NSAIDs + Paracetamol Flashcards
Thromboxane
Platelet COX 1;
Vasoconstriction and Platelet Aggregation
- Hence NSAIDs w high COX2 ratio is pro-platelet
- Aspirin is highly antiplatelet
Why antiplatelet effect if PGI2 is also inhibited?
COX enzymes in endothelial cells can regenerate in hours while completely new Platelet regeneration takes weeks - for TXA2; otherwise PGI2 continues production, and inhibits platelet aggregation;
Leukotriene function
Bronchoconstriction, Mucous Secretion, Increase permeability of blood vessels
Key in asthma
Typical NSAIDs functions
Antipyretic - normally IL1 cytokine will activate production of PGE2, leading to fever
Analgesia - PGE2 and pain - PG increases sensitivity of nociceptors
Anti-inflammatory - limit vasodilation and permeability by PGI2 and PGE2
Hence Heat, Redness and Swelling;
NSAIDs and Aspirin on blood thinning (anti-platelet)
All NSAIDs will have an effect on blood thinning, but aspirin is stronger due to irreversible inhibition;
Otherwise if NSAID has high COX2 affinity, then pro-platelet effect instead
Aspirin High Dose SE and Contra-I
Low Dose: standard COX inhibitory effects
High Dose: Salicylate toxicity - Renal Failure
Contra-I: Children w Viral infection can lead to Reye’s syndrome w brain, liver damage
Typical NSAIDs SE
GI: Dyspepsia (indigestion), N&V
- PG function of mucus, bicarb secretion, and reducing gastric acid;
Renal:
- PGE2: usually blocks 25% Na reabsorption at ascending limb, hence NSAIDs lead to hypernatremia, edema, water retention
- PGI2: usually stimulates RAS, hence 1-2% reabsorption at Distal Convoluted Tubule, but NSAIDs still lead to hypernatremia; and blocking RAS leads to Hyperkalemia
Anti-platelet: Bleeding (not ALL NSAIDs antiplatelet)
Bronchospasm: Asthma
- Shunting of AAA to Leukotrienes;
- “Pseudo-allergy due to LK surge”
COX2 selectivity location and benefits
Induced by inflammatory stimulus
More anti-inflammatory, analgesic
More pro-platelet;
Found on WBC and endothelial cells
COX2 inhibition SE
- Coxibs
Renal toxicity - both COX1 and COX2 found
Pregnancy; ALL NSAIDs have COX2 inhibition and is Contra-I
- delay follicular rupture - reduce child bearing ability
- premature closure of ductus arteriosus in LATE pregnancy
Limits Wound Healing - PG from inflammatory cells for wound healing - exacerbate current ulcers;
Pro-platelet aggregation due to AA shunts to COX1, TXA2 (both isoforms are found in tissues)
Paracetamol MOA
CNS-selective COX inhibition
- antipyretic
Does not target COX in periphery
- GI is safe
- weak anti-inflammatory effect
Overall Adverse Effects, range from COX-1
COX-1
GI
Bleeding (antiplatelet due to TXA2 inhibition)
Renal-Renal
COX-2
Reproductive (less PG)
Wound Healing (less PG)
Thrombosis (pro-platelet due to TXA2)
Overall Positive Effects, range from COX-1
Anti-platelet
Anti-pyretic
Analgesic
Anti-inflammatory
