Podcast
Questions and Answers
What is the primary pathway for drug elimination from the body?
What is the primary pathway for drug elimination from the body?
Which of the following statements accurately describes the concept of drug clearance?
Which of the following statements accurately describes the concept of drug clearance?
How does an increase in clearance affect the half-life of a drug?
How does an increase in clearance affect the half-life of a drug?
The elimination rate constant (Ke) of a drug is calculated using which of the following formulas?
The elimination rate constant (Ke) of a drug is calculated using which of the following formulas?
Signup and view all the answers
What effect does a smaller clearance have on steady-state plasma levels of a drug?
What effect does a smaller clearance have on steady-state plasma levels of a drug?
Signup and view all the answers
Which of the following pairs of parameters are independent of each other?
Which of the following pairs of parameters are independent of each other?
Signup and view all the answers
The sum of all clearance processes in the body is referred to as what?
The sum of all clearance processes in the body is referred to as what?
Signup and view all the answers
Which of the following factors does NOT influence the rate of drug elimination?
Which of the following factors does NOT influence the rate of drug elimination?
Signup and view all the answers
What determines the terminal half-life of a metabolite compared to its parent drug?
What determines the terminal half-life of a metabolite compared to its parent drug?
Signup and view all the answers
Which statement is correct regarding the clearance and elimination of a drug?
Which statement is correct regarding the clearance and elimination of a drug?
Signup and view all the answers
What happens to the rate of extraction if the incoming concentration (C in) of a drug doubles?
What happens to the rate of extraction if the incoming concentration (C in) of a drug doubles?
Signup and view all the answers
Which factor is NOT a determinant of hepatic clearance?
Which factor is NOT a determinant of hepatic clearance?
Signup and view all the answers
How does intrinsic clearance relate to enzymatic metabolism?
How does intrinsic clearance relate to enzymatic metabolism?
Signup and view all the answers
What characterizes high extraction drugs?
What characterizes high extraction drugs?
Signup and view all the answers
Which of the following best describes the relationship between clearance and drug concentration?
Which of the following best describes the relationship between clearance and drug concentration?
Signup and view all the answers
How is the extraction ratio (E) calculated?
How is the extraction ratio (E) calculated?
Signup and view all the answers
What happens to the metabolism rate if enzyme systems are saturated?
What happens to the metabolism rate if enzyme systems are saturated?
Signup and view all the answers
In the context of hepatic clearance, what does Q represent?
In the context of hepatic clearance, what does Q represent?
Signup and view all the answers
Which statement about low extraction drugs is true?
Which statement about low extraction drugs is true?
Signup and view all the answers
How does hepatic clearance primarily function for high extraction drugs?
How does hepatic clearance primarily function for high extraction drugs?
Signup and view all the answers
What is the effect of plasma protein binding on hepatic clearance?
What is the effect of plasma protein binding on hepatic clearance?
Signup and view all the answers
What is intrinsic clearance a measure of?
What is intrinsic clearance a measure of?
Signup and view all the answers
What is the primary purpose of Phase I drug metabolism?
What is the primary purpose of Phase I drug metabolism?
Signup and view all the answers
Which enzyme system is primarily responsible for oxidation reactions in drug metabolism?
Which enzyme system is primarily responsible for oxidation reactions in drug metabolism?
Signup and view all the answers
Which of the following statements about Phase II reactions is true?
Which of the following statements about Phase II reactions is true?
Signup and view all the answers
How can liver disease affect drug metabolism?
How can liver disease affect drug metabolism?
Signup and view all the answers
What is the effect of enzyme induction on drug clearance?
What is the effect of enzyme induction on drug clearance?
Signup and view all the answers
Which scenario indicates a metabolite with a longer half-life than its parent drug?
Which scenario indicates a metabolite with a longer half-life than its parent drug?
Signup and view all the answers
Which of the following is an example of enzyme inhibition in drug interactions?
Which of the following is an example of enzyme inhibition in drug interactions?
Signup and view all the answers
What is a common characteristic of drug metabolism in newborns compared to adults?
What is a common characteristic of drug metabolism in newborns compared to adults?
Signup and view all the answers
Which drug is associated with competitive inhibition leading to increased blood concentrations?
Which drug is associated with competitive inhibition leading to increased blood concentrations?
Signup and view all the answers
What measures the variability in drug metabolism across different populations?
What measures the variability in drug metabolism across different populations?
Signup and view all the answers
Which of the following statements regarding enzyme induction is false?
Which of the following statements regarding enzyme induction is false?
Signup and view all the answers
Which condition may lead to changes in drug clearance due to genetic factors?
Which condition may lead to changes in drug clearance due to genetic factors?
Signup and view all the answers
How is hepatic clearance primarily determined?
How is hepatic clearance primarily determined?
Signup and view all the answers
What is the effect of a larger clearance on the area under the curve (AUC)?
What is the effect of a larger clearance on the area under the curve (AUC)?
Signup and view all the answers
Which statement about clearance and volume of distribution is true?
Which statement about clearance and volume of distribution is true?
Signup and view all the answers
What does a higher extraction ratio (E) indicate about a drug?
What does a higher extraction ratio (E) indicate about a drug?
Signup and view all the answers
Which factor affects portal blood flow in the liver?
Which factor affects portal blood flow in the liver?
Signup and view all the answers
What happens to drugs in the bloodstream that are bound to proteins?
What happens to drugs in the bloodstream that are bound to proteins?
Signup and view all the answers
How is oral bioavailability primarily determined?
How is oral bioavailability primarily determined?
Signup and view all the answers
What unit is used to express drug clearance?
What unit is used to express drug clearance?
Signup and view all the answers
What does a larger volume of distribution result in regarding drug concentration?
What does a larger volume of distribution result in regarding drug concentration?
Signup and view all the answers
What role does the liver play after a drug is taken orally?
What role does the liver play after a drug is taken orally?
Signup and view all the answers
What does the hepatic central vein do?
What does the hepatic central vein do?
Signup and view all the answers
Which of the following is true about drugs with a hepatic extraction ratio of one?
Which of the following is true about drugs with a hepatic extraction ratio of one?
Signup and view all the answers
What is primarily involved in hepatic metabolism?
What is primarily involved in hepatic metabolism?
Signup and view all the answers
How does the rate of blood flow through the liver in a healthy adult compare to the volume of distribution?
How does the rate of blood flow through the liver in a healthy adult compare to the volume of distribution?
Signup and view all the answers
Which statement accurately describes oral bioavailability for low extraction drugs?
Which statement accurately describes oral bioavailability for low extraction drugs?
Signup and view all the answers
What impact does increased intrinsic clearance have on oral bioavailability for high extraction drugs?
What impact does increased intrinsic clearance have on oral bioavailability for high extraction drugs?
Signup and view all the answers
Which of the following drugs is exemplified as a low extraction drug in the content?
Which of the following drugs is exemplified as a low extraction drug in the content?
Signup and view all the answers
What is the primary determinant of oral bioavailability in the context of high extraction drugs?
What is the primary determinant of oral bioavailability in the context of high extraction drugs?
Signup and view all the answers
What happens to oral bioavailability if liver blood flow is reduced for low extraction drugs?
What happens to oral bioavailability if liver blood flow is reduced for low extraction drugs?
Signup and view all the answers
Which factor does NOT significantly affect the clearance of high extraction drugs?
Which factor does NOT significantly affect the clearance of high extraction drugs?
Signup and view all the answers
For high extraction drugs, which formula correctly represents oral bioavailability?
For high extraction drugs, which formula correctly represents oral bioavailability?
Signup and view all the answers
In the context of biliary excretion, which type of compounds are primarily eliminated?
In the context of biliary excretion, which type of compounds are primarily eliminated?
Signup and view all the answers
What can result from a 50% reduction in Theophylline's intrinsic clearance due to the addition of Cimetidine?
What can result from a 50% reduction in Theophylline's intrinsic clearance due to the addition of Cimetidine?
Signup and view all the answers
What is the extraction ratio (E) inversely related to in the context of oral bioavailability?
What is the extraction ratio (E) inversely related to in the context of oral bioavailability?
Signup and view all the answers
Which process describes the phenomenon where drugs are reabsorbed from the intestine after being secreted into the bile?
Which process describes the phenomenon where drugs are reabsorbed from the intestine after being secreted into the bile?
Signup and view all the answers
In which scenario would increased liver blood flow likely result in a clinically significant change?
In which scenario would increased liver blood flow likely result in a clinically significant change?
Signup and view all the answers
What would happen to the area under the curve (AUC) if hepatic clearance increases?
What would happen to the area under the curve (AUC) if hepatic clearance increases?
Signup and view all the answers
What is the relationship between liver blood flow and oral bioavailability for high extraction drugs?
What is the relationship between liver blood flow and oral bioavailability for high extraction drugs?
Signup and view all the answers
What primarily determines the hepatic clearance of low extraction drugs?
What primarily determines the hepatic clearance of low extraction drugs?
Signup and view all the answers
Which statement about liver blood flow and low extraction drugs is true?
Which statement about liver blood flow and low extraction drugs is true?
Signup and view all the answers
If the fraction unbound (fu) increases for a low extraction drug, what is the expected outcome?
If the fraction unbound (fu) increases for a low extraction drug, what is the expected outcome?
Signup and view all the answers
What is the relationship between intrinsic clearance and hepatic clearance for low extraction drugs?
What is the relationship between intrinsic clearance and hepatic clearance for low extraction drugs?
Signup and view all the answers
In the analogy of fishing, who represents the low extraction drug?
In the analogy of fishing, who represents the low extraction drug?
Signup and view all the answers
What happens to hepatic clearance if there is a decrease in metabolic liver enzymes?
What happens to hepatic clearance if there is a decrease in metabolic liver enzymes?
Signup and view all the answers
What does a low extraction drug's extraction ratio represent?
What does a low extraction drug's extraction ratio represent?
Signup and view all the answers
How does binding to blood cells affect low extraction drugs?
How does binding to blood cells affect low extraction drugs?
Signup and view all the answers
What is the effect of increasing the volume of fat cells in terms of drug distribution?
What is the effect of increasing the volume of fat cells in terms of drug distribution?
Signup and view all the answers
During the first-pass effect, what happens to the drug entering the liver?
During the first-pass effect, what happens to the drug entering the liver?
Signup and view all the answers
Which statement correctly describes the extraction ratio for high extraction drugs?
Which statement correctly describes the extraction ratio for high extraction drugs?
Signup and view all the answers
What is the primary factor affecting the clearance in high extraction drugs?
What is the primary factor affecting the clearance in high extraction drugs?
Signup and view all the answers
How does doubling the number of enzymes affect clearance for low extraction drugs?
How does doubling the number of enzymes affect clearance for low extraction drugs?
Signup and view all the answers
What effect does increasing plasma protein binding have on a lipophilic, low extraction drug's clearance?
What effect does increasing plasma protein binding have on a lipophilic, low extraction drug's clearance?
Signup and view all the answers
Study Notes
Drug Clearance Overview
- Clearance is a measure of the body's ability to remove a drug from plasma, a crucial pharmacokinetic parameter.
- It's independent of mathematical models and is determined by volume of distribution and elimination rate.
- Clearance influences steady-state levels; lower clearance leads to higher levels.
Elimination Pathways
- Major pathways: hepatic metabolism, renal excretion, and biliary excretion.
- Minor pathways include exhalation and skin elimination.
- Hepatic metabolism is the primary metabolic organ.
Clearance Calculation
- Clearance (CL) is the volume of body fluid cleared of a drug per unit time.
- Total body clearance is the sum of all clearance processes.
Clearance and Volume of Distribution
- Clearance and volume of distribution (Vd) are independent parameters; changes in one don't affect the other.
- They determine drug half-life (Ke = CL/Vd) and the elimination rate constant.
- Increased clearance results in a shorter half-life.
Clearance and AUC
- Clearance can be calculated from dose and area under the curve (AUC).
- AUC is affected by clearance, not volume of distribution.
- CL = Dose / AUC.
Hepatic Clearance
-
Hepatic clearance is determined by liver blood flow (Q) and extraction ratio (E).
-
E is the fraction of drug metabolized by the liver.
-
CLhepatic = Q * E
- High extraction drugs: clearance approximates liver blood flow (Q), largely independent of intrinsic clearance or unbound fraction.
- Low extraction drugs: clearance approximates intrinsic clearance (CLint) * free fraction (fu), independent of liver blood flow
Intrinsic Clearance
- Intrinsic clearance (CLint) represents the rate a drug is metabolized by enzymes, independent of blood flow and unbound fraction.
- It is determined by Michaelis-Menten constants (Vmax and Km).
High vs. Low Extraction Drugs
- High extraction: CLhepatic ≈ Q; liver blood flow is the major determinant. Enzymes are highly effective.
- Low extraction: CLhepatic ≈ CLint * fu; intrinsic clearance and unbound fraction are important determinants. Enzymes are less effective.
Oral bioavailability (F)
- F is influenced by the first-pass effect—drug metabolism occurring before systemic circulation.
- For high extraction drugs, F is small and heavily affected by both hepatic blood flow and intrinsic clearance.
- For low extraction drugs, F is close to one.
Biliary Excretion
- Some drugs are actively transported into bile for elimination.
- Enterohepatic circulation can cause double peaks in drug concentrations.
- Biliary excretion is driven by transporters and important for polar compounds.
Drug-Drug Interactions
- Enzyme induction or inhibition can alter clearance, impacting drug concentrations.
- Careful consideration is necessary for narrow-therapeutic index drugs.
Key Concepts
- Clearance and Vd are independent parameters, affecting drug concentrations and half-life.
- Clearance is crucial in determining steady-state plasma levels.
- Hepatic clearance is significant, dependent on intrinsic clearance, blood flow, and extraction ratio.
- Oral bioavailability is affected by hepatic metabolism via the first-pass effect. High extraction drugs have low bioavailability. Low extraction drugs have close to 100% bioavailability.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Explore the important pharmacokinetic concept of drug clearance, detailing its measurement and influence on drug elimination. This quiz covers various elimination pathways and calculations relating to clearance and volume of distribution.