Absorption

Question 1

What is the most important factors in absorption of drug?

Answer 1

1.Lipophilicity since it allows drugs to diffuse across the cell membranes

2.Molecular size

Question 2

Methods that chemicals cross the cell membranes

Answer 2

1.Passive transport
2. Filtration (bulk flow)
3. Facilitated diffusion
4. Active Transport

Question 3

Passive transport

Answer 3

**most common
-simple diffusion from high to low concentration
-drug molecule must be lipophilic
-transcellular diffusion

Question 4

Filtration (bulk flow)

Answer 4

-passive transport of drug (moving with water) through cell junctions due to pressure gradient
-paracellular transport
- size of drug important because gaps between cells vary

Question 5

Typical cell gap sizes

Answer 5

Most cells: 4nm
Most blood vessels: 2nm
Glomerulus: 70nm
CNS: 0nm

Question 6

Facilitated diffusion

Answer 6

-passive transport following a concentration gradient but needs a transporter
-important for nutrients and electrolytes; with certain drugs competing with them
-also important for excretion

Question 7

Major families of facilitated diffusion transporters

Answer 7

1. Organic anion transporters (OATs)
2. Organic cation transporters (OCTs)

Question 8

Active transport

Answer 8

-movement against concentration gradient
-needs ATP
-important for excretion
-present in systems in brain, liver, kidney

Question 9

Major families of Active transporters

Answer 9

**All ATP-binding cassette (ABC) proteins

1. multi-drug resistance proteins (MDRs and MRPs)
2. Breast cancer resistance protein (BCRP)

-often high expression in cancer cells; lipophilic vacuum cleaners that pump drugs out of cell… reason why drugs don’t stay in cancer cells long enough for effect

Question 10

Pharmaceutical categories influencing absorption

Answer 10

1. Lipophilic organic chemicals
2. Weak organic acids and bases

Question 11

Weak organic acids and bases

Answer 11

• 75% drugs are weak acids or bases that exist as either ionized or nonionized forms depending on the drugs pKa and solutions pH

Question 12

What form of weak acids and bases can passively diffuse across cell membranes?

Answer 12

only the nonionized form

Acid: protonated form = HA
Base: nonprotonated form = B

Question 13

Henderson-Hasselbalch equation

Answer 13

Log ([protonated]/[nonprotonated]) = pKa - pH

Question 14

Like is nonionized in like

Answer 14

1. Weak acid is more nonionized in acidic solution= can diffuse
2. Weak base is more nonionized in basic solutions

Question 15

Using henderson hasselbalch, what would a higher number ratio mean for an acid and a base

Answer 15

Weak acid: higher ratio= more protonated= more nonionized (better diffuser)

Weak base: higher ratio= more protonated= more ionized (worse diffuser)

Question 16

Ion trapping- breast milk

Answer 16

When more nonionized form of weak base diffuses into a more acidic solution, it results in more of the drug becoming ionized and therefore TRAPPED.

Ex. treating mammary gland infection with weak base antimicrobial drug will result in increased drug concentration at site of infection= increased efficacy