NSAIDS Flashcards
Explain the biochemistry cascade from cytokines
to give eicosanoids
Eicosanoid functions
Differentiate between COX 1 and COX 2
use pg I for inhibitory
PLA2 forms Arachidonic Acid from cell membrane
AAA then gives
- LOX - Leukotrienes
- COX - Thromboxane, PGE2, PGI2 (PGI2 aka prostacyclins)
LT for bronchospams, mucous production
Thromboxane - pro platelet, VASOCONSTRICTOR
PGE2 - pain trigger; pyretic trigger
PGI2 - antiplatelet, vasodilator
note PG also for increased permeability during inflammation
COX1 - ‘housekeeping’
- all 3 made;; GI, Platelet; kidney;
- platelet, etc – think that constitutively on is Platelet function;
COX2 - ‘inducible’
- endothelial cells; kidney; others
- WBCs
- specifically wound healing; delayed ovulation follicular rupture; early closure of ductus arteriosus in foetus;
NSAIDs
- functions
- AE for NSAIDs (also specific COX2)
- renal later
Function
- antiplatelet
- antipyretic
- analgesic
- anti inflammatory
AE
- GI disturbance (cox 1), PUD
- cos PGE2 for decrease acid secretion, increase mucosal blood flow, increase bicarb and mucous production;; recall Misoprostol synthetic PGE
- Renal (both cox 1 and 2)
- OBGYN (cox 2)
- bleeding risk (cox 1 cos of platelets)
- worsen asthma (shunting to LOX leukotriene)
- Wound healing (cox2)
COXIB
Advantages
AEs
Note COXIB stronger analgesic, pyretic w PGE2 and PGI2 managing fever and inflammation respectively;
- but block antiplatelet effect of PGI2 increase risk of thrombosis cos COX 1 w thromboxane;
- Renal (non-specific)
- WOUND HEALING cox 2
- OBGYN: delayed ovulation, early closure of DA;
- Thrombosis (shunt to COX 1 thromboxane)
Gimme the range of effects and AE in terms of COX1 COX2 ratio
Towards COX2 block
- more anti-inflammatory
- less GI disturbances
- Thrombotic
- Pyretic, Pain is middle
Towards COX1
- bleed - ANTIPLATELET
- GI disturbances
Renal and Prostaglandins
PGE2 block Na reabsorption @ ascending limb
- if blocked - hypernatremia, hypertension
PGI2 enable renin secretion, aldosterone
- if blocked - hyperkalaemia
NSAIDs Contra 1 [2]
Pregnancy 3rd trimester
Children w Viral - scared of Reye’s syndrome
- But Kawasaki kids given for vasculitis
Low dose and high dose aspirin AE
GI disturbances; Bleeding (cos COX1 blocked)
High dose
- renal failure
- Salicylate toxicity
Explain anti-platelet effect of NSAID
Both COX1 in platelet and COX2 endothelial cells blocked
Platelet need TXA, weeks to regen
Endothelial cells hours to regen COX2 and PGI2 regenerates for anti-platelet
hence net antiplatelet
- note endothelial cells have both COX1 and COX2
Explain renal failure of NSAID
PG normally dilate the afferent arterioles of the glomeruli. This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of kidney function.
- renal failure
- sodium retention, HTN
Note Aspirin is irreversible
Note
Naproxen (period pain)
Diclofenac (joint pain) are NSAIDs;
ok
How come GI ulcers dont give NSAIDs
Impair wound healing; ulcers already present
- give after
Paracetamol
- Functions
- AE
CNS SELECTIVE COX inhibition;
- Antipyretic
- analgesic
- SPARES GI - cos go to CNS
BUT weakly anti-inflammatory in the PNS
- also hepatic toxicity
