.....I believe that the anion of paracetamol is more water soluble; there is an increase in pH that allows some of the anion to form and increase solubility, and as you say the effervescent action also exposes the paracetamol to a greater surface area which helps with solubility. I believe that most of the paracetamol is dispersed rather then dissolved, I have not personally consumed these tablets though.......
Hmm, how could the paracetamol molecule somehow become negatively charge? The only way could be a rxn bonding a negatively charged species with the molecule. Non of the metabolites go through this process. I'm not quite sure what you mean here!
In fact, paracetamol itself is rather non-polar (aka, is immiscible with water). Which is not to say there is no charge, the charge itself is just balanced over the entire molecule.
In terms of solvents/solutes and solubilities, the common mantra "like dissolves like" is used. Water (being the best solvent in the world) is polar, hence it is most effective on other polar (dipoles, induced dipoles, H-bonding) compounds. Non-polar best dissolves non-polar. In this instance, in chemistry non-polar compounds such as ethanol or dimethyl- is often used. "STP" or "standard temperature and pressure" are also the first starting point of compounds like these as both of these play a role in intermolecular forces, saturation points, etc.
warning: tl;dr.....
Are you saying this "anion" property in relation to the it causing (anion gap) metabolic acidosis? If so, it's not (afaik) true that paracetamol (or any of it's metabolites) are negatively charged, nor that this is the cause of toxicity.
Without getting to much into the pharmacology/chemistry here as it's more appropriate in the Adv.DD but ….. this disorder - basically acidosis - is cause by the an excess of anions, in this case an excess of acidity in blood serum, this in tern caused by the interference of the body's bicarbonate buffering system and hence a reduction in bicarbonate. The loss of bicarbonate in this case is due to (in those predisposed - those pregnant, diabetic, chronic drug/alcohol use, those who are liver impaired, concomitant use of some drugs, etc) an accumulation of a pyroglutamic acid, which usually would be removed by glutathione (required for the removal of free-radicals, essentially a detoxification agent). This is basically all caused by the
covalently (I highlighted 'covalent' to show there's no dipole/* interaction. That is, no polarity) bonding of one of the paracetamol metabolites to glutathione, preventing action, and creating an accumulation of the pyroglutamic acid.
In fact, this is the why the prep. is produced as a salt - mixed with HCl causing a neutral[ish] drug. Aka, no overall charge.
If this isn't what you were getting at M_B, disregard
Otherwise, lets that this into ADD since I'm not sure how appropriate it would be here.
These are the few papers I'm getting my info from. Regardless, they're quite interesting re paracetamol and heptatoxicity.
Paracetamol use and high anion gap metabolic acidosis -
http://journal.ics.ac.uk/pdf/1301054.pdf (pretty easy to read!)
ACETAMINOPHEN-INDUCED HEPATOTOXICITY -
http://dmd.aspetjournals.org/content/31/12/1499.full
Mechanisms of Acetaminophen-Induced Liver Necrosis -
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836803/
Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione S-transferase Pi -
http://www.pnas.org/content/97/23/12741.full.pdf (extremely heavy!)
-Tyrael
edit : the MOA of paracetamol, the MOA of toxicity and the adduct of the paracetamol metabolites and glutathione are obviously afaik. forgive me if it's slightly off, it's rather late a night. additionally, there is a lot which
still isn't known.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
Just speculation here though.
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