Therapeutic Drug Monitoring

Question 1

Definition of therapeutic drug monitoring?

Answer 1

The measurement of drug concentrations in body fluids (plasma, serum, blood etc.)

Question 2

Why is it important to monitor plasma drug concentrations?

Answer 2

Avoid toxicity
Optimize dose and/or therapeutic response
Detect changes in pharmacokinetics
Monitor compliance

Question 3

ADME rates are based on?

Answer 3

Age, weight gender
Genetics
Co-morbid diseases

Question 4

Which drugs are suitable for TDM?

Answer 4

High inter-patient variability in plasma concentrations

Narrow therapeutic range

When the pharmacological effect persists and is dependent on the plasma concentrations

Availability of cost-effective, accurate drug assays with rapid turn around time and a small blood volume requirement

Question 5

Examples of wide therapeutic range drugs requiring TDM?

Answer 5

NSAIDS
Most antibiotics
Beta-blockers

Question 6

Examples of narrow therapeutic range drugs requiring TDM?

Answer 6

Lithium
Warfarin
Neuroleptics (e.g. phenytoin, phenobarbital)
Gentamcyin, vancomycin, amikacin
Digoxin
Immunosuppressives

Question 7

What is the rationale for TDM?

Answer 7

A closer relationship exists between serum concentration of a drug and the effect compared to the dose of the drug and the effect

Question 8

Indications for TDM?

Answer 8

Patient factors:
Lack of clinical response
Non/poor adherence
Suspected toxicity

Co-morbidities:
Drug-drug interactions
Renal/hepatic impairment
Malabsoprtion

Special populations:
Pregnancy
Paediatrics

Question 9

Goals in therapy?

Answer 9

Provide constant concentrations
Achieve transient high concentrations without toxicity
Varying concentrations between individuals on same dose

Question 10

How many half-lifes does it take to reach steady state?

Answer 10

5 half-lives

Question 11

Definition of “steady-state”?

Answer 11

When renal intake and excretion are equal

Question 12

What must one do if they want to reach the steady state quicker?

Answer 12

Administer a loading dose

Question 13

MEC?

Answer 13

Minimal effective concentration - the concentration above which efficacy is expected in most patients

Question 14

MTC?

Answer 14

Maximum total concentration - upper concentration above which the rate and severity of adverse effects becomes unacceptable

Question 15

Things to consider when interpreting a drug concentration?

Answer 15

Time of sample collection
Time of last dose
Dosage regime
Indication for drug monitoring

Question 16

Possible reasons for the drug concentration to be lower than expected?

Answer 16

Incorrect dose given
Patient non-compliance
Rapid elimination
Timing of sample

Question 17

Possible reasons for the drug concentration to be higher than expected?

Answer 17

Error in dosage regime
Overdose
Decreased renal/hepatic function
Slow elimination

Question 18

Definition of “saturable” metabolism?

Answer 18

If a certain concentration reached, the elimination will not increase, but there will be an increased risk of toxicity

Question 19

“Non-saturable” metabolism?

Answer 19

If the dose increases, the elimination increases

Question 20

Why TDM with phenytoin?

Answer 20

Concentration-time profile unpredictable in an individual (PK variable)
Saturable metabolism
Small dose increases can produce disproportionate rises in blood levels and toxicity

Question 21

Why TDM with Theophylline?

Answer 21

Narrow therapeutic index
Increased metabolism if used with anticonvulsants, Rif, smokers
Decreased metabolism if used with cardiac failure, elderly, liver disease, drugs