NSAIDs

Question 1

What are the objectives of using NSAIDs?

Answer 1

Used to minimize the unpleasant aspects of inflammation without altering the mental status

Question 2

What are the functions f COX1?

Answer 2

Numerous functions in homeostasis including gastroprotectant (mucous protection), platelet aggregation, and regulation of renal blood flow

Question 3

T/F COX1 activity is required for homeostasis

Answer 3

TRUE

Question 4

T/F If given the choice, you would prefer to inhibit COX1

Answer 4

FALSE; want to try and avoid this

Question 5

T/F COX2 has a major function in homeostasis with a high basal activity

Answer 5

FALSE; COX2 has a minor role in homeostasis and a low basal activity

Question 6

What does COX2 play a role in?

Answer 6

Kidney and renin system

Pregnancy: implantation

Question 7

COX2 is constitutively and inducibly produced. Which ones occurs more?

Answer 7

Inducibly

Question 8

Inducible COX2 leads to:

Answer 8

Pain
Inflammation
Fever

Question 9

COX3 is a major regulator of:

Answer 9

pyresis

Question 10

What is the mechanism of action for NSAIDs?

Answer 10

Physically interact with and thus inhibit the action of COX

Question 11

What are the 4 indications and therapeutic uses for NSAIDs?

Answer 11

Alleviation of mild to moderate pain
Anti-pyrexia
Anti-inflammatory
Anti-coagulation

Question 12

What types of pain does NSAIDs alleviate?

Answer 12

Chronic pain 
Increase the threshold for activating nociceptors
Neuropathic pain partially 
Hyperalgesia
Allodynia: partially 
Visceral pain is alleviated by 1 NSAID

Question 13

What is the one type of pain no NSAID alleviates?

Answer 13

Acute and/or severe pain

Question 14

What COX does an NSAID target to alleviate fever?

Answer 14

COX3; restores the status quo of thermoregulation

Question 15

How do NSAIDs work as anti-inflammatories?

Answer 15

Block PGE2 mediated vasodialtion, including cause by LPS

Block PGE2 mediated synthesis of numerous pro-inflammatory mediators

Question 16

How do NSAIDs work as anti-coagulants?

Answer 16

Block the synthesis of thromboxanes

Question 17

LOX activity is inducible as part of what?

Answer 17

Severe inflammation

Question 18

T/F Inhibition of LOX has no effect upon pain

Answer 18

TRUE

Question 19

What are some of the adverse side effects seen with NSAID use?

Answer 19

GI ulceration: Key to producing gastric mucous
Hepatotoxic: mechanism unclear
Nephrotoxic: PGs modulate renal effects upon fluid elimination and renin secretion
CV issues: GI2 is key to prevent platelet aggregation and maintain shape of vascular endothelium

Question 20

What would you use with NSAIDs to prtoect the GI mucosa?

Answer 20

Misoprostol; a PGE1 analog

LOX inhibition is also gastroprotective

Question 21

Name 4 adverse drug reations/interactions involving NSAIDs

Answer 21

W/ corticosteroids: indifferent to each others activity and both harm the GI
W/ anticoagulants: potentiate each other. Patient becomes super anti-coagulant
W/ antihypertensives: antagonize each other
W/ aminoglycoside: both drugs are nephrotoxic

Question 22

Why can’t you just go around hammering COX2 all willy nilly like?

Answer 22

It plays very specific homeostatic functions like kidney hemodynamics and CV integrity

Question 23

Why doesn’t NSAIDs work against Rheumatoid arthritis?

Answer 23

Activated platelets release microparticles that erode the joint surfaces and that release is COX-independent

Question 24

In surgery, which COX is king?

Answer 24

COX1&raquo_space;> COX2

Question 25

In inflammation/infection what is the COX of the walk?

Answer 25

COX 2&raquo_space;> COX 1

Question 26

Name 3 functions of COX1 in homeostasis:

Answer 26

1. Gastroprotectant
2. Platelet aggregation
3. Regulation of renal blood flow

Question 27

How do NSAIDs alter nociception?

Answer 27

Increases the threshold for activating nociceptors; requires a more powerful stimulus

Question 28

How do COX1 and COX2 differ with regards to basal activity?

Answer 28

COX1 = high basal activity 
COX2 = low basal activity

Question 29

What is a potentially better NSAID target, COX1 or COX2?

Answer 29

COX2