Wednesday, July 5, 2023

activated charcoal, drug testing and the enterohepatic cycle

 The oral consumption of activated charcoal is not expected to have a significant effect on drug use and drug testing in relation to the enterohepatic cycle. 

 

The oral consumption of activated charcoal

 is believed to work by absorbing toxins and drugs in the following way:


Activated charcoal is a specially processed form of carbon that has a large surface area and a highly porous structure. This unique structure allows activated charcoal to adsorb (not absorb) substances onto its surface through a process called adsorption. Adsorption refers to the adhesion of molecules to the surface of another material without being assimilated or dissolved into it.


When activated charcoal is ingested orally, it travels through the digestive system and comes into contact with various substances present in the gastrointestinal tract. The porous structure of activated charcoal attracts and binds to a wide range of molecules, including toxins and drugs. These molecules adhere to the surface of the charcoal, effectively trapping them within its pores.


The principle behind using activated charcoal to treat poisoning or drug overdoses is that by adsorbing these substances, it may prevent their absorption into the bloodstream. This can reduce their systemic effects and potentially limit their toxicity.


It's important to note that activated charcoal is most effective in adsorbing certain types of drugs and toxins. It works best for adsorbing substances that are relatively large, nonpolar, and not readily absorbed by the body. Examples of such substances include some drugs, chemicals, and certain toxins.


Activated charcoal is not effective against all substances. It may not work well for adsorbing substances such as alcohol, heavy metals, certain acids, or substances that have already been absorbed into the bloodstream. Additionally, it does not reverse the effects of substances that have already exerted their effects on the body.


The enterohepatic cycle

 refers to a complex process that occurs between the liver and the small intestine, involving the absorption, secretion, and re absorption of certain substances. This cycle primarily involves bile acids, which are produced in the liver and play a crucial role in the digestion and absorption of dietary fats.


Here's a step-by-step explanation of the enterohepatic cycle:


Bile acid synthesis: Bile acids are synthesized in the liver from cholesterol. They are then conjugated with the amino acids glycine or taurine to form bile salts.

Bile secretion: Bile salts, along with other components such as cholesterol, phospholipids, and bilirubin, are excreted from the liver as bile. Bile is stored in the gallbladder until it is needed for digestion.

Fat digestion:
When dietary fats enter the small intestine, bile salts are released from the gallbladder and secreted into the duodenum (the first part of the small intestine). Bile salts emulsify the fats, breaking them down into smaller droplets, which increases the surface area for enzyme action.

Micelle formation and fat absorption:
Bile salts form micelles with the digested fats, aiding in their absorption. The micelles transport the fats to the surface of the intestinal cells (enterocytes), where they are absorbed.

Bile acid reabsorption: After aiding in fat absorption, a portion of the bile salts is actively reabsorbed by the enterocytes in the ileum (the last part of the small intestine) and transported back to the liver through the portal vein.

Bile acid recycling: Once the reabsorbed bile salts reach the liver, they are taken up by hepatocytes (liver cells) and returned to the bile canaliculi (small ducts) within the liver. From there, they are re-secreted into the bile ducts and stored in the gallbladder for future use.


This enterohepatic circulation of bile salts allows for the efficient reuse of bile acids, which would otherwise be excreted in the feces. By recycling bile acids, the enterohepatic cycle helps to conserve energy and maintain the necessary levels of bile salts for effective fat digestion and absorption.


Enterohepatic Recycling

 
Enterohepatic recycling (EHR) is a feedback mechanism resulting from the combined roles of the liver and intestine. EHR begins with drug absorption across the intestine into the portal circulation, followed by uptake into the hepatocytes. Next, drug and or conjugated metabolites are secreted into the bile and returned to the intestine, where drug can be reabsorbed into the circulation, in some cases after deconjugation in the GI tract (Figure 9.10). As described previously, a number of drugs are secreted by the liver into bile, and are therefore capable of undergoing enterohepatic recycling. These include antibiotics, NSAIDS, hormones, opioids, digoxin, and warfarin.


In cases of acute drug intoxications, activated charcoal is a commonly used treatment because of its ability to adsorb materials with a high capacity. Although timely single-dose administration is effective in preventing drug absorption of orally ingested drugs, repeated doses of activated charcoal have been shown to increase drug clearance, resulting in reduced plasma exposure of drug (Figure 9.11). This is the result of decreased enterohepatic recycling and increased drug exsorption from the intestine.


However, when it comes to the enterohepatic cycle and drug use, the impact of oral charcoal consumption is limited. Activated charcoal primarily works in the gastrointestinal tract, where it can bind to drugs present in the digestive system before they are absorbed into the bloodstream. This means that it may be useful in preventing the absorption of drugs that have not yet entered the systemic circulation.


Once a drug has been absorbed into the bloodstream and gone through metabolism in the liver, the enterohepatic cycle is already underway. At this stage, activated charcoal taken orally is unlikely to have a significant impact on the drug's fate in the body. The drug has already been metabolized and has gone through the necessary processes in the liver. Charcoal consumed orally cannot reverse or interrupt this cycle.


Regarding drug testing, the enterohepatic cycle is not directly affected by activated charcoal consumption. Drug tests typically analyze metabolites or traces of drugs in bodily fluids or tissues. These metabolites are the byproducts of drug metabolism in the liver and are not affected by activated charcoal in the digestive system.


In summary, while activated charcoal can be effective in preventing the absorption of drugs in the gastrointestinal tract before they enter the bloodstream,
its impact on drugs that have already been absorbed and undergone metabolism is limited. Therefore, oral consumption of charcoal is unlikely to have a significant effect on drug use or drug testing in relation to the enterohepatic cycle.

 

 

 

 

 citing sources -

 David R. Taft, in Pharmacology, 2009

 Timothy A. Bertram, ... Sureshkumar Muthupalani, in Haschek and Rousseaux's Handbook of Toxicologic Pathology (Third Edition), 2013

 Joseph A. Ware, ... Shiew-Mei Huang, in Principles of Clinical Pharmacology (Third Edition), 2012

 https://www.sciencedirect.com/topics/medicine-and-dentistry/enterohepatic-circulation

 https://www.sciencedirect.com/topics/medicine-and-dentistry/enterohepatic-circulation#:~:text=As%20described%20previously%2C%20a%20number,opioids%2C%20digoxin%2C%20and%20warfarin.

 

17. Watson WA. Factors influencing the clinical efficacy of activated charcoal. Drug Intell Clin Pharm. 1987;21:160–166. [PubMed] []
18. Andersen AH. Experimental studies on the pharmacology of activated charcoal; the effect of pH on the adsorption by charcoal from aqueous solutions. Acta Pharmacol Toxicol (Copenh) 1947;3:119–218. [PubMed] []
19. Jürgens G, Hoegberg LC, Graudal NA. The effect of activated charcoal on drug exposure in healthy volunteers: a meta-analysis. Clin Pharmacol Ther. 2009;85:501–505. [PubMed] []
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620762/#:~:text=Activated%20charcoal%20adsorbs%20many%20noxious,8%2C%2015%2C%2016).

No comments:

Post a Comment