NSAIDs Flashcards
What is the main action of NSAIDs?
- inhibits downstream products of arachidonic acid decreasing the production of prostanoids which include prostaglandins, prostacyclin (PGI2) and thromboxanes (TXA2).
- Inhibition of COX as it competes with arachidonic acid for hydrophobic site of COX.
Function of prostaglandin such as PGE2
GI mucosal protection
Pain, pyrexia, inflammation
Function of PGI2 - prostacyclin
- Inhibits platelet Aggregation therefore, it is cytoprotective
- Vasodilator
- Released from endothelial cells and bind to platelet receptors, increasing cAMP = decrease in Ca2+ therefore, decreased platelet aggregation.
Function of TXA2
- Platelet aggregation
- Vasoconstriction
Describe the analgesic action of NSAIDs
- blockage of PGE2 reduces peripheral pain fibre sensitivity
- In the CNS, decreased PGE2 synthesis in the dorsal horn therefore, less neurotransmitter release and decreased excitability of the neurones in pain relay pathway.
Describe the anti-inflammatory action of NSAIDs
- NSAIDs reduce the production of prostaglandins that are released during injury so less oedema as vasoconstriction is promoted.
- NSAIDs inhibit vasodilation in capillary venues so decreased permeability and decreased swelling.
- Symptomatic relief by COX inhibition
Describe action of NSAIDs as an anti-pyretic?
- Inhbition of hypothalamic COX-2 where cytokines induced prostaglandins synthesis decreases and this results in a reduction in temperature.
Describe NSAID COX selectivity and the drugs that fall under each COX inhibition
- COX-2 selective compijnds inhibit COX-2 with much greater selectivity than COX-1 at therapeutic doses.
- Aspirin, Ibuprofen, Naproxen, diclofenac, celecoxib, etoricoxib (COX1 to 2)
What are the main ADRs of NSAIDs
- GI: reduced mucus and birch onset secretion leading to increased acid secretion therefore, prescribe PPI with it
- decreased mucosal blood flow leading to enhanced cytotoxicity and hypoxia
Renal: NSAIDs produce reversible decreased GFR and renal blood flow. NSAIDs inhibit prostaglandin synthesis so lack of vasodilation of AA to try maintain GFR therefore it drops. More likely to occur in CKD or heart failure (RAAS activated).
- NSAIDs inhibit action of NSAIDs prostaglandin which inhibits sodium abortion in CD = hypertension. Avoid antihypertensives as contradicting effects occur.
Name some selective COX-2 inhibitors
- Celecoxib
- Etoricoxib
Mechanism of action of selective COX-2 inhibitors
- Impaired PGI2 leading to unopposed platelet aggregation and vasoconstriction.
- Has less of an analgesic effect
What are selective COX-2 inhibitors preferred over non-selective inhibitor and COX-1
- Less GI and renal ADRs
Contraindications of NSAIDs
- Sulfonylureas as they cause hypoglycaemia
- Methotrexate - accumulation is hepatotoxic
- Warfarin which increases risk of bleeding
Competitive displacement with NSAIDs will increase plasma concentration of these drugs and effects will be exacerbated.
- ACEi and ARBs - decreased GFR
- Diuretics - causes natriuresis which contraindicates action of NSAIDs when it inhibits prostaglandin which prevents sodium absorption.
Uses for NSAIDs
- inflammatory conditions
- Osteoarthritis
- Post op pain
- Menorrhagia
- Low dose aspirin for platelet aggregation Inhibition as it inhibits TXA2
- Opioid sparing when used in combination
Paracetamol is not an NSAID but describe its mechanism of action and use
- Antipyretic action
- Used for milked to moderate analgesia
- COX-2 selective inhibition in CNS decreasing pain signals to higher centres as less PGE2 is produced
- Peroxidases in peripheral inflammation inhibits action of paracetamol so it has little anti-inflammatory action on periphery.
