Drug Disposition and Ionization

Question 1

What is Paracellular movement?

Answer 1

• passive diffusion

- diffusion through intercellular aqueous channels

Question 2

What is Transmembrane movement?

Answer 2

• passive diffusion
• diffusion through lipid membranes and aqueous protein channels in the cell membrane
• bulk-flow resulting from osmotic or hydrostatic differences across membranes

Question 3

What is Passive Diffusion?

Answer 3

• movement down a concentration gradient

- from high to low concentration

Question 4

What is the lipid/water partition coefficient?

Answer 4

• the relative solubility of a drug in lipid as compared to water
• the higher the lipid solubility, the faster it crosses cell membranes

Question 5

What is the diffusion coefficient?

Answer 5

a measure of the diffusional mobility of a particular molecule

Question 6

What is Facilitated Diffusion?

Answer 6

• movement with a concentration gradient facilitated by a carrier
• no energy required

Question 7

What is carrier-mediated facilitated diffusion?

Answer 7

• transfer of substances across the membrane involving attachment to a specific macromolecular carrier
• this carrier system is saturable

Question 8

What is channel-mediated facilitated diffusion?

Answer 8

transport across the membrane involving opening of ion channel proteins

Question 9

What is Active Transport?

Answer 9

• carrier-mediated transport
• saturable, selective
• movement against a concentration gradient
• requires energy

Question 10

What is Primary active transport?

Answer 10

• energy directly from ATP

- uses Na-K ATPase

Question 11

What is Secondary active transport?

Answer 11

• stored energy in the Na electrochemical gradient generated by using ATP
• Na-GLU transporter in kidney
• Na-Ca exchanger in heart

Question 12

What is drug efflux?

Name an example

Answer 12

• removes drugs after being absorbed into specific cells or tissue sites
• Permeability glycoprotein system

Question 13

What is pinocytosis?

Answer 13

• drugs bind to the surface of the membrane that then invaginates and interiorizes the drug
• requires energy

Question 14

What does ionization depend on?

Answer 14

• whether the drug is a weak acid or weak base
• the pKa of the drug
• the pH of the medium

Question 15

What is the pKa?

Answer 15

equal to the pH of the medium at which the dissolved drug is 50% ionized and 50% non-ionized

Question 16

In what environment do acidic drugs ionize?

Basic drugs?

Answer 16

• acidic drugs ionize in basic environments

- basic drugs ionize in acidic environments

Question 17

What are the ionization equations for weak bases?

Answer 17

10(pKa-pH) = I/N
pKa = pH + Log[BH+]/[B]

Question 18

What are the ionization equations for weak acids?

Answer 18

10(pKa-pH) = N/I
pKa = pH + Log[AH]/[A-]

Question 19

What happens in ion trapping for weak acids?

Weak bases?

Answer 19

• weak acids are absorbed from an acidic environment and sequestered in an alkaline medium
• weak bases are absorbed from an alkaline environment and sequestered in an acid medium