1. Branch of pharmacology
    Study of harmful effects of chemicals on living systems
  2. Any substance/chemical that is foreign to the human body
    • Xenobiotic
    • gr. "xenos"-stranger
  3. Prodrug
    Drug that requires bioactivation to release the active form of a drug
  4. Most are proteins

    Site of action of the drug

    Binding site cannot be manipulated
  5. actions of the drug on the body

    concentration vs. effect

    MOA determines drug class
    • Pharmacodynamics
    • PD
  6. actions of the body on a drug

    concentration vs. time

    ADME properties of a drug
    • Pharmacokinetics
    • PK
  7. Pharmacogenomics
    aka Pharmacogenetics
    Study of genetic variations among humans that cause differences in PD and PK
  8. Image Upload 1
    Ideal drug will shift to the right

    Lousy drug will shift to the left
  9. number of receptors the drug selects to bind to

    measured by binding affinity
    • Drug selectivity
    • aka selective binding
  10. number of specific effects (toxic/therapeutic) that the drug produces on the body
    Drug specificity
  11. Drugs are only _______ in their actions they are not _______.

  12. No drug causes a single effect because of what 2 things?
    1) the drug will bind to more than one type of receptor

    2) the postreceptor processes are linked to many other functions
  13. List 4 things that affect selective binding
    • 1) the MW (100-1000)
    • 2) type of bond
    • 3) chirality (stereochemistry)
    • 4) effect of the receptor site
  14. Drug molecules that form _____ bonds with receptors are likely to be highly _______ and _____-acting.


  15. List the 3 types of bonds in order from strongest to weakest
    • 1) covalent (irreversible)
    • 2) electrostatic (ionic, hydrogen, van der waals)
    • 3) hydrophobic (requires a precise fit)
  16. How do you terminate covalent binding?
    The body must degrade the drug-receptor complex and synthesize a new receptor molecule
  17. What do these drugs have in common?

    Asprin, Plavix (clopidrogel), Beta-lactam antibiotics
    They all form covalent bonds with the receptor molecule
  18. The more chiral a drug is the more ______ the binding.
  19. "Dextro" signifies the ____-enatiomer
    S (+)
  20. "Levo" signifies the ___-enatiomer
    R (-)
  21. With some racemic mistures the patient is receiving doses where 50% is either _________ or _________.

  22. Racemic mixtures are sometimes used because of the _________ of the molecule in the body
  23. bind to and activate the receptor
  24. What is an effector?
    Binds to and indirectly activates the receptor via signal transduction that produces the effect
  25. Some drugs mimic the effect of the receptor agonist by ________ the molecules responsible for terminating the action of the __________ agonist, and do NOT bind to the receptor but ______ the pharamcological effect


  26. activates the receptor

    has maximum pharmacological effect

    has high intrinsic efficacy

    stabilizes receptor into the active conformation
    Full agonists
  27. activates the receptor

    has a low pharmacological effect

    has low intrinisc efficacy

    can act as an agonist or antagonist
    Partial agonists
  28. does not activate the receptor

    stabilizes the receptor in its inactive conformation

    opposite effects of conventional agonists
    Inverse agonists
  29. enhances the efficacy/binding affinity of the agonists

    bind to an allosteric site other than the binding site of the agonist
    • Allosteric agonists
    • aka allosteric activators
  30. bind to but do not activate the receptor

    block the binding of agonists

    receptor specific

    can be competetive/noncompetitive
    • Pharmacologic antagonists
    • aka blockers
    • aka receptor-specific antagonists
  31. inhibit/reduce the binding affinity of the agonist

    binds to allosteric sites on the receptor

    non-competitive & receptor specific

    not overcome by increasing concentration of the agonist
    • Allosteric antagonists
    • aka allosteric inhibitors
    • aka receptor-specific allosteric antagonists
    • aka noncompetitive allosteric antagonists
  32. What does ADME stand for?
    • A-Absorption
    • D-Distribution
    • M-Metabolisim
    • E-Excretion
  33. True or false, the Ri conformation is favored in equilibrium?
    True-the inactive conformation is more stable
  34. In the ___ confirmation the receptor can produce an effect in the _______ of a ligand.

  35. What is consitutive activity?
    The effect produced in the absence of a ligand in Ra confirmation
  36. What factors determine the degree of constitutive activity? (4 total)
    1- The equilibrium between Ri and Ra

    2- receptor density

    3- concentration of coupling molecules

    4- number of effector molecules
  37. Humans exist in a _____ level of constitutive activity in the absence of an agonist
  38. _____ agoinsts have a high affinty for binding to the _R__ confirmation and fully stabilize it.

  39. A partial agonist has an affinity for which form(s)?
    Both the active and inactive
  40. Partial agonists have what type of intrinsic efficacy?
  41. In the presence of a full agonist a partial agonist acts as ___________
    an antagonist (blocker)
  42. Binding to a pharmacologic antagonist does what to the equilibrium?
    It does NOT shift it

    No effect will be observed
  43. __________ has equal affinity for binding to both the Ra and Ri forms.
    Pharmacologic antagonists
  44. Inverse agonists have a higher affinity for binding to the _______ form of the receptor molecule
  45. What two mechanisms terminate drug action at the receptor?
    1- dissociation of the drug from the receptor

    2- biosynthesis of a new receptor molecule
  46. What is an inert binding site?
    Binding of a drug to a nonregulatory inert molecule that will NOT alter the biologic function of response
  47. Name 4 types of drug receptors:
    • 1- regulatory proteins
    • 2- enzymes
    • 3- transport proteins
    • 4- structural proteins
  48. In what 3 ways does the receptor influence clinical use of drugs:
    • 1- responsible for establishing the relationsihps between dose/concentration vs. pharmacologic effects
    • 2- responsible for selectivity of drug action
    • 3- mediate actions of agonists and antagonists
  49. Image Upload 2

    What is the name of this equation?

    What does it tell us?
    Graded dose-response curve

    Concentration vs. effect
  50. What is Emax?
    Maxium response produced by the drug

    Highest value on y-axis

    Measures drug efficacy
  51. What is EC50? (ED50)?
    The concentration that produces 50% of the maximum effect

    • C=concentration
    • D=dose
  52. EC50 and potency have a(n) ________ relationship

    (When EC 50 is ____ potency is _____)


  53. Image Upload 3

    What is the name for this equation?

    What does it tell us?
    Graded dose-binding curve

    Bound drug vs. Unbound drug
  54. What is Bmax?
    Total concentration of receptor sites that are bound to the drug

    Maximum number of drug-receptor complexes you can form at the receptor site
  55. What is KD?
    What does it tell us?
    • Equilibrium dissociation constant
    • Characterizes affinity for binding
  56. KD and binding affinity have a(n) ________ relationship

    (When KD is ____ affinity is ______)


  57. Emax and drug potency have a(n) _______ relationship

    (When Emax is ____ drug efficacy is _____)
    • direct
    • low
    • low
  58. Efficency in coupling is determined by what 2 things?
    1- Initial conformational change in the receptor

    2- Biochemical events (and how complicated they are)
  59. Spare receptors are said to exist if.....
    ....the Emax(max pharmacologic effect) is obtained at less than max occupation of receptor molecules (Bmax)
  60. If EC50 is ______ than the KD spare receptors are said to exist
  61. What does it mean when EC50 and KD are equal?
    Spare receptors do not exist
  62. Spare receptors are caused by what 2 mechanisims?
    1- duration of activation may be much greater than the duration of the drug-receptor interaction

    2- The number of receptor molecules may exceed the number of effector molecules
  63. Sensitivity of a cell or tissue depends on what 2 things?
    1- affinity of the receptor for binding of the agonist

    2- degree of spareness of the receptor
  64. Spareness and sensitivity have a _______ relationship

    (____ spareness leads to ______ sensitivity in the tissue)


  65. reversibly bind to the same binding site of the agonist on the receptor molecule without activating the receptor
    • competitive antagonists
    • aka reversible

  66. The success of competetive agonists depends on what 2 things?
    1- its own concentration

    2- concentration of the endogenous agonist

    **you would have to adjust the dose frequently
  67. irreversibly bind to the same binding site of the agonist without activating the receptor
    • noncompetitive antagonists
    • aka irreversible

  68. Irreversible binding can be caused by what 2 things?
    1- extremely high affinity for that antagonist to bind

    2- they form covalent bonds
  69. Irreversible antagonists cause a ________ shift of the max in dose-response curve

    (tell you the receptors are being sealed up which is why you cannot see full max effect)
  70. The duration of action of an irreverible antagonist depends on what?
    The rate of turnover of receptor molecules
  71. What is a disadvantage of irreversible antagonists?
    there is no way to cure an overdose
  72. Partial agonists produce a ______ response than do full agonists
  73. Partial agonists are also used as ________
    competitive antagonists
  74. What do these 3 drugs have in common?
    protaminm dimercaprol, pralidoxime
    They are all chemical antagonists
  75. What is chemical antagonism?
    Occurs when 1 drug prevents the second drug from binding to its receptor site
  76. True or false, a chemical antagonist does not depend on interaction with the agonist's receptor
    true, it is NOT receptor-specific
  77. What do these 3 hormones have in common?
    insulin, epinephrine, glucagon
    They are all physiologic antagonists
  78. What is physiologic antagonism?
    The physiologic antagonist binds to a different receptor molecule producing an opposite effect than the drug it antagonizes

    *NOT receptor-specific
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