Question about quinidine

[Phloston]

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UWSA#2 spoiler - warning



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P. 273 of FA2012 says "*Quinidine can both induce and inhibit isoforms of P-450. Induction is the more important effect."

Anyway, UWorld's gotta question in UWSA2 that mentions a guy in the hospital with chest pain, atrial fibrillation, C. difficile colitis and seizures. They then go on to say that he was discharged on warfarin but that his INR is low.

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The obvious is that there's induction of P-450. The only two possibilities out of the answer choices were quinidine and phenobarbital.

I went with quinidine because I figured quinidine Tx of AF is > probability than seizure Tx with phenobarbital. Let alone that fact, it stood out in my mind that FA said quinidine's inducing effects are more important.

The answer was phenobarbital. 54% found that to be cake-obvious. Priceless.

UWorld said that quinidine is not significantly involved in warfarin metabolism, and that it is a CYP2D6 inhibitor.

My question is: has anyone encountered anything with respect to quinidine and its P-450 effects / does anyone know what quinidine interacts with most significantly? I'm a bit worried now about considering it to be an inducer, quite frankly.

 

[Myxedema]

In reality, many drugs can be both inducer and inhibitors at the same time. They may inhibit one form and induce another. I've complied this list, I hope this is useful for you:

p450 inducers

1. Anti-convulsants: Phenytoin, carbamazepine, barbiturates
2. Anti-microbials: Rifampin, griseofulvin
3. Anti-arrhythmic: Quinidine
4. Glucocorticoids
5. St. John’s wort
6. Chronic alcohol abuse

p450 inhibitors

1. Anti-convulsant: Valproic acid
2. Anti-ulcer: Cimetidine, omeprazole
3. Anti-microbials
   Chloramphenicol
   Macrolides (except azithromycin)
   Sulfonamides
   Anti-TB: INH
   Anti-fungal: Ketokonazole
   Anti-viral: HIV protease inhibitors
4. Grapefruit juice
5. Acute alcohol

 

[ijn]

From: http://mims.com/USA/interaction/Search/warfarin|quinidine
"Quinidine may increase the effects of oral anticoagulants by inhibiting the synthesis of vitamin K-dependent clotting factors. Coadministration has been shown to increase the risk of bleeding. In contrast, one isolated report described an increase in the anticoagulant dose requirement when quinidine was coadministered. Monitor INR and adjust anticoagulant dose as needed. "

I would only worry about quinidine + warfarin and quinidine/verapamil + digoxin in terms of drug-drug interactions.

 

[Charles_Carmichael]

According to FA2012, quinidine is a P450 inhibitor, not an inducer. (Look at the errata online, Pholston). I've always treated quinidine as a P450 inhibitor and I know that phenobarbital is an inducer, so if the question was basically asking which one of the answer choices was a P450-inducer, I would've gone with phenobarbital.

Edit: An old abstract regarding it being an inhibitor of the CYP2D6 -- http://www.jbc.org/content/280/46/38617.abstract

A bunch of other stuff I looked at (Wikipedia and Goodman & Gilman's The Pharmacological basis of Therapeutics) also suggests that it's a potent inhibitor, not an inducer. That's also how it was taught to us in class as well as in Kaplan pharm.

 

[Phloston]

According to FA2012, quinidine is a P450 inhibitor, not an inducer. (Look at the errata online, Pholston). I've always treated quinidine as a P450 inhibitor and I know that phenobarbital is an inducer, so if the question was basically asking which one of the answer choices was a P450-inducer, I would've gone with phenobarbital.

Edit: An old abstract regarding it being an inhibitor of the CYP2D6 -- http://www.jbc.org/content/280/46/38617.abstract

A bunch of other stuff I looked at (Wikipedia and Goodman & Gilman's The Pharmacological basis of Therapeutics) also suggests that it's a potent inhibitor, not an inducer. That's also how it was taught to us in class as well as in Kaplan pharm.

WTF. I seriously went through that entire errata document a few months ago and that was not in there (for the p.273 correction). I'm glad they continually need to update it. Very annoying actually. I really don't want to spend the time going through that document AGAIN.

 

[tednfs]

While it is not a consolation, the latest errata from July/August doesn't take too long to correct,compared to the first time going through it.

 

[Phloston]

While it is not a consolation, the latest errata from July/August doesn't take too long to correct,compared to the first time going through it.

I'm not 100% sure which specific document you're referring to. Do you mind posting a link to it?

 

[thehundredthone]

It's on the errata link you posted. Updated 30/7 I think.