CPT2: PK principles

Question 1

What is ADME?

Answer 1

Absorption

Distribution

Metabolism

Excretion

Question 2

What is Vd?

Answer 2

The apparent Vd is the volume of fluid required to contain the drug in the body at the same concentration as in the blood

Question 3

What is bioavailability (F)?

Answer 3

The fraction of administered dose that reaches the systemic circulation in a chemically unaltered form.

Quote in % or decimal. No units

Question 4

What is the extraction ratio (E)?

How is this calculated?

Answer 4

Extraction ratio (E) is the fraction of drug that is removed from the blood or plasma as it passes through the liver

E= (C in- C out) / C in

Cl = Q_H x E

Question 5

Describe plasma protein binding in terms of drug getting to its target

Answer 5

Drug can bind to macromolecules e.g. plasma proteins. This prevents movement to the tissues as the complex is too large to pass through lipid membrane pores

Question 6

What is elimination half life? (t1/2)

Answer 6

The time taken for the concentration of drug in the body to reduce by half

Question 7

What is the rate constant (Ke)

How does this related to t1/2?

Answer 7

The fraction of a substance removed per unit time (s, min, hrs..)

They are inverse to each other. E.g. Ke high, T1/2 low.

Ke = o.693/ t1/2

t1/2 = 0.693/ Ke

Question 8

What is the relationship between t1/2 and Cl and Vd?

Answer 8

T1/2 = (0.693 x Vd) / Cl

Vd and t1/2 are proportional i.e. if Vd incr so does t1/2

Cl and t1/2 are inversely proportional i.e if Cl incr t1/2 decr

Question 9

What is the equation used to determine drug conc at a particular time?

Answer 9

Ct = C0 x e^{-ke x t}

Ct = conc at time t

C0 = conc at zero time

Ke = elimmination rate constant

t = time since drug given

Question 10

What is steady state concentration?

Answer 10

Steady-state concentration (Css) occurs when the amount of a drug being absorbed is the same amount that’s being cleared from the body when the drug is given continuously or repeatedly. … Steady-state concentration is the time during which the concentration of the drug in the body stays consistent.

Question 11

Why is steady state concentration important?

When is this reached?

Answer 11

1. Some drugs have what’s known as a narrow therapeutic window. So there’s a narrow difference between the maximum and the minimum concentrations that you would expect to find within the plasma that are acceptable. So accumulation to a steady state, that being a concentration that doesn’t fluctuate much and is within them effective but non-toxic range. Concentration range is something that’s really important.
2. within 3-5 elimination half lives (88-97% Css)

Question 12

What is the equation to work out Css?

Answer 12

Css = Rinf/ Cl

Rinf - rate of infusion

Cl - clearance

Question 13

Where might a loading dose be appropriate to use?

Answer 13

In a life threatening situation a patient may not be able to wait until for the concentratin of drug to reach the therapeutic window therefore a loading dose would be appropriate

Question 14

Question 15

What is the concept of dosing intervals?

Answer 15

T is determined by the interplay of the therapeutic window and t1/2.

Basically the balance between the right dose and frequency of dose that leads to the concentration of drug reaching the therapuetic window without exceeding that range.

The frequency and dose interval have a inverse relstioship

Question 16

What is creatinine and how does it relate to GFR?

Why is this important in regards to ADME?

Answer 16

• Waste product of muscle break down
• Creatinine is not reabsorbed, actively secreted and is filtered by the kidneys therefore i approx equal to GFR.
• This is important as drugs excreted renally are closely linked to GFR. We can therefore assume the clearance of a drug is the same of Creatinine

Question 17

What factors affect serum creatinine conc?

Answer 17

1. Production which is dependent on muscle mass which in turn depends on:
   
   1. Gender
   2. Age (declines with age)
   3. Body weight
2. Clearance rate

Question 18

Question 19

What happens to the amount of weak acid and basic drugs excreted from the body when the pH of urine varies. Why?

Answer 19

WA: When urine alkaline more excreted. When urine acidic less excreted

WB: When urine acidic more excreted. When urine alkaline less excreted.

This is due to ion trapping. In the rest of the body the drugs are failrly unionsed. They pass into the urine. If it is alkaline an WA drug will become ionised and unable to move across the biological membrane so will be cleareed