I'm confused about how a drugs half life relates to the duration of its effects

[Mycotheologist]

According to wikipedia, diazepam has a half-life of 20-100 hours and its active metabolite, desmethyldiazepam has a half life of 36-200 hours. I read that its anxiolytic effects only last 6 hours. How can a drug with an insanely long half life only last 6 hours? According to wikipedia, phenibut has a half life of 5 hours but I know from my own and the experiences of others that the effects of this drug last around 18 hours, with aftereffects lasting up to 36 hours. How can a drug with such a short half life have such long lasting effects? If I take a high dose of diazepam of say 40mg, then my blood should contain an amount of the drug that is within (or higher than) the therapeutic range for days because after 24 hours, there will be 20mg left and after another 24 hours, 10mg left in my system etc.

 

[endotropic]

According to wikipedia, diazepam has a half-life of 20-100 hours and its active metabolite, desmethyldiazepam has a half life of 36-200 hours. I read that its anxiolytic effects only last 6 hours. How can a drug with an insanely long half life only last 6 hours?

What you're noticing is that a drug's effect and its blood concentration are not always perfectly correlated. There's a psychological component to this, where the initial novelty of the altered state wears off and you feel almost normal while a considerable amount of drug is still on board. This mechanism plays a big part on the attenuated effects of alcohol late in the evening when your BAC levels are falling. There can also be a tolerance component, where within a single experience the drug's receptor desensitizes and no longer responds to the same stimuli as strongly. Both of these effects can contribute to the absence of drug effect while blood concentration is still high.

According to wikipedia, phenibut has a half life of 5 hours but I know from my own and the experiences of others that the effects of this drug last around 18 hours, with aftereffects lasting up to 36 hours. How can a drug with such a short half life have such long lasting effects?

On this one I'm not so sure. For one thing a drug is not completely eliminated after one half life, it takes around 5-6 half lives for the drug to be completely eliminated. Maybe the doses you're taking are high enough that even when only 1/16 of the initial dose is left you still have enough on board to feel an effect. There could also be active metabolites that stick around for much longer than the parent compound, but I'm not sure that this is the case for phenibut.

 

[Dr. Drugs]

Most drugs are metabolized by what's known as the cytochrome P450 family of metabolic enzymes. Half-lives can vary considerably between people due to individual differences in expression and efficiency of these enzymes. Everyone has different levels of metabolic enzymes, so its hard to put an exact number on a drug's half-life that applies to everyone. Genetics, race, age, and drugs all affect the workings of one's levels of different enzymes.

Typically, the longer end of a half-life range (like 100h for diazepam) is only seen in the elderly or people classified as "poor metabolizers".

 

[Hiltoniano]

I am still confused as I was also wondering a similar thing. So is what I'm understanding that the drugs half life can 'not' be related to the duration of effect? That's interesting but it seems to defy intuition. Can anyone elaborate on more plausible reasons behind this phenomenon?

 

[sekio]

Short term receptor desensitization, probably mediated by autoreceptors in part, is probably to blame.

Some drugs need a certain threshold concentration to produce an effect & as such they will no longer work if there is not enough in the system. (MDMA)

Drugs can also re-distribute to other tissues that do not produce the central effects desired, for instance diazepam & metabolites partitioning to ody fat plays a role in their effect wearing off/down before the drug's half life is elapsed.

 

[Haoma]

Drugs can also re-distribute to other tissues that do not produce the central effects desired, for instance diazepam & metabolites partitioning to ody fat plays a role in their effect wearing off/down before the drug's half life is elapsed.

This would only be true for lipid soluble substances, Or are there tissues other than body fat you were referring to?

 

[sekio]

Lungs, blood protien, etc. Generally water soluble compounds exhibit much less of this effect, though, you are correct.