Analgesics and NSAIDS

Question 1

What is the cell damage pathway to arachidonic acid?

Answer 1

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

Question 1

cox1 vs cox2

Answer 1

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.

Question 2

Pharmacokinetics of NSAIDs

Answer 2

weak acids
highly protein bound

Question 3

NSAIDs MOA

Answer 3

inhibit cox
decreases sensitivity of vessel to histamines and bradykinin which reverses vasodilation

Also inhibit platelet aggregation if they are cox1 specific

Question 4

side effects of NSAIDS

Answer 4

GI irritation
nephrotoxicity
hepatotoxicity

Question 5

irreversible inhibition of aspirin MOA and why it’s important

Answer 5

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.

Question 6

These NSAIDs effect COX1 and COX2 equally

Answer 6

ibuprofen
Tordal

Question 7

What is the NSAID that does not have any GI effects? why?

Answer 7

Celebrex
More Cox2 specific

Question 8

How do NSAIDs reduce fever

Answer 8

cause peripheral vasodilation and central vasoconstriction

Question 9

MOA of GI upset with all NSAIDs

Answer 9

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.

Question 10

Black box warning NSAIDS

Answer 10

avoid in pregnancy >20 weeks d/t fetal kidney development being impacted

decreases amniotic fluid (placental abruption risk)

use Tylenol instead

Question 11

What is the only cox 2 specific drug still on the market?

Answer 11

celebrex

Question 12

pros and cons to cox 2 specific drugs

Answer 12

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

Question 13

acute and chronic effects of glucocorticoids

Answer 13

acute (you want these)
* suppress inflammation
* mobilize energy stores
* salt and water retention

chronic(problematic)
* immunosuppression
* diabetes
* obesity
* HTN

Question 14

MOA of glucocorticoids

Answer 14

block transcription and translation

Question 15

DMARD stands for:

Answer 15

disease modifying anti rheumatic drugs

Question 16

What is celebrex used for?

Answer 16

arthritis

Question 17

Toxicity with celebrex

Answer 17

sulfonamide and black box warning for serious CV events

Question 18

meloxicam things to know

Answer 18

inhibits cox-2 over cox-1
not as selective as other coxibs
Fewer GI effects
toxicities similar to NSAIDs

Question 19

Diclofenac things to know

Answer 19

nonselective cox inhibitor
pain and fever

20% have adverse GI effects. Take Cytotec to help with adverse effects

Question 20

ibuprofen adverse effects

Answer 20

agranulocytosis (decreased wbc)
and
aplastic anemia(decreased rbc)

Question 21

indomethacin

Answer 21

high toxicity index
potent Cox 1 and 2 inhibitor
reduces T and B cell proliferation

Question 22

indomethacin uses:

Answer 22

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

Question 23

Explain the 3 things that increase and 1 thing that decreases with glucocorticoid transcription:

Answer 23

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

Question 24

Abatacept drug class and what does it do?

Answer 24

DMARD
blocks T-cell activation

Question 25

Rituximab MOA

Answer 25

depletes B lymphocytes which is beneficial bc these are what produce antibodies during inflammatory responses.

Question 26

List the DMARDS

Answer 26

Abatacept
Rituximab
Humira (Adalimumab)

Question 27

Humira MOA

Answer 27

anti Tumor Necrosis Factor alpha
these block TNF to reduce inflammation