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Re: high dose lithium » Squiggles

Posted by Larry Hoover on June 29, 2007, at 7:35:53

In reply to Re: high dose lithium » Larry Hoover, posted by Squiggles on June 27, 2007, at 20:09:37

> I know all that. But once your doctor
> has established a satisfatory dose for you,
> the anything beyond that, is due to the
> extra-therapeutic factors i mentioned.

I am not literally concerned with your knowledge, but instead, the potential to mislead the lurking public. You are correct, but simultaneously not. Oscillations in lithium blood concentration which enter the realm of toxicosis could not possibly occur absent sufficient underlying intake (the daily dose), the primary factor. That we have identified the secondary factors which influence blood concentration oscillations in the short term is not sufficient argument to implicate them in the toxic reaction. They are simply the secondary variables of concern when a subject is subjected to near toxic intake of a toxicant with a narrow therapeutic index. Once the therapeutic baseline is established by dose (primary factor), perturbations in that baseline must be minimized (secondary factor(s)).

This is not an argument of semantics. Lithium is toxic in all doses. The frank toxicosis is a graded response only slightly elevated from the sub-acute toxicosis we call therapeutic.

> And btw, you can feel your dose going toxic,
> as you can with other antidepressants and antipsychotics with extrapyramidic effects.

You completely misunderstand, as demonstrated by this argument. Side effects are quite distinguishable from toxic effects. Lithium toxicosis involves disruption of sodium channels, an effect for which there is no physiological means by which the body can overcome it, until such time as it can reduce the concentration of lithium ions (if it survives the toxic effect). Extrapyramidal side effects are regulatory in nature.

Notwithstanding those who take the position that psych meds are poisonous, the term does not apply to any antidepressant or antipsychotic at doses even uncommonly employed in therapeutic interventions.....their therapeutic indices are typically in the 100's or 1000's (or undefined, being so large as to not be relevant).

> It's just that lithium is so well-publicized.

No, it's not, or I wouldn't belabour the issue. You're arguing with a toxicologist.

> Other drugs can kill you from crossing the narrow therapeutic index too, e.g. imipramine's cardiac
> toxicity effects, to mention one.
>
> Squiggles

Situations like you are suggesting are idiosyncratic in nature. They do not happen to all (or even most) subjects at the same dose. Far from it.

Example: The black box warning on nefazodone arose due to rare toxic reactions involving fulminant liver failure. However, those deaths were exceptional. The LD50 was not changed by these occurrences. The therapuetic index for this drug was not changed. It was simply recognized that rare idiosyncratic toxicoses can occur, and the risk/benefit analysis had to take these occurrences into account.

Lithium toxicosis is the general occurrence. It happens to all subjects so exposed, with only minor variation in the specific (individual) concentrations at which the specific symptoms of the toxicosis arise.

My point is how different lithium is from all other drugs in common use. Even calling it a drug is really a misnomer. It is a prescription substance because of the risk of toxicosis. There is no other reason.

Lar

 

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