Anti-Inflammatory Drugs Flashcards
What are examples of immune mediators?
Cytokines (interleukins, interferon, TNF-alpha) Chemokines (IL-8, MCP-1) Colony-stimulating factors (GM-CSF) Adhesion molecules (ICAM-1, integrins) Eicosinoids (Prostaglandins) Endocrine (steroids, catecholamines)
How do steroids act?
Via intracellular receptors to regulate gene transcription.
What is a glucocorticoid?
An adrenal steroid that have immuno-suppressive effects.
How is the glucocorticoid receptor activated?
By cortisol and aldosterone.
The glucocorticoid receptor also interferes with what major inflammation-associated transcription factor?
NF-kB
List the pro-inflammatory genes that are down regulated by glucocorticoids.
- pro-inflam cytokines
- COX-2
- Phospholipase A2 (PLA2)
- Cell adhesion molecules
- Endothelins
- Inducible nitric oxide synthase (iNOS)
What are genes that are up regulated by glucocorticoids?
- IL-10/IL-4 (anti-inflam cytokines)
- Lipocortins/annexins (PLA2 inhibitor)
What are different routes for glucocorticoids?
Oral: Prednisone, dexamethasone
Inhalable: Fluticasone (Flixanase)
Topical: Prednisone, dexamethasone (deep heat)
In summary, what are steroidal drugs good for?
General anti-inflam drugs, BUT can have serious side effects.
What do NSAIDs do?
They inhibit prostaglandin (PFH2) biosynthesis via COX enzymes, thus they bock the enzymatic activity of COX.
Name 4 common NSAIDs.
- Aspirin
- Ibuprofen
- Diclofenac
- Naproxen
What does COX convert arachidonic acid into?
Prostaglandin H2
What does Aspirin do?
It irreversibly inhibits COX-1, so is an effective inhibitor of PG-mediated pain.
It also inhibits TXA2 release by platelets (anti-thrombotic)
Usually for migraine
What does Paracetamol do?
Good for fever and pain relief.
It reduces PG synthesis but is a pretty weak inhibitor of COX-1 and COX-2.
Where is Paracetamol metabolised?
Liver, into a toxic intermediate which can cause damage.