NSAIDS and Paracetamol Flashcards
What are the mediators that can induce pain/inflammation:
- prostaglandins, leukotriene, substance P, bradykinin
= there are a number of medications used in treatment of pain and inflammation that affects these of these mediators
Examples of non-selective NSAIDS
(cox 1 and cox 2)
- aspirin
- ibuprofen
- naproxen
Examples of selective NSAIDS?
(Cox 2 inhibitors only)
- celecoxib
- meloxicam
- parecoxib
What is the MOA of NSAIDS?
= NSAIDS inhibit the COX enzyme
- inhabitation of COX1 = impaired gastric cytoprotection and anti platelet effects
- inhabitation of COX 2 = anti inflammatory and analgesic action
What are the pharmacological effects of NSAIDS/
- analgesia
- anti-inflammatory
- anti platelet
- antipyretic
Therapeutic uses of NSAIDS?
- Backache
- muscular pains and aches
- osteoarthritis, rhematorid
- thrombotic events
Compare and contrast between COX 1 and COX 2 inhibitors?
COX 1
- Found in most cells - Constitutive enzyme which synthesises production of prostaglandins involved in homeostasis - (Housekeeping or Good prostaglandins
COX 2
- induced by inflammatory stimuli and synthesises prostaglandins involved in pain and inflammation (Bad Prostaglandins) - also constitutive enzyme in some areas (kidney and vascular tissue) - thought to be involved in some cancers
What are the side effects of NSAIDS
Traditional NSAIDS block both COX 1 and COX 2 - by blocking the good prostaglandins it leads to adverse reactions
COX 1
1. maintain muscle gastric production - protect underlying tissues from acids and enzymes of stomach by:
- increasing bicarbonate ion secretion
- increase mucus secretion
- increase blood flow
- reduce gastric acid secretion
= NSAIDS reduce these effects - GI bleeding and ulcers
- Regulate platelet function
Interactions with NSAIDS
- CYP450 enzyme
- anticoagulant factors
- ACE inhibitors
- Beta blockers
- diuretics
Paracetamol use
USEd when NSAIDS are contradicted
- analgesic & antipyretic activity inhibits synthesis of PGE2 in hypothalamus
- DOES NOT HAVE ANTI-INFLAMMATORY EFFECT that NSAIDS have
- DOES NOT block COX 1 or COX 2 in peripheral tissues
Paracetamol does not cause;
- GI bleeding or ulcers
- increased bleeding tendency
- reduced renal function
- sodium and water retention
Paracetamol overdose?
Overdose: those glucuronidation/sulphation pathways become saturated more NABQI formed
- glutathione stores become depleted
- NABQI no longer inactivated combines with cellular components cell death & liver failure (hepatic necrosis)
- can also result in renal damage
Antidote for paracetamol overdose?
Antidote: acetylcysteine restores glutathione levels &/or inactivates NABQI
- most effective if administered within 10-12 hours of overdose
