Diffusion and First-order processes in PK

Question 1

We base diffusion on Fick’s Law and assume that these processes are governed by first-order kinetics. What it Fick’s law?

Answer 1

A solute will move from an area of high concentration into an area of low concentration down a concentration gradient.

Question 2

Initially the drug molecules will all be in one bulk. How do they become evenly dispersed in the solution?

Answer 2

The initial bulk will hold a lot of energy, meaning the molecules will collide against each other. Some molecules are sent in a direction, but a collision with another molecule will send it back to the bulk. Eventually, a molecule will collide and change direction, and no other collision will occur so it will keep diffusing away from the bulk. This will happen to more and more molecules and eventually, all the molecules from the initial bulk will be evenly dispersed in the solution.

Question 3

The one compartment model assumes that equilibrium between blood and organs is achieved instantaneously. When looking at the equilibrium between different organs we say that the equilibrium is PROPORTIONAL. What does this mean?

Answer 3

The concentration in all tissues won’t be the same but once equilibrium is reached, when the concentration in one tissue increases, the concentration in all other tissues will also increase proportionally. Same if concentration decreases.

Question 4

What does the two compartment disposition model imply?

Answer 4

The equilibrium between blood and some tissues will be achieved instantaneously with some tissues but will take longer in others that have slower perfusion.

Question 5

Looking at first order kinetics, how does increasing drug concentration in the body affect the rate of elimination and metabolism?

Answer 5

The higher the concentration in the body, the higher the rate of metabolism and elimination. 1st order = straight line on graph.

Question 6

What would cause the relationship between concentration and elimination to become a zero order process?

Answer 6

When the concentration of drug has become so high that all the enzyme receptor sites have become saturated so the rate of metabolism can’t increase any further. zero order = non-linear graph.

Question 7

A first order reaction depends on the concentration of how many reactants?

Answer 7

one

Question 8

What does the fraction remaining (e-K.t) tell us?

Answer 8

As time increases, the fraction of drug remaining to be absorbed/eliminated decreases.

Question 9

Name 5 ways elimination half-life can be useful in a clinical setting?

Answer 9

1. ) Duration of action
2. ) Rate of elimination
3. )Time to steady state
4. ) Dosing intervals
5. ) Time until all of drug has been eliminated from body

Question 10

What is zero-order absorption?

Answer 10

Zero-order absorption in when a drug enters the circulation at a constant rate e.g. modified release patches, IV infusion, depot injections. The rate of absorption is independent of concentration.

Question 11

What is first order absorption?

Answer 11

The rate of absorption depends on the concentration of drug available at the absorption site e.g. oral, inhaled, transdermal, IM, SC injection.