Immunosuppressants & Immunomodulators Flashcards
(39 cards)
What are eicosanoids?
Signaling molecules derived from FA (plasma membrane lipids –> Arachidonic Acid (AA) –> eicosanoids
What enzymes are involved in eicosanoids production?
- Phospholipases (PLA2): plasma membrane lipids –>AA
2. Cyclooxygenase (Cox 1/2): AA –> eicosanoids
What are eicosanoids/prostanoids we have to know?
Prostaglandins (PGE2) & Thromboxanes (TXA2)
What is the MoA of Cox Inhibitors?
Inhibit the synthesis of prostanoids
What is the main role of COX 1 & 2?
Cox 1 is constitutive (maintains homeostatic function)
- Renal, GI, Platelet formation
- Usually produce toxic effects when inhibited
Cox 2 is inducible (promote inflammatory response)
- Pain, fever, inflammation
- Usually produce therapeutic effects when inhibited
What are main COX inhibitors and their toxicities?
NSAIDS
- Gastic Damage (bleeding, ulcers)
- Nephron/kidney damage
- Inhibits platelet activation & clotting
What is the MoA of NSAID for Gastic Damage?
NSAIDs inhibit PGE2 (important mucosal component) which leads to weakened mucous layer in the stomach (bleeding, ulcers).
What is the MoA of NSAID for Nephron Damage?
NSAIDs inhibit PGE2 (vasodilator) acting on glomerulus of kidney which leads to nephron damage.
What is the MoA of NSAID for Platelet Inactivation?
NSAIDs inhibit TXA2 (promotes platelet activation) which leads to clotting inability.
- NSAIDs can provide therapeutic effect for type II MI/stroke in older patients.
How is Asprin used off-label as a treatment?
Aspirin is used in conjunction with IVIG to treat kawasaki
What are examples of Aspirin toxicity?
- Reye’s Syndrome (when given asprin during viral infections)
- Bronchoconstriction (causes aspirin-sensitive asthma by promoting production of brochoconstricting products)
- Acute & Chronic Aspirin Poisoning
What asprin-related drugs can cause chronic aspirin poisoning?
subsalicylate
What NSAIDs are non-selective (affect COX 1/2)?
- Ibuprofen
- Naproxen
- Aspirin
What NSAIDs are selective COX-2 inhibitors?
- Celecoxib
2. Rofecoxib
What is the advantage of selective COX-2 inhibitors?
fewer GI toxicities
What is the disadvantage of selective COX-2 inhibitors?
more CV toxicities like heart attack because COX-2 inhibitors also inhibit the prostacyclin (PGI2) synthesis which are anti-clotting.
What are coticosteroid drugs we have to know?
- Hydrocortisone
- Prednisone
- Methylprednisolone
- Dexamethasone
What are 2 therapeutic mechanisms of Corticosteroids?
- Inhibit pro-inflammatory cytokines
- Increase anti-inflammatory lipocortin/annexin 1 (inhibits PLA2)
* Both mechanisms alter the gene transcription in target cells
What are examples of corticosteroid toxicities?
- Oral inhalation (like inhaler for asthma) can cause thrush and penumonia.
- Cushing Syndrome (aka. hypercortisolim) including affected skin and bones.
Corticosteroids can weaken bone in cushing syndrome by decreasing production of
osteocalcin
Corticosteroids can weaken skin in cushing syndrome by decreasing production of
keratin
What drugs are calcineurin inhibitors?
- Cyclosporin
2. Tacrolimus
What is the mechanism of calcineurin inhibitors?
They inhibit T cell activation by binding to calcineurin to prevent TCR signaling to produce more IL-2.
What is the most common calcineurin toxicity?
Non-Hodgkin’s lymphoma