Hepatic Blood Flow: Clinical Situations
Summary
TLDRThis script delves into the factors influencing the liver's ability to clear drugs, focusing on hepatic blood flow (Q_subh), which typically averages 1,500 mL/min. It discusses challenges in measuring this flow and how conditions like congestive heart failure, myocardial infarction, and chronic liver disease can decrease it. The script uses lidocaine as an example of a drug with a high extraction ratio, whose hepatic clearance is affected by blood flow. It highlights the lack of precise dosing guidelines for patients with compromised liver function, urging pharmacists to be cautious and consider serum concentration monitoring.
Takeaways
- 🚀 The well-stirred model is used to understand how quickly the liver can clear drugs from the body, with hepatic blood flow (Q subh) being a key factor.
- 🌡️ Hepatic blood flow is typically around 1,500 mL per minute, but it's challenging to measure directly in clinical practice.
- 🔍 Techniques like tracer substances and ultrasound scans are more common in research rather than routine patient care.
- 💔 Conditions such as congestive heart failure, myocardial infarction, and chronic liver disease can reduce hepatic blood flow.
- 💊 Lidocaine, a high extraction ratio drug, is dependent on hepatic blood flow for clearance and is commonly used as a local anesthetic and to control heart rhythms.
- 📜 The package insert for lidocaine provides information on how conditions affecting liver function may alter its kinetics, but does not specify dosage adjustments.
- 🤔 There is no official dosage adjustment recommendation for patients with conditions like congestive heart failure or shock.
- 🔄 Some sources recommend reducing the dose by 25 to 50%, while others emphasize the importance of monitoring serum concentrations.
- 🚨 Pharmacists must be extra careful with drugs that have a high extraction ratio and when patients have conditions that could reduce liver blood flow.
- 🛑 Esophageal varices, a condition caused by reduced liver blood flow, can present with severe symptoms like vomiting blood or black tar stools.
- ⚠️ Drugs with a narrow therapeutic index require careful monitoring to avoid toxicities that may arise from high serum concentrations.
Q & A
What is the well-stirred model in the context of drug clearance by the liver?
-The well-stirred model is a theoretical construct used to describe how the liver clears drugs from the bloodstream. 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 Q sub h represent in the hepatic clearance equation?
-Q sub h represents hepatic blood flow, which is the volume of blood that flows through the liver per minute, typically around 1,500 mL.
Why is it difficult to directly measure hepatic blood flow?
-Direct measurement of hepatic blood flow is challenging because it usually requires invasive techniques or the use of tracer substances, which are more common in research settings than in everyday clinical practice.
What are some disease states that can reduce hepatic blood flow?
-Disease states such as congestive heart failure, massive myocardial infarction, and chronic liver disease can reduce hepatic blood flow by affecting the heart's pumping efficiency or by causing resistance within the liver itself.
How does congestive heart failure affect hepatic blood flow?
-In congestive heart failure, the heart does not pump blood as efficiently, leading to lower blood flow throughout the body, including the liver.
What is the impact of a massive myocardial infarction on hepatic blood flow?
-A massive myocardial infarction can cause a significant drop in cardiac output, resulting in shock and low blood flow to the liver and other organs.
How does chronic liver disease affect hepatic blood flow?
-Chronic liver disease can cause the liver to become fibrotic, which may lead to the shunting of blood away from the liver and reduced blood flow.
What is the significance of esophageal varices in the context of reduced hepatic blood flow?
-Esophageal varices are swollen veins in the lower esophagus that can result from the back-up of blood due to reduced hepatic blood flow. They are prone to bursting, leading to bleeding.
What is the high extraction ratio and why is it important in drug metabolism?
-A high extraction ratio indicates that a drug is rapidly removed from the blood by the liver upon its first pass, making its hepatic clearance highly dependent on hepatic blood flow.
How is lidocaine used in clinical settings, and what does its high extraction ratio imply for its administration?
-Lidocaine is commonly used as a local anesthetic and, in larger doses, to control heart rhythms. Its high extraction ratio implies that its hepatic clearance is highly dependent on hepatic blood flow, so conditions affecting liver function or blood flow could alter its kinetics.
What should a pharmacist consider when adjusting the dose of a drug like lidocaine for patients with reduced hepatic blood flow?
-A pharmacist should consider the lack of a definitive answer for dose adjustment, the importance of monitoring serum concentrations, and the patient's specific disease state that might affect hepatic blood flow.
Why is it challenging to determine the exact dose adjustment for drugs like lidocaine in patients with reduced hepatic blood flow?
-It is challenging because the package insert does not provide specific dosage adjustments and suggests being extra careful, but does not quantify what 'extra careful' entails, leaving the pharmacist to make an educated guess.
Outlines
🩺 Hepatic Blood Flow and Drug Clearance
This paragraph discusses the factors that influence how quickly the liver can clear drugs from the body, focusing on hepatic blood flow represented by Q_subh. It is normally around 1,500 mL per minute, but measuring it directly is challenging and typically involves research techniques. The paragraph highlights conditions that can reduce blood flow, such as congestive heart failure, myocardial infarction leading to shock, and chronic liver disease causing resistance to blood flow. It also explains the implications for drugs like lidocaine, which has a high extraction ratio and is dependent on hepatic blood flow, and the challenges in adjusting dosages for patients with compromised liver function due to the lack of direct measurement methods.
Mindmap
Keywords
💡Well-stirred model
💡Hepatic blood flow (Q subh)
💡Tracer substances
💡Congestive heart failure
💡Myocardial infarction
💡Chronic liver disease
💡Esophageal varices
💡High extraction ratio
💡Lidocaine
💡Narrow therapeutic index
💡Serum concentrations
Highlights
The liver's ability to clear drugs can be modeled using the well-stirred model, with hepatic blood flow (Q subh) being a key factor.
Hepatic blood flow is approximately 1,500 mL per minute under normal conditions.
Direct measurement of hepatic blood flow is challenging and typically involves tracer substances or ultrasound scans.
Pharmacists must anticipate issues based on patient conditions, considering diseases that can affect blood flow.
Congestive heart failure can lead to reduced blood flow, including to the liver, due to inefficient heart pumping.
A massive myocardial infarction can cause shock, resulting in significantly decreased cardiac output and low liver blood flow.
Chronic liver disease may cause reduced blood flow due to liver resistance, often resulting from conditions like viral hepatitis or cirrhosis.
Liver resistance can lead to blood shunting away from the liver and cause pressure in other parts of the body, leading to esophageal varices.
Esophageal varices can present with symptoms such as vomiting blood or black tar stools.
Lidocaine, with a high extraction ratio, is dependent on hepatic blood flow for clearance and is commonly used as a local anesthetic.
In higher doses and intravenous administration, lidocaine is used to control heart rhythms.
When hepatic blood flow is suspected to be low, the package insert for lidocaine provides guidance on altered kinetics but not specific dosage adjustments.
There is no official dosage adjustment recommendation for patients with conditions affecting liver function.
Some sources recommend decreasing the dose of drugs like lidocaine by 25 to 50% in cases of reduced hepatic blood flow.
Checking serum concentrations is suggested as a method to manage drug dosage in the absence of direct hepatic blood flow measurement.
The lack of a definitive answer for dosage adjustment can be frustrating for pharmacy students.
Extra caution is advised when the drug has a high extraction ratio, the patient has a disease affecting liver blood flow, or the drug has a narrow therapeutic index with potential toxicities.
Transcripts
let's look into more factors that affect
how quickly the liver can clear drug
from the body using the well stirred
model this time we're going to explore
hepatic blood flow in the equation it's
represented by Q subh normally about
1,500 mL of blood flows through the
liver every minute unfortunately there
really isn't an easy way to directly
measure hepatic blood flow there are
techniques involving Tracer substances
injected into the blood or ultrasound
scans but they used more for research
than for day-to-day practice so the
pharmacist is usually left trying to
anticipate possible problems based on
the patient's condition there are
various disease states that can reduce
blood flow we have to consider them when
deciding on doses for our patients in
what situations would hepatic blood flow
decrease
incase one common situation is
congestive heart failure in heart
failure the heart is not pumping as
efficiently less blood is being pushed
out of the left ventricle with each beat
this leads to lower blood flow
throughout much of the body including
the liver a patient who suffers a
massive myocardial infarction may have a
significant drop in cardiac output the
heart might be damaged enough that it
can't pump enough blood to peruse the
patient's organs this is called Shock
and the liver suffers low blood flow
along with the rest of the body chronic
liver disease can cause reduced blood
flow now this time it's not because the
heart isn't pumping the blood enough
it's that the liver is resisting the
flow of blood into the organ viral
hepatitis or chronic alcoholism can
cause cause curosis of the liver the
liver tissue becomes fibrotic and may
actually shunt the blood that's coming
towards it away from the liver sometimes
this resistance causes blood to back up
so much that it gets forced into smaller
veins in other parts of the body that
aren't accustomed to so much pressure
these veins sometimes swell and burst
leading to bleeding ing the veins in the
lower esophagus are particularly
affected by this process leading to a
condition called esophagal varices the
patient with esophageal varices may
present vomiting blood or with black tar
stools lidocaine has a high extraction
ratio which means that the hepatic
clearance is highly dependent on how
quickly the blood can get the drug into
the liver most of you are familiar with
lidocaine as a local anesthetic if
you've ever had a dentist numb your gum
lidocaine is most likely what they used
in much larger doses however and given
intravenously we use lidocaine to
control heart rhythms what do we do when
we suspect our patient on lidocaine has
low hepatic blood flow if we look at the
package insert for lidocaine injection
it tells us that because of the rapid
rate at which lidocaine is metabolized
any condition that alters liver function
including changes in liver blood flow
which could result from a congestive
heart failure or shock May alter Li
Deane kinetics that's nice to know but
the package insert doesn't tell us how
much to change the dose in patients with
CHF or shock do we change it a little a
lot the problem is that there really
isn't an official answer some sources
might recommend that you decrease the
dose 25 to 50% others might stress the
importance of checking serum
concentrations and since we don't have a
really good way of directly measuring
hepatic blood flow we'd be guessing
anyway this often frustrates Pharmacy
students because it seems like there
should be a correct answer but many
sources like the package insert just
suggest something along the lines of be
extra careful so when should we be extra
careful if the drug has a high
extraction ratio and thus the liver a
high intrinsic
clearance if the patient has some
disease state that would reduce the
amount of blood flowing through the
liver if it's a drug with a narrow
theraputic index and significant
toxicities that might occur if the serum
concentrations get too high
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