6
$\begingroup$

I was reading the lidocaine user's manual for dentistry use and according to it and I quote "Lidocaine in concomitant use with acetazolamide, thiazides and loop acting diuretics. The hypokalemia ("a low level of potassium (K+) in the blood serum") induced by these drugs, antagonizes the lidocaine effects" which seems a bit weird as a potassium deficit would hyper-polarize the membrane increasing membrane potential making it to hard to get to the threshold potential right?

$\endgroup$
4
  • $\begingroup$ Thanks for adding the quote; I agree it's odd. I could see systemic concerns with lidocaine reducing heart rate which would be a bad combo with hypokalemia, but antagonism is not the concern there. Is this possibly a bad translation? Is there other context beyond what you quoted? $\endgroup$
    – Bryan Krause
    May 30 at 19:23
  • 1
    $\begingroup$ As a matter of fact, I couldn't find the exact same info in the English version, but I can guarantee you there is no translation error. I could provide you with a copy of it if you wanted to. $\endgroup$
    – Quique
    May 30 at 23:38
  • 1
    $\begingroup$ Here is the link where you can download the Spanish version of the manual zeyco.com/producto/fd is the part about drug interactions $\endgroup$
    – Quique
    May 31 at 12:51
  • $\begingroup$ Thanks; it's clearly in both English and Spanish inserts. Inserts for similar formulations like accessdata.fda.gov/drugsatfda_docs/label/2018/021381s006lbl.pdf or accessdata.fda.gov/drugsatfda_docs/label/2018/006488s097lbl.pdf don't mention any such antagonism. Certainly it makes sense as a possible contraindication for other reasons, but I agree with you that the mechanism and concern they mention isn't making much sense to me. $\endgroup$
    – Bryan Krause
    May 31 at 14:15

1 Answer 1

-1
$\begingroup$

The following is a suggested answer only -- and is NOT intended to be authoritative; since it is not clear from the literature on Lidocaine why its efficacy is reduced in hypokalemia.

While it is true that hypokalemia will tend to induce hyperpolarisation of cell membranes, which in the case of neurons inhibits the elaboration of the action potential (by increasing membrane potential), other effects should also be considered, in the first instance that the concomitant tendency for K+ to flow out of cells generally also implies the countervailing tendency for Na+ channels to promote the transport of Na+ into cells -- more channels operating with greater facility.

Since Lidocaine is a sodium channel blocker -- which prolongs the inactivation of voltage-gated Na+ channels -- then prima facie, a generalised condition of hypokalemia suggests that the associated operation of more sodium channels will tend to antagonise its action.

At the same time, since the Na+/K+ ATPase would be operating to maintain homeostasis of intracellular cations (K+ in particular) in the face of any such efflux of K+ from cells, this effect would likely be accentuated by virtue of the corresponding efflux of Na+ from the same cells; notwithstanding the findings cited in the study below [1] concentrating on myocardial activity, that ''hypokalemia significantly inhibits Na+/K+-ATPase pump activity causing intracellular Na+ and Ca2+ accumulation''. In that case, it is presumably the implication of the Na+/Ca2+ pump which complicates any effect on Na+ channels.

Additionally, the finding that hypokalemia inhibits the Na+/K+ pump would imply a tendency to recalcitrance in the opening and function of sodium channels which, since that would favour the action of Lidocaine (as a sodium channel blocker), contradicts the premise of the question.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399982/

https://en.wikipedia.org/wiki/Sodium%E2%80%93potassium_pump

$\endgroup$
3
  • $\begingroup$ @Bryan Krause (or whoever down-voted the answer) Please indicate what is wrong with the reasoning. I think any objection deserves explanation. While I don't KNOW that this answer is correct, whatever the answer is, presuming the premise of the question is valid, almost certainly involves some effect of hypokalemia on Na+ channels presumably as a consequence of changes in IC K+. If it is true that the Na+/K+ pump is inhibited in hypokalemia, it would suggest recalcitrance in the opening of Na+ channels favouring the action of Lidocaine which contradicts the premise of the question. $\endgroup$
    – jeremiah
    Jun 7 at 7:46
  • $\begingroup$ Thank you very much! Although I wonder why hipokalemia improves sodium channels activity. $\endgroup$
    – Quique
    Jun 11 at 13:52
  • $\begingroup$ @Quique I'm not sure that it does -- it was merely a suggestion based on the idea that since K+ will flow out of cells in order to redress a condition of hypokalemia, then it is likely that Na+ will flow into the same cells via the most efficient mechanism, which would be sodium channels. However, my answer was not well-received so there is probably some more obvious effect which I'm overlooking. There still doesn't seem to be any explanation for the effect you cite on Lidocaine activity. The consensus among the erudite here seems to be, ''We dunno and it's not really important''. Fair enough. $\endgroup$
    – jeremiah
    Jun 13 at 14:22

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.