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Comment by cmendel | Hacker News Reader

>>Always buy generic drugs, they're exactly the same.

I'm sorry to say. This is false.

This will be a bit technical but often, generic drugs are a racemic mix (both L and D conformations in some mixture) where as a branded drug may be a specific conformation or specific racemic mix (e.g. 75% L, 25% D.)

The issue comes from the fact that L-conformations may have different (better, worse, otherwise) effects than the D-conformations.

TL;DR Not all generics are the same as their branded counterparts and they might effect you differently. Caveat emptor.

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I have no idea what that comment meant to say. Am I being thick or it the same for anyone not manufacturing drugs for a living/as a hobby?

I'll do my best to explain. So in chemistry, there is a thing called 'chirality' essentially this has to do with how a molecule is shaped. It's assessed by how a beam of polarized light that is passed through a molecule rotates.

There are a few different types:

Achiral, no change Levorotary (L), Rotates anticlockwise Dextrorotary(D), Rotates clockwise

The reason that it matters and what I was talking about above is that the sites in your body that a drug interacts with aren't universal. So if you have a (L) version of a drug that might have different effects and interactions than a (D) version.

A 1:1 mix of both (L) and (D) is called a racemic mix.

When you are talking about Brand name drugs, you're typically discussing a particular mix (e.g. Adderall XR is a 3:1 (D):(L) mix) or a particular conformation. That is not necessarily true with generics which may have a different ratio of (D):(L).

To give an example of how different the effects can be: Penicillamine (L) is used in the treatment of primary chronic arthritis. Penicillamine (D) not only has no therapeutic effect, it is highly toxic.

Here's a link to some Wikipedia pages on it if you're interested: https://en.wikipedia.org/wiki/Chirality#Chemistry https://en.wikipedia.org/wiki/Racemic_mixture

Do note that this is a bit of an oversimplification, but it's 3AM here so I hope you can forgive me.

Thank you, that was informative.

If generic drugs have a different L:D ratio and L molecules have a different effect than D molecules, then surely the generic has a different effect and result than the brand name which would make or the other work better. Wouldn’t that come up and be an issue leading to either reformulating the generic to better match the brand name, or pulling the generic altogether?

> To give an example of how different the effects can be: Penicillamine (L) is used in the treatment of primary chronic arthritis. Penicillamine (D) not only has no therapeutic effect, it is highly toxic.

I think, as a layman, Thalidomide is probably a good striking example.

One chirality does what it says on the tin. The other causes babies to be born missing limbs and with other birth defects.

In theory, if we could produce Thalidomide with only the correct isomer, it would not only be effective but 100% safe for pregnant women.

Thanks TIL, I had no idea. I'll stop giving medical advice I guess.

Ha, no worries! I'd thought the same until I went off and got a degree in Chemistry.

Fwiw, I have a degree in chemistry and it never occurred to me that generics would potentially have a different chiral mixture to the original.

Given that we know (like you point out) that different enantiomers can have very different effects, it seems particularly dangerous for generics to be marketed as alternatives to the branded drug when, in some cases, they really are not.

thank you!

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