Intrinsic Clearance - Biliary excretion
Summary
TLDRThis script explores the liver's role in drug clearance through intrinsic clearance (CLi), which includes metabolism and biliary excretion. It highlights doxorubicin as a drug partially excreted in bile, and discusses cholestasis, a condition that impedes bile flow, potentially leading to drug accumulation. The script also covers enterohepatic circulation, where drugs like morphine and digoxin are reabsorbed after initial excretion. A strategy to mitigate adverse effects involves using cholestyramine to trap drugs in the intestine, preventing reabsorption and promoting elimination.
Takeaways
- 🧪 The liver's ability to clear drugs from the body is influenced by intrinsic clearance (CLi), which includes metabolism and biliary excretion.
- 💊 Doxorubicin, a cancer drug, is partially excreted in the bile unchanged and some of its metabolites are also active.
- 🔁 Cholestasis is a condition where bile flow from the liver to the duodenum is obstructed, potentially by gallstones, cancer, or certain drugs.
- 🚨 Elevated serum bilirubin concentration is a warning sign of impaired bile flow and may require dosage adjustment for drugs like doxorubicin.
- 🌡 Normal total bilirubin levels in adults are less than 1.2 milligrams per deciliter, and deviations may indicate the need for reduced medication dosages.
- 🔄 Enterohepatic circulation is the process where drugs excreted into the bile are reabsorbed into the bloodstream as they travel through the intestine.
- 💊 Morphine and digoxin are examples of drugs that may undergo enterohepatic circulation.
- 🛑 Cholestyramine can be used to mitigate adverse effects from drugs that undergo enterohepatic circulation by trapping them in the gut, preventing reabsorption.
- 🌀 Cholestyramine works by binding to bile acids and any trapped drugs, facilitating their passage out of the body in feces instead of reabsorption.
- 📚 The prescribing information for drugs like doxorubicin includes guidance on monitoring serum bilirubin levels to adjust dosages in cases of cholestasis.
- 🔍 Monitoring and understanding the liver's clearance mechanisms, such as intrinsic clearance and enterohepatic circulation, are crucial for safe and effective drug administration.
Q & A
What is the well-stirred model in the context of liver drug clearance?
-The well-stirred model is a theoretical construct used to describe how the liver clears drugs from the body. It assumes that the liver and blood are well-mixed, allowing for a uniform concentration of the drug in the liver and blood.
What does CL sub i represent in the context of the liver's drug clearance?
-CL sub i, or intrinsic clearance, represents the liver's ability to remove a drug through metabolism and biliary excretion, reflecting the efficiency of the liver in eliminating the drug.
How does the liver excrete waste products related to drug metabolism?
-The liver excretes waste products in the bile, which then travels through the bile duct and is dumped into the duodenum as part of the digestive process.
What is an example of a drug that is partially excreted in the bile unchanged?
-Doxorubicin, a drug used to treat some cancers, is an example of a drug that is partially excreted in the bile unchanged, with about 40% of it coming back out in the bile.
What is cholestasis and how can it affect drug clearance?
-Cholestasis is a condition where bile is not properly moved from the liver to the duodenum, which can be caused by various factors such as gallstones, cancer, or certain drugs. This can lead to a buildup of drugs like doxorubicin in the body, affecting their clearance.
Why is it important to monitor a patient's serum bilirubin concentration when they are on doxorubicin?
-Monitoring serum bilirubin concentration is important because elevated levels can indicate that substances are not moving efficiently from the liver to the duodenum, which may be a sign of cholestasis affecting drug clearance.
What is the normal total bilirubin concentration range for adults?
-The normal total bilirubin concentration for adults is less than 1.2 milligrams per deciliter (mg/dL).
How might a clinician adjust the doxorubicin dose if a patient has elevated serum bilirubin levels?
-If a patient has elevated serum bilirubin levels, indicating potential cholestasis, the clinician might reduce the doxorubicin dose to half or even a quarter of the normal dosage to compensate for the reduced clearance.
What is enterohepatic circulation and which drugs are known to undergo this process?
-Enterohepatic circulation is a process where a drug excreted into the bile is reabsorbed as it travels down the intestine, effectively circulating between the liver and the intestine. Drugs such as morphine and digoxin are known to undergo enterohepatic circulation.
How can cholestyramine be used to help remove a drug from a patient's body experiencing adverse effects?
-Cholestyramine can be given orally to bind to the drug being excreted in the bile, preventing its reabsorption and allowing it to pass out of the body through the feces, thus aiding in the removal of the drug from the patient's system.
What is the role of cholestyramine in the context of enterohepatic circulation?
-Cholestyramine, when administered orally, is not absorbed by the gut but can bind to drugs in the bile as it re-enters the duodenum. This binding prevents the drug from being reabsorbed into the bloodstream, facilitating its elimination through feces.
Outlines
💊 Liver Clearance and Drug Metabolism
This paragraph discusses the liver's role in drug clearance using the well-stirred model, focusing on intrinsic clearance (CLi). It explains how the liver metabolizes and excretes drugs through biliary pathways, with examples like doxorubicin, a chemotherapy drug partially excreted in bile. The paragraph also touches on cholestasis, a condition hindering bile flow, which can affect drug accumulation in the body. Monitoring serum bilirubin levels is crucial for assessing liver function and adjusting drug dosages accordingly. The concept of enterohepatic circulation, where drugs are reabsorbed after initial excretion, is introduced with drugs like morphine and digoxin as examples. The use of cholestyramine to enhance drug elimination by preventing reabsorption during enterohepatic circulation is also mentioned.
Mindmap
Keywords
💡Intrinsic Clearance (CL sub i)
💡Well-stirred Model
💡Biliary Excretion
💡Doxorubicin
💡Cholestasis
💡Bilirubin
💡Enterohepatic Circulation
💡Morphine
💡Digoxin
💡Cholestyramine
💡Olsalazine
Highlights
Intrinsic clearance (CLi) reflects the liver's ability to remove drugs through metabolism and biliary excretion.
The liver excretes waste products in the bile, which travels through the bile duct and is dumped into the duodenum.
Some drugs, like doxorubicin, are partially excreted in the bile unchanged.
Doxorubicin metabolites can also be active, and about 40% of the drug comes back out in the bile unchanged.
Cholestasis is a condition where bile is not moved from the liver to the duodenum, potentially caused by gallstones, cancer, or certain drugs.
Doxorubicin can build up in the body if bile movement is impaired, necessitating monitoring of serum bilirubin concentration.
Elevated serum bilirubin concentration indicates impaired movement of substances from the liver to the duodenum.
Normal total bilirubin concentrations in adults are less than 1.2 milligrams per deciliter.
If a patient's total bilirubin is higher than normal, the doxorubicin dose may need to be reduced.
Enterohepatic circulation is the process where drugs reabsorbed in the intestine end up in the blood for a second time.
Drugs like morphine and digoxin are thought to undergo enterohepatic circulation.
Cholestyramine can be used to trap drugs in the bile, preventing reabsorption and aiding in drug elimination.
Cholestyramine is not absorbed from the gut and helps to bind and remove drugs from the body.
Leflunomide, used for rheumatoid arthritis, is an example of a drug that undergoes enterohepatic circulation.
Clinicians may administer cholestyramine to patients experiencing adverse effects from drugs to facilitate quicker elimination.
The trapped drug with cholestyramine passes out unabsorbed into the feces, aiding in drug clearance.
Transcripts
let's look at the more factors that
affect how quickly the liver can clear
drugs from the body using the
well-stirred model this time we're going
to look at intrinsic clearance and the
well-stirred equation intrinsic
clearance is represented by CL sub i
intrinsic clearance reflects how well
the liver removes the drug by metabolism
and by biliary excretion the liver
excretes waste products in the bile
which then travels through the bile duct
and is dumped into the duodenum there
are a few drugs that we know get at
least partially excreted in the bile
unchanged one such drug is doxorubicin
which is a drug used to treat some
cancers notice the doxorubicin given to
a patient gets metabolized with some of
the metabolites also being active about
40% of the doxorubicin comes back out in
the bile unchanged cholestasis is a
condition where bile is not being moved
from the liver to the duodenum might be
caused by a gallstone blocking the duct
cancer and even some drugs like birth
control pills
bactrim or erythromycin might cause
cholestasis when bile isn't moving
doxorubicin can build up in the body to
compensate for this possibility the
prescribing information for doxorubicin
tells us to watch the patient's serum
bilirubin concentration bilirubin is
also extreme
accumulates in the blood during
cholestasis if the patient has an
elevated serum bilirubin concentration
that should warn the clinician that
substances aren't moving from the liver
to the duodenum normal total bilirubin
concentrations and adults are less than
1.2 milligrams for death
later if a patient's total bilirubin is
higher than that we might need to cut
the doxorubicin dose in half or even to
a quarter of what we might normally give
what makes things even more interesting
is sometimes that drug that gets passed
by the liver into the duodenum via the
bile duct is not at the end of its
journey sometimes that drug gets
reabsorbed as it travels down the
intestine and ends up in the blood of
second time this is known as
enterohepatic circulation some common
drugs such as morphine and digoxin are
thought to undergo some a neuropathic
circulation an interesting trick with an
aromatic circulation to be done with
less solute Imai which is a drug used
for rheumatoid arthritis the flu demise
undergoes enterohepatic circulation if a
patient is having adverse effects from a
drug and the clinician wants to try to
get it out of the patient as quickly as
possible they sometimes give the patient
outlets tyramine
by mouth cholestyramine isn't absorbed
from the gut but as it passes through
the LeFleur demise that's being excreted
in bile back into the duodenum gets
trapped onto the cold starving
then as the trapped drug passes down the
intestine instead of getting reabsorbed
like it might normally do it passes out
on absorbed into the feces
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