NBME Practice Question on Toxicity

[rj44]

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Four drugs produce the same therapeutic effect by the same mechanism, but each has a unique toxicity. When used at a maximally effective therapeutic dose, the drug with which of the following sets of characteristics is most likely to have the highest incidence of toxicity?​

Median Toxic Dose1 /EffectiveDose99

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Effective Dose
(A) 0.5x 2.8
(B) 1x 2.1
(C) 5x 4.0​

(D) 33x 3.0


The answer is B. Can someone please explain why?? Thanks!!

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[rj44]

sorry the format got messed up...the first column is median effect dose and all the numbers end in 'x' (.5x, 1x, 5x, 33x) and the second is toxic dose1/effective dose99 (2.8, 2.1, 4.0, 3.0).

It's from the free set given by the NBME from this year, #49.

 

[SeminoleFan3]

The one that has the lowest toxic dose is going to be the one with the greater toxicity because there's less of a therapeutic window.

 

[Rik825]

You just need to look at the 2nd column, which is the therapeutic index (TI). The higher the TI, the safer the drug. The lower the TI, the more dangerous.

In this question, for choice A the toxic dose (TD50) is 1.4, and for choice B the TD50 is 2.1. So you might think that drug A would cause more toxicity because you need a lower dose to start causing problems. But The TI matters more than the absolute numbers, so the opposite is true.

 

[rj44]

Thanks! Does anyone know why the mean effective dose is listed as 1, 0.5, 'x'?