Test 1.16

Front 1

Inflammation and Prostaglandins:

Back 1

*Prostaglandins are important mediators of inflammation. They enhance blood flow to the site of injury=edema formation and leukocyte. PGs (E and F) sensitize pain receptors at nerve terminals=increase sensitivity to painful stimuli.

Front 2

Arachidonic Acid Pathway: (review pathway)

Back 2

*Arachidonic acid is released from membrane phospholipids mainly by **phospholipase A type 2 enzymes (PLA2). Also released by a combo of phospholipase C (PLC) and diglyceride lipase. decrease inflammation and decrease pain.

Front 3

Arachidonic Acid:

Back 3

*Major eicosanoid precursor (eicosa=20)
*5, 8, 11, 14-eicosatetraenoic acid (C20:4-6)
*Omega 6 fatty acid
*COX enzymes synthesize LTs from AA
*COX and LOX products are pro-inflammatory

Front 4

COX-1:

Back 4

*Constitutive (present normally) in most cells

Front 5

COX-2:

Back 5

*Inducible in activated macrophages and other tissues at the site of inflammation

Front 6

COX-3:

Back 6

*a cyclooxygenase-1 variant inhibited by APAP and other analgesic/antipyretic drugs: Cloning, structure and expression

Front 7

Leukotrienes:

Back 7

*5-lipoxygenase (5-LOX) enzyme converts arachidonic acid to leukotrienes (LTs). LTs are involved in bronchoconstriction, allergic and inflammatory reactions. LTs have chemotactic (directs movement of bacteria due to chemicals) according properties.

Front 8

Eicosanoids: AA metabolites
*Prostanoids:

Back 8

**Prostaglandins
**Prostacyclin
**Thromboxanes
**Mainly involved in inflammation and platelet activation.

Front 9

Eicosanoids: AA metabolites:
Leukotrienes:

Back 9

**Synthesized by LOX
**LTB4
**LTC4
**LTD4
**LTE4
**Mainly involved in inflammation and bronchoconstriction
**inhibit LOX=decreased inflam and bronchoconstriction

Front 10

Anti-inflammatory drugs:

Back 10

*Reduce eicosanoid synthesis;
*Steroidal-4 ring structure
*Non-steroidal-NSAIDS

Front 11

*Steroidal Anti-inflammatory Drugs

Back 11

*Cyclopentanoperhydrophenanthrene (CPPP) skeleton
*Ex: Vit. D, Digoxin,
*Betamethasone
*Dexamethaone
*Prenisolone

Front 12

*Corticosteroids:

Back 12

**Review pathway
*Corticosteroids are used clinically for their anti-inflammatory effects. CS inhibit phospholipase A2 enzyme the reduce the production of prostanoids. CS also reduces induced expression of COX-2 enzyme
*Betamethasone
*Dexamethasone
*Prednisone
*Fluticasone

Front 13

Extra on Steroids:

Back 13

**CS can be used for asthma, inflammation and pain
**Taking NSAIDS bad in Asthma, increase Arachidonic acis, increase Leukotrienes

Front 14

*LOOk at table:
Mineralcorticoidal activity:

Back 14

**increased mineralcorticoidal activity maintain Na and H2O.
**Wants CS with low mineralcorticoidal activity and high inflammation.
Newer CS have this, old CS are opposite.

Front 15

Prednisone (Deltasone)

Back 15

*Commonly prescribed oral corticosteroid
*Synthetic glucocorticoid
*MOA: Inhibit PLA2 and reduce COX-2 induction; At a molecular level, bind with high affinity to specific cytoplasmic receptors and modifes protein syntheisis=inhibition of leukocyte infiltration at the site of inflammation,, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses.
*IND: Allergic condition, inflammatory condition of sev. tissues, RA (short-term use suggested)
ADRs: endocrine abnormalities, fluid retention, hy[ertenion, CHF in susceptible pts, suppression of prowth in peds pts, immune suppression on long term, peptic ulcer=decrease COX-1
*CIs: Cushing's syndrome, fungal infection, varicella, measles
**Prednisolone is similar