Analgesics and NSAIDS Flashcards
What is the cell damage pathway to arachidonic acid?
cell damage
releases eicosanoids (signaling molecule) to release membrane phospholipids
phospholipase uses those to create arachidonic acid.
AA can do the cox or Lox pathway
cox1 vs cox2
cox1-constitutive, widespread, converts aa into pg and txa2
“housekeeping” does homeostatic functions so generally don’t want to inhibit
Cox2- stimulus (cytokines) dependent. Facilitates inflammatory response so inhibiting is beneficial.
Pharmacokinetics of NSAIDs
weak acids
highly protein bound
NSAIDs MOA
inhibit cox
decreases sensitivity of vessel to histamines and bradykinin which reverses vasodilation
Also inhibit platelet aggregation if they are cox1 specific
side effects of NSAIDS
GI irritation
nephrotoxicity
hepatotoxicity
irreversible inhibition of aspirin MOA and why it’s important
aspirin binds to serine molecule and prevents aa from getting into the cell
which blocks COX which blocks TXa2 which prevents plt. aggregation and it forms and irreversible block.
plts that are circulating for 8-10 days will be impacted as well as all the plts being produced
This is why you have to stop asa several days before surgery.
These NSAIDs effect COX1 and COX2 equally
ibuprofen
Tordal
What is the NSAID that does not have any GI effects? why?
Celebrex
More Cox2 specific
How do NSAIDs reduce fever
cause peripheral vasodilation and central vasoconstriction
MOA of GI upset with all NSAIDs
they block the protective Prostaglandins that produce mucous in the stomach so acid eats away at the stomach lining since there isn’t any mucous to protect it.
Get bleeding ulcers.
Black box warning NSAIDS
avoid in pregnancy >20 weeks d/t fetal kidney development being impacted
decreases amniotic fluid (placental abruption risk)
use Tylenol instead
What is the only cox 2 specific drug still on the market?
celebrex
pros and cons to cox 2 specific drugs
pros:
* no impact on plt aggregation
* no GI effects
* no impact on COX 1
- good for arthritis
cons:
* debilitating side effects
* sulfonamide so allergy risk
* black box warning for adverse CV events
acute and chronic effects of glucocorticoids
acute (you want these)
* suppress inflammation
* mobilize energy stores
* salt and water retention
chronic(problematic)
* immunosuppression
* diabetes
* obesity
* HTN
MOA of glucocorticoids
block transcription and translation
DMARD stands for:
disease modifying anti rheumatic drugs
What is celebrex used for?
arthritis
Toxicity with celebrex
sulfonamide and black box warning for serious CV events
meloxicam things to know
inhibits cox-2 over cox-1
not as selective as other coxibs
Fewer GI effects
toxicities similar to NSAIDs
Diclofenac things to know
nonselective cox inhibitor
pain and fever
20% have adverse GI effects. Take Cytotec to help with adverse effects
ibuprofen adverse effects
agranulocytosis (decreased wbc)
and
aplastic anemia(decreased rbc)
indomethacin
high toxicity index
potent Cox 1 and 2 inhibitor
reduces T and B cell proliferation
indomethacin uses:
rheumatism
gout
patent ductus arteriosus
(prostaglandins keep duct open in the womb, should close when you are born because pg levels decrease) If baby has high PG, hole will stay open- give indomethacin to treat by blocking pg
Explain the 3 things that increase and 1 thing that decreases with glucocorticoid transcription:
Increases:
1. annexin 1
2. SLPI
3. IL10
These suppress phospholipase A2 which inhibits the leukocyte response
inhibits
1. NFkB
which is proinflammatory so this decreases inflammation
Abatacept drug class and what does it do?
DMARD
blocks T-cell activation
Rituximab MOA
depletes B lymphocytes which is beneficial bc these are what produce antibodies during inflammatory responses.
List the DMARDS
Abatacept
Rituximab
Humira (Adalimumab)
Humira MOA
anti Tumor Necrosis Factor alpha
these block TNF to reduce inflammation
