Mediators of inflammation Flashcards
what are the 3 pathways of the complement pathway?
classical (antibody-regulated), lectin (mannose-binding lectin (MBL)) alternative (peptides)
what do all the pathways in the complement pathway lead to?
c3 convertase,which breaks down C3 –> C3a and C3b.
how is the complement pathway regulated?
C3a/c5a is broken down into C3a desarg/C5a desarg via carboxypeptide N/B/R
what is the effect of ACE- inhibitors on complement pathway?
ACE-I also inhibits carboxypeptide N/B/R, which leads to excess C3a/C5a. This is the cause of ACE-I induced iatrogenic angioedema.
what are causes for severe angioedema?
hereditary, genetic mutation leading to a loss-of-function of the C1q inhibitor. This leads to a build up of C1q.
Lipid mediator pathway:
Phospholipase A2 converts…
converts phospholipids into arachidonates and lyso-glyceryl-phosphorylcholine (precursor of PAF)
how do glucocorticoids affect the lipid mediator pathway?
effect on inflammation?
Glucocorticoids upregulate:
Lipocortin I/Annexin, which inhibit phospholipase A2.
This is a major suppressor of inflammation.
Cyclooxygease (COX) converts arachidonates into…
cyclo-endoperoxidases:
prostaglandins and thrombohexanes,
what does 5-lipooxygenease convert arachinodates into?
into 5-HPETE and eventually leukotrines
effect of NSAIDs and glucocorticoids?
what products are left over?
block cyclooxygenase–> less prostaglandins and thrombohexanes produced,
more leukotrines being produced.
Zileuton
5-lipoxygenase inhibitor
Montelukast
leukotriene receptor antagonist
effects of PGE2
vasodilator, bronchodilation,
hyperalgesia (more prone to pain),
fever,
gastric protection
(little effect on its own but large synergistic effect with other mediators)
main contraindication for NSAIDs (cox-1 inhibitors)
give what instead?
gastric ulcer patients.
Give a PPI or H2 antagonist where necessary to minimise side effects.
effects of PGI2
mainly found in vascular endothelium
vasodilator,
hyperalgesia,
inhibit platelet aggregation
