Inflammation/NSAIDs/DMARDs Flashcards
Acute or Chronic inflammation?
Accumulation of fluid & plasma proteins
Acute
Acute or Chronic inflammation?
Exudation occurs
Acute
what is exudation
accumulation of fluids/plasma proteins
Acute or Chronic inflammation?
Accumulation of Neutrophils
acute
Acute or Chronic inflammation?
TNF, IL-1, Chemokines
Acute
Acute or Chronic inflammation?
Tissue destruction by inflammatory cells
chronic
Acute or Chronic inflammation?
vascular proliferation and fibrosis
chronic (this is also known as scarring..)
Acute or Chronic inflammation?
Influx of lymphocytes and macrophages
chronic
Acute or Chronic inflammation?
IFN-gamma by T cells
Chronic
Acute or Chronic inflammation?
IL-12 released by macrophages
chronic
Main 4 Steps of Inflammation
1 - Vascular Changes
2 - Leukocyte Recruitment
3 - Leuckocyte Activation
4 - Leuckocyte induced tissue injury
Leuckocyte Recruitment:
Loose attachment/Rolling is done by _______
and
Adhesion is done by ________
selections; integrins
Which chemical mediators on inflammation are vasoactive amines
histamine/serotonin
what do vasoactive amines do
cause vasodilation
what chemical mediators of inflammation are eicosaniods
prostaglandins, leukotrienes, lipoxins
Lipoxin _________ inflammaiton
suppress
Eicosanoids are (short or long ) lived mediators that do autocrine AND paracrine signaling
short!
Eicosanoids bind to _________ receptors
G-coupled
what are the chemical mediators of inflammation for the coagulation/kinin systems
- bradykinin
- thrombin
- fibrinopeptides
what are the chemical meditors of inflammation for cytokines
TNF and IL-1 and IFN-gamma
IFN- gamma for acute or chronic inflammation
chronic
TNF for acute or chronic inflammation
acute
IL-1 for acute or chronic inflammation
acute
chemical mediators for inflammation that are complement components
C3a, C5a
Role of PGE(2) in the body
- dilates blood vessels
- dilates uterus (oxytoxic)
- dilates bronchi
(E = Expand = Dilate!)
Role of PGE(F2a) in the body
- constricts blood vessels
- constricts bronchi
(F = Fasten = constrict!)
Role of PGI(2)
- inhibits aggregation of platelets
- dilates
(I = inhibit = if you no platelets — airway more open = dilated)
Role of TXA(2)
- promotes aggregation of platelets
- constriction
(A = aggregate = less room in vessel = constrict)
Where does Arachidonic acid come from
- released form membrane phospholipids by PLA (phospholipase A2)
Corticosteroids and Arachidonic Acid relationship
if corticosteroids are given - it will suppress the production of PLA2 –> no arachidonic acid is made –> reduction in eicosanoid production
PGH Synthase pathway in Oxygenation of Arachidonic acid is also known as _______
COX pathway!
COX pathway results in _________
prostaglandins and thromboxanes
Lipoxygenase pathway results in __________
leukotrienes (5HPETE, Lipoxins)
COX 1 or COX 2:
aka PGH Synthase 1
COX 1
COX 1 or COX 2:
Constitutively expressed in various tissues
COX 1
COX 1 or COX 2:
Does gastric cyroprotection as a part of its “Housekeeping” functions
COX 1
COX 1 or COX 2:
Expressed upon stimulus in inflammatory/immune cells
COX 2
COX 1 or COX 2:
stimulated by growth factors, tumor promoters, and cytokines
COX 2
Final Product in COX pathway - the “non-specific” product
going for the answer PGH-2
not prostaglandin or thromboxane since those are made specifically at different tissues
Corticosteroids: block (some or all) pathways of eicosanoid synthesis
ALL! - because it inhibits PLA2 via making lipocortins
do NSAIDs block production of leukotrienes?
NAH - only prostaglandins and thromboxanes (aka the products from the COX pathway)
Eicosanoid Drugs:
Alprastodil what kind of prostaglandin drug
PGE1
what does Alprastodil do
- relaxes smooth muscle/expands blood vessels
aka
is used for erectile dysfunction by injection or suppository
Eicosanoid Drugs:
Misoprostol is what kind of prostaglandin drug
PGE1 derivative
what does Misoprostol do?
its cytoprotective/prevents peptic ulcer
- also used to terminate early pregnancy if used with mifepristone
Eicosanoid Drug:
Latanprost is what kind of prostaglandin durg
PGF(2) derivative/Prodrug
what is lantanprost used for
it constricts blood vessels - aka used to treat high pressure in the eye (aka glaucoma)
Eicosanoid Drug:
Prostacyclin - is what kind of prostaglandin drug
PGI2
Eicosanoid Drug:
Prostacyclin is used for what?
well it inhibits aggregation of platelets –> is powerful vasodilator –> used to Treat pulmonary arterial HTN
aka dont use w/ anticoagulants
What are the pharmacological activities of NSAIDs
- anti-inflammatory
- anti-pyretic
- analgesic
MOA of NSAIDs
inhibit PGH synthase (aka COX enzymes - most NSAIDs inhibit both cox 1 and 2) –> less prostaglandins are important
MOA of aspirin that makes it inhibit blood coagulation
aspirin irreversibly inhibits of platelets COX -1
What is Reye’s Syndrome
rara acute life threatening condition characterized by vomiting/delirium/coma due to salicylates -
who should not get aspirin when trying to prevent Reyes Syndrome
kids under 12 who have a fever
Common Drug Interaction w/ NSAID
anticoagulants and NSAIDs because they both to compete for albumin
what is the role (structure activity) of alpha-methyl in arylpropionic acids
the alpha methyl separates the acidic ring from the aromatic ring which tends to increase activity
How does MOA for APAP differ from NSAIDs
APAP does NOT inhibit archidonic acid from binding to PGHS
APAP DOES scavenge peroxynitrites required for PGHS activity
How do we have selective COX 2 Inhibitors (structure wise)
the NSAID binding site in COX 1 and COX 2 are different
COX 2 has larger binding site (has valine in there instead of COX1 has isoleucine which is more bulky)
MOA of Methotrexate -
inhibits ribonucleotide transformylase and thymidylate synthetase
Why do COX 2 inhibitors have CV risk side effects
COX 2 inhibitors lead to an imbalance of prostaglandins and thromboxanes which leads to more platelet aggregation
MOA for Leflunomide
prodrug for pyrimidine synthesis inhibitor - will deplete pyrimidines/inhibit T cell proliferation
MOA for Hydroxychloroquine
accumulates in lysosomes and inhibits protein secretion
MOA of Sulfasalazine
Suppress release of cytokines from macrophages
MOA of Abatacept
has CTLA-4 domain to inhibit co-stimulation of T-Cells by APCs
MOA of Rituximab
induces apoptosis of CD20+ - will reduce inflammation by reducing activation of T cells