Pharmacokinetics- graphs

Question 1

How does plasma drug concentration change over time following a single dose?

Answer 1

Immediate absorption and distribution then elimination following metabolism and excretion
Lipid-soluble then more water soluble after metabolism
Amount of drug falls progressively with time

Question 2

What are the types of concentration-time relationships?

Answer 2

• First order (exponential) kinetics= a constant fraction of drug is cleared per unit time
• Zero order (saturation) kinetics= a constant amount of drug is cleared per unit time

Question 3

How does law of mass action link to first order kinetics?

Answer 3

Rate of metabolism or elimination of the drug depends on its concentration (enzyme exposure, renal filtration)
Time for plasma drug conc to half is constant
Exponential graph

Question 4

Describe first order kinetics

Answer 4

Most drugs at therapeutic conc
Predictable effect of increasing drug dose
Half-life describes the kinetics

Question 5

What is the zero order graph?

Answer 5

Linear and decreasing, half life irrelevant (depends on plasma drug conc)- saturated mechanism, as fast as elimination can go
Can’t predict exposure

Question 6

Describe zero-order kinetics

Answer 6

Metabolism has limited capacity so saturated
Elimination rate reached max (limited enzyme)
No room for further response even if drug dose inc
If administered at faster rate than clearance- progressively accumulate (ethanol, phenytoin epileptic)

Question 7

Contrast first and zero order graphs

Answer 7

Elimination rate vs dose= 1st linear, 0 increasing then plateau (saturation_
Plasma conc vs dose= 1st linear, 0 increasingly exponential (accumulation)

Question 8

How can you move from first order to zero order?

Answer 8

Enzyme saturation and rate limiting
Increasing dose increases peak plasma conc, metabolism saturated, more exposure to drug
Half-life no longer constant

Question 9

What is half-life?

Answer 9

Time taken for plasma conc to half
Only relates to first-order metabolism
Constant throughout elimination

Question 10

What happens to plasma conc when drug doses are repeated?

Answer 10

Conc needed to be kept in effective range for prolonged period of time- progressively accumulate
Accumulation continues until steady state= rate of administration= rate of elimination

Question 11

What does steady state involve?

Answer 11

Fluctuations in drug conc, peaks after administration and troughs prior to next administration
Troughs in effective range and peaks not high enough to cause adverse effects- no fluctuations if constant IV
Saw tooth degree depends on half life and frequency of administration

Question 12

Contrast long vs short half lives

Answer 12

Long= slow to reach steady-state, loading dose may be needed, slow to be eliminated, less regular dosing, atenolol (8hr)
Slow= rapid steady state, fine control, not suitable orally, more regular dosing required, dobutamine 2 hrs

Question 13

Why is it sometimes necessary to use a loading dose?

Answer 13

Long half-life drugs will not reach steady state concentration for a week- as it accumulates, conc insufficient to yield necessary pharmological effects
(sub-therapeutic)

Question 14

What is a loading dose?

Answer 14

Initial dose much higher than the maintenance dose, equivalent to amount of drug required in the body at steady state
Achieve target plasma conc before 5 half lives

Question 15

What is the optimal dose interval?

Answer 15

A compromise between convenience (adherence) and constant level of drug exposure

Question 16

What are modified release formulas?

Answer 16

Peak conc lower, trough conc higher, prolonged period in therapeutic range (nifedipine)
Allow drugs with short half-life to be given less often while having smooth onset and decline in effect

Question 17

What is the therapeutic index?

Answer 17

Ratio between the plasma conc that is required for therapeutic effects and adverse effects
Typically 50, can be as low as 3

Question 18

What factors alter the pharmacokinetic handling of drugs in individual patients?

Answer 18

Age/ Sex/ Body weight/ drug interactions/ renal, liver and GI diseases

Question 19

What is therapeutic drug monitoring?

Answer 19

Drug effect ideal way to monitor therapy progress but may not be easy to assess (antibiotics) or undesirable to wait for therapeutic failure/ adverse effects (anti-epileptics and lithium)
Requires plasma drug conc closely related to clinical effect- look for beneficial effects/ avoid adverse effects/ check for adherence