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The Myth of Drug Expiration Dates

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Re: The Myth of Drug Expiration Dates

#261
post #61
post #47

Earlier quoted context omitted.

Any idea whether the chemicals they decompose into are ever more harmful than the original?

Aspirin is a bad actor in this regard. It tends to revert back to salicylic acid, which is ok for some specific topical uses, but has potential to be pretty harmful orally. Sniffing an old bottle of aspirin will tell you whether they're still good enough

For the record, what you're smelling for is acetic acid (vinegar). When aspirin (acetylsalicylic acid) hydrolyzes into salicylic acid, the other product of that reactions is acetic acid, which is what's in vinegar.

Re: The Myth of Drug Expiration Dates

#262
post #161

Earlier quoted context omitted.

There's also the not-irrelevant issue that testing is slow and potentially other than free. How do you find out when a drug expires? You have a bunch of it sit around and test it periodically, right? I assume that would be done after bringing a drug to market, otherwise drugs could easily be delayed 10+ years if they're shelf-stable.

If scientists are able to calculate the longevity of chemicals, food, and other products without having to wait the actual time period, I don't see how or why pharmaceutical drugs would be any different. It's very likely it is not favorable to companies to look into this, just as it was revealed that the EpiPen expiration date was not really true.

You're absolutely right! Those calculations can be done without actual testing. The only wrinkle is that doing so comes with the risk of failing to foresee something or otherwise being wrong. So there are some error bars involved.

What kind of error rate are you willing to accept in models of pharmaceutical shelf stability? Bearing in mind that errors potentially translate into deaths, probably disproportionately of the less privileged among us?

Re: The Myth of Drug Expiration Dates

#263
post #261
post #61

Earlier quoted context omitted.

Aspirin is a bad actor in this regard. It tends to revert back to salicylic acid, which is ok for some specific topical uses, but has potential to be pretty harmful orally. Sniffing an old bottle of aspirin will tell you whether they're still good enough

For the record, what you're smelling for is acetic acid (vinegar). When aspirin (acetylsalicylic acid) hydrolyzes into salicylic acid, the other product of that reactions is acetic acid, which is what's in vinegar.

Thanks! It's been 25 years since my last pharmacology class, the details are all getting a bit vague.

Re: The Myth of Drug Expiration Dates

#264

Earlier quoted context omitted.

LSD is an agonist for most classes of serotonin, dopamine, and adrenergic receptors - most of which have sensitive, nonlinear responses and all of which uptake the agonist at very different rates depending on individual biochemistry. We don't have the data to say for certain because of prohibition and the DEA's reluctance to allow researchers to study LSD but every other drug combination that operates on such a diver…

IME bad trips are mostly determined by how neurotic the tripper is. If you can accurately say that a 25% increase causes a 10% increase in bad trips, you must have quite a lot of experience. I at least know that if some people take one tab and others take two at the same time, the ones who took two don't go flying off the walls. Saying that a 25% change is more significant for more potent drugs is illogical on the fa…

> Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it.

Actually, the reverse is illogical because few biochemical systems have linear responses, especially when you're talking about something as complicated as the neurotransmitter systems that LSD effects. Potency depends on two factors: the affinity of the drug, or how well it binds to its target receptors, and efficacy, or the relationship between the concentration of the drug (and second order neurotransmitters) and the ability of the receptors to initiate a cellular response. Neither of those two factors are linear and they both change as the concentrations of the drug and its byproducts change. As neuron receptors are activated by LSD, they cause cells to release a flood of other neurotransmitters at varying concentrations (dependent on LSD concentration and individual brain chemistry) that start interacting in complex ways like preventing the LSD and other neurotransmitters from binding as effectively (lowering their affinity), potentiating the cellular response (increasing its strength aka increasing efficacy), or building tolerance (lowering efficacy due to exposure). Each receptor and neurotransmitter pair behaves differently. Neurotransmitters in general can't activate cellular responses before they are above a threshold potential that causes the neuron to react, after which the cellular response is never linear. A 2x increase in concentration will rarely achieve a 2x response unless it falls in a small range where the curve is mostly linear, and even then the complex interactions between all of the neurotransmitters will usually compound into a nonlinear response anyway.

These interactions get so complicated, for example, that you get many cases were an opiate A, which is technically 10x more potent than an opiate B, can actually be less potent at treating mild pain because it has a steep response curve that doesn't ramp up until a certain dose. 10mcg/kg of opiate B might be 10x stronger than 10mcg/kg of opiate A (which could be too low to even feel the painkilling effects of opiate A) but once you hit 50mcg/kg concentrations, opiate A might be 10x more potent than opiate B, whose effects plateau with doses higher than 20mcg/kg. Potency is typically expressed as the [A]50 - the concentration of the drug at which you reach 50% of the maximum effect, which depends on the therapeutic effect you're looking for. So in this example, the [A]50 of opiate A in mild pain scenarios can be 25mcg/kg versus opiate B's 7 mcg/kg while with severe pain, the [A]50 of opiate B can be above its LD50 and opiate A's can be 30 mcg/kg because from 25 to 30 mcg/kg opiate A has an exponential response curve. Like I said, it's very complicated and when measuring potency, you're actually measuring the effects of concentration on "arbitrary units," which could be something concrete like a chemo drug's effectiveness at killing cancer cells or something subjective like pain relief. When it's the latter, especially, potency has a very specific meaning in pharmacology that is very different from how the word is used colloquially.

Re: The Myth of Drug Expiration Dates

#265

Earlier quoted context omitted.

IME bad trips are mostly determined by how neurotic the tripper is. If you can accurately say that a 25% increase causes a 10% increase in bad trips, you must have quite a lot of experience. I at least know that if some people take one tab and others take two at the same time, the ones who took two don't go flying off the walls. Saying that a 25% change is more significant for more potent drugs is illogical on the fa…

> Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it. Actually, the reverse is illogical because few biochemical systems have linear responses, especially when you're talking about something as complicated as the neurotransmitter systems that LSD effects. Po…

This is just throwing around a lot of irrelevant details to obscure the fact that your original statement violates the dimensional analysis smell test -- I could make a shitty prodrug of LSD where the threshold dose is 1g instead of 50ug, but you wouldn't expect the 1g version to be less sensitive to a 25% change because it's "less potent." If you wanted to give examples of a drug where a 25% change is a big concern then warfarin or synthroid are much better examples than LSD. As it turns out, you know your shit, but it is still a sloppy statement.

Re: The Myth of Drug Expiration Dates

#266

Earlier quoted context omitted.

The point is we don't necessarily know, or know to the degree of certainty the FDA requires, how many of these things degrade. Perhaps in certain conditions, they degrade at one rate, but in other conditions (such as a temperature difference), they degrade at a different rate. Testing how drugs perform years after production in multiple different scenarios is necessarily time consuming, because it takes at least that…

I see medicines in foreign countries wrapped in some kind of aluminum foil. Will that prolong the life of the medicine given there is no oxygen to react? Given the amount of money spent on medicines, I really think there is a good moral business case to identify the correct expiration dates and save money for people. We just went through the Health care ordeal. Money saved anywhere is money saved for people who despe…

Except the medicines themselves aren't expensive. The prices are that high because the pharma companies demand it, because of all the tests, which are their main source of income. That is why prices in the US are so much higher than elsewhere (because of the political power of lobbying and cultural acceptance of price screwing the public on medical things).

Given that it's the very same party that would be doing the testing for expiration dates, I kind of doubt they would research this out of the goodness of their corporate hearts. Effectively the same outcome could be realised without the effort of extra testing anything: by just lowering the price of medicine a bit; big pharma would make less money, the public would have more medicine for cheaper.

Re: The Myth of Drug Expiration Dates

#268
post #81
post #56

Earlier quoted context omitted.

This is completely wrong. Dosage studies happens between Phase 2 and Phase 3 trials (and Phase 4 "post marketing" too) and are the most expensive, longest and most scientific process that arguably any business engages in in the entire world. Phase 1 is a safety test in healthy ~men. These seek to find the maximum dose before adverse effects appear in the healthiest humans. Phase 2 is a safety/dosage test in a much la…

Sounds like you don't know what you are talking about. Your source is a book written with heavy influence by the Pharmaceutical industry to justify the obscene costs of their drugs, making billions in profits off of sick, poor people. You are the one who is completely wrong. The dosages most certainly do start out with a "best guess" in the pre-clinical phase. For any given drug we would guess at the doses based on o…

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Re: The Myth of Drug Expiration Dates

#269

> The findings surprised both researchers: A dozen of the 14 compounds were still as potent as they were when they were manufactured, some at almost 100 percent of their labeled concentrations. What kind of reporting is this? Anything less than 100% is not "as potent as when manufactured", and the sentence implies some of those dozen weren't close to 100%. > The idea that drugs expire on specified dates goes back at…

When working with biological systems, most of the time your acceptable error margin is between 10-25%. There are a few compounds (like fentanyl or LSD) where the dosages are so small and the compound so potent that 10-25% makes a difference but for the majority, precision isn't that critical. The ones where it does matter are tightly controlled and clinically applied by a professional with active monitoring. The only…

You're talking about the study linked as "2006 study of 122 drugs", right? I can't find amphetamines in the tables or the text, what page is it on? (or was it maybe another paper linked in the article?)

I have a prescription for dexamphetamine, but I don't use/need it a lot, so I have some bottles left that are a bit old--not past the expiration date, which appears to be slightly less than 3 years (after the date of the recipe), on the bottle I'm currently looking at. So I was curious about the amphetamines in particular, and if it's just efficacy deteriorating a bit that's fine, because in my personal experience the effect (which is quickly and clearly noticeable) varies easily by 25% already, depending on so many other factors (like what/how much I eat, how well I slept, stuff like that).

Re: The Myth of Drug Expiration Dates

#270

Earlier quoted context omitted.

> Saying that a 25% change is more significant for more potent drugs is illogical on the face of it, because a % is a dimensionless quantity. If there is some subtle reason why this trend exists I'd love to hear it. Actually, the reverse is illogical because few biochemical systems have linear responses, especially when you're talking about something as complicated as the neurotransmitter systems that LSD effects. Po…

This is just throwing around a lot of irrelevant details to obscure the fact that your original statement violates the dimensional analysis smell test -- I could make a shitty prodrug of LSD where the threshold dose is 1g instead of 50ug, but you wouldn't expect the 1g version to be less sensitive to a 25% change because it's "less potent." If you wanted to give examples of a drug where a 25% change is a big concern…

I tried explaining why you are wrong but I give up. You are incapable of accepting basic facts about biological systems and neuroscience that have been known for many decades, no matter how hard I try to explain it to you. Your "dimensional analysis smell test" is entirely idiotic in the face of those basic facts as accepted by the entire medical and biological research fields.

Please don't talk about pharmacology. Period. You don't know what you are talking about and someone might make the mistake of believing otherwise and do something dangerous.

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