PHRD5985 Pharmacotherapy Lecture 2 - Pharmacotherapy Foundations

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  1. what the body does to the drug

    (description of changes in drug concentrations over time)
    pharmacokinetics (PK)
  2. the study of ADME
    pharmacokinetics (PK)
  3. rate and extent to which an unchanged drug leaves its site of administration
  4. movement of drug from the systemic circulation to the body tissues and intended site of action
  5. chemical alteration of a drug through an enzymatic process
  6. elimination of drugs and metabolites from the body (form of drug upon elimination)
  7. what the drug does to the body
    pharmacodynamics (PD)
  8. relationship between drug concentration and drug effect/response
    pharmacodynamics (PD)
  9. determines therapeutic effect (response, non-response, toxicity)
  10. factors of pharmacokinetics (3)
    • 1) drug dose
    • 2) biological fluid concentration
    • 3) effect site concentration
  11. factors of pharmacodynamics (2)
    • 1) effect site concentration
    • 2) pharmacologic effect
  12. the magnitude of the desired therapeutic response, and likelihood for potential toxicity, are a function of...
    the drug concentration at its site of action
  13. 2 reasons drug therapy fails
    • 1) therapy is ineffective bc concentrations are too low
    • 2) unacceptable toxicity bc concentrations are too high
  14. between upper & lower limits of concentration where region of desirable concentrations lie
    window OR range OR index
  15. PD parameters out of our control (2)
    • 1) intrinsic ADME properties of drug
    • 2) pharmacodynamics
  16. similar to adverse reaction, but usually fairly mild
    side effect
  17. unwanted/unexpected negative reaction to a medication/treatment that is used in an approved manner
    adverse reaction
  18. adverse reaction which is more severe in nature with potentially more severe consequences
  19. dose regimens (dose & frequency) are determined by... (2)
    • 1) width of therapeutic range
    • 2) ADME characteristics of drug
  20. results in standard dosing regimens being effective for some pts and ineffective or unacceptably toxic for others
    pharmacokinetic variability
  21. from a PK standpoint, absorption is defined by... (2)
    • 1) rate
    • 2) extent
  22. extent of absorption of intact drug from the site of administration into the systemic circulation
    bioavailability (F)

    expressed as % or fraction of administered dose which achieves intact absorption
  23. drug distribution is a _____ process
  24. smaller Vd = ____ concentration in blood
    • higher concentration in blood
    • (doesn't distribute well into body)
  25. units of Vd
    volume (L, mL)
  26. "apparent volume of distribution" can be calculated from ... (2)
    • 1) measured dose administered
    • 2) measured resultant concentrations
  27. important determinant of Vd
    • drug binding
    • (assumed that only unbound drug is pharmacologically active/free to distribute throughout body)
  28. most important plasma drug-binding proteins (2)
    • 1) albumin (for acidic drugs)
    • 2) Image Upload 11-acid glycoprotein (for basic drugs)
  29. 2 processes of elimination
    • 1) metabolism
    • 2) excretion
  30. loss of drug activity
  31. Type I drug metabolism
    modifications in molecular structure of drug (oxidation, hydrolysis)
  32. Type II drug metabolism
    "conjugation" of drug molecule with other compounds (sulfation, glucuronidation)
  33. most common family of metabolizing enzymes
  34. active process of kidney excretion
    tubular secretion
  35. passive process of kidney excretion
    tubular reabsorption
  36. serves as index of drug elimination; reflects intrinsic ability of organs to metabolize/excrete drug
    clearance (CL)
  37. T1/2 is influenced by... (2)
    • 1) Vd
    • 2) CL
  38. where in kidney drug reabsorption occurs
    distal convoluted tubule
  39. where in kidney drug secretion occurs
    proximal convoluted tubule
  40. volume of plasma filtered across the renal glomerulus per unit of time
    GFR (glomerular filtration rate)
  41. renal excretion of drugs correlates best with...
  42. commonly used together to assess renal function (2)
    • 1) BUN
    • 2) serum creatinine
  43. BUN
    • blood urea nitrogen
    • metabolism of amino acids into urea
  44. SCr
    • serum creatinine
    • breakdown product of creatine & phosphocreatine in skeletal muscle tissues; primarily filtered through glomerulus
  45. frequently used as an estimate of GFR
    clearance of creatinine (CrCL)
  46. Cockcroft-Gault Equation for determining CrCL
    Image Upload 2 mL/min

    *0.85 for females
  47. male IBW (kg)
    50+(2.3 * inches>60)
  48. female IBW (kg)
  49. if ABW<IBW...
    use ABW
  50. if obese (>130% IBW)...
    • use adjusted dosing weight (ADW)
    • ADW=IBW+[0.4*(ABW-IBW)]
  51. limitations of CG equation (3)
    • 1) accurate only in adult pts w/ stable kidney fcn
    • 2) CrCL calc overestimates actual GFR
    • 3) not accurate in pts w/ liver disease
  52. measurement of prothrombin time (PT) is an assessment of...
    • protein synthetic fcn
    • clotting
  53. measurement of albumin is an assessment of...
    protein synthetic fcn
  54. measurement of bilirubin is an assessment of...
    secretory function
  55. measurement of alkaline phosphatase is an assessment of... (3)
    • 1) hepatocyte integrity
    • 2) secretory fcn
    • 3) inflammation
  56. measurement of aspartate aminotransferase/alanine aminotransferase (AST/ALT) is an assessment of... (2)
    • 1) hepatocyte integrity
    • 2) inflammation
  57. Child-Pugh scored for worst liver function
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PHRD5985 Pharmacotherapy Lecture 2 - Pharmacotherapy Foundations
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