Pharmacokinetics

Question 1

Define pharmacokinetics. (2)

Answer 1

What the body does to the drug.

Absorption, distribution, metabolism, excretion.

Question 2

Describe 10 patient factors that determine the pharmokinetics of a drug. (10)

Answer 2

Renal function, age, sex, diet, liver function, pyrexia, exercise, infection, pregnancy/breastfeeding, immunisations.

Question 3

Define bioavailability. (4)

Answer 3

A measure of drug absorption into the body compartment where it can be used, normally the circulation.
Bioavailability = (Area under curve for oral intake) / (Area under curve for IV administration) x 100.

Question 4

Describe what affects bioavailability. (4)

Answer 4

Absorption factors: formulation, age, presence of food, vomiting, malabsorption.
First pass metabolism: metabolism before reaching the systemic circulation (gut wall / lumen or liver)

Question 5

Describe the properties of a drug or a patient that will affect the distribution of a drug. (8)

Answer 5

Blood flow - highly vascular target = more distribution to target organ.
Lipophilicity - increased lipophilicity = more distribution across cell membranes
Protein binding - more protein binding = different distribution.
Volume of distribution of the drug.

Question 6

Explain the negative things about highly protein bound drugs. (4)

Answer 6

Long mechanism of action because it will slowly dissociate
Slow mechanism of action because only free drug exerts effect.
Can be displaced from the protein by another drug and suddenly have a large concentration in the plasma, which can be toxic.

Question 7

Describe Vd. (5)

Answer 7

Dose / [Drug]plasma at T=0.
A hypothetical measure of how widely a drug is distributed.
The amount of fluid required to contain the total amount of drug in the body at the same concentration as in the plasma before any secondary metabolism occurs ([Drug]plasma).

Question 8

Describe the different characteristics of drugs with high or low Vds. (2)

Answer 8

Smaller Vd = drug confined to plasma and extracellular fluid.
Larger Vd = drug widely distributed throughout all tissues.

Question 9

Describe the stages of metabolism that follow drugs administration. (3)

Answer 9

Phase I enzymes - CYP450s
Phase II enzymes
Conjugation and excretion

Question 10

Describe how Phase I enzymes can change drugs into active forms. (4)

Answer 10

Can activate them - LDOPA > dopamine

Can change structure - codeine > morphine

Question 11

Describe patient factors that can affect Phase I metabolism. (7)

Answer 11

Age, race, sex, hepatic Disease, blood flow, alcohol and cigarette history.

Question 12

Describe the Phase I metabolism based issues that are highlighted with polypharmacy. (2)

Answer 12

CYP inducers or inhibitors can affect the metabolism of the other drugs.

Question 13

Describe the forms of elimination. (8)

Answer 13

Mostly renal

But also sweat, breast milk, pulmonary, biliary, faeces, saliva, genital.

Question 14

Describe the factors that affect the elimination of water soluble drugs (6)

Answer 14

GFR
Protein binding 
Competition for transporters
Lipid soluability 
pH of drug
Flow rate

Question 15

Describe t1/2. (4)

Answer 15

t1/2 = 0.693 x (Vd / Clearance).
Time in which [plasma] of drug decreases by half.
t1/2 is proportional to Vd and inversely proportional to clearance.

Question 16

Describe cases when the clearance is compromised. (5)

Answer 16

Reduced drug metabolism
Renal or hepatic stenosis 
DDIs
Haemorrhage 
Reduced GFR

Question 17

Explain the differences between zero order and first order kinetics. (4)

Answer 17

Zero order = rate of elimination is constant (so as the dose increases, the elimination doesn’t, so it builds up in the blood.
First order = rate of elimination is proportional to drug concentration (so as the dose increases, so does the elimination rate).

Question 18

Describe drugs that exhibit different orders of kinetics. (5)

Answer 18

Most drugs exhibit first order kinetics at thereputic doses (so they can excrete more when there is more) and zero order kinetics at higher doses (they reach their max excretion rate, so it is independent of how much drug there is).
Alcohol, aspirin and phenytoin all exhibit zero order kinetics anyway.

Question 19

Explain the term “steady state”. (3)

Answer 19

The state where the variance of a drug in concentration between doses exists exclusively within the therapeutic range. This occurs in about 4-5 t1/2.

Question 20

Describe the use of a loading dose. (2)

Give an example of a case where you would need a loading dose. (1)

Answer 20

Give a high dose initially to get into the therapeutic ranges, and then give the maintenance dose to keep it there.
Where you would need immediate control eg anti-epileptics.

Question 21

Explain how you would work out the loading dose recruited for a specific drug. (3)

Answer 21

Loading dose = Vd x [Drug]target (CpSS) / bioavailability.

Question 22

Describe the method of calculating the maintenance dose. (4)

Answer 22

Once the CpSS has been reached, dosing should match clearance to maintain the desired clinical effect
Dose(m) = clearance x (CpSS/bioavailability)
Only works in first order kinetics