1.C Flashcards
What is inflammation?
a physiologic response to tissue injury and infection
chronic or acute
True or false: inflammation is present in almost all diseases or conditions
true
What are some symptoms of acute inflammation?
swelling
redness
heat
pain
What is the purpose acute inflammatory response?
provides protection by:
-restricting damage to the localized site
-recruiting immune cells to eliminate invading pathogens
-initiating wound repair
How do the clotting and kinin systems aid in acute inflammation?
clotting: fibrin strands accumulate to stop the spread of infection and bleeding to outside
kinin: produces bradykinin which induces vasodilation and increased permeability
What is the role of mast cells in the acute inflammatory response?
degranulate to release histamine and activates prostaglandins and leukotrienes
this allows leakage of fluid from the blood vessels to the damaged tissue
Is acute inflammation a negative or positive feedback loop?
positive
more cells are recruited until the problem is resolved
What is the cause of heat, redness, and swelling during acute inflammation?
vasodilation (more fluid arrives and moves)
What is the cause of pain during acute inflammation?
swelling or the activation of nociceptors
What is diapedesis?
the movement of leukocytes out of the blood into the site of infection or tissue damage
What are the 4 steps in diapedesis?
- chemoattraction: granular substances draw leukocytes to the site of damage
- rolling adhesion: leukocyte makes weak bonds to receptors on the endothelial cell wall
- tight adhesion: cytokines and integrins bond strongly to the endothelial cell wall
- transmigration: leukocytes squeeze into tissue
What do leukocytes do after diapedesis?
phagocytize the invading pathogen and release mediators
(cytokines, histamines, PG, LT)
What do mediators do?
coordinate and regulate immune cell activities
antiviral, pro-inflammatory, or anti-inflammatory activity
act locally or systemically
they guide cells where to go (chemoattraction)
What does the chronic inflammatory response do?
continues after the acute response
cleans up debris
facilitates healing
What is chronic inflammation the result of?
continuous exposure to the offender
How do we characterize chronic inflammation?
accumulation and activation of macrophages and lymphocytes
fibroblasts that replace the original, damaged, or necrotic tissue
Where are inflammatory mediators found?
newly synthesized or preformed in granules
What are cytokines?
soluble factors secreted by activated immune cells
What are the major activities of cytokines?
promote inflammation and mediate natural immunity (IL-1, IL-8, IL-, TNF, IFN-a)
support allergic inflammation (IL-4, IL-5, IL-13)
immunoregulatory (IL-10, IL-12, TGF-b, IFN-y)
act as hematopoietic growth factors (IL-3, Il-12, GM-CSF)
What are “biologics”?
designed to affect cytokines
medications produced using biological processes
large and complex molecules
harvested from living sources
How do monoclonal antibodies work?
the antibody is the delivery system to target receptors or pathogens
attach a drug to an antibody which then only targets and affects specific cells
What kind of drug is Infliximab? How does it work?
biologic
Mab designed to target the cytokine TNF to reduce inflammatory bowel disease
What is typically used in patients with MS? What does it target?
natalizumab (a biologic)
a monoclonal antibody that blocks a4 integrin
Which type of antihistamines have a stronger anticholingergic effect?
1st gen
True or false: prostaglandins and leukotrienes are newly generated mediators
true
What is the pre-cursor for prostaglandins and leukotrienes?
arachidonic acid
Which pathway converts arachidonic acid to prostaglandins? Leukotrienes?
prostaglandins=cyclooxygenase
leukotrienes=lipoxygenase
True or false: the cyclooxygenase and lipoxygenase pathways occur at different times when arachidonic acid is released
false, they occur at the same time
What are a few functions of prostaglandins?
various functions:
constrict/dilate vascular tissue
aggregation/disaggregation of platelets
induce labour
produce a fever
menstruation
GI mucosal production
What is the enzyme that converts arachidonic acid into a prostaglandin?
cyclooxygenase
Compare and contrast COX-1 and COX-2.
COX-1: in all tissues, involved in platelet aggregation
COX-2: specific for inflamed tissue
What are the 5 types of drugs that affect inflammation?
biologics
anti-histamines
NSAIDs
LTRAs
corticosteroids
Which enzyme do NSAIDS target? What effect does this have?
inhibits cyclooxygenase
reduces prostaglandin synthesis=less inflammation
True or false: NSAIDS can affect prostaglandins that have been synthesized
false
What are some other uses of NSAIDS?
analgesic
antipyretic
What do classic NSAIDS target? COX-2 inhibtors? Provide examples for both.
classic NSAIDS: inhibit COX-1 and COX-2 (ibuprofen, naproxen, ketorolac, diclofenac, meloxicam)
COX-2 inhibitors: specific inflamed tissue (celecoxib)
What are a few adverse effects of NSAIDS?
nausea
dyspepsia
hypertension (long term NSAID use)
anti-platelet
Where are leukotrienes particularly active?
smooth muscle lining the bronchioles
Which pathophysiological condition do leukotrienes contribute to?
asthma
How do leukotriene receptor antagonists (LTRAs) work? Drug example?
reduce inflammation by blocking leukotriene receptors
montelukast
True or false: LTRAs are a rescue drug
false
What is cortisol?
a hormone released in response to stress
job is to bring the body back to homeostasis
What kind of effects does cortisol have?
anti-inflammatory
immunosuppressive
Where are cortisol receptors?
all over the body
How are corticosteroids designed?
to mimic our endogenous cortisol
they are not very specific
How are corticosteroids categorized?
pharmacokinetics
potencies
When using corticosteroids, why do we attempt to administer locally?
to try and prevent adverse effects
Describe the anti-inflammatory and immunosuppressant MOA of cortisol.
anti-inflammatory: decrease production of PG, LT, leukocytes, decrease recruitment of leukocyte to site of injury, stabilize mast cells
immunosuppressant: induce T cell apoptosis, decrease T cell recruitment to antigens, no B cell activity, increase T cell redistribution to lymph nodes
