Hepatic Blood Flow: Clinical Situations

Summary

This 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

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🩺 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.

Keywords

💡Well-stirred model

The well-stirred model is a theoretical construct used to describe how quickly the liver can clear drugs from the body. It assumes that the liver and blood are well mixed, allowing for a uniform concentration of drug throughout the liver. This model is central to the video's theme, as it provides a framework for discussing how various factors can affect drug clearance rates.

💡Hepatic blood flow (Q subh)

Hepatic blood flow, denoted as Q subh in the script, refers to the volume of blood that flows through the liver per minute, typically around 1,500 mL. It is a key determinant of drug clearance as it influences how quickly the liver can metabolize substances. The script emphasizes the importance of hepatic blood flow in the context of drug metabolism and its variability in different health conditions.

💡Tracer substances

Tracer substances are used in medical research to measure blood flow indirectly. They are injected into the bloodstream and their movement is tracked to infer blood flow rates. In the video, tracer substances are mentioned as a method to measure hepatic blood flow, highlighting the challenges in directly assessing this parameter in clinical practice.

💡Congestive heart failure

Congestive heart failure is a condition where the heart is not pumping blood efficiently, leading to reduced blood flow throughout the body, including the liver. The script uses congestive heart failure as an example of a disease state that can decrease hepatic blood flow, which in turn affects drug clearance rates.

💡Myocardial infarction

A myocardial infarction, commonly known as a heart attack, is a situation where the heart muscle is damaged due to blocked blood flow. The script mentions that a massive myocardial infarction can lead to shock, characterized by a significant drop in cardiac output and consequently low hepatic blood flow.

💡Chronic liver disease

Chronic liver disease, such as viral hepatitis or cirrhosis due to chronic alcoholism, can lead to reduced hepatic blood flow. The script explains that the liver tissue may become fibrotic, resisting blood flow and potentially causing blood to be shunted away from the liver, affecting drug clearance.

💡Esophageal varices

Esophageal varices are swollen veins in the lower esophagus that can result from chronic liver disease and portal hypertension. The script describes how reduced hepatic blood flow due to liver resistance can lead to the formation of esophageal varices, which can cause severe bleeding.

💡High extraction ratio

A high extraction ratio indicates that a drug is rapidly removed from the blood by the liver, making its clearance highly dependent on hepatic blood flow. Lidocaine, mentioned in the script, has a high extraction ratio, and its hepatic clearance is directly related to blood flow rates.

💡Lidocaine

Lidocaine is a medication commonly used as a local anesthetic in dentistry and in larger doses, intravenously, to control heart rhythms. The script discusses how the hepatic clearance of lidocaine is highly dependent on blood flow, emphasizing the need for careful dosing considerations in patients with compromised hepatic blood flow.

💡Narrow therapeutic index

A drug with a narrow therapeutic index has a small margin between its effective dose and the dose that can cause toxicity. The script points out that when a drug has a high extraction ratio and a narrow therapeutic index, it is especially important to be cautious with dosing to avoid potential toxicities due to reduced hepatic blood flow.

💡Serum concentrations

Serum concentrations refer to the levels of a drug or substance in the blood. The script suggests that monitoring serum concentrations can be a way to adjust dosing for drugs like lidocaine in patients with conditions that may affect hepatic blood flow, despite the lack of direct measurement methods for blood flow.

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