NSAIDs Flashcards
Where is Arachidonic acid primarily derived from?
Dietary linoleic acid (vegetable oils converted hepatically to Arachidonic acid and incorporated into phospholipid membrane)
Arachidonic acid is found throughout the body, but in what in what 4 tissues/ organs mainly?
- Brain
- Muscle
- Liver
- Kidney
List 3 types of Prostanoids
- Prostaglandins
- Prostacyclins (E.g PGI2)
- Thromboxanes
Describe the production of Prostanoids
- Produced from Arachidonic acid via Cyclooxygenase pathways
- Produced locally on demand via different enzymes
What feature of Prostanoids allows their concentration to be finely controlled?
Short half lives
How do TXA2 and PGI2’s effects differ?
PGI2- Protective for CVS
TXA2- Bad for CVS (causes platelet aggregation and vasodilation)
Fine balance needed between them
Which Prostanoids are good for the stomach and how?
PGE2: Regulates acid secretion from Parietal cells
PGI2: Maintains blood flow and mucosal repair
Do Prostanoids act through GPCRs?
Yes
A diet rich in what can lead to conversion of TXA3 and PGI3 (healthier prostanoids) reducing CVD incidence?
Fish oils/ Omega fatty acids
Compare 2 functional isomers of COX enzymes
COX-1;
- Always active in most tissues
COX-2;
- Inducible (mostly) in chronic inflammation
- Always active in Brain + Kidney + Bone
(Possibly COX-3)
How do NSAIDs work?
Inhibition of COX by competing with Arachidonic acid
Thus reducing synthesis of Prostanoids
How do NSAIDs act as analgesics?
Inhibition of Prostaglandin synthesis reduced pain fibre sensitivity
How do NSAIDs act as anti-inflammatory agents
Reduces prostaglandin production-> Reduced vasodilation and oedema
List 4 ADRS of NSAIDs
- GI irritation & bleeding (peptic ulcers, perforation)
- Exacerbation of IBD
- Reversible drop in GFR and Renal Blood Flow
- Increased Na absorption-> Raised BP
List some DDIs of NSAIDs
Can all increase GI irritation, so may have to give a PPI;
- Aspirin
- Glucocorticoid steroids
- Anticoagulants
- ACEi, ARB, Diuretics
List some contraindications of NSAIDs
- Eldery
- Chronic use
- Smoking & alcohol
- History of peptic ulcers
- Helicobacter pylori
- CKD, Heart failure
How can NSAIDs taken with ARBs/ ACEi/ Diuretics affect the kidney?
NSAIDs: Inhibit Afferent Arteriole vasodilation
ARB/ ACEi/ Diuretics: Inhibit Efferent Arteriole vasoconstriction
Thus, reduced GFR-> possible Renal impairment
What class of drug are Celecoxib and Etoricoxib?
What brought about the creation of this class of drugs?
Selective COX-2 inhibitors
GI side effects of COX-1 inhibitors
Compare the effects of COX-1 and COX-2 inhibitors
COX-1;
- More GI ADRs
- Antiplatelet action-> Inhibit platelet aggregation
COX-2;
- Less GI ADRs, similar renal ADRs
- Promote platelet aggregation (via PGI2 inhibition)
What feature of COX-2 inhibitors may allow them to be used in the long-term treatment of patients with severe Osteo- and Rheumatoid arthritis?
(Still need to be monitored)
Reduced GI effects
Which NSAIDs increase risk of MI?
All
Describe the effect of NSAIDs on other protein-bound drugs
Name 3 highly protein bound drugs that can be affected by NSAIDs
NSAIDs act strongly to displace protein-bound drugs increasing the free drug concentration in plasma.
Can displace protein-bound;
- Warfarin
- Methotrexate
- Sulphonylureas drugs
Why is Paracetamol unique?
A non-NSAID, non-Opiate with Antipyretic and Analgesic action
(For mild-moderate analgesia and fever)
Does Paracetamol have any anti-inflammatory action?
Very little
How much Paracetamol needs to be taken to cause irreversible damage?
150mg/kg
Describe the course of Paracetamol Overdose
- Can be asymptomatic for many hours
- First 24h: Nausea, Vomiting, Ab pain
- At 3-4 days: Maximal liver damage occurs
What can be taken to combat a very recent paracetamol OD?
Activated charcoal (would also counter any other drugs the patient is on)
