The therapeutic index (or therapeutic ratio) is the ratio between the normal therapeutic dose and the toxic/fatal dose. It's a consideration in drug design. It becomes an overwhelming concern for widely prescribed drugs that patients take home. For example, the common SSRI antidepressants were designed, in large part, to have a very large therapeutic index. It's one of their main advantages over the earlier MAOI or tricyclic antidepressants. (You don't want to prescribe a drug easily fatal in overdose to depressed people, if you can avoid it.)

For SSRIs it's like 20 - 100+. For benzodiazepines it's about 10 - 50+ or so. A much dangerous drug class like opiates are more like 5 - 10 or so. Blood thinners like warfarin have a very small one, where simply doubling the dose can be extremely dangerous.

Tylenol (acetaminophen/paracetamol) is like that. The label says take up to 4000 mg a day. Taking like 2 - 4x as much as the maximum daily dose can cause liver failure and death. It is one of the smallest therapeutic indices of any commonly used over the counter drug. There are relatively few other over-the-counter drugs that are as toxic.

I like the requirement they have in the UK and a few other countries, to sell it in blister packs, of relatively small doses, like 250 mg. And an uncomfortable subject but: a very large percent of those Tylenol liver failures were suicide attempts. Public awareness that Tylenol causes liver failure which will last weeks before death might dissuade some.

> Public awareness that Tylenol causes liver failure which will last weeks before death might dissuade some.

I suspect it will: There's statistical evidence from how Britain migrated its cooking gas systems away from carbon-monoxide-heavy mixes [0] indicating overall suicide-rates are sensitive to convenience and involve short-term periods of vulnerability. As contrasted to "if they really want to they'll find a way no matter what." [1]

__________

[0] https://www.npr.org/2008/07/08/92319314/in-suicide-preventio...

[1] That said, I wouldn't be surprised if there's a bimodal distribution lurking in there, between "depressed but otherwise healthy" versus "terminal diagnosis and chronic pain." The latter-group might not be deterred by inconvenience.

Sure but it’s pretty easy overdose on paracetamol.

Since it’s a mild and really common painkiller, sometimes seen as not dangerous, someone uneducated about it who is really suffering could easily take 3 or 4 times the dose.

Unlike a lot of drugs, you are not going to have a lot of immediate side effects if you overdose on paracetamol. You’ll just horribly die some days after,

> someone uneducated about it who is really suffering could easily take 3 or 4 times the dose.

And the solution is simple: educate people about that.

And it's not something hard to do, just have pharmacists say “respect the dose as it will kill you if you don't” every time they sell things and it'll work.

But Tylenol/acetaminophen/paracetamol is an over the counter drug, so there is no pharmacist involved in most sales. And I certainly wouldn't count on everyone reading the tiny text on the bottle.

That's entirely a sales (de)regulation problem though.

It's funny that in a country where you can win massive sums of money on stupid trials a drug like paracetamol is sold without supervision.

How can you reach adulthood and think it's ok to take 3 or 4x the specific dose of any medication? If you're in that much pain you go to a doctor. Which makes me think maybe the issue is the private health system and not the drug.

Conversely, my grandmother's Alzheimer's became apparent when she was overdosing on either ibuprofen or aspirin, I forget which.

She would take a dose for a headache, ten minutes later she'd forgotten so she'd take another dose, ten minutes later, she had forgotten, take another dose, rinse and repeat until it's time for a trip to the hospital.

Maybe it wasn't ten minutes between, probably fewer given how much she'd ended up taking. This happened thirty or so years ago.