NSAIDS (Drugs used in inflammatory diseases) Flashcards
When is paracetamol preferred over NSAIDs?
- In the elderly- more at risk of adverse effects from NSAIDs
- Patients with hypertension, CVD, Renal impairment, GI issues
- Patients of medicines that interact with NSAIDs e.g. Warfarin
What are the usual doses for Aspirin is an antiplatelet + an analgesic?
- Anelgesic and anti platelet- inhibit thrombus formation in vessels in primary and secondary prevention of CVD. Standard dose is 75mg daily (can be increased to 300mg od)
Analgesic- standard dose is 300-900mg every 4 hours PRN
Analgesic effects start soon after 1st dose and full effect is obtained within a week
Anti-inflammatory effects- Effect may not be achieved for up to 3 weeks
What are the special patient groups where aspirin is contra-indicated or cautioned?
- Not used in under 16 year olds- due to risk of Reye’s syndrome. Only EXCEPTION is if child has Kawasaki syndrome
- Patients with peptic ulcerations
- Bleeding disorders
-Severe cardiac failure - Elderly- at risk of NSAID side effects- GI, bleeding kidney problems
- Cautioned in asthma- can cause bronchospasm
What are some of the NSAID drug interactions?
- Drugs that increase risk go GI irritation and bleeding:
SSRIs
NSAIDs
Streroids
Anticoagulants - Drugs that increase risk of renal side effects
Bisphosphonates - Drugs where Aspirin can increase the toxicity of other drugs
Methotrexate
What are the ‘classes’ of NSAIDs with examples?
- Standard non-selective NSAIDs e.g. Ibuprofen, Indometacin, Mefenamic acid, Naproxen
- Standard NSAID- non-selective, but have a COX-2 preference e.g. Diclofenac, Etodolac, Meloxicam
- Coxibs- COX-2 selective e.g. Celecoxib, Etoricoxib
What are the side effects of NSAIDs?
- GI side effects- epithelial damage, ulceration, bleeding
- Renal effects- can cause sodium and water retention leading to oedema and hypertension. Also, AKIs
- Cardiovascular- due to increased cox-2 inhibition over cox-1. Increased risk of thrombotic events e.g. MI, stroke with cox-2 inhibitors and non-selective NSAIDs e.g. Diclofenac and high dose ibuprofen
- Bronchospasm- caution in asthma
What causes the GI side effects associated with NSAIDs?
e.g. Epithelial damage, ulceration and bleeding
- This is caused by:
1. Suppression of physiological homeostatic prostanoid (COX-1) inhibition:
- Reduced mucus production
- Reduced bicarbonate production
- Reduced mucosal blood flow
2. Topical irritation and direct epithelial damage
Which class of NSAIDs have a lower risk of GI side effects and why?
All NSAIDs have a GI risk, but the coxibs (selective COX-2 inhibitors) have the lowest risk as they inhibit the prostanoids of cox-2 which are involved in inflammation = side effects
Also, Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme spare COX-1 in the gastric mucosa and, hence, do not inhibit the production of mucosal prostaglandins = reduced GI disturbance.
Which NSAIDs are considered high, intermediate and low risk of causing GI disturbance?
Highest= Piroxicam, Ketoprofen, Ketorolac
Intermediate= Indometacin, Diclofenac, Naproxen
Lowest= Ibuprofen and the coxibs
Can you take multiple NSAIDs at the same time?
NO!
How should NSAIDs be prescribed/taken?
- Should prescribe the lowest risk drug at the lowest dose for the shortest duration
- Don’t use multiple NSAIDs simultaneously
- Take with food
- Often prescribed with gastroprotection e.g a PPI
What side effects should patients report when taking NSAIDs?
- GI ulceration
- Signs of gi bleeding such as dark stools and coughing up blood (haemoptysis)
Which NSAIDs have the highest risk of causing adverse cardiovascular effects?
- Diclofenac= 150mg/day
- Ibuprofen = 2.4g + a day
Lowest = Naproxen 1g
Which NSAID has the lowest risk of causing adverse cardiovascular effects?
Naproxen 1g/day
- and there is no evidence of risk with ibuprofen at a dose of 1.2g per day or less
Which NSAIDs have been contra-indicated in patients with Ischemic heart disease, cerebrovascular disease and heart failure (others are just cautioned)?
- COX-2 inhibitors- Celecoxib, Etoricoxib
- Diclofenac
- High dose ibuprofen
The cox-2 selective inhibitors, diclofenac and high-dose ibuprofen are contra-indicated in which 3 conditions?
- Ischaemic heart disease
- Cerebrovascular disease
- Heart failure
(other NSAIDs have been cautioned)
In which patient groups should compensatory prostaglandins be given with NSAIDs to reduce renal problems?
- Elderly
- Renally impaired
- Heart failure
- Volume depletion
- Liver cirrhosis
What can NSAIDs do to a patient’s renal function?
NSAIDs can decrease a patient’s renal function as inhibition of COX-2 can lead to sodium and water retention leading to oedema and hypertension and inhibition of COX-1 can cause decreased renal blood flow and lead to increased risk of AKI
What should be monitored in patients taking NSAIDs who are at risk of renal side effects?
- Renal function- eGFR, urine output
- Blood pressure
- Electrolytes- sodium and potassium
- oedema- increased weight, swelling
Are NSAIDs recommended for those on anti-coagulants?
NO
NSAIDS are known to cause upper gastrointestinal (GI) ulceration and bleeding. In anticoagulated patients this may increase the severity of upper GI bleeding. Many NSAIDs also have antiplatelet activity which can prolong bleeding times
What are the therapeutic effects of COX-inhibitors?
- Inhibit cox enzymes = inhibit prostanoid synthesis in inflammatory cells, inhibition of cox-2 causes:
- Decrease in prostaglandin E2 - decrease in vasodilation and platelet aggregation, bronchoconstriction
- Analgesic effect- decreased prostaglandin generation = less sensation of nerve endings to inflammatory mediators e.g. bradykinin
- Anti-pyretic effects- IL-1 releases prostaglandins in CNS- increased hypothalamus temp control = fever- NSAIDs prevent this
