Follow Forum_Psych on Twitter
Search
 
 

Display results as :
 


Rechercher Advanced Search

Statistics
We have 222 registered users
The newest registered user is raheelmemon

Our users have posted a total of 1140 messages in 613 subjects
If you are seeing this, you have attempted to link to the UpToDate widget but are experiencing a problem. Please visit UpToDate for more information.
Share

Valproate (Depakote): Check Your Basics

View previous topic View next topic Go down

Valproate (Depakote): Check Your Basics

Post  Admin on Sun Jan 15, 2012 9:27 pm

Valproate (Depakote): Check Your Basics


Q- Which of the following statement is FALSE regarding Valproate:

(a) Valproate can result in falsely abnormal thyroid function test.
(b) Asymptomatic elevation of transaminases >3 times normal, is common and do not require any changes in dosage.
(c) Carbamazepine decreases plasma conc of Valproate, whereas Valproate increases plasma conc of Carbamazepine.
(d) Valproate increases plasma conc of Phenytoin
(e) Amitriptyline increases plasma conc of Valproate, and Valproate also increases plasma conc of Amitriptyline.





Last edited by Admin on Mon Oct 15, 2012 8:29 pm; edited 1 time in total

*****************
Click on to post your comments
avatar
Admin
Admin
Admin

Posts : 948
Points : 2102
Reputation : 0
Join date : 2011-02-19
Location : Philadelphia

http://psychiatry.find-forum.net

Back to top Go down

Re: Valproate (Depakote): Check Your Basics

Post  P450 on Thu Jan 26, 2012 9:03 pm


(a) Valproate can result in falsely abnormal thyroid function test.

I don't recall VPA causing altered labs for thyroid hormones. Correct answer?

(b) Asymptomatic elevation of transaminases >3 times normal, is common and do not require any changes in dosage.

This is probably true. Asymptomatic elevation is normal. Not sure about the range though.

(c) Carbamazepine decreases plasma conc of Valproate, whereas Valproate increases plasma conc of Carbamazepine.

This is true. Carbamezepine is a pan inducer and will lead to decrease VPA levels. VPA inhibits epoxide hydrolase which metabolizes the principle metabolite of carbamezepine.

(d) Valproate increases plasma conc of Phenytoin

True. Through inhibition of 2C9 and UGT enzymes.

(e) Amitriptyline increases plasma conc of Valproate, and Valproate also increases plasma conc of Amitriptyline.

Amitriptyline is also a mild inhibitor of 2D6 and 2C19. None of those are metabolic pathways for VPA (CYP 2A6, 2C9, and several UGT enzymes). I don't think it can increase VPA concentration although maybe there are metabolic pathways I don't know about.

Amitriptyline is metabolized by several CYP enzymes (including 2C9) as well as partially by UGT1A2 so VPA, being an inhibitor of UGT1A2 and 2C9, can increase amitriptriptyline's serum concentration.

So I'll go with A I guess.

P450
Moderator
Moderator

Posts : 34
Points : 34
Reputation : 0
Join date : 2012-01-15

Back to top Go down

Re: Valproate (Depakote): Check Your Basics

Post  Admin on Fri Jan 27, 2012 10:55 am

Correct Answer: D

Choice A & B are correct:
Investigations indicated prior to starting Valproate:

CBC (White cell & Platelet count), and LFTs ----> Repeat at 1 month (if normal) ---> repeat every 6-14 months (if normal)
Mild increase in transaminases (< 3 times normal) ---> repeat every 1-2 week ---> if stable --> monitor every 3 monthly
Pronounced increase in transaminases (>3 times normal)+ symptomatic--->Reduce/ discontinue Valproate
Note: Asymptomatic elevation of transaminases >3 times normal, is common and do not require any changes in dosage.


Laboratory Errors:
- False positive urine ketones
- falsely abnormal thyroid function test
- increase in serum fatty acids


Choice C & E are correct:

- Valproate increases plasma conc of:
* Carbamazepine
* Diazepam
* Amitriptyline, Nortriptyline
* Phenobarbital

- Valproate decreases plasma conc of:
* Phenytoin
* Desipramine

- Plasma conc of Valproate increased by:
* Guanfacine
* Amitriptyline
* Fluoxetine

- Plasma conc of Valproate decreased by:
* Carbamazepine

Source: Kaplan and Sadock



*****************
Click on to post your comments
avatar
Admin
Admin
Admin

Posts : 948
Points : 2102
Reputation : 0
Join date : 2011-02-19
Location : Philadelphia

http://psychiatry.find-forum.net

Back to top Go down

Re: Valproate (Depakote): Check Your Basics

Post  adisuper on Mon Oct 15, 2012 12:31 pm

option d is correct,not a false statement. Valproate do increase concentration of phenytoin by metabolic interaction and also its free drug conc. by plasma protien binding interaction.
I think as valproate is an enzyme inhibitor it only could raise drug conc. and not decrease the conc. of any drug.
source:Kaplan and Sadck's CTP 9th ed. table no. 31.33-8

adisuper

Posts : 28
Points : 32
Reputation : 0
Join date : 2012-06-04

Back to top Go down

Re: Valproate (Depakote): Check Your Basics

Post  Admin on Mon Oct 15, 2012 8:27 pm

adisuper wrote:option d is correct,not a false statement. Valproate do increase concentration of phenytoin by metabolic interaction and also its free drug conc. by plasma protien binding interaction.
I think as valproate is an enzyme inhibitor it only could raise drug conc. and not decrease the conc. of any drug.
source:Kaplan and Sadck's CTP 9th ed. table no. 31.33-8

Good point Adisuper.
I made these question after reading chapter on Valproate from Kaplan and Sadock (10th edition).
Table 36.35-3 says that- Serum concentration of Phenytoin is decreased by Valproate (Mechanism not provided).

After checking some articles, found this interesting mechanism of interaction between Valproate and Phenytoin:-

Pharmacologic Mechanism: Complex interaction occur between Phenytoin and Valproate, in that Valproate BOTH displaces Phenytoin from plasma protein AND weakly inhibits the metabolism of Phenytoin. in MOST patients TOTAL Phenytoin plasma concentration tends to decline and this generally does not require any Phenytoin dose adjustment BECAUSE the FREE (pharmacologically active) Phenytoin concentration is unchanged.
Note: IN SOME PATIENTS this combination can result in rise on both FREE and TOTAL Phenytoin concentration and cause intoxication.
Response Needed in Clinical Practice:- Patient management should be guided by monitoring unbound (pharmacologically active) Phenytoin concentration.

Source: Epilepsia. 2002 Apr;43(4):365-85.

PLEASE ADD YOUR VIEWS ON THIS IMPORTANT TOPIC.




*****************
Click on to post your comments
avatar
Admin
Admin
Admin

Posts : 948
Points : 2102
Reputation : 0
Join date : 2011-02-19
Location : Philadelphia

http://psychiatry.find-forum.net

Back to top Go down

Re: Valproate (Depakote): Check Your Basics

Post  adisuper on Tue Oct 16, 2012 8:59 am

thanks admin
the point was confusing becoz of the contradictory info given in CTP and synopsis.After ur reply i searched again and found that valproate do decrease phenytoin total conc but had no clinicaly significant interactions
on searching i found this possible mechanism:
The total phenytoin concentration falls during valproate administration related to redistribution of the drug after plasma protien displaced and to enhancement of total clearance of phenytoin
inhibition of phenytoin metabolism by valproate is unlikely to occur commonly in the clinical situation
Br J Clin Pharmacol. 1984 July; 18(1): 17–20
Effect of valproate on free plasma phenytoin concentrations.
L M Tsanaclis, J Allen, E Perucca, P A Routledge, and A Richens

adisuper

Posts : 28
Points : 32
Reputation : 0
Join date : 2012-06-04

Back to top Go down

Re: Valproate (Depakote): Check Your Basics

Post  Sponsored content


Sponsored content


Back to top Go down

View previous topic View next topic Back to top

- Similar topics

 
Permissions in this forum:
You cannot reply to topics in this forum