Absorption and Factors Affecting Absorption

Question 1

Cell membrane characteristics?

Answer 1

Passive transport by simple diffusion (Log P)

• Phospholipid bilayer
• Protein channels
• Aqueous channels

Question 2

Log P Database?

Answer 2

1. .) Based on octanol /water coefficient
2. ) Fat solubles diffuse easier
3. ) Water soluble do not readily diffuse

Question 3

Routes of absorption?

Answer 3

1. .) Ingestion - environmental
2. ) Inhalation - occupational
3. ) Dermal/skin - both
4. ) IP, SQ, IV, IM - experimental animal

Question 4

Weak acids and bases characteristics?

Answer 4

Weak acids:
-       Mostly unionized
-       Lipid soluble
-       Absorbed through membranes
Weak bases:
-       Mostly ionized
-       Water soluble
-       Not absorbed through skin

Question 5

Impact of pH on absorption?

Answer 5

At low ph:
- Weak acids not ionized - absorbed
- Weak bases ionized
At high pH
- Weak acids ionized
- Weak bases not ionized - absorbed

Question 6

Special transport?

Answer 6

Active transport - energy required
- Most common
- Transport cycle with transporter proteins
Facilitated transport/diffusion
- Similar but no concentration gradient required
- May use proteins as transporters

Question 7

Characteristics of active transport?

Answer 7

1. .) Movement against electrochemical or concentration gradient
2. ) Saturated at high concentrations
3. ) Competition possible for chemicals of like structure
4. ) Energy required - can be slowed by inhibitors

Question 8

Oral Ingestion? (What, How, Mechanism)

Answer 8

What - Foods & water
How - Hand to mouth contact (major route of exposure to children**)
Mechanism:
- Passive diffusion predominates
- Limited active transport
- Occurs all along GI tract from mouth to anus

Question 9

Factors affecting oral absorption?

Answer 9

Passive diffusion:

• Solubility in GI tract
• pH of chemical and portion of GI tract
• Surface area of parts of GI tract
• Residence time in segment

Question 10

Susceptibility of newborns? (Oral Ingestion)

Answer 10

1. .) pH of newborn GI tract higher
   - More absorption of weak acids
2. ) More E. coli

Question 11

Species variability? (Oral Ingestion)

Answer 11

1. .) pH varies by two orders of magnitude
2. ) man has very few microbes compared to rodents w/ monkey having the most
3. ) Changes in rate of excretion between species

Question 12

Inhalation exposure?

Answer 12

Common in workplace, env.
Gases and vapors:
-       Passive diffusion most common
-       The turbinates of the nose
-       Mucosal solubility** -> water solubles

Question 13

Rates of absorption? (Inhalation)

Answer 13

1. ) Perfusion limited - gases with low blood/air partition coefficient depends on blood flow
2. ) Ventilation limited - gases with high blood/air partition coefficient depends on rate of respiration

Question 14

Inhalation of aerosols and particles? (The bronchial tree)

Answer 14

Nasopharyngeal
-       > 5 microns
Tracheobronchial
-       2-5 microns
Pulmonary
-       Alveoli < 1 micron

Question 15

Clearance issues with particles?

Answer 15

1. .) Particles in N. area removed by blowing, sneezing, wiping
2. ) Particles in T. area cleared by action of cilia
   - Asbestos and smoking
3. ) Particles in alveoli poorly cleared

Question 16

Percutaneous?

Answer 16

1. .) Occupational and env.
2. ) Skin Structure
   - Epidermis
   - Appendages

Question 17

Cross section of skin?

Answer 17

Epidermis:
-       Stratum corneum
-       Outer barrier, diffusion
-       Rate-limiting step
-       Penetration dependent on Flux
Dermis:
-       Easily penetrated

Question 18

Skin structure - the appendages?

Answer 18

1. .) Sweat glands
2. ) Hair follicles
3. ) Minor route of exposure

Question 19

Factors affecting dermal absorption?

Answer 19

1. .) Thickness of the stratum cornium
2. ) Hydration of stratum cornium
3. ) Degree of appendages
4. ) Hair cover
5. ) Species differences - pesticides

Question 20

What is absorbed? (dermal absorption)

Answer 20

1. .) Stratum cornium hydration favors water soluble
2. ) Stratum cornium lipid center favors non polar
3. ) Substances at extremes NOT absorbed

Question 21

Special routes - animal research?

Answer 21

1. .) Intravenous (IV) - directly into blood
2. ) Intraperitoneal (IP) - rapid absorption
3. ) Subcutaneous (SQ) - under the skin, slower
4. ) Intramuscularly (IM) - slow absorption

Question 22

What does toxicity depend on?

Answer 22

Rate of absorption, must also consider metabolism**