PHA 327-Membranes

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kyleannkelsey
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219134
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PHA 327-Membranes
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2013-05-11 20:02:05
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PHA 327 Membranes
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PHA 327-Membranes
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  1. What are the players in drug delivery?
    • Dosage form
    • Absorption organ
    • Target Organ
    • Target Cell
  2. What is the ophthalmic route of administration?
    Eye
  3. What is the site of auricular/otic drug delivery?
    Ear
  4. What phase is the lipid bilayer?
    Fluid
  5. What are the types of Carrier mediated movement across membranes?
    • Facilitated diffusion
    • Active transport
  6. What is another term for vesicular mediated transport?
    Phagocytosis
  7. What are the types of Passive transport?
    • Around cells
    • Diffusion though membranes
  8. What would you expect from a Vmax/Concentration plot of an actively transported molecule?
  9. What would you expect from a Vmax/Concentration plot of an passively transported molecule?
  10. What is the long term for ABC transporters?
    ATP binding cassette transporters
  11. What do ABC transporters do?
    • Aid in movement across the membrane
    • RNA translation
    • DNA repair
  12. Describe the composition and location of ABC transporters:
    Membrane proteins
  13. What health related activities are ABC transporters involved in?
    • Cystic fibrosis and other diseases
    • Tumor resistance
  14. What are the drug substrates for Amino acid transporters?
    • Baclofen
    • Cyclosporin
    • L-dopa
    • Gabapentin
    • methyldopa
  15. What are the drug substrates for Peptide transporters?
    • b-lactam antibiotics
    • ACE inhibitors
    • methyldopa
    • Cyclosporins
    • Cephalexins
  16. What two transporters are peptide transporters?
    hPEPT1 and HPT1
  17. What two transporters are nucleoside transporters?
    CNT1 and 2
  18. What three transporters are organic anion transporters?
    OATP1, 3, and 8
  19. What three transporters are Organic cation transporters?
    OCT1 and OCT2
  20. What two transporters are Bile acid transporters?
    • IBAT
    • ISBT
  21. What are the drug substrates for Nuscleoside transporters?
    • Zidovudine
    • Zalcitabine
    • dupyridamole
  22. What are the drug substrates for Organic anion transporters?
    • Ceftriaxoine
    • Benzoic Acid
    • Mthotrexate
    • Pravastatin
  23. What are the drug substrates for Organic cation transporters?
    • Thiamine
    • Desipramine
    • Quinidine
    • Midazolam
    • verapamil
  24. What are the drug substrates for Bile acid transporters?
    • Chlorambucil
    • Thyroxine
  25. What law describes passive movement across a membrane?
    Fick's law
  26. What is diffusion?
    Process of mass molecular transfer due to random molecular motion and a concentration gradient
  27. What is the driving force for diffusion?
    Concentration gradient
  28. What pharmaceutical examples were given for diffusion?
    • Transport of drugs through a polymeric membrane
    • Percutaneous absorption
    • GI absorption of a drug
  29. What is a Barrier in terms of diffusion?
    An area of resistance to diffusion
  30. What is a Membrane?
    A solid or semisolid sheet that separates and regulates phases or materials passing through it.
  31. What is Flux (J)?
    The amount of material moving through a cross-sectional area over time.
  32. What is Fick's Law used to measure?
    Flux
  33. What is proportional to?
    The concentration gradient
  34. Is the diffusion coefficient a constant?
    No
  35. Does the diffusion coefficient stay the same for a given product?
    • No, changes with:
    • Temperature
    • Concentration
    • Solvent properties
    • Chemical nature of the diffusant
    • Pressure
  36. Summarize Fick's first law:
    The Flux is proportional to the Concentration gradient
  37. Summarize Fick's second Law:
    The rate of change in a concentration gradient within the diffusional field is proportional to the rate of change in the conc. gradient at the point in the field
  38. What law would you use to describe diffusion through anisotropic membrane?
    Fick's first law
  39. What is isotropic?
    Not varying in magnitude
  40. What are the assumptions of Diffusion through isotropic membranes?
    • Quasi steady state
    • No aqueous boundary layer exists
  41. Describe graph of release vs Time of a drug diffusing through an isotropic membrane:
    2
  42. Non-linear at first
    Later becomes constantly linear
  43. What is the Lag time in terms of the graph:
    The point of interaction for the extrapolated steady state portion of the curve
  44. What is the lag time in terms of the movement of the diffusant?
    The time for the penetrant to establish a uniform concentration gradient
  45. What is a transporter that moves substances out of the cell?
    Efflux transporter
  46. What type of transporter moves substances into the cell?
    Uptake transporter
  47. What are the critical factors in influencing whether a transporter is creating efflux or uptake?
    The orientation and location in the cell
  48. Describe the rate of drug uptake of a carrier mediated drug:
    Fastest at the beginning, slows and eventually plateaus
  49. Describe the rate of transport of a drug that moves by passive diffusion:
    Steady state of flux (linear)
  50. Are there more transporters on the Apical (lumen side) of the epithelial GI cells or the basolateral side?
    The Lumen side
  51. Where is P-gp located within the cell?
    Apical membrane
  52. Where is P-gp located within the body?
    GI, Liver, Kidneys, Blood Brain Barrier
  53. The action (efflux or uptake) of PGP is what?
    Depends on the location in the membrane and cell
  54. What is P-gp?
    Transporter called P-Glycoprotein
  55. What Drug properties are important when considering transportation (7)?
    • Size
    • Polarity
    • Charge
    • Diffusion
    • Facilitated diffusion
    • Administration (IV vs Oral)
    • Competitive binding
  56. What transporter factors contribute to drug movements?
    Location on apical or basolateral surface (Uptake vs. Efflux)
  57. What family of transporters does P-Glycoprotein belong to?
    • ABC transporters
    • Encoded for by MDR1
    • Efflux pump
    • Apical epithelial cell expression
  58. What therapies does P-gp effect?
    Chemotherapies and others
  59. Why is P-gp so important?
    It expels drugs
  60. What is a P-gp substrate?
    A drug that is expelled by P-gp
  61. What considerations are applicable to P-gp substrates?
    Need to consider the route of administration (GI especially tough)
  62. Describe the basic characteristics of a P-gp substrate:
    • MW = 250-1200
    • Usually lipophilic
    • Usually basic or uncharged
  63. Describe the significance of Loperamide and P-gp:
    • Loperamide is an m-opioid receptor antagonist which could have analgesia, sedation, etc. (systemic effects)
    • Does not have any systemic effects, only GI
    • Is a P-gp substrate that is expelled in the GI
  64. If Loperamide is administered PO, what effects does it have?
    Anti-diarrheal
  65. What drug can elevate the effects and allow Loperamide to enter the CNS?
    Quinidine
  66. What would a patient experience if quinidine were administered with loperamide?
    Increased anti-diarrheal effects and increased CNS effects
  67. What is quinidine?
    Potent P-gp inhibitor
  68. The majority of drug movement happens through what process?
    Passive mechanisms
  69. What are the critical parameters of drug movement?
    • Concentration gradient
    • Rate constants
  70. What is pharmacodynamics?
    What the drug does to the body
  71. What is Pharmacokinetics?
    What the body does to the drug

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