1&2 – Intro + Absorption

Question 1

Pharmacokinetics

Answer 1

• “what the body does to the drug”
• A: absorption
• D: distribution
• M: metabolism
• E: excretion
• Determines concentration of drug at its sites of action (dose) and intensity of effect (response)

Question 2

Influences of ADME

Answer 2

• Genetics
• Life history (ex. age)
• Environment (ex. diet)

Question 3

Pharmacodynamics

Answer 3

• “what the drug does to the body”
• Biochemical and physiological effects of drugs and their mechanisms of action

Question 4

What is the most important factor allowing a drug to cross cell membranes?

Answer 4

• Lipophilicity
• (molecular size)

Question 5

How chemicals can cross cell membranes

Answer 5

1. Passive transport: transcellular diffusion
2. Filtration (bulk flow): paracellular transport
3. Facilitated diffusion
4. Active transport
5. Phagocytosis and pinocytosis

Question 6

1. Passive transport: transcellular diffusion

Answer 6

a. Concentration gradient
b. *most common way for drugs to cross membranes
i. Must be lipophilic

Question 7

2. Filtration (bulk flow): paracellular transport

Answer 7

a. Passive transport through cell junctions due to PRESSURE gradient
b. Most cells gaps=4nm
c. BBB gaps=0nm
d. Glomerulus gap: 70nm
e. *size of drug molecules is MOST important

Question 8

3. Facilitated diffusion

Answer 8

a. Passive transport but requires transporter to assist movement across membrane
b. Important for nutrients and electrolytes
c. Organic anion transporters (OATs) AND organic cation transporters (OCTs)
d. *important for excretion

Question 9

4. Active transport

Answer 9

a. Movement AGAINST concentration gradient
b. Requires ATP
c. All are ABC proteins (ATP-binding cassette)

Question 10

ABC proteins

Answer 10

i. Major families are multi-drug resistant proteins (MDRs and MRPs) and breast cancer resistance protein (BCRP)
ii. Names from high expression in certain cancer cells=limits chemotherapeutic treatments (‘lipophilic vacuum cleaners”)

Question 11

Two types of chemicals: pharmaceuticals

Answer 11

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

Question 12

1. Lipophilic organic chemicals

Answer 12

a. 25% of drugs, varying degrees of lipid solubility

Question 13

2. Weak organic acids and bases

Answer 13

a. 75% of drugs
b. *only non-ionized form of drug (HA or B) can passively diffuse
c. Log([protonated]/[non-protonated]) = pKa – pH
d. “like is nonionized in like”
i. Ex. weak acids are more non-ionized in an acidic solution

Question 14

Example questions: Henderson-Hasselbalch

Answer 14

1. What would be more preferentially absorbed from stomach (pH=2): a weak acid with pKa=3 or a weak acid with pKa=4?
   a. Log[HA]/[A-] = 3-2 =1, [HA]/[A-]=10
   b. Log[HA]/[A-] = 4-2 =2, [HA]/[A-]=100
   c. *drug of pKa=4 is 10x more non-ionized =more absorbed