Pharmacokinetics + Pharmacodynamics

Question 1

What is the bioavailability for drug administered via IV?

Answer 1

100%
Doesn’t have to be metabolised or absorbed

Question 2

How do you calculate bioavailability?

Answer 2

AUC_oral / AUC_IV

Question 3

What is bioavailability affected by?

Answer 3

Absorption:
- formulation
- age
- food
- vomiting/malaboprtion
- previous surgery
.
First pass metabolism:
- metabolism before reaching systemic circulation

Question 4

What are the four processes involved in pharmacokinetics?

Answer 4

Absorption
Distribution
Metabolism
Excretion

Question 5

Pharmacodynamics vs pharmacokinetics

Answer 5

• pharmacodynamics: what the drug does to the body
• pharmacokinetics: what the body does to the drug

Question 6

What is bioavailability?

Answer 6

The proportion of a drug which entered circulation after being introduced to the body to exert an effect

Question 7

What factors affect therapeutic distribution?

Answer 7

• blood flow
• capillary structure
• lipophilicity + hydrophilicity
• protein binding (albumin + glycoproteins)

Question 8

Types of protein binding of drugs

Answer 8

• albumin: acidic drugs
• glycoproteins: basic drugs

Question 9

How do you calculate Vd?

Answer 9

dose / [drug]_plasma

Question 10

Why shouldn’t modified release tablets be crushed/removed from capsules before taking?

Answer 10

• Modified release tablets are designed to release dose in controlled gradual manner over extended periods.
• Crushing tablet will change the release profile
• Given a greater dose in a shorter duration
• possible GI irritation

Question 11

What is bioequivalence?

Answer 11

The similarity of two medications:
- expansive brand name vs cheap non branded
- both the same drug + have the same effect

Question 12

What does a smaller + larger apparent Vd suggest?

Answer 12

• smaller Vd: drug is confined to plasma + ECF
• larger Vd: drug is distributed throughout tissues

Question 13

What factors affect CYP450 enzymes?

Answer 13

Age
Hepatic disease
Blood flow
Chronic alochol
Smoking

Question 14

Routes of drug excretion

Answer 14

• urine
• sweat
• tears
• breast milk
• faeces
• hair?

Question 15

Why is the apparent volume of distribution described as apparent?

Answer 15

It is a hypothetical value that assumes the drug is uniformly distributed throughout the body at the same concentration as the plasma

Question 16

Why is apparent volume of distribution useful clinically?

Answer 16

Drug distribution information
Dosage adjustments
Drug half life predictions

Question 17

What are the three outcomes of initial drug metabolism in terms of drug activity?

Answer 17

• no change in activity
• activation
• deactivation

Question 18

What is the clinical significant of drug protein binding in regards to distribution?

Answer 18

• only unbound drug molecules are active + able to distribute + exert their effects
• high protein bound drugs tend to have a smaller Vd > large proportion remains in bloodstream

Question 19

What is clearance?
What are the units?

Answer 19

Volume of blood cleared per unit time
ml/min

Question 20

How do you calculate clearance?

Answer 20

Rate of elimination from body/[drug]_plasma

Question 21

Zero order vs first order elimination kinetics

Answer 21

• zero order: same amount is being eliminated per given time | linear
• first order: same proportion is being eliminated per given time | curved line (

Question 22

How to calculate half life

Answer 22

t_1/2 = 0.693 x V_d / CL

Question 23

What is the half life?

Answer 23

When 50% of drug has been eliminated
t_1/2

Question 24

What types of elimination kinetics do most drugs exhibit?

Answer 24

First order kinetics
Same proportion of drug is eliminated per time

Question 25

Relationship between rate contrast (k) and clearance

Answer 25

k is proportional to CL

Question 26

Relationship between rate contrast (k) and Vd

Answer 26

k is inversely proportional Vd

Question 27

How could you increase the half life?

Answer 27

Decrease clearance
Increase Vd (not really possible)

Question 28

What exhibits zero order elimination kinetics?

Answer 28

Very high doses of drugs
Alcohol
Salicylic acid
Phenytoin

Question 29

What is needed to reach the steady state plasma concentration?

Answer 29

4-5 half lives

Question 30

Why are you still able to pick up traces of recreational or performance enhancing drugs long periods of time after taking?

Answer 30

It takes 4-5 half lives for the conc. to be negligible
This can take a while to occur

Question 31

How do you calculate the rate of administration?

Answer 31

Maintenance dose x bioavailabilty / t

Question 32

How do you calculate the maintenance dose?

Answer 32

Clearance x [plasma]that we want
———————————————— x dose interval
Bioavailability

Question 33

How do you calculate loading dose?

Answer 33

Loading dose = Css x V_d

Question 34

What is Css?

Answer 34

Steady state plasma conc

Question 35

What needs to be considered in dosing schedules?

Answer 35

• to be safe
• maintain dose within therapeutic range
• achieve adherence

Question 36

Why may a drug be preferentially delivered by oral administration?

Answer 36

• slower administration - first pass metabolism needed for pro drugs
• less invasive
• adherence
• can be taken at home
• if target is within the gut

Question 37

How do you calculate the therapeutic index?

Answer 37

Median toxic / median effective

Question 38

CYP table

Question 39

What are the 4 main pharmacodynamic targets?

Answer 39

Receptors
Ion channels
Enzymes
DNA