 inhibition
ANTI-INFLAMMATORY
Blocks prostaglandins
- usually responsible for inflammation, pain, fever
Blocks PGI1 (Prostacycline) - usually responsible for vasodilation, inhibition of platelet aggregation
Which of the following drugs can cause gout?
Allopurinol Amlodipine Atorvastatin Bendroflumethiazide Ramipril
Bendroflumethiazide
- commonly causes hyperuricaemia
Which of the following drugs can treat an acute gout attack?
Aspirin Colchicine Diclofenac Febuxostat Canakinumab Prednisolone
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
Key side effect of colchicine?
Diarrhoea
State three anti-inflammatory indications for NSAIDs
What else must be given in these conditions?
- 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
Give three indications for which you might prescribe NSAIDs for analgesic purposes orally
- Headache
- Dysmenorrhoea
- Osteoarthritis and RA
- Soft tissue rheumatism and back pain
- Minor injury
- Dental pain
Give two indications for which you might prescribe NSAIDs for analgesic purposes paraenterally
- Oeri-and postoperative pain
- Ureteric colic
Describe the role of prostaglandins in pyrexia
During an inflammatory reaction IL1 releases prostaglandin in the CNS
Prostaglandins elevate the hypothalamic set point for temperature control
NSAIDs prevent this
Which NSAID is predominantly used in CVD? Why?
Give three indications for this use
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
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
Gastritis is a very common side effect of NSAIDs
Why are NSAIDs contraindicated in those with brittle asthma?
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
State 5 common side effects of NSAIDs
GI discomfort Nausea Diarrhoea Oesophagitis Gastritis Renal impairment
State 5 less common side effects of NSAIDs
- 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
Describe the interaction with NSAIDs for the following drugs
- Anticoagulants
- SSRis and Venlaflaxine
Increased risk of GI bleeding
Describe the interaction with NSAIDs for the following drugs
- ACEi
- Antihypertensives
- Diuretics
Antagonism of hypotensive effetc
ACEi
- also increase in renal impairment and hyperkalaemia
Diuretics
- also nephrotoxic
Describe the interaction with NSAIDs for the following drugs
- Digoxin
May increase plasma concentration of digoxin, increased risk of HF, decreased renal function
Which patient group are at increased risk of GI complications
- Hx of GI complications
- > 65
- concomitant drugs (anticoagulation, steroids, SSRIs)
- on multiple NSAIDs
Which patient group are at increased risk of cardiovascular and renal adverse effects
- > 65
- established CVD (HF)
- HTN
- renal and hepatic impairment
Are there any other patient groups who are at risk from NSAID use?
- asthma
- hypersensitivity
- coagulation defects
- pregnancy and breast feeding
