Pharmacology Course: Pharmacokinetics and Bioavailability
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Questions and Answers

What is the process of glycine conjugation with?

  • Estrogens
  • Acetaminophen
  • Nicotinic acid (correct)
  • Paraaminosalicylate

    • Which of the following is NOT a factor that decreases the first pass effect?

  • Enzyme induction (correct)
  • IV administration
  • Saturation of metabolizing enzymes
  • Hepatic diseases

    • Which enzyme inducer is known to affect the metabolism of benzodiazepines and paracetamol?

  • Barbiturates
  • Carbamazepine
  • Cigarettes (correct)
  • Ethanol

    • What is the result of enzyme induction on microsomal metabolizing enzymes?

    <p>Reduced plasma half-life</p> Signup and view all the answers

    Which of the following is an example of intestinal first pass effect?

    <p>Intestinal lumen</p> Signup and view all the answers

    What is the result of hepatic enzyme inhibition on the first pass effect?

    <p>Decreased first pass effect</p> Signup and view all the answers

    Which of the following is NOT a consequence of enzyme induction?

    <p>Increased plasma half-life</p> Signup and view all the answers

    What is the result of saturation of metabolizing enzymes on the first pass effect?

    <p>Decreased first pass effect</p> Signup and view all the answers

    Which of the following enzymes is induced by cimetidine?

    <p>Hepatic microsomal enzyme</p> Signup and view all the answers

    Which of the following is an example of a pro-drug?

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

    Which of the following routes of excretion involves Glomerular filtration?

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

    Which of the following enzymes is responsible for the metabolism of Suxamethonium?

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

    What is the effect of Erythromycin on drug metabolism?

    <p>Inhibits hepatic microsomal enzymes</p> Signup and view all the answers

    What is the result of biotransformation of a drug?

    <p>Biologically inactive metabolite is formed</p> Signup and view all the answers

    Which of the following factors can affect drug metabolism?

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

    What is the term for the time required for the concentration of a drug in the body to decrease by half?

    <p>Half-life</p> Signup and view all the answers

    What is the term for the fraction of the administered dose that reaches the systemic circulation?

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

    Which of the following is NOT a biological factor that determines bioavailability?

    <p>Particle size</p> Signup and view all the answers

    What is the formula to calculate the Volume of Distribution (Vd)?

    <p>Vd = Cp</p> Signup and view all the answers

    What is the mechanism by which water-soluble drugs cross the blood-brain barrier?

    <p>Passive diffusion</p> Signup and view all the answers

    Which phase of metabolism involves the addition of an endogenous water-soluble group?

    <p>Phase II reaction</p> Signup and view all the answers

    What is the type of reaction that involves the oxidation of drugs?

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

    Which of the following drugs undergoes acetylation in Phase II metabolism?

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

    What is the purpose of metabolic processes in the body?

    <p>To convert lipid-soluble drugs into water-soluble products</p> Signup and view all the answers

    Which of the following factors decreases the rate and extent of renal excretion of drugs?

    <p>Plasma protein-binding</p> Signup and view all the answers

    Which route of excretion is responsible for the elimination of basic drugs such as morphine in cases of poisoning?

    <p>Gastrointestinal tract</p> Signup and view all the answers

    What is the total clearance of a drug equal to?

    <p>Cl renal + Cl liver + Cl others</p> Signup and view all the answers

    Which of the following drugs has a clearance that is less than the glomerular filtration rate (GFR)?

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

    What is the characteristic of a drug that follows zero-order kinetics?

    <p>Saturable and dose-dependent elimination</p> Signup and view all the answers

    What determines the duration of the half-life of a drug?

    <p>Rate of clearance and distribution</p> Signup and view all the answers

    What is the characteristic of a drug that follows first-order kinetics?

    <p>Non-saturable and constant half-life</p> Signup and view all the answers

    What is the expected clearance of a drug that is excreted by renal tubular secretion?

    <p>Less than renal plasma flow</p> Signup and view all the answers

    What is the primary reason why t ½ is not indicative of duration of action and dosage schedule in the case of 'hit and run' drugs?

    <p>Because their effects are irreversible</p> Signup and view all the answers

    In a two-compartment model, what is the characteristic of the early distribution phase?

    <p>It is associated with a shorter t ½</p> Signup and view all the answers

    What is the primary factor that determines the time to reach steady state levels in a drug that follows first-order kinetics?

    <p>The half-life of the drug</p> Signup and view all the answers

    Which of the following is a characteristic of single dose treatment?

    <p>It is used for acute conditions</p> Signup and view all the answers

    What is the primary reason why multiple dosing is preferred over single dose treatment?

    <p>It allows for a more consistent therapeutic level</p> Signup and view all the answers

    What is the primary factor that determines the steady state level of a drug that follows first-order kinetics?

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

    What is the primary difference between a single-compartment model and a two-compartment model?

    <p>The number of compartments of drug distribution</p> Signup and view all the answers

    Which of the following is a variant of dosage schedule?

    <p>Drugs with short plasma half-life</p> Signup and view all the answers

    What is the primary mechanism by which drugs exert their effects on the body?

    <p>By interacting with specialized target macromolecules called receptors</p> Signup and view all the answers

    Which type of drug action involves the binding of a drug molecule to the target site, making it inactive by sequestration?

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

    What is the term for a drug that binds to a site on a receptor protein and activates it to initiate a series of reactions?

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

    What is the process by which a drug-receptor complex initiates alterations in biochemical and/or molecular activity of a cell?

    <p>Signal transduction</p> Signup and view all the answers

    What is the primary role of receptors in the process of drug action?

    <p>To detect the signal and initiate a response</p> Signup and view all the answers

    Which of the following is an example of a drug that exhibits its action by inhibiting a process or selectively deaccelerating a process?

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

    What is the primary mechanism by which deferoxamine exhibits its action?

    <p>Complexation with an ion</p> Signup and view all the answers

    Which of the following is an example of a drug that exhibits its action by neutralizing the action of an existing molecule?

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

    What is the characteristic of a drug that has intrinsic activity?

    <p>It has affinity to receptors and produces a response</p> Signup and view all the answers

    Which type of drug has affinity to receptors but produces an effect opposite to that of an agonist?

    <p>Inverse agonist</p> Signup and view all the answers

    What is the term for the ratio of the range of effective doses to the range of toxic doses?

    <p>Therapeutic index</p> Signup and view all the answers

    Which mechanism of drug action involves the binding of a drug to a receptor on the surface of a cell?

    <p>Action of receptors of agonists and antagonists</p> Signup and view all the answers

    What is the term for the phenomenon where two drugs produce an effect that is greater than the sum of their individual effects?

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

    Which type of drug has affinity to receptors but produces a limited response?

    <p>Partial agonist</p> Signup and view all the answers

    What is the term for the range of doses of a drug that produces a therapeutic effect?

    <p>Effective dose range</p> Signup and view all the answers

    Which mechanism of drug action involves the binding of a drug to a receptor in the nucleus of a cell?

    <p>Cytosolic or nuclear receptors</p> Signup and view all the answers

    What is the result of long-term administration of an antagonist on the receptors?

    <p>Upregulation of receptors</p> Signup and view all the answers

    What is the difference between desensitization and tachyphylaxis?

    <p>Desensitization and tachyphylaxis are the same phenomenon</p> Signup and view all the answers

    What is the mechanism of tolerance to a drug?

    <p>A gradual decrease in responsiveness to a drug over days or weeks</p> Signup and view all the answers

    What is the result of receptor subtype variation in drug response?

    <p>Different receptors mediate different effects</p> Signup and view all the answers

    What is the effect of competitive antagonists on agonist responses?

    <p>They inhibit both responses of the agonist</p> Signup and view all the answers

    What is stereoselectivity in drug molecules?

    <p>Different biological activity for each 3-dimensional configuration of a drug molecule</p> Signup and view all the answers

    What is the relationship between structure and activity of a drug?

    <p>The structure of a drug determines its activity</p> Signup and view all the answers

    What is the significance of receptor classes in drug response?

    <p>Receptor classes influence the selectivity of a drug</p> Signup and view all the answers

    What is the primary difference between potency and efficacy of a drug?

    <p>Potency is a measure of the amount of drug necessary to produce an effect, while efficacy is a measure of the maximum effect of a drug</p> Signup and view all the answers

    What is the significance of the EC50 value in a graded dose-response curve?

    <p>It is the concentration of drug producing 50% of the maximum effect</p> Signup and view all the answers

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

    <p>A full agonist causes a maximum response, while a partial agonist causes a sub-maximal response</p> Signup and view all the answers

    What is the significance of the Emax value in a graded dose-response curve?

    <p>It is the maximum effect of a drug</p> Signup and view all the answers

    What is the primary advantage of a drug with high efficacy over a drug with high potency?

    <p>A drug with high efficacy is more therapeutically beneficial, while a drug with high potency is more toxic</p> Signup and view all the answers

    What is the primary difference between the effect of a full agonist and an antagonist on a receptor?

    <p>A full agonist activates the receptor, while an antagonist does not activate the receptor</p> Signup and view all the answers

    What is the primary reason why efficacy is a more clinically useful characteristic than potency?

    <p>Efficacy is a more therapeutically relevant characteristic than potency</p> Signup and view all the answers

    What is the primary difference between the graded dose-response relationships of a full agonist and a partial agonist?

    <p>A full agonist has a higher maximum response, while a partial agonist has a lower maximum response</p> Signup and view all the answers

    Which type of receptor is directly linked to an ion channel that opens and closes in response to agonist binding?

    <p>Ligand-gated ion channels</p> Signup and view all the answers

    What is the typical duration of responses triggered by G protein–coupled receptors?

    <p>Several seconds to minutes</p> Signup and view all the answers

    What is the primary function of the intracellular portion of G protein–coupled receptors?

    <p>G protein interaction</p> Signup and view all the answers

    Which type of receptor undergoes conformational changes to activate intracellular enzymes?

    <p>Enzyme-linked receptors</p> Signup and view all the answers

    What is the term for the molecules produced by effectors that further activate other effectors in the cell?

    <p>Second messengers</p> Signup and view all the answers

    Which of the following receptors is an example of a transmembrane ligand-gated ion channel?

    <p>Cholinergic nicotinic receptor</p> Signup and view all the answers

    What is the primary function of G proteins in G protein–coupled receptors?

    <p>Signal transduction</p> Signup and view all the answers

    Which type of receptor family does not involve a G protein in the signal transduction process?

    <p>Ligand-gated ion channels</p> Signup and view all the answers

    Study Notes

    Pharmacokinetics

    • Bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation
    • Factors that determine bioavailability:
      • Biological factors: GIT degradation, food and other drugs, absorption, first-pass metabolism, and entero-hepatic circulation
      • Pharmaceutical factors: particle size, disintegration agents, and type of excipient

    Distribution

    • Volume of distribution (Vd) is the apparent volume in which a drug is distributed in the body
    • Calculated by: Vd = Volume of distribution / Cp (plasma concentration per liter at the time of plasma-tissue equilibrium after i.v. injection)
    • Distribution involves:
      • Blood-brain and CSF barriers: water-soluble drugs cannot filter into CSF or brain; crossing occurs by diffusion or carrier-mediated transport
      • Placental barrier
      • Plasma protein binding

    Metabolism (Biotransformation)

    • Metabolic processes convert lipid-soluble drugs into water-soluble products for elimination
    • Two types of chemical reactions:
      1. Phase I reaction (non-synthetic): oxidation, reduction, and hydrolysis by microsomal enzymes
      2. Phase II reaction (synthetic): conjugation involving addition of an endogenous water-soluble group by transferases enzymes (e.g., glucuronidation, acetylation, methylation)

    Metabolism (Biotransformation) - First Pass Effect

    • Pre-systemic elimination that occurs after oral administration only
    • Includes:
      • Intestinal first pass effect (intestinal lumen and intestinal wall)
      • Hepatic first pass effect (portal circulation and microsomal enzymes)
    • Factors affecting the first pass effect:
      • Hepatic diseases (decrease first pass effect)
      • Hepatic enzyme induction (increase first pass effect)
      • Hepatic enzyme inhibition (decrease first pass effect)
      • Saturation of metabolizing enzymes (decrease first pass effect)

    Enzyme Induction and Inhibition

    • Enzyme induction: microsomal metabolizing enzymes increase, reducing drug efficacy and plasma half-life
    • Examples of enzyme inducers and affected drugs:
      • Cigarettes (benzpyrene): benzodiazepines, paracetamol, propoxyphine, and theophyline
      • Barbiturates (phenobarbitone): barbiturates, phenytoin, warfarin, and doxycycline
      • ...
    • Enzyme inhibition: microsomal metabolizing enzymes decrease, increasing drug efficacy and plasma half-life
    • Examples of enzyme inhibitors and affected drugs:
      • Cimetidine: diazepam, phenytoin, antidepressants, and theophylline
      • Erythromycin: theophylline, warfarin, and cyclosporine
      • ...

    Factors Affecting Metabolism

    • Age and sex
    • Diseases
    • Drugs
    • Genetic factors

    Metabolic Products

    • Usually biologically active → biologically inactive
    • Or active drug → active metabolite (e.g., diazepam → oxazepam and desmethyldiazepam)
    • Pro-drug (inactive) → active metabolite (e.g., prednisone → prednisolone)
    • Metabolic product can be toxic (e.g., sulphonamides → acetyl derivative)

    Elimination

    • Routes of excretion:
      • Renal
      • Liver (bile excretion)
      • Lungs (volatile gases, gaseous anesthetics, and few ethanol)
      • Gastrointestinal tract (GIT)
      • Breast milk
      • Miscellaneous (sweat, saliva, hair, nails, skin)
    • Clearance:
      • Total clearance = Cl renal + Cl liver + Cl others
      • Rate of clearance
      • Kinetics of clearance (first-order kinetics and zero-order kinetics)

    Elimination - Half-Life (t ½)

    • Time taken for circulatory plasma concentration to fall by 50%
    • Factors affecting t ½:
      • Rate of clearance
      • Distribution and storage
      • Plasma protein binding
    • Expectation of t ½:
      • Not indicative of duration of action and dosage schedule in certain cases (e.g., active metabolites, "hit and run" drugs, dose-dependent pharmacokinetics, and pathological conditions)

    Pharmacokinetic Models

    • Multi-compartment distribution: two-compartment model with an early distribution phase followed by a slower elimination phase
    • Single-compartment distribution: some drugs behave as if they are distributed to only one compartment

    Steady-State Level (SS)

    • When intake of a drug is equal to its elimination, reached after 5 half-lives (t ½)
    • Two important points:
      1. Time to reach SS level is a function of t ½ (5 half-lives) irrespective of dose or dose interval
      2. SS level reached is a function of dose and dose interval, not of t ½

    Dosage Regimen

    • Variables to consider:
      • Amount of single dose
      • Route of administration
      • Dose interval
      • Total duration of therapy
    • Single-dose treatment (e.g., hypnotics, analgesics, and purgatives) and multiple dosing
    • Variants of dosage schedule:
      • Drugs with short plasma t ½ (e.g., dopamine)

    Pharmacodynamics

    • Describes the actions of a drug on the body
    • Most drugs exert effects by interacting with specialized target macromolecules called receptors, which are present on or in the cell

    Fundamentals of Drug Action

    • Activation: A drug molecule binds to the target site, stimulating a process or selectively accelerating it (e.g., caffeine causes CNS stimulation and increased alertness)
    • Inhibition: A drug molecule binds to the target site, inhibiting a process or selectively deaccelerating it (e.g., aspirin inhibits cyclooxygenase, thereby inhibiting the formation of prostaglandins)
    • Complexation: A drug molecule binds to the target site, making a complex, thereby making it inactive by sequestration (e.g., deferoxamine chelates iron)
    • Neutralization: A drug molecule binds to the target site, neutralizing the action of the existing molecule directly through a chemical reaction or physical interaction (e.g., antacids, polyvalent anti-snake venom)

    Signal Transduction

    • Drugs act as signals, and receptors act as signal detectors
    • An agonist binds to a site on a receptor protein, activating it to initiate a series of reactions that ultimately result in a specific intracellular response
    • "Second messenger" or effector molecules are part of the cascade of events that translates agonist binding into a cellular response

    Major Receptor Families

    • Transmembrane Ligand-Gated Ion Channels: The channel is usually closed until the receptor is activated by an agonist, which opens the channel for a few milliseconds (e.g., cholinergic nicotinic receptor)
    • Transmembrane G Protein-Coupled Receptors: The extracellular portion of this receptor contains the ligand-binding site, and the intracellular portion interacts with a G protein when activated (e.g., α and β adrenoceptors)
    • Enzyme-Linked Receptors: This family of receptors undergoes conformational changes when activated by a ligand, resulting in increased intracellular enzyme activity (e.g., growth factors and insulin receptors possess tyrosine kinase activity)

    Response of Drug-Receptor Interaction

    • Agonists: Drugs that bind to receptors and produce a response (e.g., noradrenaline, acetylcholine)
    • Antagonists: Drugs that have affinity to receptors without intrinsic activity (e.g., antiadrenergic)
    • Partial Agonists: Drugs that have affinity but very low intrinsic activity
    • Inverse Agonists: Drugs that produce actions specifically opposite to those of agonists (e.g., B-carbolines)

    Combined Use of Drugs

    • Synergism: The combined effect of two drugs is greater than the sum of their individual effects (e.g., additive, potentiation)
    • Antagonism: The combined effect of two drugs is less than the sum of their individual effects (e.g., naloxone and opioid drugs)

    Therapeutic Index (Safety Margin)

    • The range of effective doses and the range of toxic doses are determined in humans
    • The therapeutic index is a measure of the safety margin of a drug, which is the ratio of the toxic dose to the effective dose

    Mechanism of Drug Action

    • On Cell Membrane: Action of receptors, enzymes, and pumps, as well as physico-chemical interactions
    • On Intracellular Constituents: Action on cytosolic or nuclear receptors, enzymes, DNA or RNA, and transport carrier molecules
    • Outside the Cell: Chemical interaction, physical mechanisms, and antimicrobial action

    Structure-Activity and Receptor Classes

    • Structure-Activity Relationship: The same receptor type may mediate two effects, and a competitive antagonist will inhibit both responses of the agonist
    • Stereoselectivity: Drug molecules have more than one 3-dimensional configuration, with different biological activity for each
    • Receptor Classes: There are multiple receptor subtypes for each endogenous ligand (e.g., Ach, NA, H, 5-HT)

    Quantitative Variation in Drug Response

    • Up and Down Regulation of Receptors: The number of receptors can increase or decrease in response to changes in receptor activity
    • Desensitization and Tachyphylaxis: A decrease in responsiveness to a drug due to changes in receptors or the loss of receptors
    • Tolerance: A gradual decrease in responsiveness to a drug over time, requiring higher doses to achieve the same effect
    • Drug Resistance: A decrease in responsiveness to a drug due to genetic changes or other factors

    Dose-Response Relationships

    • Graded Dose-Response Relations: The pharmacologic effect of a drug increases gradually as the concentration of the drug increases
    • Potency: A measure of the amount of drug necessary to produce an effect, determined by the EC50 (the concentration of drug producing 50% of the maximum effect)
    • Efficacy: The magnitude of response a drug causes when it interacts with a receptor, dependent on the number of drug-receptor complexes formed and the intrinsic activity of the drug

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    Description

    This quiz covers the concepts of pharmacokinetics and bioavailability, including the factors that determine bioavailability of a drug in the human body.

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