How do medical professionals figure out the lethal dose of drugs?

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Discussion Overview

The discussion revolves around how medical professionals and researchers determine the lethal dose of drugs, exploring methodologies such as animal testing, overdose data analysis, and clinical trials. The scope includes theoretical considerations, practical applications in pharmacology, and the ethical implications of drug testing.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • Some participants suggest that lethal dose determination may involve animal testing and extrapolation to humans, alongside patterns observed from overdose cases.
  • Others argue that researchers prioritize establishing a safe dose during initial human trials, using prior animal data and non-clinical information to inform dosing decisions.
  • A participant mentions that overdose data can accumulate over time, potentially providing sufficient information to determine lethal doses for many drugs, though this may not apply universally.
  • Another point raised is the availability of individual case reports from toxicology centers, which can provide insights into overdose incidents when established LD50 values are lacking.

Areas of Agreement / Disagreement

Participants express varying views on the methods used to determine lethal doses, indicating that there is no consensus on a singular approach. The discussion reflects multiple competing perspectives on the reliance on animal studies, clinical trials, and overdose data.

Contextual Notes

Limitations include the potential variability in drug responses among individuals, the ethical considerations of testing, and the dependence on existing data from both animal studies and clinical experiences.

Flatland
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How do medical professionals, scientists or whoever studies this stuff figure out the lethal dose of a particular drug? It's not like they can perform experiments on humans. Do they just test them on animals and then extrapolate that to humans? Do they find some kind of pattern from people overdosing? Or is it just an educated guess and a combination of the above?
 
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Flatland said:
How do medical professionals, scientists or whoever studies this stuff figure out the lethal dose of a particular drug? It's not like they can perform experiments on humans. Do they just test them on animals and then extrapolate that to humans? Do they find some kind of pattern from people overdosing? Or is it just an educated guess and a combination of the above?
... all of the above.

Researchers are not so concerned with the lethal dose as much as a reasonable safe dose. This properly starts with the stage 1 human trial thought they will likely be other information from animal tests and non-clinical use that will be taken into account. You don't go into a human trial without knowing that the initial dose is harmless. You can then step up doses and closely monitor the results.

Once a drug is on the market, the research does not stop - what may count as a lethal dose and in what circumstances is the sort of thing that can become clear after a few autopsies (and close rescues).

See: phases of clinical trials.
http://www.nlm.nih.gov/services/ctphases.html
 
Last edited by a moderator:
Please search LD50.
 
Last edited by a moderator:
In medical school pharmacology, the professor said that for a lot of drugs, there accumulates ample overdose data to sufficiently determine the number. Of course I'm not sure if this applies to all or even most drugs, so take it for what it is worth.
Source: Recent pharmacology lecture at an American M.D. school

It is interesting that if you search for "X drug overdose" on a program like Epocrates or LexiComp, if there is not an established LD50 there are usually links to individual case reports from toxicology centers about a patient who at one time took a whole bottle of something and then describes what went on to happen.
Source: personal experience using Epocrates
 

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