Psychopharm kinetics

[393656]

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Hey guys I am a new member here, a 4th year psych resident. I love psychopharm as do most of you I am sure! I had something that has been buggin me lately and cannot figure it out.

How this got started is the ridiculous amount of polypharmacy used EVERYWHEREr including my own attendings which is disapointing. One of the most common ones is piling on the anti-histamines by using remeron, hydroxyzine and seroquel for example. Then benadryl as a PRN.

So I have came across Ki values that I do not have right now but let me give an example that hopefully someone can clarify. Lets say Remeron and benadryl have a similar Ki for histamine affinity receptor (I believe remeron is a tad higher but for ease of question). Now how do you take into account the mg dose of each one if you are comparing dose to dose.

Remeron 15mg v. benadryl 50mg. Although equal Ki, how do you account for each dosing. Is "15mg remeron" equal to "50mg benadryl" as far as H1 binding. Hopefully I am clear and apologize if not. Maybe I am missing something silly!

The other place this comes up were the following examples-

1.comparing 5HT2 antagonism of traz v. remeron v. hydroxyzine v. atypicals
2.Seroquel v. remeron v. benadryl (or other sedating anti-hist)
3.alpha 1 blockade of risperdal to prazosin-

Now its easy to find the Ki for all of those but the problem is how to take into account the dose.

My thought was to convert mg to moles for everything and compare--Ok any thoughts?? thanks guys!

 

[nitemagi]

I think it's tough to compare doses alone. It would probably need its own study for each comparison.

Ki alone fails to take into account a lot of other factors - selectivity (other receptors hit), bioavailability, time to peak blood level, half-life, drug interactions, pathway of metabolism and excretion.

 

[393656]

hmmm good call! More entailed than I think is possible to calculate. Ok that is relieving! Thanks nite! you are full of great answers and resources

Thanks!

 

[IAmAUser]

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[393656]

Not sure how comparing relative Ki's would answer the question comparing different drugs. That is the whole dilemma. And of course you can compare Ki's across different drugs. Have you ever looked at any psychopharm text that has tables of neuroleptics, tricyclics and all their many receptor listed with receptor affinity in Ki.

As people mentioned in this thread its hard to account for the many other factors such as affinity to other receptors and such however the best comparison we have is Ki. It has always given me a "relative" idea to what frame of reference I am looking at. 2 drugs with the same Ki indicate both have in vivo binding to a certain receptor at a certain strength.

I must disagree with your entire post! But hey that is why pharmacokinetics is fun! Even being able to discuss this is miles ahead of most doctors I see so I am always willing to learn and accept I am wrong however this is something I am 100 percent sure on

 

[IAmAUser]

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[393656]

Well that was the point of my thread. Standardizing the doses to create a way to compare different drugs. However in general if you look at side-effect burden clinically they usually match up pretty well to the Ki values at various receptors and although I agree you cannot compare number for number, you can compare meds with Ki's in the same ballpark as being low, medium, high or whatever.

Decimal place or number to exact number obviously is not even close. I guess I meant relative comparisons that 2 drugs with very low Ki's likely bind to X-receptor and show effects from that binding clinically more than another drug with a signifigantly higher Ki.