B2.071 - Pharmacokinetics Of Acetominophen

Question 1

What are the 3 routes that acetominophen can be metabolized by

Answer 1

Glucuronosyl transferase
Sulfo transferase
Cytochrome

Question 2

In a normal therapeutic dose which route does acetaminophen take most often

Answer 2

Glucuronosyltransferase

Question 3

With a therapeutic amount of acetominophen rank which routs it will take starting with most often to least

Answer 3

Glucuronyl > Sulfo > Cytochrome then GSH > Cytochrome then binds with protein

Question 4

Which pathways caps out first

Answer 4

Sulfotransferase

Question 5

What does GSH do

Answer 5

Detoxifies the NAPQI intermediate

Question 6

Liver GSH levels are inversely proportional to what

Answer 6

Liver protein adductor

Question 7

What does NAPQI do toxicity wise in the liver

Answer 7

Damages the mitochondrial membranes through protein modification

Question 8

Why does acetaminophen toxicity happen

Answer 8

50% intentional

50% unintentional

Question 9

Why are there so many intentional overdose

Answer 9

Common suicide attempt method

Question 10

What are some ways to prevent intentional acetaminophen overdose

Answer 10

Suicide prevention, counseling
Education
Lower dosage
Blister packs

Question 11

What are some of the ways people unintentionally overdose on acetaminophen

Answer 11

Many OTC products have it

Many opioids have it

Question 12

What are 3 aspects of pharmacokinetic variability

Answer 12

Genetics
Expression
Inhibition

Question 13

What are some polymorphic genes that affect acetaminophen toxicity

Answer 13

UGTs - Gluc pathway
GST - GSH pathway
CYP2E1

Question 14

Nearly all polymorphic drug metabolizing enzymes show

Answer 14

Diminished or no activity

Question 15

What are ways diminished activity could cause both more or less tolerance to acetaminophen toxicity

Answer 15

UGT and GST diminished activity will make it more toxic

diminished CYP2E1 activity may decrease hepatotoxicity

Question 16

What are some inducers of CYP2E1

Answer 16

Ethanol, isoniazid

Question 17

What are some drugs that inhibit conjugation of acetaminophen and will enhance hepatotoxicity

Answer 17

Phenobarbital and phenytoin

Question 18

Does ethanol inhibit hepatotoxicity or promote it

Answer 18

Both, ethanol is a competing substrate of CYP2E1 so it can protect against hepatotoxicity

But

Chronic ethanol use will induce CYP2E1 enhancing acetaminophen hepatotoxicity

Question 19

How does nutritional status affect how acetaminophen is metabolized

Answer 19

Production of cofactors requires ATP

Question 20

What can alter responses to drugs?

Answer 20

Age
BMI
Other drugs
Diet
Social Habits
Genetics
Disease processes

Question 21

What contributes to intra individual responses to drugs

Answer 21

Changes in BMI, other drugs, diet, social habits, disease

Question 22

What primarily contributes to inter individual variability

Answer 22

Genetic differences

Question 23

What are potential treatment targets for acetaminophen overdose

Answer 23

Prevent absorption
Inhibit NAPQI
Enhance scavenging of NAPQI
Remove from systemic circulation

Question 24

How do you prevent absorption of acetaminophen

Answer 24

Gastrointestinal lovage and activated charcoal

Question 25

How do you inhibit NAPQI formation

Answer 25

CYP2E1 inhibitors

Question 26

How do you enhance scavenging of NAPQI

Answer 26

increase/replenish GSH (NAC)

Question 27

How do you remove acetaminophen from systemic circulation

Answer 27

Hemodialysis

Question 28

What is the preferred route of administration of NAC

Answer 28

IV, its faster

Question 29

When should NAC be administered

Answer 29

Within 8 hours of ingenstion but could be partially effective when given as late as 24-36