NSAIDs Flashcards
Name the 3 Groups of NSAIDs
- Aspirin/Salicylates
- Traditional Non-Selective NSAIDs (ibuprofen)
- Coxibs (COX inhibitors)
A: How does Cell/Tissue Damage lead to Pain/Inflammation/Fever?
1: Damage induces ________ to produce ________
2: ________ binds to Cyclooxygenase and is converted into ________
3: ________ is then modified by multiple syntheses into
what 3 major compounds?
4: ________ can then go to induce pain/inflammation/fever.
B: What is the rate limiting step for this reaction?
A: How does Cell/Tissue Damage lead to Pain/Inflammation/Fever?
1: Damage induces [Phospholipase A2] to produce [Arachidonic Acid]
2: [Arachidonic Acid] binds to Cyclooxygenase and is converted into [Prostaglandin H2] = RATE LIMITING STEP!
3: [Prostaglandin H2] is then modified by multiple syntheses into
- [Prostacyclin]
- [Prostaglandin E2]
- [Thromboxane TXA2]
4: [Prostaglandins] can then go to induce pain/inflammation/fever.
B: What is the rate limiting step for this reaction?
[Arachidonic Acid] conversation into [PGH2] by Cyclooxygenase
Aspirin
MOA
IRREVERSIBLE NON-Competitive COX inhibitor
A: COX1 Expression
B: COX1 Location
A: Expressed constitutively and does NOT need to be induced
B: COX1 is UBIQUITOUSLY EXPRESSED IN MOST TISSUE
A: COX-TWO Expression
B: COX-TWO Location
- Where can it be Induced? (4)
- Where is it constitutively expressed? (2)
A: INDUCIBLE in many cell types in response to [pro-inflammatory]/mitogenic stimuli
B:
-INDUCED in [macrophages/monocytes], [Dorsal Horn Neurons], osteoblast and Fibroblast
-has low level constitutive expression in KIDNEY AND ENDOTHELIUM
COX1
A: Physiological Role (4)
B: What compounds do COX1 produce that facilitate these roles?
HOUSEKEEPING:
1. Platelet Regulation (monitors blood clotting)
- Kidney Function
- Cytoprotection of Stomach by regulating Acid/Mucus production & [gastric blood flow]
- Maintains Patent Ductus Arteriosus for Fetus and stimulates [Uterine contractions during labor (involves PGF2a) ]
(COX1 is NOT inhibited by Celecoxib)
B: [PGE2/PGi2]
COX-TWO
Physiological Role
PRO-INFLAMMATORY RESPONSE (Mitogenesis and Signaling)
How do Prostaglandins cause Peripheral Pain Sensitization?
[Prostaglandin E2] produced by a [COXTWO inflammatory cell] DEC PAIN THRESHOLD for [Primary afferent neurons]—> [Peripheral Pain Sensitization]
How do Prostaglandins cause CENTRAL Pain Sensitization
1st: [B.I.T.] produced by a [COXTWO inflammatory cell] travels to [Dorsal Horn Neurons] and induces COXTWO expression there.
2nd: [Dorsal Horn Neurons] now produce Prostaglandins which bind to PGE2 Receptors in the [Dorsal Horn Neurons] to ENHANCE the depolarization of [Secondary Afferent neurons]
[B.I.T.] = [Bradykinin/ IL-1 / TNFa]
Elucidate the steps of Fever Production starting with Tissue Damage
- Damaged Tissue produces [____ and ______] which travels to the CNS
- [____ and ______] stimulate endothelial cells of the [_______ blood vessels] to express _______ and [____ synthase]
- _____ and _____ in the endothelial cells of the [_____ blood vessel] produce [______] which goes to stimulate hypOthalamus to INC body temperature
Elucidate the steps of Fever Production starting with Tissue Damage
- Damaged Tissue produces [IL-1 and TNFa] which travels to the CNS
- [IL-1 and TNFa] stimulate endothelial cells of the [hypOthalamus blood vessels] to express COXTWO and [PGE synthase]
- [COXTWO/PGEsynthase] in the endothelial cells of the [hypOthalamus blood vessel] produce [Prostaglandin E2] which goes to stimulate hypOthalamus to INC body temperature
A: What is another name for PGi2?
B: What are its roles? (2)
C: Endothelial cells express COX1 or COXTWO? What are the primary compounds produced from Endothelial cells?
A: Prostacyclin!
B:
1) VasoDilates
2) INHIBITS Clotting
C: Endothelial cells express BOTH COX1 and COXTWO! They primarily produce [PGi2/PGE2] because they do NOT contain the [Thromboxane synthase]
“(PGi2 Prostacyclin) | (PGE2) “
A: Platelets express ONLY _____[COX⬜] but primarily produce ________.
B: What are the roles of the compound produced? (2)
A: Platelets express ONLY COX1 but primarily produce [Thromboxane].
B: What are the roles of the compound produced? (2)
1) vasoconstricts
2) promotes clotting
A: Why is PGi2 particularly important in Pt with Renal Dz or Heart Failure? (3)
B: Is [ ______-medicated acute renal failure] caused by taking NSAIDs in a diseased state, reversible?
A: [Renal Dz and Heart Failure]—> INC Renal VasoCONSTRICTORS. [PGi2] is a vasodilator that will
- INC Renal Blood flow to prevent Renal ischemia
- INC GFR
- INC water and Na+ excretion
B: Is [ HEMODYNAMICALLY-medicated acute renal failure] caused by taking NSAIDs in a diseased state, reversible?
->YES! JUST TAKE THEM OFF OF THE NSAIDS!
A: Why is Aspirin READILY absorbed in the stomach and [upper small intestine]?
ASA (AcetylSalicylicAcid) is a weak acid and in the acidic environment of the stomach it will be in a [NEUTRAL PROTONATED FORM]—> Allows EASY ABSORPTION!
Aspirin Recommended Dosing
- Anti-Platelet activity = ⬜ dose
- Anti-Pyretic = ⬜ dose
- Analgesic = ⬜ dose
- Anti-Inflammation= ⬜ dose
Aspirin Recommended Dosing
- Anti-Platelet activity = [81mg qD]
_________________ - Anti-Pyretic(must cross BBB) = [400mg BID]
_________________ - ]Anti-Pain (Analgesic)] = [400mg BID]
_________________ - [Anti-Puff (anti-Inflammation)= [4,000mg - 6,000mg qD]