Exam 1B
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Questions and Answers

What is the result of a receptor spending 80% of its time in the inactive state and 20% of its time in the active state?

  • The receptor is partially active (correct)
  • The receptor is always inactive
  • The receptor's activity cannot be changed
  • The receptor is always active

    • What is the primary difference between competitive and non-competitive antagonism?

  • The potency of the antagonist
  • The location of the antagonist binding
  • The reversibility of the antagonist's binding to the receptor (correct)
  • The type of bond formed between the antagonist and the receptor

    • What is the effect of an inverse agonist on the receptor?

  • It turns off the constituent activity of the receptor (correct)
  • It increases the receptor's activity
  • It decreases the receptor's activity
  • It has no effect on the receptor

    • What is the primary function of an agonist in relation to a receptor?

    <p>To bind to the receptor and activate it (D)</p> Signup and view all the answers

    What is the primary mechanism of non-competitive antagonism?

    <p>Permanent binding to the receptor (D)</p> Signup and view all the answers

    What is the term for a partial agonist that also has antagonist activity?

    <p>Agonist-antagonist (D)</p> Signup and view all the answers

    What is the term for the process by which the body reduces the effect of a drug over time, requiring larger doses to achieve the same effect?

    <p>Tolerance (C)</p> Signup and view all the answers

    Where is the primary location of hepatic microsomal enzyme activity responsible for drug clearance?

    <p>Liver smooth ER (C)</p> Signup and view all the answers

    What is the term for the movement of drugs in the body, including absorption, metabolism, distribution, and elimination?

    <p>Pharmacokinetics (A)</p> Signup and view all the answers

    What is the primary function of phase II reactions in drug metabolism?

    <p>Conjugate drugs to make them water soluble (D)</p> Signup and view all the answers

    What do acidic drugs tend to bind to?

    <p>Albumin (B)</p> Signup and view all the answers

    What is the term for the fraction of inflowing drug extracted by the liver?

    <p>Extraction ratio (B)</p> Signup and view all the answers

    What is the term for the decrease in receptor sensitivity to a ligand or a decrease in receptor density as a result of repeated or continuous stimulation?

    <p>Cellular tolerance (C)</p> Signup and view all the answers

    What is the term for the rate of metabolism of a drug, which is proportional to the drug concentration?

    <p>Clearance (B)</p> Signup and view all the answers

    What is the primary mechanism by which the renal system clears drugs from the bloodstream?

    <p>Glomerular filtration (D)</p> Signup and view all the answers

    What is the term for the amount of drug that is required to produce a desired effect?

    <p>Potency (A)</p> Signup and view all the answers

    What is the term for the ability of a drug to produce a desired effect?

    <p>Efficacy (B)</p> Signup and view all the answers

    What is the term for the time necessary for the plasma drug concentration to decrease by 50% during the elimination phase?

    <p>Elimination half-time (D)</p> Signup and view all the answers

    What is the term for the process by which the liver eliminates a fixed amount of drug per unit time?

    <p>Zero-order kinetics (C)</p> Signup and view all the answers

    What is the term for the initial volume of distribution of a drug?

    <p>Vdi (B)</p> Signup and view all the answers

    What is the term for the process by which the liver eliminates 50% of drug per unit time?

    <p>First-order kinetics (A)</p> Signup and view all the answers

    What is the term for the amount of drug that remains in the body after a single dose?

    <p>Volume of distribution (D)</p> Signup and view all the answers

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

    <p>Agonists activate the receptor, while antagonists do not (B)</p> Signup and view all the answers

    What is the primary mechanism by which covalent bonding affects receptor activity?

    <p>Forming a permanent bond with the receptor (B)</p> Signup and view all the answers

    What is the primary implication of a drug having high lipid solubility?

    <p>It will have a large volume of distribution (B)</p> Signup and view all the answers

    Which type of drugs tend to bind to alpha1 acid glycoprotein?

    <p>Basic drugs (B)</p> Signup and view all the answers

    What is the primary consequence of protein binding on drug availability?

    <p>It decreases the availability of the drug for hepatic extraction and glomerular filtration (B)</p> Signup and view all the answers

    What is the primary characteristic of a partial agonist?

    <p>It activates the receptor less completely than a full agonist (B)</p> Signup and view all the answers

    What is the primary consequence of increasing the concentration of a competitive antagonist?

    <p>Receptor activation is inhibited (D)</p> Signup and view all the answers

    What is the primary outcome of metabolism on lipid soluble drugs?

    <p>It converts them to more water soluble drugs (D)</p> Signup and view all the answers

    Which of the following is a characteristic of highly protein bound drugs?

    <p>They are highly sensitive to changes in plasma protein concentration (C)</p> Signup and view all the answers

    What is the primary function of Phase I Reactions in drug metabolism?

    <p>To increase the polarity of a drug (C)</p> Signup and view all the answers

    What is the purpose of conjugation in Phase II Reactions?

    <p>To tie the agent to a polar compound, increasing its water solubility (D)</p> Signup and view all the answers

    What is the formula used to quantify the process of drug metabolism?

    <p>R = Q(Cin-Cout) (A)</p> Signup and view all the answers

    What is the definition of Clearance in the context of drug metabolism?

    <p>The volume of plasma cleared of a drug per unit of time (D)</p> Signup and view all the answers

    What is the location of hepatic microsomal enzyme activity responsible for drug clearance?

    <p>Hepatic smooth ER (B)</p> Signup and view all the answers

    What is the rate of metabolism for most anesthetic drugs proportional to?

    <p>Drug concentration (C)</p> Signup and view all the answers

    What is the primary fate of highly fat-soluble drugs in the initial distribution phase?

    <p>They are taken up by the lung (B)</p> Signup and view all the answers

    What is the primary term for the phenomenon where the body reduces the effect of a drug over time?

    <p>Tolerance (D)</p> Signup and view all the answers

    What is the primary mechanism by which IV injection delivers drugs to the vessel-rich group?

    <p>Through the central compartment (B)</p> Signup and view all the answers

    What is the primary term for the effect of a drug that is opposite to that of an agonist?

    <p>Antagonist (A)</p> Signup and view all the answers

    What is the primary term for the phenomenon where the effect of a drug is greatly increased when combined with another drug?

    <p>Synergistic effect (C)</p> Signup and view all the answers

    What is the primary factor that determines the distribution of a drug to tissues?

    <p>Blood flow (B)</p> Signup and view all the answers

    What is the term for the concentration of a drug in the plasma at which the drug's effect is observed?

    <p>ED50 (D)</p> Signup and view all the answers

    Which of the following drugs is characterized by a shorter effect-site equilibration?

    <p>Remifentanil (A)</p> Signup and view all the answers

    What is the primary determinant of potency for drugs with very different time courses?

    <p>Time of measurement (D)</p> Signup and view all the answers

    What is the term for the movement of a drug from the central compartment to other compartments?

    <p>Distribution (C)</p> Signup and view all the answers

    What is the primary determinant of tissue storage capacity?

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

    What is pharmacodynamics?

    <p>The study of the effects of drugs on the body (A)</p> Signup and view all the answers

    What are some factors that influence pharmacokinetic variability in individuals?

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

    What are some factors that influence pharmacodynamic variability in individuals?

    <p>Enzyme activity and gender differences (A)</p> Signup and view all the answers

    What type of effect do anesthetic drugs tend to have?

    <p>Synergistic (B)</p> Signup and view all the answers

    What is a racemic mixture?

    <p>A mixture of two enantiomers that are equal in amount (B)</p> Signup and view all the answers

    Enantiomers often have different pharmacokinetic and pharmacodynamic properties.

    <p>True (A)</p> Signup and view all the answers

    Administering drugs in high doses may mask interpatient variability

    <p>True (A)</p> Signup and view all the answers

    Drugs excreted unchanged by the kidneys tend to have greater pharmacokinetic differences than metabolized drugs.

    <p>False (B)</p> Signup and view all the answers

    In drugs with a high extraction ratio, a change in hepatic blood flow produces a proportional change in clearance

    <p>True (A)</p> Signup and view all the answers

    Administration of inhalation agents alter hepatic, circulatory and renal function and may alter drug pharmacokinetics.

    <p>True (A)</p> Signup and view all the answers

    What is the therapeutic index of a drug?

    <p>The ratio of the LD50 to the ED50 (D)</p> Signup and view all the answers

    What is the LD50?

    <p>Lethal dose that kills 50% of a test population (A)</p> Signup and view all the answers

    What is the ED50?

    <p>The dose of a drug that produces a desired response in 50% of test subjects. (A)</p> Signup and view all the answers

    What factors influence potency of a drug?

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

    Fentanyl is more efficacious than Tylenol because it produces better analgesia

    <p>True (A)</p> Signup and view all the answers

    Sufentanyl is more potent than fentanyl because 1/5 of a dose of sufentanyl produces the same effect as 1 fentanyl

    <p>True (A)</p> Signup and view all the answers

    What is the elimination half-time directly proportional to?

    <p>Volume of distribution (A)</p> Signup and view all the answers

    What is the elimination half-time inversely proportional to?

    <p>The clearance (C)</p> Signup and view all the answers

    What is the elimination half-life?

    <p>The time it takes to eliminate half the drug from the body after rapid IV injection. (A)</p> Signup and view all the answers

    What is the context sensitive half-time?

    <p>The time it takes for the concentration of a substance to decrease by half i.e. half life where the context = duration of infusion (A)</p> Signup and view all the answers

    What is the primary function of the CSHT?

    <p>To provide clinically useful guidance on the expected increase in the time required to eliminate the drug (B)</p> Signup and view all the answers

    What is the primary benefit of using the CSHT in drug administration?

    <p>It helps clinicians to adjust the dosage and administration schedule to optimize the drug's effect (D)</p> Signup and view all the answers

    What is the relationship between the duration of drug administration and the expected increase in elimination time according to the CSHT?

    <p>The elimination time increases as the duration of drug administration increases (A)</p> Signup and view all the answers

    What is an advantage of using Propofol perioperatively?

    <p>context sensitive half time doesn't change (A)</p> Signup and view all the answers

    Drugs that have the most rapid onset have the greatest effect site equilibration

    <p>True (A)</p> Signup and view all the answers

    The plasma is almost never the effect site

    <p>True (A)</p> Signup and view all the answers

    What is the effect site equilibration?

    <p>The process of achieving equilibrium between the concentration of a drug in the blood and at the site of action (A)</p> Signup and view all the answers

    What intervals should be adjusted to reflect effect-site equilibration?

    <p>Dosing intervals (A)</p> Signup and view all the answers

    In what drugs would effect-site equilibration be short?

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

    In what drugs would effect-site equilibration be longer?

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

    What is PKA?

    <p>constant that represents the pH in which a drug is 50% ionized (A)</p> Signup and view all the answers

    Where does the drug have to return first in order to be eliminated?

    <p>Plasma of central compartment (C)</p> Signup and view all the answers

    What enzyme aids in the metabolism of lipid soluble molecules?

    <p>Cytochrome P450 (A)</p> Signup and view all the answers

    What are the phase I reactions?

    <p>all of the above (D)</p> Signup and view all the answers

    What is the purpose of phase I reactions?

    <p>to increase drug polarity (B)</p> Signup and view all the answers

    Oxidation and reduction involve CP450

    <p>True (A)</p> Signup and view all the answers

    In phase II reactions, what is the role of conjugation?

    <p>Tying agent to a polar compound to increase its water solubility and its ability to be excreted (B)</p> Signup and view all the answers

    When drugs are first administered, they are rapidly absorbed by the vessel rich group

    <p>True (A)</p> Signup and view all the answers

    Drugs tied to proteins and large molecules do not get filtered through the kidneys

    <p>True (A)</p> Signup and view all the answers

    Bound fractions are available for hepatic extraction and glomerular filtration

    <p>False (B)</p> Signup and view all the answers

    What is a free fraction in pharmacology?

    <p>The unbound fraction of a drug in plasma that is able to diffuse out of bloodstream and exert its effect (A)</p> Signup and view all the answers

    Ionized drugs are inactive and excreted by the kidneys

    <p>True (A)</p> Signup and view all the answers

    Non-ionized drugs undergo renal metabolism and are water-soluble

    <p>False (B)</p> Signup and view all the answers

    What is the primary determinant of tissue uptake?

    <p>Blood flow (A)</p> Signup and view all the answers

    Blood flow, concentration gradient, the blood brain barrier, and physicochemical properties of drugs (ionization, lipid solubility, protein binding) are important determinants of tissue uptake

    <p>True (A)</p> Signup and view all the answers

    In the three compartment model, rapid equilibration first occurs between which two tissues?

    <p>Plasma and vascular rich (A)</p> Signup and view all the answers

    Is it true that potent drugs produce a greater response at lower doses?

    <p>True (A)</p> Signup and view all the answers

    What is a characteristic of drug efficacy?

    <p>The maximum response that can be produced by a drug (A)</p> Signup and view all the answers

    What is the biophase in pharmacology?

    <p>The biological phase of a drug's distribution (A)</p> Signup and view all the answers

    What type of transport is tubular reabsorption in the renal system?

    <p>Passive transport (B)</p> Signup and view all the answers

    What type of transport is tubular secretion in the renal system?

    <p>Active transport (B)</p> Signup and view all the answers

    What factors determine the amount of drug entering the renal lumen?

    <p>GFR, and protein binding (A)</p> Signup and view all the answers

    Tubular reabsorption is most prominent in what type of drug?

    <p>Lipid soluble (A)</p> Signup and view all the answers

    What is the relationship between blood flow and clearance in drugs with a high extraction ratio?

    <p>Clearance is directly proportional to blood flow (B)</p> Signup and view all the answers

    For drugs with a low extraction ratio, clearance is nearly independent of which physiological factor?

    <p>Rate of liver blood flow (capacity limited) (A)</p> Signup and view all the answers

    What is true about a drug with an extremely low intrinsic clearance?

    <p>Hepatic blood flow will have minimal influence on its metabolic rate (C)</p> Signup and view all the answers

    If the intrinsic clearance for a drug is very high, what limits its metabolism by the liver?

    <p>Hepatic blood flow (B)</p> Signup and view all the answers

    What is allosteric inhibition?

    <p>A type of enzyme inhibition that binds to a site other than the active site (B)</p> Signup and view all the answers

    What is drug sensitivity?

    <p>The dose that causes a threshold response (B)</p> Signup and view all the answers

    What is drug reactivity?

    <p>The rate of response to a drug (A)</p> Signup and view all the answers

    What is the main difference between tachyphylaxis and anaphylaxis?

    <p>Tachyphylaxis is an acute desensitization to a drug, while anaphylaxis is a severe, life-threatening allergic reaction. (A)</p> Signup and view all the answers

    What is the additive effect in pharmacology?

    <p>When two medicines have the same effect, increasing the overall response (B)</p> Signup and view all the answers

    What does protein binding tend to parallel?

    <p>Lipid solubility (A)</p> Signup and view all the answers

    Doubling the initial IV dose of a drug will

    <p>increase the duration of action by one half lfe (A)</p> Signup and view all the answers

    What is the effect of doubling the initial IV dose of a drug on the duration of action?

    <p>Increase the duration of action by 1 half-life (A)</p> Signup and view all the answers

    Study Notes

    Receptors

    • Receptors can be found on the membrane or cytoplasm of a cell
    • Receptors can increase (upregulate) or decrease (downregulate) in response to stimuli
    • Receptors have multiple states and can switch spontaneously between them
    • Agonists bind to and activate receptors, increasing the amount of time they are active
    • Partial agonists activate receptors less completely than full agonists, and may also have antagonist activity
    • Inverse agonists turn off the constitutive activity of receptors
    • Antagonists bind to receptors without activating them, and can be competitive or non-competitive

    Receptor States

    • Receptors can fluctuate between active and inactive states
    • Ligands can alter the relative time spent in each state

    Competitive Antagonism

    • Increasing the concentration of an antagonist progressively inhibits the response to an agonist
    • Occurs when a protein binds to a receptor and prevents it from being activated
    • If enough agonist is present, it may overcome the antagonist
    • Works by binding to the receptor (reversibly) and preventing a normal ligand from binding

    Non-Competitive Antagonism

    • No amount of agonist can overcome the antagonist
    • Works by binding to the receptor (permanently) and preventing a normal ligand from binding
    • Involves covalent bonding
    • Allosteric inhibition is an example of non-competitive antagonism

    Tolerance and Sensitivity

    • Tolerance: any process that diminishes a drug's effect
    • Tachyphylaxis: decreased response to the same dose, often rapid and short-lived
    • Cellular tolerance: results from decreased receptor sensitivity or density
    • Hyperreactive: strong response to stimuli
    • Hyporeactive: weak response to stimuli
    • Hypersensitive: increased response to stimuli

    Pharmacokinetics

    • Absorption: the process of a drug entering the body
    • Metabolism: the conversion of a drug into a more water-soluble form
    • Distribution: the movement of a drug throughout the body
    • Elimination: the removal of a drug from the body
    • Clearance: the rate of metabolism of a drug
    • Volume of distribution: the amount of drug in the body divided by the plasma concentration

    Pharmacodynamics

    • What the drug does to the body
    • Dynamics: the study of the effects of a drug on the body
    • Potency: the amount of drug required to produce a desired effect
    • Efficacy: the ability of a drug to produce a desired effect

    Elimination Half-Life

    • The time necessary for the plasma drug concentration to decrease by 50% during the elimination phase
    • Directly proportional to the volume of distribution
    • Inversely proportional to clearance

    First Order and Zero Order Kinetics

    • First order kinetics: the rate of elimination is proportional to the plasma concentration
    • Zero order kinetics: the rate of elimination is constant and independent of the plasma concentration

    Receptor Theory

    • Traditional thinking characterized receptor states as binary: effect is produced by ligand binding, and effect is absent when not bound by the ligand
    • An agonist binds to and activates a receptor, while an antagonist binds to the receptor without activating it
    • Receptors probably fluctuate between active and inactive conformations, spending various proportions of time between the two states
    • Ligands may alter the relative time spent in each state
    • Competitive antagonism: increasing concentration of the antagonist progressively inhibits the response to the agonist
    • Noncompetitive antagonism: antagonist administration prevents receptor activation even when exposed to high concentrations of the agonist
    • Partial agonists/agonist-antagonists: activate the receptor less completely than full agonists, can reduce agonist effects
    • Inverse agonists “turn off” the constituent activity of the receptor

    Receptor Basics

    • Receptors may increase (up-regulate) or decrease (down-regulate) in response to specific stimuli
    • May exist on the surface of a cell (membrane-bound) or within cytoplasm of a cell
    • May respond to ligand or alterations in polarity of adjacent cell membranes
    • May either allow something into or out of a cell
    • Cause a process to start, accelerate, decelerate, or stop a cellular activity (usually protein or enzyme-mediated)

    Pharmacokinetics of Injected Drugs

    • Determines the concentration in the plasma or effect site: Absorption, Distribution, Metabolism, and Elimination
    • Important terms to learn:
      • Hyperreactive
      • Hyporeactive
      • Hypersensitive
      • Tolerance
      • Tachyphylaxis
      • Agonist
      • Antagonist
      • Additive effect
      • Synergistic effect

    Distribution

    • Initial distribution (within 1 minute) mixing within the central compartment
    • IV injection delivers drugs to the vessel-rich group
    • Highly fat-soluble drugs may be vigorously taken up by the lung
    • Non-polar molecules (lipid-soluble) will be preferentially taken up by fat
    • Drug concentrations in the various compartments will be reflected in the calculated volume of distribution (Vd)
    • Pharmacologic effects may or may not reflect the current or steady-state concentration in the various compartments

    Protein Binding

    • Acidic drugs tend to bind to albumin
    • Basic drugs tend to bind to alpha1 acid glycoprotein
    • Protein binding parallels lipid solubility (hydrophobic drugs are more likely to bind to plasma proteins or fat)
    • Only free fractions can cross cell membranes
    • Bound fractions are not available for hepatic extraction nor glomerular filtration

    Metabolism of Drugs

    • Generally, metabolism converts active lipid-soluble drugs to water-soluble pharmacodynamically inactive drugs
    • Phase I reactions are mediated by CP450, and non-CP450 enzymes and mono-oxygenase enzymes
    • Phase II Reactions: Conjugation ties the agent to a polar compound, increasing its water solubility ability to be excreted

    Hepatic Clearance

    • The rate of metabolism for most anesthetic drugs is proportional to drug concentration
    • Hepatic microsomal enzyme activity is located in the hepatic smooth ER

    Clearance

    • The rate of clearance is proportional to drug concentration
    • Clearance is the volume of plasma cleared of a drug per unit of time
    • If the liver could completely extract the drug from afferent flow, clearance would equal liver blood flow

    Zero-Order Kinetics

    • The rate of metabolism is independent of concentration

    Three-Compartment Model

    • Initially, drug flows from the central compartment to the two other compartments
    • After rapid equilibration, the concentration in the central compartment falls below that of the rapid equilibration compartment, and the flow of drug is reversed
    • When the concentration in the central compartment falls below the concentration of the other two compartments, decreases in plasma concentration are dependent on elimination

    Distribution and Tissue Uptake

    • Determinants of tissue uptake:
      • Blood flow
      • Concentration gradient
      • Solubility
      • Tissue mass
      • Binding to macromolecules
      • pH

    Effect-Site Equilibration

    • The plasma is almost never the effect site (biophase)
    • Effect-site equilibration may be short (e.g., remifentanil, alfentanil, thiopental, propofol) or long (e.g., fentanyl, sufentanil, midazolam)
    • Dosing intervals should be adjusted to reflect effect-site equilibration

    Context-Sensitive Half-Time

    • The time required for the concentration to decrease by 50%

    Potency and Efficacy

    • Determinants of potency:
      • Absorption
      • Distribution
      • Metabolism
      • Excretion
      • Receptor affinity
    • Efficacy is a measure of the intrinsic ability to produce a given physiologic or clinical effect

    Dose Response Curve

    • The ED50 is the dose required to produce the desired effect in 50% of patients.

    Pharmacokinetics

    • Clearance: the amount of blood completely cleared of drug per unit time
    • CSHT: provides clinically useful guidance on the expected increase in the time required to eliminate the drug as a function of the duration of drug administration
    • Infusion rate: to maintain a given steady-state arterial drug concentration, we must infuse drug at the same rate that it is being metabolized (Infusion rate = metabolic rate = Clearance × Cinflow)
    • Renal clearance: involves glomerular filtration, active tubular secretion, and passive tubular reabsorption
    • Volume of Distribution (Vd): the dose of drug administered / plasma concentration prior to elimination beginning; larger Vd means slower elimination of drug

    Pharmacodynamics

    • Receptors: may be found on the membrane or cytoplasm of a cell; may increase (upregulate) or decrease (downregulate) in response to stimuli
    • Agonist: binds to and activates a receptor, increasing the amount of time it is active
    • Partial agonist: activates a receptor less completely than a full agonist, may also have antagonist activity
    • Inverse agonist: binds to a receptor and turns off its constituent activity
    • Antagonist: binds to a receptor without activating it, blocking the effect of an agonist

    Pharmacokinetic Models

    • Simple pharmacokinetic model: 1-1/2 time, lose half of the drug; 2-1/2 time, lose half of the remaining half
    • Elimination half-time: the time necessary for the plasma drug concentration to decrease by 50% during the elimination phase
    • Three-compartment model: initially, the drug flows from the central compartment to the two other compartments; after rapid equilibration, the concentration in the central compartment falls below that of the rapid equilibration compartment, and the flow of drug is reversed

    Pharmacological Effects

    • Potency: the amount of drug required to produce a desired effect
    • Efficacy: the ability of a drug to produce a desired effect
    • Additive effect: the combined effect of two or more drugs
    • Synergistic effect: the combined effect of two or more drugs that is greater than the sum of their individual effects
    • Tolerance: any process that diminishes a drug's effect
    • Tachyphylaxis: a rapid decrease in response to repeated doses over a short period of time

    Pharmacokinetics and Pharmacodynamics

    • Kinetics: the movement of drugs in the body; what the body does to the drug
    • Dynamics: what the drug does to the body; the effects of the drug on the body
    • Distribution: the movement of drug from the site of administration to the site of action
    • Metabolism: the conversion of active lipid-soluble drugs to water-soluble pharmacodynamically inactive drugs
    • Clearance: the rate of metabolism for most anesthetic drugs is proportional to drug concentration

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