Nagelhout video's: non-opioid agonists

Question 1

What is paracetamol

Answer 1

Acetaminophen

(Paracetamol is the active ingredient in acetaminophen)

Question 2

T/F: Aspirin, Acetaminophen, and NSAIDs are all antipyretics, analgesics, and anti inflammatory

Answer 2

False

-All are antipyretic and analgesics but acetaminophen is NOT anti-inflammatory

Question 3

How does Decadron produce analgesia?

Answer 3

by inhibiting peripheral phospholipase
>decreases the pain-producing substances from the cyclooxygenase and lipoxygenase pathways (prostaglandins- associated with inflammation and pain)

-also reduces serotonin which is implicated in the pain response
-decreases tryptophan (precursor to serotonin)
-decreases serotonin turnover in the brain
-reduces serotonin release in the gut
-inhibits the NTS which has outflow tracts to the gut via the vagus nerve (serotonin receptors)

Question 4

Primary MOA of NSAIDs

Answer 4

block COX

(cyclooxygenase)

Question 5

When you turnover cells in the body (RBCs, WBCs, platelets), prior to eliminating the dead cell membrane of these cells through the urine, your body extracts some chemicals from these dead cell membranes so it doesn’t have to make new ones (recycles substances) is what?

Answer 5

Arachidonic acid

Question 6

What is arachidonic acid?

What enzyme acts upon it?

Answer 6

An acid compound found in cell membranes that the body extracts and recycles after the cell dies

COX acts upon it (cyclooxygenase)

Question 7

Which COX enzyme is constitutive vs inducible and what does that mean?

Answer 7

Cox-1 is constitutive which means it’s found in the body all the time

Cox-2 is inducible - meaning it’s usually latent in the body
*until tissue is injured, then COX-2 is released

Ie) so if you sprain your ankle, your body is going to activate/release COX-2 to help break down arachidonic acid to release more prostaglandins and thromboxanes to help stabilize the cell membranes and aggregate platelets

Question 8

What does COX-1 break down?

Answer 8

Arachidonic acid to prostaglandins and Thromboxanes (TXA2)

Prostaglandins put a protective coating over the gastric mucosa

TXA2 preserves endothelial function (support cell membrane integrity, support platelet aggregation)

Question 9

What is the specific COX-inhibitor that remains on the market today

Answer 9

Celebrex

Question 10

What’s Reyes Syndrome?

Answer 10

-fatal condition caused by giving aspirin to children

Question 11

MOA of NSAIDs

Answer 11

They block the synthesis of prostaglandins by inhibiting COX-1 & COX-2

Question 12

Side effects of NSAIDS (4)

Answer 12

1. Block platelet aggregation
   >increased bleeding
2. Renal Dysfunction
   >with long-term use
   (prostaglandins are necessary to maintain normal renal function)
3. GI hemorrhage/ulcers
   >with long-term use
4. Slow bone healing + block osteoneogenisis

Question 13

Do NSAIDs inhibit platelets competitively or noncompetitively?

When would you be concerned about potential bleeding…if your patient took something when?

Answer 13

Competitively - once you stop taking NSAIDs, platelet function resumes (avoid 24 hours before surgery)

Question 14

T/F: Tylenol has anti-inflammatory properties

Answer 14

False

Question 15

T/F: Tylenol’s MOA includes reducing prostaglandins by blocking COX-1 and COX-2

Answer 15

True (but poorly understood bc it doesn’t reduce inflammation)

Question 16

The mechanism by which NSAIDs lead to GI bleeding

Answer 16

by inhibition of COX-1 which helps protect the endothelial lining of the GI tract

Question 17

Whether to take Tylenol or Advil?

Answer 17

Headache/Fever- prob Tylenol (less side effects)

Anything with tissue damage or swelling - NSAD

Question 18

Explain the metabolism of Acetaminophen
- what’s it conjugated with
-what’s it broken down by, to what?
-what happens to that

Answer 18

It’s conjugated with glucuronide + sulfate

+ broken down by CYP2E1 to NAPQI*

N-Acetyl-p-benzo-quinone-imine

• small amounts can be detoxified by glutathione in the liver into nontoxic metabolites

if you produce more NAPQI than the glutathione can detoxify, that’s when you get liver damage

Question 19

Treatment of Tyelonol OD

Answer 19

Acetylcysteine
>replenishes glutathione (enzyme that helps detoxify the toxic metabolite of NAPQI)

Question 20

What lab test would you do to assess for aspirin levels?

Answer 20

bleeding time

Question 21

They say people can safely continue taking their aspirin throughout the peri-op period (they are on it for a reason and the risk of stopping it prob outweighs the benefit of less bleeding)

What are 3 circumstances you would want the patient to stop their aspirin 7-10 days prior to surgery?

Answer 21

Risk for large amount of bleeding into closed spaces

1. Eye surgery (closed space- any kind of bleeding will increase IOP and be bad)
2. Brain Surgery
3. Prostate Surgery (super vascular)

Question 22

Should you give Toradol to an asthmatic?

Answer 22

Probably not- only if you ask them before hand if they take NSAIDs or not

(some people have aspirin-induced asthma and there can be a cross-allergy amongst the other NSAIDS)

Question 23

TCAs can be given for chronic pain management, how do they work?

Answer 23

block reuptake of serotonin and NE

(I thought serotonin increased pain? Maybe it has something to do with acute vs chronic pathway)