cytochrome p450 inducers/inhibitors.

[HiddenTruth]

Alrite, so this pharm blows--there's like 50 of these inducers and inhibitors for these isozymes. So, can someone explain to me very generically in the grand scheme of things what is the point of this system and all these drugs i gotta memorize that alter it.

Unfortunately, I don't have a text with me --and just have some notes which aren't very helpful. So do all drugs get metbolized through this mechanism--of cyto 450? And the only thing I get out of it is that it is impt to know for drug itneractions--that if u're taking one drug as a substrate and u administer another that induces or inhibits--it can alter the half life and duration of action of the substrate drug (the drug that is metabolized by the enzyme) in the body. Is there much more to it than that?

And, also, do we have all these difft isozymes in our body--like cyp123, cypA34, etc. (I just made those up--I haven't quite memorized them yet). Alrite, fill me in. Thanks for the help. I haven't quite had this lecture, so I'm kinda' lost.

Later

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[28657]

From what I've learned in pharmacy school so far is that most drugs are metabolized by the P450 enzymes, but not all. The most common P450 family is 3A4 and will be the concern for the most drug interactions. Some drugs induce, whereas others inhibit the substrate. People are supposed to have every P450 enzyme, but some people either don't have the enzyme or don't have the right levels of the enzyme - thus, one of the needs for pharmacogenomics.

 

[Idiopathic]

Know the big inducers:

Rifampin
Barbiturates
Carbemazapine
Phenytoin
Griseofulvin
Rifampin

Know the big inhibitors:

Isoniazid
Quinidine (controversial - FA is wrong on this one)
Cimetidine
Ketoconazole
Erythromycin
Grapefruit Juice
Sulfonylureas

Understand that oral contraceptives can be screwed up by this system, as well as by killing of gut flora (i.e. i had a ? about which Abx was more likely to result in someone on OC's getting pregnant...it was rifampin, more than likely, even though it is awfully unlikely that someone would actually take rifampin these days)

That would answer every ? I had on the USMLE (about 3 total). COMLEX is a different story

 

[bigfrank]

Agreed, and NO, you don't have to know the individual P450 enzymes. The only one I can think of that might be on there (but probably not) is the fact that alcohol (+) P450-2E1 that then enhances a dangerous b/d product of acetaminophen (--> oxidative damage, etc.).

But I didn't worry about isotypes of those P450's.

 

[Long Dong]

Anybody have any mnenonics for remembering inhibitors vs inducers.

 

[mpp]

How about just how it is written above (minus the controversial quinidine):

Inhibitors = I 'see' KEGS

 

[Samoa]

The other important thing to remember, just on a global basis, is that an inhibitor will have a rapid effect on the drug levels of its interacting drug, because it basically works competitively at that enzyme. In contrast, the onset and resolution of cyp450 induction takes a week or two because it involves upregulation of enzyme synthesis.

 

[HiddenTruth]

The other important thing to remember, just on a global basis, is that an inhibitor will have a rapid effect on the drug levels of its interacting drug, because it basically works competitively at that enzyme. In contrast, the onset and resolution of cyp450 induction takes a week or two because it involves upregulation of enzyme synthesis.

Not only is the rate of protein synthesis responsible for the slow onset, but the half life of the inducing agent maybe long which may also delay the appearance of the maximal inducing effect. Ok, I don't understand the latter half--this is from my notes. How does half life correlate with the delay in onset?

 

[Long Dong]

How about KEGS Cause (cimetidine) IQ inhibition. And for the inducers RBC, Granulocytes (griseofulvin), Platelets (Phenytion), since I have to remember what comes from the trilineage myeloid stem cell anyway.

 

[wooo]

(quote from above) Unfortunately, I don't have a text with me --and just have some notes which aren't very helpful. So do all drugs get metbolized through this mechanism--of cyto 450? And the only thing I get out of it is that it is impt to know for drug itneractions--that if u're taking one drug as a substrate and u administer another that induces or inhibits--it can alter the half life and duration of action of the substrate drug (the drug that is metabolized by the enzyme) in the body. Is there much more to it than that?





inhibit the enzyme (such as with the drugs mentioned) substrate builds up.
up regulate enzyme(such as with the drugs mentioned) substrate is removed quicker

simple as that