NSAIDS Flashcards
How are NSAIDs used for Arthritis?
Management of oedema & tissue damage resulting from the inflammatory joint disease
What are the Primary indications of NSAIDs?
Rheumatoid Arthritis
Osteoarthritis
Ankylosing Spondylitis
Tissue damage - due to Arthritis
How are Prostaglandins biosynthesised?
From Arachidonic acid - which is found esterified on cell membrane phospholipid
conc of Arachidonic acid - very low
Arachidonic acid + Cyclooxygenase & 2 molecules of O2 = forms Prostaglandin-G2
Prostaglandin + Peroxidase = forms Prostaglandin-H2
What is the MOA of NSAIDs?
They inhibit Prostaglandin synthesis
by specifically inhibiting cyclooxygenase
Where are COX-1 enzymes present?
Intestine
Platelets
Stomach
Kidney
Where are COX-2 enzyme present?
Macrophages
Leukocytes
Fibroblasts
Endothelial cells
What are some examples of Salicylates, and what are their properties?
Salicylic acid
Aspirin
Diflunisal
Benorylate
Potent anti-inflammatory activity
Mild analgesic & antipyretic activity
COX-1 selective
GI tract irritation
How does Aspirin work?
Covalently & irreversibly modifies both COX-1 & COX-2 by acetylating serine-530 in the active site.
Acetylation of COX-1 creating a steric block that prevents binding of arachidonic acid at COX active site
What are the properties of Profens?
Phenyl propanoic acids
S(+) isomer - more potent cox inhibitor
All Profens - marketed as racemates
Except Naproxen - marketed as S-Naproxen - since R-Naproxen - liver toxicity
In the body, Profens undergo a metabolic inversion at chiral carbon - thus inactive R-enantiomer is converted to S-enantiomer
Thus normally only S-enantiomer is present in plasma
What are some examples of Profens?
Ibuprofen Fenoprofen Ketoprofen Fluroprofen Naproxen - more selective for COX-2
Anti-inflammatory, Analgesic, Antipyretic
Slightly COX-1 selective
For RA & OA
Give examples of Arylacetic Acids, and summarise them
Indomethacin
- COX-1 selective
- CNS toxicity
Sulindac
- Prodrug - Sulfide is 500x more active
- COX-1 selective
Both primarily anti-inflammatory and for RA & OA
Give examples of COX-2 inhibitors
Meloxicam
Piroxicam
More COX-2 selective than many NSAIDs
How does paracetamol work?
Effective as analgesic & antipyretic
In OD - liver damage main concern
Toxicity can be managed - IV administration of Sulfhydryl donors - N-acetylcysteine
Give examples of selective COX-2 inhibitors.
Celecoxib
Etoricoxib
Refecoxib
Low ulceration potential
Can cause infertility & Cardiovascular risk
