Drug Detox and Lipids Uptake

[justadream]

TBR Book I pg 46 #26

“Lidocaine is administered through injection, rather than orally because lidocaine is___”

Answer: “biotransformed by reactions occurring in the liver”



Two questions

1) I understand that nutrients (except fats) go to the liver via the hepatic portal system before being released into the blood. So why don’t ALL drugs that we ingest orally get degraded immediately by the liver?

2) The passage indicates that lidocaine has a lipid component. So why isn’t this taken up like a fat? Is it because it’s not completely lipid? If so, then does that mean something that is like 99.99% lipid and .01% something else would not be taken up by lacteals?

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[Czarcasm]

TBR Book I pg 46 #26

“Lidocaine is administered through injection, rather than orally because lidocaine is___”

Answer: “biotransformed by reactions occurring in the liver”



Two questions

1) I understand that nutrients (except fats) go to the liver via the hepatic portal system before being released into the blood. So why don’t ALL drugs that we ingest orally get degraded immediately by the liver?

2) The passage indicates that lidocaine has a lipid component. So why isn’t this taken up like a fat? Is it because it’s not completely lipid? If so, then does that mean something that is like 99.99% lipid and .01% something else would not be taken up by lacteals?

It's likely this drug is nonpolar throughout the ingestion process as it passes the acidic pH of the stomach, but as it enters the alkaline pH of small intestines, it's probable a protic region (for ex.) -OH) of this lipid has a pKa below this range in pH (9-11) and therefore becomes deprotonated and charged. A charged region on a lipid as compared to a totally uncharged lipid is very polar. Intravenously, you would avoid the basicidity of the small intestines (blood has a pH around 7.35), so as long as this protic region of this molecule has a pKa above blood pH, it remains and behaves as a lipid.

EDIT: What'd you know, I just looked it up and Lidocaine has a pKa of 7.7 (above blood's pH of 7.35). It's still very close to blood's pH though - not even 1 pH unit higher, which means, a small portion of this drug does become deprotonated. It's basically in it's buffer region, but you have more of the protonated (nonpolar) form. In the small intestines, having a pKa of 7.7 compared to the pH of small intestines (~9), most of this drug would exist largely or entirely in it's deprotonated form (because pKa is less than the pH).