Half life vs duration of action

[Stay see?]

I'm just wondering how its it that duration of action is not directly correlated to half life, such as ativan having a longer duration of action than valium, even though valium's half life is much longer? And does anyone know the duration of action on klonopin? I have switched from the ativan to klonopin, with much better results, but the very respected Ashton taper is what is commonly used to taper off because of the half life, yet it seems to me it doesn't help with the anxiety for very long, which may lead to a relapse.

I find the klonopin to be much better for my anxiety, only taking it once in the morning. Although I'm not trying to taper off, so I can't say what would be better by experience, only that I know if I take an equivalent dose of valium in the morning, I'm anxious after a couple hours.

Ok, this is kinda all over the place but if anyone can comment as to why duration of action is not directly correlated to half life? And does anyone know the duration of action of klonopin? And any thoughts about if valium really is the best way to taper, or if anyone found klonopin to be better? Thanks in advance.

 

[23536]

Diazepam is very highly protein-bound, much more than clonazepam. I imagine this is the reason for the relatively short duration of action?

The long half life is due to storage in body tissue (I think).

 

[Stay see?]

That helps, thanks. I can kinda see why they are not always related now. Thx. Doesn't it seem like that maybe valium wouldn't be the best for tapering off of benzo's. I know anxiety would cause a relapse in me. Maybe klonopin would be the better choice. Unless withdrawal is what is causing all your anxiety. I just know personally I would not be sticking to my medication correctly if they had not put me on the klonopin. I would still be taking a ton of ativan and valium..
I guess this is not pertinent to add, but maybe will help someone struggling with benzo's.

 

[23536]

The standard tapering advice is to first switch to diazepam and then taper. My theory on this is that diazepam stays in the system at sub-therapeutic doses for a long time, so as to bring about a more gentle withdrawal and help your GABA receptor density increase.

Personally, I came off a six year Xanax dependency by tapering the Xanax from 3 mg per day to half a milligram every two days (at bedtime) over the course of 4 months (taking trazodone on benzo-less nights so I could sleep).

 

[Epsilon Alpha]

Protein binding is one of many factors for the discrepancy between halflife and duration of effects, however if you saturate the plasma proteins the drug binds to you can get massive increases of free drug in the plasma. You also have the issue of tachyphylaxis, which is determined by receptor/signalling pathway sensitivity over the course of the day, I'm not too well versed with benzo's but I've heard it's more of a individual thing as to which drug will produce more.

As far as tapering goes, I've actually heard good things about using pregabalin and gabapentin to slowly replace or, if used very carefully, augment benzo's

 

[basement_shaman]

Another factor could be that many benzodiazepines are also prodrugs and thus have active metabolites with sometimes even longer half-lives that contribute to the overall pharmacological activity of the drug.