Only One Exit?

We’ve all made it! Through the fireworks and the gunshots fired in glee (I do live in Arizona, right near an arroyo). Welcome to the first SlowItDownCKD blog of 2020. Our world is crazy, dangerous, lovely, and delicious at this time. As Charles Dickens wrote in A Tale of Two Cities:

 “It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of light, it was the season of darkness, it was the spring of hope, it was the winter of despair,” but these are the times we live in… and the times when science seems to be changing quickly.

Case in point, I’d always thought some drugs exited the body via the kidneys, others via the liver. Apparently, that isn’t so. According to the National Kidney Foundation at https://www.kidney.org/atoz/content/drugs-your-kidneys:

“Every drug you put into your body passes through your kidneys. If the drug is not taken following your healthcare provider’s instructions, or if it is an illegal substance, it can cause injury to the kidneys.”

Yet, other sources have a different take on this. Wait a minute. The National Kidney Foundation is saying the drugs you take pass through your kidneys, not exit via your kidneys. Well then, how else do drugs – both illicit and prescribed – exit your body?

The Merck Manuals Consumer Version at https://www.merckmanuals.com/home/drugs/administration-and-kinetics-of-drugs/drug-eliminationtell us:

“Drug elimination in the bile

Some drugs pass through the liver unchanged and are excreted in the bile. Other drugs are converted to metabolites in the liver before they are excreted in the bile. In both scenarios, the bile then enters the digestive tract. From there, drugs are either eliminated in feces or reabsorbed into the bloodstream and thus recycled.

If the liver is not functioning normally, the dosage of a drug that is eliminated primarily by metabolism in the liver may need to be adjusted. However, there are no simple ways to estimate how well the liver will metabolize (and thus eliminate) drugs like there are for kidney function.

Other forms of drug elimination

Some drugs are excreted in saliva, sweat, breast milk, and even exhaled air. Most are excreted in small amounts. The excretion of drugs in breast milk is significant only because the drug may affect the breastfeeding infant (see Drugs That Should Not Be Taken While Breastfeeding). Excretion in exhaled air is the main way that inhaled anesthetics are eliminated.”

Here’s a bit more about the Merck Manuals for those new to them.

“The first Merck Manual was published in 1899 by Merck & Co. as a pocket-sized reference aid for doctors and pharmacists. The intended audience expanded in 1997, when the Merck Manual of Medical Information: Home Edition was added to the growing body of medical reference resources. In 2014, Merck published Merck Manuals (North America) and MSD Manuals (as it is known outside of North America) exclusively online to advance their ‘Global Medical Knowledge 2020’ initiative to provide access to current, credible medical information to ‘up to three billion professionals and patients on every continent by 2020’ …. The Merck Veterinary Manual is a separate publication that is not reviewed here.

With the relaunch, the publishers decided to offer the content of Merck Manuals completely free of charge and to translate the online offerings into ten languages. Merck Manuals is available in English and Spanish. According to publisher Melissa Adams, by the end of 2016, this list will also include Chinese, Korean, French, German, Italian, Portuguese, Russian, and Japanese …. Other developments in process for Merck Manuals at the time of writing include a widget that can be used on any website to connect users directly to either the consumer or professional version of the site and a free app for iOS and Android that will provide access to the entire resource.”

This sounds like something both you and I should explore.

Wasn’t there something about drugs exiting the body via the bile? I need more on that, especially since I no longer have a gall bladder to store the bile (Thanks for that, pancreatic cancer.)

I dug all the way back to find Daniel Kapusta’s article in xPharm: The Comprehensive Pharmacology Reference, 2007 on ScienceDirect at https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/drug-excretion,

“Drugs entering the hepatic circulation may also enter the bile and be excreted into the duodenum and small intestines. Depending on the chemical properties of the drug, it may then be re-absorbed from the small intestine and recirculate throughout the body (enterohepatic recycling). Those drugs that are not re-absorbed will pass through the large intestines and be excreted in the feces.”

You may need a little help here, just as I did. Hepatic means of the liver and the duodenum is “the first short section of the small intestine immediately beyond the stomach,” as the Encarta Dictionary tells us. That made it easier for me to understand. Hopefully, it helped you, too.

Stan K. Bardal BSc (Pharm), MBA, PhD, … Douglas S. Martin PhD, in Applied Pharmacology, 2011 further explained at https://www.sciencedirect.com/book/9781437703108/applied-pharmacology,

Pulmonary excretion is important for gaseous lipophilic [Gail here: Encarta Dictionary defines lipids as ‘a biological compound that is not soluble in water, e.g. a fat. The group also includes waxes, oils, sterols, triglycerides, phosphatides, and phospholipids.’] The gaseous general anesthetics are the most common example. Drug diffuses from the plasma into the alveolar [Me again – and back to Encarta: relating to air sac in lung] and is excreted during expiration.

 

Excretion via Breast Milk

Breast milk is a quantitatively relatively minor route of drug excretion. Nevertheless, it is clinically important for breastfeeding mothers and their infants. The baby will ingest drugs excreted in the breast milk. Moreover, breast milk has a lower pH than plasma. Accordingly, basic drugs will be concentrated in the breast milk through the phenomenon of ion (pH) trapping. A number of drugs can reach clinically significant concentrations in the breast milk and thereby affect nursing babies.”

So there’s nothing written in stone, is there? While the kidneys are the primary exit for drugs, there are other ways drugs exit the body.

Until next week,

Keep living your life!

Published in: on January 6, 2020 at 7:59 pm  Leave a Comment  

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