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25 Cards in this Set
- Front
- Back
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Briefly describe the Arachadonic Acid pathway, it's key enzymes, and products.
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Cell membrane (phospholipid) --> PLA2 --> Arachadonic Acid --> broken down by COX into Endoperoxide --> Prostaglandins.
AA--> broken down by Lipox --> Leukotriene (LTB, LTC, etc.) |
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What are the end products of Cyclooxygenase metabolism?
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Prostaglandins (PGE2, PGF2a)
Thromboxanes (TXA2, TXB2) Prostacyclin (PGI2) |
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COX-1 vs. COX-2
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COX-1 = constitutively active, involved in gastric protection, platelet aggregation, and kidney function.
COX-2= associated with INFLAMMATION and CANCER. Induced by cytokines and growth factors. |
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What makes molecules like Celecoxib selective COX inhibitors and Ibuprofen non-selective?
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Celecoxib has a bulky extra group that can only fit into the side pocket of COX-2's active binding site. Ibuprofen is a smaller molecule and can thus fit into both COX-1 and COX-2.
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What is the function of:
PGE2 and PGF2a |
PGE2- pyresis, pain and edema
PGE2 & PGF2a- increased GI motility/secretion, increased GI protection (mucous protects against acid). Uterine contraction. |
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Compare Prostacyclin and TXA2 in relation to cell of origin, platelets, and vascular effects.
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Prostacyclin (PGI2) = inhibit platelet aggregation, vasodilation (made by endothelial cell)
TXA2= stimulate platelet aggregation, vasoconstriction (made by platelets) |
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What is the MoA of Aspirin?
How does it have Analgesic effects? What about Antipyretic effects? |
MoA= irreversible COX inhibition.
Analgesia= decrease PGE2 production (which causes pain). Antipyreic= inhibit PGE2 which increases hypothalamic temperature setpoint |
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How does Aspirin cause increased bleeding time?
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It blocks TXA2 made by platelets which is involved in platelet aggregation. Thus, bleeding time is prolonged.
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What GI effects can result from Aspirin and Ibuprophen? How do these effects differ?
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Nausea, gastric irritation, dyspepsia, bleeding. Ibuprophen effects are much LESS INTENSE than Aspirin.
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Which drug holds more FDA approved indications than any other NSAIDS?
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Naproxen (OA, RA, SpA, dysmenorrhea, gout, etc.)
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What property of the Oxicam Derivatives (ex: Meloxicam or Mobic) make them particularly useful for chronic inflammatory diseases such as Arthritis?
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Long t1/2 (allows a once daily dosing)
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What is an NSAID that can be administered IV for treatment of postpoerative pain?
What NSAID is an analgesic and and anti-inflammatory but not anti-pyretic? |
Ketolerac = IV
Diflusinal= more potent than aspiring but no anti-pyrietic activity. |
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Name a selective COX-2 inhibitor.
Why does it have a black box warning? |
Celecoxib
Has less GI upset (preserves COX-1 gastric protective effects) but it also inhibits PGI2 which inhibits platelet aggregation. Thus, increased risk of MI and stroke. *treat with lowest dose for shortest period of time. |
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What is the MoA of Acetaminophen? What therapeutic effect does it NOT have that other NSAIDs do?
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MoA= reversible inhibition of COX in the CNS (not periphery!!)
Analgesic and Antipyresis (NOT an anti-inflammatory) *remember, it is conjugated to glutathione to decrease toxic metabolite |
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What are the two major groups of DMARDs? How does the size of the molecule affect it's use?
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1) Non-biologics (ex: methotrexate)- small molecules, long onset of action
2) Biologics (ex: antibodies)- large molecules, can be used for rapid action |
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How do DMARDs differ from NSAIDs (generally speaking)?
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DMARD- are disease modifying, reduce the disease activity of arthritis, SLOW PROGRESSION OF TISSUE DESTRUCTION!
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What is the MoA of Methotrexate?
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Methotrexate inhibits last enzyme in purine synthesis pathways --> adenosine builds up and has anti-inflammatory effect.
Inhibits DHFR and other enzymes necessary for DNA synthesis. Thus inhibits cytokine production and lymphocyte proliferation. |
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How does Leflunomide work? What is it absolutely contraindicated in?
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Leflunomide = small molecule DMARD. It also inhibits RNA and DNA synthesis thus causing arrest of lymphocytes.
Both this and Methotrexate are contraindicated in Pregnancy! (Teratogenic) |
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How does Chloroquine work?
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It's a DMARD (slows the progression of structural damage). MoA is not known. It inhibits lymphocyte proliferation and release of chemotactic factors. Inhibits PLA2.
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How do glucocorticoids work? When would you use them?
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Use in conjunction with a DMARD for treating flare ups from arthritis.
They work by decreasing NFkB translocation --> thus preventing proinflammatory cytokines. They also inhibit PLA2 (phospholipase A2) and thus prevent the production of AA pathway metabolites. *short course therapy, has many side effects |
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If a person has persistent moderate to high disease activity of Rheumatoid arthritis/Spa what would you consider using?
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Biological DMARDs in combination with a nonbiologic DMARD.
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What are three broad mechanisms to treat Gout?
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1. Inhibit the production of Uric Acid
2. Enhance the excretion of Uric Acid 3. Treat inflammation |
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Uric Acid is the end product of what metabolism pathway?
Most patients who have gout are affected by what problem? |
Purine metabolism
Uric acid under-excretion (not overproduction as is seen in certain genetic disorders). Here, renal excretion may be impaired or drugs may block tubular secretion. |
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What amino acid is histamine derived from?
Where is it stored? How is it released (i.e. what causes it to be released)? |
Histidine (basic amino acid)
Stored in inactive form in granules of Mast cell and Basophil. Response to C3a, C5a and bradykinin causes degranulation. Interaction with drugs or IgE causes degranulation. |
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Where is the H1 receptor (for Histamine) found?
What is meant by the statement "Antihistamines are INVERSE AGNOISTS of Histamine"?? |
H1 receptor found on - smooth muscle, endothelial cells, and CNS.
Antihistamines don't block Histamine.They shift the receptor toward the inactive conformation. |
