Interaction Potencies of

NSAIDs
Sukamto S M
Overview of Arachidonic Acid Pathways

Phospholipids

Phospholipase A2

Arachidonic acid
Cytochrome P450
Non-enzymatic epoxygenases

Isoprostanes Lipoxygenase Cyclooxygenase Epoxyeicosatetraenoic

pathways pathways acids (EETs)

Lipoxins Leukotrienes Prostaglandins

Prostacycline
Thromboxane
 Pharmacodynamic Interactions
Arachidonic acid NSAIDs (non-
COX-1 & COX-2 selective and
PGG2 selective)

PGH2

PGI2 TxA2 PGE2 PGF2 PGD2

Vasodilation Vasoconstriction Vasodilation Abortion Smooth muscle

Inhibits platelet Promotes platelet Hyperalgesia Smooth muscle contraction
aggregation aggregation Fever contraction Inhibits platelet
Diuresis Bronchoconstriction aggregation
Immune system
 NSAIDs

Nephrotoxicity

Bleeding problems

Increased blood
pressure
 COX-1 & COX-2

Property COX-1 COX-2

Expression Constitutive Mostly inducible

Tissue location Ubiquitous expression Inflamed tissues

Protection and Proinflammatory

Role
maintenance functions functions
 COX 1 and COX 2

Platelet Endothelial Cell

COX-1 NSAIDs COX-1

Coxibs COX-2

Thromboxane (TxA2) Prostacyclin (PGI2)

AINS Pharmacokinetic Properties
NSAIDs generally undergo FEW CLINICALLY
significant pharmacokinetic interactions.

Most of NSAIDs are acidic drugs

Most of NSAIDs are highly protein bound

NSAIDs are metabolized by multiple metabolic

pathways (2C9, 2C19, 2D6 & 3A4)

Acidic and basic condition of the urine will influence the

excretion of several NSAIDs
Conclude the type of interactions!

Antacid Propranolol

Gentamicin Cyclosporine

Captopril Prostaglandin + Oxytocin

 Thank you
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Interaction Potencies