Pharmacokinetics Lesson 1: Volume of Distribution
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Questions and Answers

At which pH does a drug's pKa equal, in terms of ionization and unionization?

  • pH where 75% is ionized and 25% is unionized
  • pH where 25% is ionized and 75% is unionized
  • pH where 50% is ionized and 50% is unionized (correct)
  • pH where all of the drug is ionized

    • How do weak bases behave in an acidic solution?

  • They are more unionized
  • They have no effect
  • They are more ionized (correct)
  • They become lipophilic

    • What is the effect of ionization on a drug's solubility in water?

  • Ionization decreases solubility in water
  • Ionization makes the drug lipophilic
  • Ionization increases solubility in water (correct)
  • Ionization has no effect on solubility in water

    • How does ionization affect a drug's ability to cross the blood-brain barrier (BBB)?

    <p>Ionization decreases the ability to cross the BBB</p> Signup and view all the answers

    What is the effect of ionization on a drug's activity?

    <p>Ionization decreases activity</p> Signup and view all the answers

    How does the hepatic biotransformation of a drug change with ionization?

    <p>Ionization decreases the likelihood of hepatic biotransformation</p> Signup and view all the answers

    What is the effect of ionization on a drug's renal elimination?

    <p>Ionization increases the rate of renal elimination</p> Signup and view all the answers

    Can an ionized drug diffuse across the placenta?

    <p>No, ionized drugs cannot diffuse across the placenta</p> Signup and view all the answers

    What is the main limitation of using half-times to determine the offset of anesthetic drugs?

    <p>Half-times do not take into account the duration of drug administration</p> Signup and view all the answers

    What is the primary factor that affects the ionization of a weak acid or weak base?

    <p>Both C and D</p> Signup and view all the answers

    What happens to a drug that is a weak acid when it is placed in water?

    <p>It releases a proton to water</p> Signup and view all the answers

    What is the term for the process by which a molecule gains a positive or negative charge?

    <p>Ionization</p> Signup and view all the answers

    What is the relationship between pKa and pH?

    <p>pKa and pH are independent properties</p> Signup and view all the answers

    What is the purpose of considering context sensitive half-times of opioids?

    <p>To take into account the duration of drug administration</p> Signup and view all the answers

    What is the significance of the pKa of lidocaine?

    <p>It determines the ionization of lidocaine</p> Signup and view all the answers

    What happens to the remaining fraction of a weak acid or weak base when placed in water?

    <p>It remains non-ionized</p> Signup and view all the answers

    What happens to a drug when it is released from a protein?

    <p>It is able to travel elsewhere in the body</p> Signup and view all the answers

    Which of the following factors is affected by the extent of plasma protein binding?

    <p>Intensity of drug effect and duration of action</p> Signup and view all the answers

    Which protein plays the larges role in maintaining plasma oncotic pressure?

    <p>Albumin</p> Signup and view all the answers

    Which condition is associated with decreased plasma albumin levels?

    <p>Malnutrition</p> Signup and view all the answers

    Which type of drugs bind to alpha-1 acid glycoprotein?

    <p>Basic and neutral drugs</p> Signup and view all the answers

    What is the turnaround time of albumin?

    <p>3 weeks</p> Signup and view all the answers

    Which condition is associated with increased plasma albumin levels?

    <p>None of the above</p> Signup and view all the answers

    Which protein binds to basic drugs?

    <p>Alpha-1 acid glycoprotein</p> Signup and view all the answers

    What is the primary assumption of the volume of distribution (Vd)?

    <p>The drug distribution is instantaneous and not subject to metabolism or elimination</p> Signup and view all the answers

    A drug with a volume of distribution (Vd) of 50 L in a 70 kg patient is likely to be which type of drug?

    <p>Lipophilic</p> Signup and view all the answers

    What is the unit of measurement for the volume of distribution (Vd)?

    <p>Liters per kilogram (L/kg)</p> Signup and view all the answers

    What is the relationship between the volume of distribution (Vd) and the loading dose required to achieve a given plasma concentration?

    <p>The higher the Vd, the higher the loading dose</p> Signup and view all the answers

    What is the primary factor that determines the volume of distribution (Vd) of a drug?

    <p>The lipophilicity of the drug</p> Signup and view all the answers

    What is the plasma volume of a 70 kg patient?

    <p>4 L</p> Signup and view all the answers

    What is the total body water of a 70 kg patient?

    <p>42 L</p> Signup and view all the answers

    A drug with a volume of distribution (Vd) of 20 L in a 70 kg patient is likely to be which type of drug?

    <p>Hydrophilic</p> Signup and view all the answers

    The body converts an inactive molecule into a pharmacologically active molecule. What type of molecule?

    <p>Prodrug</p> Signup and view all the answers

    What is the purpose of a phase 2 reaction in drug metabolism?

    <p>To conjugate a polar substrate to a drug molecule</p> Signup and view all the answers

    What is the term for the process by which a conjugated drug is excreted into the bile, reactivated in the intestine, and then reabsorbed into the systemic circulation?

    <p>Enterohepatic circulation</p> Signup and view all the answers

    What is the purpose of alkaline phosphatases in the metabolism of fospropofol?

    <p>To metabolize fospropofol into its active metabolite</p> Signup and view all the answers

    What is the purpose of ATP-dependent carrier proteins in drug metabolism?

    <p>To transport a drug across a cell membrane</p> Signup and view all the answers

    Which of the following is an example of a conjugation reaction?

    <p>Glucuronic acid conjugation</p> Signup and view all the answers

    What is the purpose of glucuronic acid in drug metabolism?

    <p>To conjugate a drug molecule, making it more soluble</p> Signup and view all the answers

    What type of antagonism is reversible?

    <p>Competitive antagonism</p> Signup and view all the answers

    What is the effect of an inverse agonist?

    <p>It causes an opposite effect to that of a full agonist</p> Signup and view all the answers

    What is the term for the dose that produces the expected clinical response in 50% of the population?

    <p>ED50</p> Signup and view all the answers

    What is the term for the simultaneous administration of two drugs, resulting in an effect greater than the sum of their individual effects?

    <p>Synergism</p> Signup and view all the answers

    What is the effect of a noncompetitive antagonist?

    <p>It shifts the dose-response curve for the agonist down and to the right</p> Signup and view all the answers

    What is the term for the dose that produces death in 50% of the population?

    <p>LD50</p> Signup and view all the answers

    What is the term for the effect of two drugs given at the same time, where the total effect is equal to the sum of their individual effects?

    <p>Addition</p> Signup and view all the answers

    What is the term for the effect of one drug that enhances the effect of another drug, but has no effect on its own?

    <p>Potentiation</p> Signup and view all the answers

    What is the TD50?

    <p>The dose that produces toxicity in 50% of the population</p> Signup and view all the answers

    What is the repentonic index?

    <p>The ratio between the TD50 and the ED50</p> Signup and view all the answers

    What is chirality?

    <p>The tetrahedral bonding of carbon</p> Signup and view all the answers

    What are enantiomers?

    <p>Chiral molecules that are non-superimposable mirror images of each other</p> Signup and view all the answers

    What is a racemic mixture?

    <p>A mixture of two enantiomers in equal amounts</p> Signup and view all the answers

    Why is levobupivacaine less cardiotoxic than bupivacaine?

    <p>Due to its lower affinity for the inactivated state of the cardiac Na Channel</p> Signup and view all the answers

    What are R and S enantiomers?

    <p>Non-superimposable mirror images of each other</p> Signup and view all the answers

    What does the slope of the dose-response curve indicate?

    <p>The number of receptors that must be occupied to elicit a clinical effect</p> Signup and view all the answers

    What is the main difference between a full agonist and a partial agonist?

    <p>The maximum response produced by the receptor</p> Signup and view all the answers

    What is the result of continuous administration of an agonist?

    <p>Down-regulation of the target receptors</p> Signup and view all the answers

    What is the effect of a competitive antagonist on the dose-response curve of an agonist?

    <p>The curve shifts to the right</p> Signup and view all the answers

    What is the difference between an antagonist and an inverse agonist?

    <p>The correct answer is not provided</p> Signup and view all the answers

    What is an example of a full agonist?

    <p>All of the above</p> Signup and view all the answers

    What is individual variability in pharmacodynamics?

    <p>Differences in pharmacodynamics between patients</p> Signup and view all the answers

    What is the effect of an antagonist on the receptor?

    <p>It prevents the agonist from binding to the receptor</p> Signup and view all the answers

    What is the term for the ability of a drug to elicit a given clinical effect?

    <p>Efficacy</p> Signup and view all the answers

    What is the significance of the ED50 in a dose-response curve?

    <p>It represents the dose required to achieve a given clinical effect</p> Signup and view all the answers

    What is the result of a right-shifted dose-response curve?

    <p>Decreased potency and higher required dose</p> Signup and view all the answers

    What is the significance of a left-shifted dose-response curve?

    <p>It indicates higher potency and lower required dose</p> Signup and view all the answers

    What is the term for the study of the effect of a drug on the body?

    <p>Pharmacodynamics</p> Signup and view all the answers

    Study Notes

    Pharmacokinetics

    • The volume of distribution (Vd) describes the relationship between the administered dose of a drug and the resulting plasma concentration.
    • Vd is a theoretical measure of how a drug distributes throughout the body, assuming instantaneous distribution and no metabolism or elimination.
    • A drug with a Vd that exceeds total body water (> 0.6 L/kg or > 42 L) is assumed to be lipophilic and requires a higher dose to achieve a given plasma concentration (e.g., Propofol).
    • A drug with a Vd that is less than total body water (< 0.6 L/kg or < 42 L) is assumed to be hydrophilic and requires a lower dose to achieve a given plasma concentration (e.g., NMB).

    Ionization

    • Ionization is the process where a molecule gains a positive or negative charge, affecting its ability to pass through cell membranes.
    • Weak acids or bases ionize in water, and the degree of ionization depends on the pH of the solution and the pKa of the drug.
    • pKa is a constant property of a molecule, while pH is a changeable property of a solution.

    Solubility and Pharmacologic Effects

    • Ionized molecules are lipophobic and hydrophilic, while non-ionized molecules are lipophilic and hydrophobic.
    • Ionized molecules have reduced pharmacologic activity, are more likely to undergo hepatic biotransformation, and are less likely to be eliminated by the kidneys.
    • Non-ionized molecules have increased pharmacologic activity, are less likely to undergo hepatic biotransformation, and are more likely to be eliminated by the kidneys.

    Plasma Protein Binding

    • Only when a drug is released from plasma protein binding can it travel elsewhere in the body.
    • The extent of plasma protein binding affects the intensity and duration of drug effect.
    • Albumin is the most plentiful plasma protein and primary determinant of plasma oncotic pressure.
    • α1-Acid Glycoprotein and Beta-Globulin also bind basic drugs.

    Metabolism

    • Phase 1 reactions prepare the molecule for a phase 2 reaction, including oxidation, reduction, and hydrolysis.
    • Phase 2 reactions conjugate an endogenous, highly polar, water-soluble substrate to the molecule, inactivating the drug and readying it for elimination.
    • Phase 3 reactions involve ATP-dependent carrier proteins that transport a drug across a cell membrane.
    • Enterohepatic circulation occurs when conjugated compounds are excreted in the bile, reactivated in the intestine, and reabsorbed into the systemic circulation (e.g., Valium and warfarin).

    Pharmacodynamics

    • Pharmacodynamics explains the effect of drugs on the body.
    • The biophase, or effect site, is the specific area of the body where the drug engages its receptor.

    Dose-Response Curve

    • The dose-response curve illustrates the relationship between the drug dose and its clinical effects.
    • Efficacy is the ability of a drug to elicit a given clinical effect.
    • Potency is the dose required to achieve a given clinical effect (ED50 and ED90 are measures of potency).
    • A left-shifted dose-response curve indicates higher potency and a lower required dose to achieve ED50.
    • A right-shifted dose-response curve indicates lower receptor affinity and higher dose required for ED50.

    Agonists and Antagonists

    • A full agonist instructs the receptor to produce its maximal response.
    • A partial agonist is only capable of partially activating a cellular response.
    • An antagonist binds to a receptor and prevents an agonist from binding to it.
    • Inverse agonist binds to the receptor and causes an opposite effect to that of a full agonist.

    Types of Antagonism

    • Competitive antagonism is reversible and shifts the dose-response curve for the agonist to the right.
    • Noncompetitive antagonism is not reversible and shifts the dose-response curve for the agonist downwards.

    Drug Interactions

    • Synergism: The effects of two drugs given at the same time are greater than the sum of their individual effects.
    • Addition: The effect of two drugs given at the same time are added together.
    • Potentiation: The effect of one drug is enhanced by a drug that has no effect on its own.
    • Antagonism: The simultaneous administration of one drug negates the effects of the other.

    ED50, LD50, and TD50

    • ED50 is the dose that produces the expected clinical response in 50% of the population.
    • LD50 is the dose that produces death in 50% of the population.
    • TD50 is the dose that produces toxicity in 50% of the population.
    • Therapeutic index is the ratio between the TD50 and the ED50, a measure of drug safety.

    Chirality

    • Chirality is the tetrahedral bonding of carbon (carbon binding to 4 different atoms).
    • Enantiomers are chiral molecules that are non-superimposable mirror images of each other.
    • Receptors that are stereospecific may respond differently to different enantiomers.
    • Racemic mixture contains two enantiomers in equal amounts.

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    Description

    Learn about the volume of distribution, a theoretical measure of how a drug distributes throughout the body, and its relationship with the administered dose and resulting plasma concentration.

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