Anti-inflammatories Flashcards
What are the two pathways in the arachidonic acid cascade?
1) 5-lipoxygenase (LOX)
2) Cyclo-oxygenase (COX)
What is the first thing that occurs when tissue is injured in the process of inlammation?
Arachidonic acid is released from the cell membranes, triggered by phospholipase A2
What occurs during LOX?
Arachidonic acid is metabolized into leukotrienes by LOX
What occurs during the Cox pathway?
arachidonic acid is metabolized into prostaglandins, prostacyclin and thromboxanes by COX
Two isoenzymes of COX
COX 1 and COX2
COX 1
Primarily responsible for basal prostaglandin production for normal homeostatic processes within the body, including gastric mucus production, platelet function, and, indirectly, hemostasis.
COX 2
found at sites of inflammation and some basal production of constitutive prostaglandins.
Ideally, selective inhibition of prostaglandins produced primarily by COX-2, however currently there are no pure COX2 inhibitors.
Arachidonic Acid
Present in phospholipid portion of plasma membrane.
It is an inflammatory mediator which causes vasodilation and vasoconstriction.
Inflammation = vasodilation
blood coagulation = vasoconstriction
Phospholipase A2 releases Arachidonic Acid.
Arachidonic Acid can then be broken down to prostaglandins or the leukotriens by COX or LOX respectively.
What inhibits phospholipase A2?
steroids
Therefore steroids are anti-inflammatory
NSAIDs function and adverse effects
NSAIDs inhibit COX enzyme, which inhibits formation of prostaglandins.
NSAIDs are metabolized by the liver and excreted by the kidneys.
Give with food.
Adverse side effects:
Because prostaglandins play a role in maintaining GI mucosal integrity, some of the side effects of NSAIDs are gastroenteritis, ulceration, and potentially GI perforation.
Use cautiously in patients with hypotension, hypovolemia, pre-existing renal disease (due to increased potential for renal vascular vasoconstriction which could lead to worsening of renal insufficiency)
use with caution perioperatively because of decreased platelet function –> may increase risk of operatie hemorrhage.
leukotrienes
Produced when lipoxygenase acts on arachidonic acid.
Lipid-like bronchoconstrictors that are released during the inflammatory response.
Asthma is treated with inhaled and oral medications that include beta-2 adrenergic agonist anti-inflammatory drugs and leukotriene antagonist
Prostaglandins
Produced when cyclooxygenase (COX) acts on arachidonic acid.
Many functions including:
Inflammation, Reproduction, gastric secretions, blood clotting
Two types of prostaglandins depending on tissue type.
Location: Platelets –> Thromboxane
Location: Endothelium –> Prostacyclin
Thromboxane –>vasoconstriction +bronchoconstrictor = procoagulation
Prostacyclin –> vasodilation + prevent platelet aggregation = anticoagulation
Prostaglandins protect GI mucosa from environment of stomach
Thromboxane (3 functions)
Vasoconstrictor
increases platelet aggregation
bronchoconstrictor
Prostacyclin
“keeps blood cyclin”
1. vasodilator
2. decreases platelet aggregation
Prostaglandin (PGE2) functions
- Promote fever
- promotes pain
