Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

What the body does to the drug (ADME)

Question 2

What is pharmacodynamics?

Answer 2

What the drug does to the body

Question 3

What is the volume of distribution?

Answer 3

V is a measure of drug concentration in plasma

Question 4

What are the important plasma proteins?

Answer 4

Albumin: carries acidic and neutral drugs

Alpha-1-acid glycoprotein (orosomucoid): Carries basic drugs, steroids, and protease inhibitors

Question 5

What type of drugs are likely to need a loading dose?

Answer 5

Drugs with long half lives

Question 6

What are the two routes of elimination?

Answer 6

Unchanged via the kidneys

Metabolised via the liver

Question 7

What factors affect clearance?

Answer 7

Body weight
Body surface area
Cardiac output
Drug-drug interactions
Extraction ratio
Genetics
Hepatic and renal function 
Plasma protein binding

Question 8

What is the elimination rate constant

Answer 8

K is the fraction of drug eliminated per unit time

The amount eliminated changes but the fraction is constant!

Question 9

How many half lives are needed to reach steady state?

Answer 9

4-5 half lives

Question 10

Dose independent pharmacokinetics

Answer 10

First order
Independent of C and dose
Half life, clearance, volume of distribution and K are all constant
Linear relationship

Question 11

Dose dependent pharmacokinetics

Answer 11

Non linear
Zero order
Dependent on C and dose 
Half life, CL, and V depend on C or A
One or more ADME processes are saturable

Question 12

What is the normal GFR for an adult?

Answer 12

100ml/min

Question 13

How is dose adjusted in renal impairment?

Answer 13

Croft-Gault equation

Question 14

Define absorption

Answer 14

Process by which the unchanged drug moves from the site of administration to the site of measurement within the body

Question 15

What factors affect drug distribution?

Answer 15

Body tissue characteristics
Disease state
Drug lipid solubility 
Physiological pH in various regions
Extent of protein binding

Question 16

What factors can decrease the concentration of Albumin?

Answer 16

RF
Hepatic cirrhosis
Burns
Stress/trauma
Pregnancy

Question 17

What factors increase Alpha-1-glycoprotein?

Answer 17

RF
Arthritis
Surgery
MI
Stress/trauma

Question 18

When can TDM be used?

Answer 18

High probability of therapeutic failure : low therapeutic index, pharmacokinetic variability, genetic factors, co-morbidities etc

When problems arise : non-compliance, unusually rapid elimination, pharmacodynamic resistance to drug, to confirm toxicity

No easily measurable physiological parameters

Question 19

Give examples of drugs needing TDM

Answer 19

Gentamicin
Vancomycin
Digoxin
Theophylline
Phenytoin

Question 20

Equation for loading dose

Answer 20

LD = (desiredC x V) / (S x F)

Question 21

Equation for Volume of Distribution

Answer 21

V = Dose / InitialC

Question 22

Equation for Rate of Elimination

Answer 22

CL x C = K x A

Question 23

Equation for Total Body Clearance

Answer 23

CLmetabolic + CLrenal

Question 24

Equation for Clearance

Answer 24

CL = K x V = (SFD) / Css x Dose Interval

Question 25

Equation for Concentration at time t

Answer 25

Ct = InitialC x e^(-kt)

Question 26

How does protein binding affect drug activity?

Answer 26

The unbound drug is active

Highly bound drugs are likely to have a narrow therapeutic index