GCs and NSAIDs

Question 1

GC MAO

Answer 1

• GC passes thru cell membrane -> attached to cytoplasmic receptor –> re-locate to nucleus –> bind DNA –> inc transcription of anti-inflammatory (trans-activation) and inc transcription of pro-inflammatory elements (trans-repression)
• Lipocortin - 1 trans-activation protein produced; goes on to inhibit phospholipase A2 (a key enzyme in AA release)

Question 2

GC Pos Effects

Answer 2

• Neutrophils - dec trafficking, little other effect
• Macrophages - SIG; dec trafficking, dec phagocytosis and bactericidal effects, inhibit antigen presentation, dec cytokine production
• Lymphocytes - dec trafficking, dec cytokine production, dec proliferation BUT little effect on Ig synthesis

Question 3

GC Side Effects

Answer 3

Infections, osteoporosis, Cushing, wt gain, edema, insulin resistance, skin thinning, cataracts, glaucoma, increased CV risk

Question 4

NSAID MAO

Answer 4

TREAT SYMPTOMS NOT DISEASE MODIFYING

• inhibition of COX activity –> impairs transformation of AA –> prostaglandins –> dec formation of PGE2, PGI2 and TXA2 (inflammatory)
• COX1 - expressed in most tissues; regulatory/housekeeping role (gastro-protection, vascular homeostasis, kidney function)
• COX2 - expressed in inflammatory states; not usually found in most tissues

Question 5

NSAID Side Effects

Answer 5

ALL COX1 RELATED

• Gastritis, peptic ulcer disease
• GERD
• Dec coagulation - bleeding risk (do not use if already on
  anti-coagulant)
• Acute renal failure, CKD, fluid retention –> CHF (affects regulation of blood flow to kidneys - prostaglandins)
• Inc risk thrombosis