Phenobarbital and Liver enzymes - USMLE Forums
USMLE Forums Logo
USMLE Forums         Your Reliable USMLE Online Community     Members     Posts
Home
USMLE Articles
USMLE News
USMLE Polls
USMLE Books
USMLE Apps
Go Back   USMLE Forums > USMLE Step 1 Forum

USMLE Step 1 Forum USMLE Step 1 Discussion Forum: Let's talk about anything related to USMLE Step 1 exam


Reply
 
Thread Tools Search this Thread Display Modes
  #1  
Old 04-10-2013
mutant's Avatar
USMLE Forums Addict
 
Steps History: Not yet
Posts: 142
Threads: 21
Thanked 82 Times in 54 Posts
Reputation: 92
Liver Phenobarbital and Liver enzymes

This is what I have come to know so far,

1. In Gilbert syndrome jaundice occurs with fasting or increase in alcohol or phenobarbital intake. (Goljan)

2. Criggler-Najjar type II is less severe and responds to phenobarbital, which increase liver enzyme synthesis. (FA)

While in Gilbert syndrome phenobarbital induces jaundice, it reduces jaundice in Crigler-Najjar syndrome. In both conditions UDP-glucoronyl transferase activity is decreased, so how is it that phenobartibal have opposite effects?

-
__________________
What you seek is seeking you Rumi
Reply With Quote Quick reply to this message



  #2  
Old 04-10-2013
USMLE Forums Veteran
 
Steps History: CS Only
Posts: 219
Threads: 44
Thanked 44 Times in 33 Posts
Reputation: 54
Default

My best educated guess:
In gilbert there is also decrease in bilirubin uptake by hepatocyte.
Crigler is just about the enzyme, if u increase its synthesis u improve the condition.
Reply With Quote Quick reply to this message
The above post was thanked by:
mutant (04-10-2013)
  #3  
Old 04-10-2013
mutant's Avatar
USMLE Forums Addict
 
Steps History: Not yet
Posts: 142
Threads: 21
Thanked 82 Times in 54 Posts
Reputation: 92
Default

Quote:
Originally Posted by ` Faith ` View Post
My best educated guess:
In gilbert there is also decrease in bilirubin uptake by hepatocyte.
Crigler is just about the enzyme, if u increase its synthesis u improve the condition.
But there is also decreased activity of enzyme. So the patient develops jaundice whenever placed under stress b/c that exceed the capacity of enzyme to conjugate. Why phenobarbital is stressor here why not increase the enzyme activity?
__________________
What you seek is seeking you Rumi
Reply With Quote Quick reply to this message
  #4  
Old 04-10-2013
USMLE Forums Veteran
 
Steps History: CS Only
Posts: 219
Threads: 44
Thanked 44 Times in 33 Posts
Reputation: 54
Default

It does increase enzyme activity
(Integrating with porphyria: barbiturates aggravate porphyria cuz it + P450 > revs up the heme synthesis pathway )
So, if phenobarb increases heme synthesis > more heme to be broken into bilirubin > but hepatocyte cant take up the bilirubin (even if conjugation is now corrected by increased liver enzyme synthesis, it wont improve the condition cuz bilirubin is still stuck outside the liver)

In criglar, barbs increase liver enzyme synthesis ( improves the condition, no problem in taking up bilirubin by hepatocyte)

Again, this is my guess on this
Reply With Quote Quick reply to this message
The above post was thanked by:
jeniaz (11-06-2015), mutant (04-10-2013), pathophysio (09-12-2016), singular (04-10-2013)
  #5  
Old 04-10-2013
mutant's Avatar
USMLE Forums Addict
 
Steps History: Not yet
Posts: 142
Threads: 21
Thanked 82 Times in 54 Posts
Reputation: 92
Correct Answer

Quote:
Originally Posted by ` Faith ` View Post
It does increase enzyme activity
(Integrating with porphyria: barbiturates aggravate porphyria cuz it + P450 > revs up the heme synthesis pathway )
So, if phenobarb increases heme synthesis > more heme to be broken into bilirubin > but hepatocyte cant take up the bilirubin (even if conjugation is now corrected by increased liver enzyme synthesis, it wont improve the condition cuz bilirubin is still stuck outside the liver)

In criglar, barbs increase liver enzyme synthesis ( improves the condition, no problem in taking up bilirubin by hepatocyte)

Again, this is my guess on this
This makes sense. very very deep correlation! Thanks
__________________
What you seek is seeking you Rumi
Reply With Quote Quick reply to this message
  #6  
Old 04-10-2013
USMLE Forums Veteran
 
Steps History: CS Only
Posts: 219
Threads: 44
Thanked 44 Times in 33 Posts
Reputation: 54
Default

Welcome ^^'
Reply With Quote Quick reply to this message
  #7  
Old 04-11-2013
Dr Mungli's Avatar
USMLE Forums Newbie
 
Steps History: ---
Posts: 7
Threads: 0
Thanked 5 Times in 4 Posts
Reputation: 15
Smile Inherited causes for increase in unconjugated bilirubin!!

These are the inherited cases for increase in unconjugated bilirubin.

1. Criggler-Najjar syndrome (CNS) type I is due to complete absence of enzyme UDP-glucoronosyl transferase (UDPGT1A1). Due to this there is no conjugation, unconjugated bilirubin is usually found more at more than 25 mg/dl and patients are at risk of kernicterus. These patients do not respond to phenobarbiturates.


What is the rationale for suing phenobarbiturates? Generally phenobarbiturates are detoxified in hepatocytes by two mechanism 1. By microsomal CYP 450 mono oxygenase system, a heme containing proteins. 2. By conjugating with glucorononic acid. So as like phenobarbiturates induce ALA synthase in heme synthesis to produce CYP 450, they also induce UDPGT1A1 enzymes for them to add glucorononic acid to phenobarbiturates for detoxification.


2. CNS type 2 is due to decreased synthesis of UDPGT but not complete absence, unconjugated bilirubin is usually between 6-25 mg/dl, they are not at risk of kernicterus, and these patients responds to phenobarbiturates, so when phenobarbiturates are given, they induce UDPGT enzyme there by there will be decrease in unconjugated bilirubin.


3. Gilbert syndrome is due to reduced levels of UDPGT because of mutation in TATA box of its gene, this leads to mild increase in unconjugated hyperbilirubinemia, this syndrome is common in general population at around 5%. I'm not sure about your source as you said In Gilbert syndrome giving phenobarbiturates will increase jaundice but giving phenobarbiturates will decrease jaundice because they induce UDPGT enzyme thereby conjugating process improves. These patients lead almost normal life except for the unconjugated bilirubin in the blood.


Hope this helps.


Dr Mungli
Reply With Quote Quick reply to this message
The above post was thanked by:
zhaobinxu (01-01-2015)



Reply

Tags
Gastrointestinal-Tract-, Pharmacology-

Quick Reply
Message:
Options

Register Now

In order to be able to post messages on the USMLE Forums forums, you must first register.
Please enter your desired user name, your email address and other required details in the form below.
User Name:
Password
Please enter a password for your user account. Note that passwords are case-sensitive.
Password:
Confirm Password:
Email Address
Please enter a valid email address for yourself.
Email Address:
Medical School
Choose "---" if you don't want to tell. AMG for US & Canadian medical schools. IMG for all other medical schools.
USMLE Steps History
What steps finished! Example: 1+CK+CS+3 = Passed Step 1, Step 2 CK, Step 2 CS, and Step 3.

Choose "---" if you don't want to tell.

Favorite USMLE Books
What USMLE books you really think are useful. Leave blank if you don't want to tell.
Location
Where you live. Leave blank if you don't want to tell.

Log-in

Human Verification

In order to verify that you are a human and not a spam bot, please enter the answer into the following box below based on the instructions contained in the graphic.



Thread Tools Search this Thread
Search this Thread:

Advanced Search
Display Modes


Similar Threads
Thread Thread Starter Forum Replies Last Post
Enzymes and Alcoholic Hypoglycemia! Casandra USMLE Step 1 Forum 5 07-02-2012 07:19 PM
Liver disease that does not need a Liver Biopsy? FSUSTC USMLE Step 2 CK Forum 7 04-27-2011 06:07 AM
Enzymes using NAD+ Aditya USMLE Step 1 Forum 1 02-27-2010 01:26 PM
Pancreatic Enzymes MLE-Love USMLE Step 2 CK Mnemonics 0 02-25-2010 08:36 PM
RBC Enzymes Question Krishna USMLE Step 1 Forum 5 12-03-2009 05:47 PM

RSS Feed
Find Us on Facebook
vBulletin Security provided by vBSecurity v2.2.2 (Pro) - vBulletin Mods & Addons Copyright © 2017 DragonByte Technologies Ltd.

USMLE® & other trade marks belong to their respective owners, read full disclaimer
USMLE Forums created under Creative Commons 3.0 License. (2009-2014)