Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
66 Cards in this Set
- Front
- Back
Acute inflammation
|
Immediate response to local mediators
|
|
What are the Autacoids
|
Histamine, serotonin, bradykinin, prostaglandins, leukotrienes
*locally acting substances |
|
What is the affect of autacoids?
|
Vasodilation, increased vascular permeability chemotaxis, pain
|
|
Chronic inflammation occurs in response to what mediators?
|
Interleukins
Granulocyte-macrophage colony-stimulating factor (GM-CSF) TNF alpha and beta Interferons PDGF |
|
Most common chronic inflammatory condition
|
Rhematoid Arthritis
|
|
Which enzyme converts Aracodonic Acid(AA) to Leukotrienes
|
Lipoxygenase
|
|
Which enzyme converts AA to prostacyclins, thromboxanes, and prostaglandins
|
Cyclooxygenase
|
|
What do leukotrienes cause?
|
Bronchoconstricion
|
|
What does thromboxane cause?
|
Platelet aggregation
|
|
What do Prostacyclins (PGX, PGI) cause?
|
Antiaggregating factor release
|
|
What does PGE2 cause?
|
Edema, erythema, pain, fever
|
|
What does PGF2alpha cause?
|
Uterine contraction
|
|
Prostacyclin (PGI2) and PGE2 have what local effect?
|
Vasodilation
|
|
Phospholipase A2 is inhibited by what?
|
Glucocorticoids
|
|
Inhibits Cyclooxygenase
|
NSAIDS
|
|
COX 1 Expression
|
Constitutively in most tissues, generates LOW levels of prostaglandins
|
|
Function of COX-1
|
Protective function (gastric mucosa), vasodilator- determines peripheral resistance to kidney
|
|
Other Functions of COX-1
|
Blood clotting, uterine contraction, muscle growth, synaptic transmission at some CNS synapses
|
|
COX-2 constituive or inducible?
|
Inducible
|
|
COX-2: Yields high or low levels of prostaglandins and thromboxanes
|
HIGH
|
|
When is COX-2 expressed in high concentration
|
After induction by inflammatory mediators
|
|
What is the major inflammatory mediator product
|
Prostaglandin E2
|
|
NF-kB
|
Induces expression of cytokines (IL-1, IL-6), interferon beta, and cell adhesion molecules = ENHANCED INFLAMMATION
|
|
What stimulates NF-kB?
|
TNF alpha
|
|
DMARD
|
Disease Modifying Anti-Rheumatic Drugs
- they delay the disease process |
|
Examples of DMARDs
|
Methotrexate
Gold Low-dose corticosteroids Leflunomide TNF alpha inhibitors |
|
Selective Cox-2 inhibitor
|
Celecoxib (sell a kox' ib)
|
|
Non selective COX inhibitors (hint: there are 7)
|
Aspirin
Sodium salicylate Indomethacin Ibuprofen Naproxen Phenylbutazone Acetaminophen |
|
Immunosuppresive Agents
(hint: 4 + 3 for gout) |
Glucocortocoids
Gold sodium thiomalate Methotrexate Leflunomide Drugs for gout: allopurinol, probenecid, sulfinpyrazole |
|
TNF alpha blockers
|
Etanercept
Infliximab |
|
How long does it take to have a therapeutic response to DMARD
|
weeks or months
|
|
Current recommendation for DMARD
|
Early in the course of RA
|
|
Methotrexate
|
most widely used DMARD
anti-inflammatory |
|
How long does it methotrexate to work?
|
4-6 weeks
|
|
Side effects of Methotrexate
|
Anorexia, vomiting, abdominal cramps, increased hepatic enzyme activity, immuno-suppresion, bone marrow supression, lymphomas
|
|
What would you combine with methotrexate to make it more effective?
|
Cyclosporine or infliximab
|
|
Gold preparations MA
|
Retard progression of bone and articular destruction
|
|
Gold sodium thiomalate MA
|
Gold accumulates in macrophages decreasing activation, migration, and therefore immune response
|
|
How is Gold sodium thiomalate excreted?
|
Urine (60-90%)
Feces (10-40%) |
|
Gold sodium thiomalate admin.
|
I.m.
|
|
Adverse effects of gold sodium thiomalate
|
~1/3 of patients
Dermatitis, thrombocytopenia, aplastic anemia(rare), proteinuria |
|
Etanercept
|
TNF alpha antagonist
|
|
Structure of Etanercept
|
composed of p75 TNF RECEPTOR coupled to Fc fragments of immunoglobulin
|
|
MA of Etanercept
|
Binds TNF alpha and blocks stiumlation of the receptors
|
|
Infliximab
|
TNF alpha chimeric monoclonal antibody
(* on exam: Fc region of IgG + Fab sequences of mouse ANTI-TNF ANTIBODY) |
|
Structure of Infliximab
|
Human Fc of IgG + Fab sequence of mouse anti-TNF Ab
|
|
MA of Infliximab
|
Binds free TNF alpha
Reduces joint swelling and damage |
|
Infliximab admin
|
I.v.
|
|
Side effects of TNF alpha antagonist?
|
Increased risk for infection, allergic rxns, and possibly malignancies
|
|
Aspirin
|
Irreversible non-selective COX enzyme inhibitor
|
|
Aspirin MA
|
Acetylates COX enzymes
|
|
Ibuprofen/Naproxen
|
Reversible non-selective COX enzyme inhibitors
|
|
Side effects of Ibuprofen/Naproxen
|
Due to (-) of COX 1, mainly gastric ulceration and bleeding, impaird kidney fxn
|
|
Salicylate
|
Weak COX inhibitor, probably a better NF-kB inhibitor (decreased IL-1,IL-6, and INF B)
|
|
Celecoxib
-advantages? |
COX-2 selective inhibitor
Reduced gastroduodenal damage, platelet aggregation is not impaired |
|
Which COX-2 selective inhibitor was recently taken off the market?
|
Rofecoxib (Vioxx)- increased risk of thromboembolic events due to unchecked Thromboxane A2 production
|
|
Acetominophen
|
Analgesic and anti-pyretic
weak COX 1 and 2 inhibitor |
|
New findings about Tylenol
|
COX-3 expressed in CNS is very sensitive to acetaminophen inhibition
|
|
Glucocorticoid 3 possible MA
|
Inhibition of AA production by (-) of phospholipase A2
Inhibition of inflam. cytokines (Interleukins,TNFa, IFNy) Inhibition of NF-kB |
|
Side effect of glucocorticoids
|
Cushing's
|
|
Why give aspirin to patients with heart conditions
|
Reduces incidence of MI by 40%
|
|
What cancer can aspirin provide protection against?
|
Colorectal
* 4 aspirin/week for 10 years of more |
|
Bartter's Syndrome
|
hyperplasia of renal JG apparatus -- hyperreninemia, hyperaldosteronism, hypokalemic alkalosis, normal BP, elevated PG excretion
USE NSAIDS |
|
Why use NSAIDs to treat Bartter's syndrome
|
Reverses the symptoms
|
|
PDA and NSAIDs
|
patent ductus arteriosus treatment with NSAIDs as 60-90% success in closing duct
|
|
What is salicylate?
|
The deacetylated metabolite of aspirin
|