Anti-Inflammatory

Question 1

What are some characteristics of acute inflammation?

Answer 1

• pulse of injury
• onset is abrupt
• prominent symptoms
• prominent vascular effects and exudate
• exudate is neutrophils
• T cell proliferation occurs after inflammation subsides

Question 2

What are some characteristics of chronic inflammation?

Answer 2

• 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

Question 3

What are the 2 phases of asthma and what happens during the two phases?

Answer 3

1. Early - bronchospasm

2. Late - inflammatory response after initial insult that triggers histamine release

Question 4

What do glucocorticoids do?

Answer 4

Bind to GR receptor and act in the nucleus to inhibit production of inflammatory mediators.
- Trans activation leads to upregulation of anti-inflammatory proteins

Question 5

What is the problem w/ glucocorticoids?

Answer 5

they have a bipolar personality that produces a host of adverse events upon chronicity of the drug

Question 6

Why do you avoid steroids in elderly patients?

Answer 6

may effect skin thinning and bone problems

Question 7

Why is it ok to give steroids for asthma even though it though it is chronically used?

Answer 7

inhalation puts the drug right where you want it and can give a small dose – minimizes potential for adverse effects

Question 8

What is the major GR isoform that glucocortcoids activate?

Answer 8

GR alpha

Question 9

What other isoform is epxressed by humans for glucocorticoids?

Answer 9

GR beta - has a role in inhibiting alpha

Question 10

What are some proposed mechanisms of glucocorticoids?

Answer 10

receptor modification, increased beta receptor expression, increased levels of pro-inflammatory transcription factors, increased levels of pGp and increased efflux of steroids

Question 11

How do steroids work at the very basic biochemical level?

Answer 11

blocks phospholipase so you can’t form AA

Question 12

How do NSAIDs work at the very basic biochemical level?

Answer 12

block COX so there is a tendency for AA to become LTs which leads to pro-inflammatory events as well

Question 13

What is used to treat gout?

Answer 13

colchicine

Question 14

What are LT receptor blockers?

Answer 14

montelukast and zafirukast

Question 15

What are LT synthesis inhibitors?

Answer 15

zileuton

Question 16

What does sodium cromolyn do?

Answer 16

blocks Cl- channels so it stops mast cells from releasing histamine

Question 17

What is omalizumab?

Answer 17

An anti-IgE antibody

Question 18

how does omalizumab work?

Answer 18

it soaks up free IgE so it can’t bind to mast cells to trigger release histamine

Question 19

How do IL13 and IL4 Stats inhibitors work?

Answer 19

block immune cells from functioning, prevent mucus secretion, and prevent eotaxin release from epithelial cells to recruit eosinophils

Question 20

In what type of patients does an IL5 antagonists work?

Answer 20

severe steroid-resistance, eosinophilic asthma, no discernible effect in milder disease

Question 21

What is phenotypic driven treatment crucial?

Answer 21

you need to be selective in who you pick phase II trials w/ to prove or disprove if your drug has clinical effects

Question 22

How do H1 receptors work?

Answer 22

they are used to counteract the effects of histamine. they are inverse agonists - binding shifts balance to inactive form
- antihistaminase

Question 23

where are h2 receptors fucntional?

Answer 23

stomach

Question 24

What are the effects of H1 receptor activation in lungs?

Answer 24

bronchoconstriction - leading to asthma symptoms

Question 25

What are the effects of H1 receptor activation in vascular smooth muscle?

Answer 25

vascular dilation and venoconstriction

Question 26

What are the effects of H1 receptor activation in vascular endothelium?

Answer 26

contraction and separation of endothelial cells to allow everything to escape - leads to a decrease in BP

Question 27

What is the difference b/w the different generation of drugs?

Answer 27

when you have something wrong or some side effect you want to improve you make new types of drug and they become 2nd generation

Question 28

What side effect did 1st generation drugs antihistaminases have?

Answer 28

produced sedation b/c they were able to cross the blood brain barrier

Question 29

How do PDE inhibitors work?

Answer 29

inhibit the conversion of cAMP to 5’ cAMP so cAMP levels go up and it decreases immune and inflammatory activity

Question 30

What are the 3 effects of PDE inhibitors?

Answer 30

1. relaxation of airway smooth muscle
2. suppression of inflammatory activity
3. inhibition of airway smooth muscle proliferation

Question 31

What is an example of a PDE inhibitor?

Answer 31

roflumilast

Question 32

What does TNF normally do?

Answer 32

it binds to either type I or type II receptors and the balance of receptors on the cell dictates response of TNF

Question 33

How do the anti-TNF Abs work?

Answer 33

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

Question 34

What are the major diseases that use TNF alpha inhibitors?

Answer 34

psoriasis, RA, ankylosing spondylitis, etc

Question 35

What is telcagepant?

Answer 35

a calcitonin gene related protein antagonist (CGRP)

Question 36

What does CGRP do?

Answer 36

sensitizes glutamatergic synapses in CNS leading to migraines

Question 37

Why use migraine sufferers often use triptans?

Answer 37

to constrict blood vessels BUT sometimes produce deleterious CV effects

Question 38

Why is it better to use CGRP?

Answer 38

they don’t constrict blood vessels and thus don’t have deletrious CV effects

Question 39

What is side effect of CGRP?

Answer 39

hepatoxicity