Pain Pathways and Non-opioid Analgesics

Question 1

What is the first line agent in rheumatoid arthritis?

Answer 1

NSAIDs

Question 2

What is the first line agent for osteoarthritis?

Answer 2

Acetaminophen, unless the treatment is by intraarticular injection

Question 3

What is the most common side effect of COX inhibition?

Answer 3

GI issues.

This can lead to gastric intolerance and ulcers. PGI2 specifically increases mucosal blood flow.

Question 4

With aspirin, is GI bleeding dose or duration related?

Answer 4

Dose

Question 5

What are the 3 mechanisms of interactions with ASA?

Answer 5

1. Interaction for plasma protein binding.
2. Competition for URAT1
3. Synergistic effects with other GI irritants.

Question 6

What is the nonselective NSAID black box warning?

Answer 6

Even when taken for only 1 week, all NSAIDs (except naproxen) have increased CV risk in cardiac patients. The worst is diclofenac.

You want to use more selective COX-1 inhibitor at a minimum dose for shortest time.

Question 7

Is the risk for renal cancer dose or duration related?

Answer 7

The risk for renal cancer is both dose and duration dependent.

Question 8

What two drugs do not cause an increase in renal cell cancer risk?

Answer 8

ASA and APAP

Question 9

When is hepatotoxicity a cause for concern in relation to an increase in liver enzymes?

Answer 9

When hepatic enzymes are >8% the normal value is when there should be concern for hepatotoxicity.

Question 10

Contraindications for NSAIDs?

Answer 10

Asthma due to ASA use
Urticaria and other hypersensitivity reactions associated with ASA

Urticaria, angioedema, rhinitis/nasal polyps, pruritis

Question 11

Why should NSAIDs not be used during the third trimester of pregnancy?

Answer 11

Possible closure of ductus arteriosis

Question 12

What are some mechanisms of drug interactions with NSAIDs?

Answer 12

Competition of PPB with oral anticoagulants. NSAIDs will knock them off of the PPB and sometimes will do this to phenytoin.

If given with warfarin it can increase the anticoagulant effect.

Question 13

What are highly selective COX-2 approved for?

Answer 13

Osteoarthritis, rheumatoid arthritis, and some pain.

Question 14

What is a benefit of COX-2 selective inhibitors compared to other NSAIDs?

Answer 14

Reduced incidence of GI side effects.

Question 15

How does APAP work?

Answer 15

Stimulates descending serotoninergic pathways to inhibit afferent pain fibers.

It is a selective COX-2 inhibitor in the CNS more than periphery.

Question 16

How does APAP affect the response to warfarin?

Answer 16

APAP can increase the INR if given >2g/day.

If there is a polymorphism in CYP2C9 warfarin will use CYP3A4, but APAP inhibits CYP3A4, therefore preventing the warfarin from working.

Question 17

What is the minimum toxic single dose in adults and children?

Answer 17

Adults: 7.5g-10g

Children->150mg/kg

Question 18

What is the primary problem of APAP intoxication?

Answer 18

hepatotoxicity
6-14hours=flu-like symptoms and increase in liver enzymes
3-5 days: acute liver and possible renal failure

Question 19

How does ethanol affect APAP in the liver?

Answer 19

Ethanol induces CYP2E1. In APAP synthesis this causes the APAP to be converted to an imine.

Question 20

Is APAP overdose more commonly unintentional or intentional?

Answer 20

Unintentional

Question 21

What percentage of liver failure cases is APAP responsible for in the US?

Answer 21

40%

Question 22

When must N-acetylcysteine be given to have an effect in APAP overdose?

Answer 22

Within 8 to 10 hours