Svensson Lec 3

Question 1

describe the effects of drug distribution on the conc. vs. time curve

Answer 1

• Can be different for different people
• When in plasma it can be readily distributed and restricted to that area and be a declining linear line (perfusion)
• When in other areas it will move to other tissues as the plasma or other area is declining and make a small to big then decreasing curve
• A drug only distributed in the vascular space will exhibit mono exponential blood conc. Vs. time curve after IV admin (permeability)

Question 2

what is perfusion rate limited

Answer 2

Readily penetrates endothelial membrane so that the delivery rate of the drug to the tissue by perfusing blood is what determines how quickly a drug will appear in tissue

Question 3

what is permeability rate limited

Answer 3

• Slowly passes across the endothelial membrane
• Drug is delivered to tissues more quickly than moving to the blood then tissues

Question 4

what is convection

Answer 4

• Pressure is the driving force
• Use of large molecules such as MABs

Question 5

what is diffusion

Answer 5

• Most drugs undergo here
• Uses concentration gradient as driving force of movement

Question 6

how can differences in pH result in drug trapping of drugs

Answer 6

• When concentration of a drug within a tissues has pH differences that lead to ionization states of the drug to in the tissue environment
• ionized drugs cant cross membranes so we change the urine pH to enhance urinary excretion of drugs

Question 7

how can plasma protein binding effects distribution and effect of drugs

Answer 7

• We want free drug as it can move back and forth
• Drugs that are bound to RBCs, proteins, etc. can’t pass the membrane
  –>Blood brain barrier
  –Tight junctions have no permeation
  –Negative head groups limits diffusion for acids
  – High conc. of Pgp leads to high efflux activity

Question 8

what are the 4 mechanisms drugs can reach the CNS

Answer 8

• Appropriate physicochemical properties
• Utilize an existing transporter
• Disruption of BBB
• Direct administration into the CNS

Question 9

what molecule or drug is best for pregnancy women

Answer 9

large polar molecules

Question 10

what are the 3 barriers of drug entry in the brain

Answer 10

1. Blood-Brain Barrier
2. Blood-Arachnoid Barrier
3. Blood-CSF Barrier