Why increasing the dose doesn't increase the duration of drugs' effect?

[cacachanel]

Considering that a "normal" dose is 50 mg, and considering a classical log half-life elimination model, shouldn't you feel like you took 50 mg after one half-life if you took 100 mg?

 

[Doclad]

Maybe it's the kinetics of the substance?

Increasing the dose of any drug makes it more intense but not necessarily longer lasting. Anyway for me the high doses of anything seem to extend in time a little more.


DocLad

 

[d1nach]

This is just my idea i having nothing to back this up but just hypothetically

Maybe the subjective effects of the drug are nonlinear. Meaning say for example


You take 100 mg of a drug
At 4 hours its 25% max level
8 hours its 50% max
12 hours its 100% max

And its half life is 4 hours so
16 hours 50% max
20 hours 25% max


If the subjective effects where linear meaning basically just a straight line
Youd expect to feel

25% high at 4 and 20 hours
50% high 8 and 16 hours
And 100% high 12 hours

But it could be nonlinear (curved) so that
You feel 0% high at 4 and 20 hours
25% high at 8 and 16 hours
And 100% high at 12 hours.

Because the relationship between concentration of the drug currently working doesnt have to cause a linear effect on how much you subjectively feel it.

 

[SheWasLvL18]

Does increasing the quantity of solute decrease the rate of dissolution? If not then the only difference between a 50 mg dose and a 100 mg dose would be the concentration in the body, not how long the drug lasts.

This seems right to me, but I also don't know.

Hoping someone who knows more chimes in.

 

[sekio]

Does increasing the quantity of solute decrease the rate of dissolution?

Yes, but the volume of distribution of most drugs (effectively how much water/tissue in the body "dissolves" the drug) is almost always measured in liters, meaning there's going to be anywhere from 1,000 to 10,000-fold excess of solvent.

 

[modocmodoc]

Half lives generally don't dictate pharmacological -activity- accurately. Drugs for recreation also develop within-binge tolerance which can be subtle.

Example - clonazepam has an effective antipanic duration of 4-12 hours depending the person, and 20-24 half life of clonazepam itself. Most opiates are a few hours half life and last longer. Methylphenidate is 3-4 oral and last 2-6.

Half lives generally don't dictate pharmacological -activity- accurately. Drugs for recreation also develop within-binge tolerance which can be subtle.

 

[Coolwhip]

Drugs for recreation also develop within-binge tolerance which can be subtle.

This gets my vote, and I've spent some time thinking about it, I always referred to the phenomena as acute tolerance, but within-binge has a certain ring to it.

 

[Limpet_Chicken]

Tachyphylaxis?

The fentanyls for example are notorious offenders when it comes to inducing tachyphylaxis. Some find that various tryptamines cause it, although it seems
very subject-variable in that case.

I find that one of the most profound cases, is with valerian root extract, when used for it's oneirogenic effect. The first night a full
dose for the purpose is taken, I'll get the full effect. Second night in a row, it'll be very, very very weakened and anaemic in response. Third night in a row only the sedative effect remains.

 

[sekio]

Another thing to consider is the elimination half life for a drug from the body is not the same as half-life of the drug in the vicinity of its active site or the brain, e.g. diazepam tends to have a short duration of effects because it preferably partitions out of the "hydrophilic" CSF into the "hydrophobic" fat cells, where there are no GABA-R's to bind.

 

[Limpet_Chicken]

So whilst of course hydrophobicity increases general half life, and of course assists in penetration of the BBB, what one might want is actually something like a synthon of a highly hydrophilic (preferably nitro-)BZD with the -OH groups masked by metabolically highly labile groups that assist penetration of the BBB and then get lopped off to leave a hydrophilic group behind, for optimum action duration and long half life?.

 

[Pomzazed]

That principle is how hydroxyzine works with so long duration