Anti-Inflammatory Flashcards
What are some characteristics of acute inflammation?
- pulse of injury
- onset is abrupt
- prominent symptoms
- prominent vascular effects and exudate
- exudate is neutrophils
- T cell proliferation occurs after inflammation subsides
What are some characteristics of chronic inflammation?
- persistent injury
- vague onset
- symptoms are often subsided
- mild tissue effects
- exudate is made of both lymphocytes and macrophages
- T cell prolieration is concurrent w/ on-going inflammation
What are the 2 phases of asthma and what happens during the two phases?
- Early - bronchospasm
2. Late - inflammatory response after initial insult that triggers histamine release
What do glucocorticoids do?
Bind to GR receptor and act in the nucleus to inhibit production of inflammatory mediators.
- Trans activation leads to upregulation of anti-inflammatory proteins
What is the problem w/ glucocorticoids?
they have a bipolar personality that produces a host of adverse events upon chronicity of the drug
Why do you avoid steroids in elderly patients?
may effect skin thinning and bone problems
Why is it ok to give steroids for asthma even though it though it is chronically used?
inhalation puts the drug right where you want it and can give a small dose – minimizes potential for adverse effects
What is the major GR isoform that glucocortcoids activate?
GR alpha
What other isoform is epxressed by humans for glucocorticoids?
GR beta - has a role in inhibiting alpha
What are some proposed mechanisms of glucocorticoids?
receptor modification, increased beta receptor expression, increased levels of pro-inflammatory transcription factors, increased levels of pGp and increased efflux of steroids
How do steroids work at the very basic biochemical level?
blocks phospholipase so you can’t form AA
How do NSAIDs work at the very basic biochemical level?
block COX so there is a tendency for AA to become LTs which leads to pro-inflammatory events as well
What is used to treat gout?
colchicine
What are LT receptor blockers?
montelukast and zafirukast
What are LT synthesis inhibitors?
zileuton
What does sodium cromolyn do?
blocks Cl- channels so it stops mast cells from releasing histamine
What is omalizumab?
An anti-IgE antibody
how does omalizumab work?
it soaks up free IgE so it can’t bind to mast cells to trigger release histamine
How do IL13 and IL4 Stats inhibitors work?
block immune cells from functioning, prevent mucus secretion, and prevent eotaxin release from epithelial cells to recruit eosinophils
In what type of patients does an IL5 antagonists work?
severe steroid-resistance, eosinophilic asthma, no discernible effect in milder disease
What is phenotypic driven treatment crucial?
you need to be selective in who you pick phase II trials w/ to prove or disprove if your drug has clinical effects
How do H1 receptors work?
they are used to counteract the effects of histamine. they are inverse agonists - binding shifts balance to inactive form
- antihistaminase
where are h2 receptors fucntional?
stomach
What are the effects of H1 receptor activation in lungs?
bronchoconstriction - leading to asthma symptoms
What are the effects of H1 receptor activation in vascular smooth muscle?
vascular dilation and venoconstriction
What are the effects of H1 receptor activation in vascular endothelium?
contraction and separation of endothelial cells to allow everything to escape - leads to a decrease in BP
What is the difference b/w the different generation of drugs?
when you have something wrong or some side effect you want to improve you make new types of drug and they become 2nd generation
What side effect did 1st generation drugs antihistaminases have?
produced sedation b/c they were able to cross the blood brain barrier
How do PDE inhibitors work?
inhibit the conversion of cAMP to 5’ cAMP so cAMP levels go up and it decreases immune and inflammatory activity
What are the 3 effects of PDE inhibitors?
- relaxation of airway smooth muscle
- suppression of inflammatory activity
- inhibition of airway smooth muscle proliferation
What is an example of a PDE inhibitor?
roflumilast
What does TNF normally do?
it binds to either type I or type II receptors and the balance of receptors on the cell dictates response of TNF
How do the anti-TNF Abs work?
they bind either to cell surface TNF or to soluble released form – net effect is decreasing amount of TNG alpha available to be bound by inflammatory cells
What are the major diseases that use TNF alpha inhibitors?
psoriasis, RA, ankylosing spondylitis, etc
What is telcagepant?
a calcitonin gene related protein antagonist (CGRP)
What does CGRP do?
sensitizes glutamatergic synapses in CNS leading to migraines
Why use migraine sufferers often use triptans?
to constrict blood vessels BUT sometimes produce deleterious CV effects
Why is it better to use CGRP?
they don’t constrict blood vessels and thus don’t have deletrious CV effects
What is side effect of CGRP?
hepatoxicity
