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Step I Question about TCA toxicity
Started by studylol
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TCAs are acidic in basis. They can cause arrhythmia because they are Na+ channel blocker and therefore even death!
Now, recall the Henderson-Hasselbach equation that says:
BH>>>B_ + H+
TCA has H+ and when added to the environment can push the equation to left. And more acid produced. As far as BH is not in the ionic form, that can be easily absorbed/reabsorbed.
With NaHco3, you can push the equation to right where ionic form, H+, is dominant and non-reabaorbable and easily excreted throughout the renal tubule as urine. The patient, now, gets rid of TCA based on chemistry equation.
Now, recall the Henderson-Hasselbach equation that says:
BH>>>B_ + H+
TCA has H+ and when added to the environment can push the equation to left. And more acid produced. As far as BH is not in the ionic form, that can be easily absorbed/reabsorbed.
With NaHco3, you can push the equation to right where ionic form, H+, is dominant and non-reabaorbable and easily excreted throughout the renal tubule as urine. The patient, now, gets rid of TCA based on chemistry equation.
Sorry I think I should have been more specific. I was thinking pharm for a long time and didn't realize it could be misinterpreted.
I meant TCA as in tricyclic antidepressants, not tricarboxylic acid which I think you are considering. Tricyclic antidepressants are basic, not acidic.
I meant TCA as in tricyclic antidepressants, not tricarboxylic acid which I think you are considering. Tricyclic antidepressants are basic, not acidic.
TCA cardiotoxicity is treated with sodium bicarb because the increase in pH promotes dissociation from the Na+ channels AND it contributes to the sodium gradient. I've also read that it promotes more plasma protein binding, effectively reducing the amount of unbound drug that is free to block sodium channels in cardiac myocytes. Plus, TCAs have a large Vd, so trying to increase its clearance won't be as effective.
Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1725608/pdf/v018p00236.pdf
http://www.calpoison.org/hcp/2007/callusvol5no1.htm
Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1725608/pdf/v018p00236.pdf
http://www.calpoison.org/hcp/2007/callusvol5no1.htm
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Thanks a lot. This is simple enough to remember so i'll just ignore that other bit 🙂
>Brown et al demonstrated that the plasma protein binding of amitriptyline increased with a more alkali pH and this as confirmed by a later study. This reduction in the pharmacologically active unbound fraction and a direct effect on myocardial contractility by correcting the metabolic acidosis present, were thought to be the causes.
>Brown et al demonstrated that the plasma protein binding of amitriptyline increased with a more alkali pH and this as confirmed by a later study. This reduction in the pharmacologically active unbound fraction and a direct effect on myocardial contractility by correcting the metabolic acidosis present, were thought to be the causes.
As far as I'm aware TCAs are positively charged, so it would probably look like:
TCA-H (+) <--> TCA + H+
Bicarb would decrease the H+ on the right side of the equation, thereby shifting the equation to the right and favoring the conjugate base form of the TCA. This uncharged form would presumably dislodge from the sodium channel, since sodium is positively charged and naturally has affinity for its own channel, so the positively charged TCA form would bind also.
TCA-H (+) <--> TCA + H+
Bicarb would decrease the H+ on the right side of the equation, thereby shifting the equation to the right and favoring the conjugate base form of the TCA. This uncharged form would presumably dislodge from the sodium channel, since sodium is positively charged and naturally has affinity for its own channel, so the positively charged TCA form would bind also.
