Lecture 2 1/24/24

Question 1

Why are membrane barriers important to drug function?

Answer 1

drugs with different absorptions can pass through different barriers, allowing different drugs to be used to target different treatment sites

Question 2

What are the potential mechanisms by which molecules cross a membrane barrier?

Answer 2

-transcellular passive transport
-paracellular passive transport
-transcellular facilitated transport
-transcellular active transport
-pinocytosis

Question 3

What are the characteristics of transcellular passive transport?

Answer 3

-driven by concentration gradient
-molecules have high degree of lipid solubility and some water solubility

Question 4

What are the characteristics of paracellular passive transport?

Answer 4

-intercellular gaps
-pore size varies
-driven by concentration gradient

Question 5

What are the characteristics of transcellular facilitated transport?

Answer 5

-driven by concentration gradient
-accelerated rate
-not active/no energy involved

Question 6

What are the characteristics of transcellular active transport?

Answer 6

-against a concentration gradient
-requires energy

Question 7

What are the characteristics of pinocytosis?

Answer 7

-engulfing of extracellular material via membrane vesicles
-less common
-used for large molecules

Question 8

Which factors impact the rate of diffusion?

Answer 8

-size, conformation, and water solubility
-membrane surface area
-lipid solubility
-membrane thickness
-concentration gradient

Question 9

Which factors that impact the rate of diffusion are limiting factors?

Answer 9

-membrane thickness
-potentially concentration gradient

Question 10

Which factors impact water and lipid solubility of a drug?

Answer 10

-polarity of drug
-degree of ionization/electrolytes

Question 11

How does polarity impact drug solubility?

Answer 11

-non-polar drugs are more lipid soluble
-polar drugs are more water soluble

Question 12

What is pKa?

Answer 12

the pH at which 50% of drug molecules are ionized and 50% are non-ionized

Question 13

What is ion trapping?

Answer 13

-an acidic drug can be trapped by placing it in an environment with high pH
-a basic drug can be trapped by placing it in an environment with low pH

Question 14

What is urine alkalinization?

Answer 14

trapping of an acidic drug in the urine by making the urine more basic, thus preventing the drug from reabsorbing

Question 15

What are the general characteristics of passive diffusion?

Answer 15

-no external energy spent
-net transfer is zero at equilibrium
-non-selective and non-saturable
-rate is proportional to amount

Question 16

What is a first order elimination pharmacokinetic system?

Answer 16

-constant proportion/percentage of drug is eliminated per unit time
-linear relationship when presented on a log scale

Question 17

How does exposure relate to dose in first order pharmacokinetics?

Answer 17

exposure/peak concentration is proportional to the dose

Question 18

What are the general characteristics of active transport?

Answer 18

-requires a carrier
-requires energy expenditure
-selective for specific drugs
-saturable

Question 19

What is a zero order elimination pharmacokinetic system?

Answer 19

-constant amount of drug is eliminated per unit time
-curved relationship when presented on a log scale

Question 20

What is a non-linear elimination pharmacokinetic system?

Answer 20

drug clearance mimics first-order kinetics at low concentration and zero-order kinetics at high concentration

Question 21

How does exposure relate to dose in non-linear and zero order pharmacokinetics?

Answer 21

exposure is not proportional to dose