Lecture 6

Question 1

Factors affecting membrane transport of chemicals

Answer 1

– Molecular weight/shape.
– Polarity.
– Membrane composition.
– Membrane thickness

Question 2

Mechanisms of transport across membranes

Answer 2

– Simple diffusion.
– Filtration.
– Facilitated diffusion.
– Active transport.
– Endocytosis.

Question 3

Simple Diffusion

Answer 3

• Transport proceeds in the direction of the concentration
  gradient.
• Transport is not saturable.
• No structural specificity.
• No energy requirement.

Question 4

Partition Coefficient

Answer 4

Governs diffusion of uncharged drugs

Question 5

Filtration

Answer 5

• Transport of xenobiotics due to bulk flow of fluid phase.
• Requires large pores within the membrane.
• Kidney is the best example.

Question 6

Facilitated Transport

Answer 6

– Proceeds in the direction of the concentration
gradient.
– Has no energy requirement

Question 7

Active Transport

Answer 7

– Can proceed against a concentration gradient.
– Requires energy.

Question 8

Endocytosis

Answer 8

Two mechanisms:
– Phagocytosis (particulates).
– Pinocytosis (bulk liquid).

Question 9

Dermal Route of Exposure

Answer 9

• Xenobiotic must cross several cell
  layers to reach blood vessels and
  be absorbed.
• Factors:
  – Lipid solubility.
  – Ionization.
  – Hydration of skin site.
  – Thickness of skin site.
• Specialized skin structures.

Question 10

Inhalation Route of Exposure

Answer 10

• Gases, vapors, and aerosols.
• Rapid absorption from lung due to:
  – Large surface area.
  – Thin barrier.
  – High rate of blood flow.
• Breathing rate and blood flow are important.

Question 11

Respiratory Excretion

Answer 11

– Exhalation of volatiles.
– Mucociliary clearance

Question 12

GI/Liver Excretion

Answer 12

– Biliary excretion.
– Unabsorbed material.
– Direct excretion.

Question 13

Urinary Excretion

Answer 13

Glomerular filtration.
– Tubular secretion

Question 14

Other Excretion

Answer 14

– Milk.
– Sweat.
– Hair.
– Nails.
– Saliva

Question 15

Prodrug

Answer 15

A pharmacologically inactive chemical entity that, when metabolized
or chemically transformed, is converted into a pharmacologically
active drug.

Question 16

Inhalation Route of Exposure

Answer 16

Gases, vapors, and aerosols.
* Rapid absorption from lung due to:
– Large surface area.
– Thin barrier.
– High rate of blood flow.
* Breathing rate and blood flow are important

Question 17

Drug Distribution Rate and extent depend on:

Answer 17

– Relative blood flow to tissues.
– Size, lipid solubility, and ionization
state of molecule.
– Plasma protein binding.
– Tissue protein binding.
– Specialized barriers

Question 18

Drug Distribution Phases:

Answer 18

– Initial phase determined by blood flow.
– Later phases determined by tissue
affinity.

Question 19

Drug Distribution Some tissues can store drugs:

Answer 19

– Fat (highly lipid soluble drugs).
– Bone (e.g., lead)

Question 20

High solubility (in blood) substances

Answer 20

have “ventilation limited” excretion

Question 21

Low solubility (in blood) substances

Answer 21

have “perfusion” limited excretion

Question 22

Elimination of Particulates from the Lung

Answer 22

• Particles cleared via the “mucociliary
  escalator”.
• Particles also cleared via lymphatic drainage.
• Dissolved substances from particles are
  removed via bloodstream or lymph.