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What primarily contributes to the reversible tissue binding of drugs?
What is the primary organ responsible for drug metabolism?
How does high plasma protein binding affect a drug's volume of distribution?
What does the volume of distribution (Vd) relate to in pharmacokinetics?
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Which of the following statements about volume of distribution (Vd) is correct?
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What major role do the kidneys play in drug elimination?
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The concentration of quinacrine in the liver compared to that in the blood can be described as:
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What distinguishes the two-compartment model from the one compartment model in drug pharmacokinetics?
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In the context of pharmacokinetics, what do the central compartment and peripheral compartment represent?
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What does drug clearance (CL) generally refer to in pharmacokinetics?
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What role does tissue binding play in pharmacokinetics?
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Which of the following organs is typically associated with the central compartment in the two-compartment model?
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Which factor is considered when determining the AUC (Area Under the Curve) in a concentration-time profile?
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Why might a two-compartment model be preferred over a one compartment model for certain drugs?
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Which tissues are grouped together into the peripheral compartment in the two-compartment model?
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What is one limitation of using the one-compartment model in pharmacokinetics?
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In pharmacokinetics, what does the term 'concentration' refer to in the concentration-time profile?
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Which aspect of drug pharmacokinetics is primarily illustrated by the AUC in the concentration-time graph?
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What is a primary characteristic of the two-compartment model?
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Which factor does NOT affect the distribution of a drug?
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What form of a drug is able to permeate biological membranes?
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To which plasma protein do acidic drugs, such as salicylates, primarily bind?
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What characteristic of protein binding makes it significant in pharmacokinetics?
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How does tissue binding impact drug concentration in tissues?
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In a multi-compartment model, how does it differ from the two-compartment model?
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What happens to the percent bound of most drugs when they are within their therapeutic plasma concentration range?
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What role does permeability of tissue membranes play in drug distribution?
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Which statement about protein binding is true concerning its impact on drug distribution?
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What is the significance of half-life (t1/2) in pharmacokinetics?
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Steady State Concentration (Css) is approximately achieved after how many half-lives?
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The elimination constant (KE) is most closely related to which pharmacokinetic property?
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What is the volume of distribution (Vd) for digoxin?
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Which of the following statements about half-life is NOT true?
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Which factor does NOT affect drug clearance?
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Which of the following factors is NOT influencing the time course of a drug in the body?
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What does a drug's clearance (CL) measure?
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Which drug is classified as a high-extraction drug due to its rapid clearance?
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What does a high volume of distribution indicate about a drug?
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What is the significance of half-life (t1/2) in pharmacokinetics?
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Which condition is associated with capacity-limited elimination of a drug?
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The measure of the body’s efficiency in eliminating a drug is known as:
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An increase in which factor would likely enhance the clearance of a high-extraction drug?
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What does a plasma volume of 2.8 L indicate about drug distribution?
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What type of kinetic process does drug decay typically follow in the context of half-life?
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Study Notes
One-Compartment Model
- The concentration-time profile (or course) of a drug following an intravenous bolus injection can be represented by a one-compartment model.
- Areas under the concentration-time curve (AUC) are used to calculate various pharmacokinetic parameters that reflect how a drug is absorbed, distributed, metabolized, and excreted.
Two-Compartment Model
- Some drugs are better described with a two-compartment model. This model divides the body into a central compartment (blood) and a peripheral compartment (tissues like fat, muscle, liver, etc.)
- The central compartment is where the drug is distributed rapidly, while the peripheral compartment represents areas with slower distribution.
Multi-Compartment Model
- When more than two compartments are necessary to accurately describe the pharmacokinetic profile of a drug.
- Less commonly used.
Drug Distribution
- The extent and rate of drug distribution are impacted by several factors:
- The physicochemical nature of the drug (e.g., its solubility, size, ionization)
- Organ perfusion rate (blood flow to organs)
- Permeability of tissue membranes (how easily the drug can cross cell membranes)
- Plasma protein binding (the extent to which the drug binds to proteins in the blood)
- Tissue binding (the extent to which the drug binds to proteins and other molecules in tissues)
Drug Distribution Principles
- Only the free (unbound) form of the drug can permeate across biological membranes.
Protein Binding
- Many drugs bind to plasma proteins:
- Acidic drugs bind to albumin (e.g., salicylates)
- Basic drugs bind to α1-acid glycoprotein (e.g., propranolol)
- Protein binding is typically reversible and saturable.
- At high drug concentrations, protein binding may become saturated.
- For most drugs, the therapeutic range is well below the saturation point, so the percent bound remains relatively constant.
Tissue Binding
- Many drugs exhibit higher concentrations in tissues compared to extracellular fluids and blood.
- For example, quinacrine (an antimalarial) can be found in much higher concentrations in the liver than in the blood.
- Tissue binding can involve cellular components like proteins, phospholipids, and nuclear proteins.
- Tissue binding is typically reversible and can act as a drug reservoir.
Distribution Principles
- Drugs with high plasma protein binding often have a small volume of distribution.
- Drugs with high tissue binding usually have a large volume of distribution.
Elimination
- Elimination involves removing drugs from the body.
- Two primary processes are responsible for elimination:
- Metabolism: primarily carried out by the liver
- Excretion: primarily performed by the kidneys, but other routes like bile are also possible
Important PK Parameters
- Volume of distribution (Vd)
- Clearance (CL)
- Half-life (t1/2)
Volume of Distribution (Vd)
- Vd is a calculated volume that relates the amount of drug in the body to the concentration in blood or plasma.
- It's an apparent volume, not a real physiological volume.
- The Vd can exceed any physical volume in the body because it represents the hypothetical volume needed to contain the drug homogeneously at the blood or plasma concentration.
Volume of Distribution Examples
- Digoxin: Vd = 500 L
- Chloroquine: Vd = 13,000 L
- Gentamicin: Vd = 18 L
- Drugs with large Vd values are not distributed evenly throughout the body.
Clearance (CL)
- Clearance is a measure of the body's efficiency at eliminating a drug.
- Clearance is the most important factor determining drug concentrations.
- It reflects the rate of drug elimination in relation to the drug concentration.
- Clearance is additive, meaning various organs can contribute to overall clearance.
Factors Affecting Clearance
- Dose:
- Some drugs, like ethanol, exhibit capacity-limited elimination, meaning clearance may be slowed at high doses.
- Organ blood flow:
- High-extraction drugs (e.g., lidocaine) are rapidly cleared by organs with high blood flow like the liver.
- Intrinsic function of the liver or kidneys:
- Reduced organ function can lower clearance.
- The unbound fraction of drug:
- The free (unbound) portion of the drug is available for clearance.
- High protein binding can decrease clearance.
Protein Binding and Clearance
- High protein binding can decrease clearance by reducing the amount of free drug available for metabolism and excretion.
Half-life (t1/2)
- Half-life (t1/2) is the time required for the amount of drug in the body to decrease by 50% during elimination or during a constant IV infusion.
- Half-life is useful for determining how long it takes for drug concentrations to reach 50% of their initial value or to reach 50% of steady-state concentration.
Half-life (t1/2) and Steady State
- For repeated oral administration, steady-state concentration (Css) is typically achieved after approximately four half-lives.
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Description
This quiz covers the various compartment models used in pharmacokinetics, including the one-compartment, two-compartment, and multi-compartment models. You'll explore how these models help in understanding the distribution of drugs within the body. Test your knowledge of drug absorption, distribution, metabolism, and excretion through this detailed overview.
