Therapeutic Drug Monitoring Flashcards
Drug response variability occurs due to:
1) Pharmacokinetics: Variation in absorption, distribution, metabolism or excretion
2) Pharmacodynamics: Variation at/or beyond tissue receptors or other macromolecular drug targets
What is the continuous variable that must be monitored when dosing?
Biological response;
What is the biological response to a drug closely linked to?
Desired therapeutic outcome of a drug
Drug monitoring is needed to reduce the risk of:
A clinical event (stroke, heart attack, pulmonary
embolism, etc.).
What biological response is monitored when taking antihypertensive drugs?
Blood pressure
What biological response is monitored when taking statins?
Serum cholesterol
What biological response is monitored when taking Warfarin?
International Normalized Ratio (INR)
Is there always a continuous variable to monitor?
No
How can you identify pharmacokinetic variability?
By measuring drug concentrations in plasma or serum
Measuring drug concentrations in plasma or serum may usefully guide:
Dose adjustment
What is therapeutic drug
monitoring?
Measuring drug concentrations in plasma or serum in order to guide dose adjustment.
Measurements of drug concentrations in plasma are most useful when:
1) There is a direct relationship between plasma concentration and pharmacological or toxic effect, and a therapeutic range has been established. (Different dose = bad)
2) Drug effect can NOT readily be assessed quantitatively by clinical observation.
3) Inter-individual variability in plasma drug concentrations from the same dose is large
4) Narrow/low therapeutic index
5) Polypharmacy with anticipation of serious interactions
6) When drug “isn’t working”: “Apparent resistance” to the action of a drug needs an explanation. (when non-compliance is suspected)
Which drugs have an established therapeutic range that shouldn’t be messed around with?
1) Drugs that act via active metabolites
2) Drugs with irreversible actions
What could restrict the usefulness of plasma
concentrations measurement?
Tolerance
Which drug has a very high inter-individual variability?
Phenytoin
Low therapeutic index means:
Ratio of toxic concentration/effective concentration is < 4
What is a non-pharmacological reason for therapeutic
drug monitoring?
Clinical toxicology purposes (Poisoning)
Drug concentration at the site of action is related to:
Drug effect
Drug effect should be proportional to:
Plasma drug concentration
A constant tissue to plasma drug concentration ratio only occurs during:
The terminal β-phase of
elimination
When does the plasma concentration NOT reflect the concentration at the site of action accurately?
Early on in the dosing interval (If you JUST gave the patient his meds, for example)
When should the therapeutic drug monitoring measurements be made?
When distribution of the drug has been completed.
What thing is CRITICAL for the therapeutic drug monitoring measurement to be useful?
Timing of blood sampling
Should you do routine or random blood sampling when therapeutic drug monitoring?
NO
When is blood sampling useful?
When the drug concentration reaches a steady-state
When is a blood sample taken if you are repeatedly dosing a patient?
Just before the next dose to assess the ‘trough’ concentration
What is the trough concentration?
The concentration of drug in the blood immediately before the next dose is administered
What is the peak concentration?
Highest level of a medication in the blood
How is the peak concentration determined?
By taking a blood sample after distribution has been completed
Advice on the interpretation of information obtained by measurement of serum drug
concentration should be obtained from:
A local therapeutic drug-monitoring service (clinical pharmacology and/or clinical pharmacy departments)
Plasma drug concentrations must always be interpreted in the context of:
The patient’s clinical state
WHAT DONT WE LIKE WHEN BLOOD SAMPLING?
RANDOM MEANINGLESS BLOOD SAMPLING
What is the optimum sampling time for Digoxin?
1) Trough
OR
2) >8 hours post-dose
Time to steady state for Digoxin?
7-10 days
What is the optimum sampling time for Lithium?
> 12h post-dose
Time to steady state for Lithium?
3-7 days
What is the optimum sampling time for Clozapine?
Trough
Time to steady state for Clozapine?
5-7 days
What is the target clozapine/norclozapine ratio for Clozapine?
1.3
What are the aminoglycoside antibiotics?
1) Gentamicin
2) Amikacin
3) Tobramycin
4) Neomycin
5) Streptomycin
What is the optimum sampling time for aminoglycoside abx?
1) Peak: 1hr post-dose (30-60)
2) Trough
What is extended-interval aminoglycoside therapy?
Aminoglycoside abx given once daily
Time to steady state for aminoglycoside antibiotics?
10-15hrs with normal renal function
What is the optimum sampling time for Vancomycin?
1) Peak: 1hr post-dose (30-60min)
2) Trough
Time to steady state for Vancomycin?
20-35hrs with normal renal function
Teicoplanin is an antibiotic used against:
Gram-positive bacteria
What is the optimum sampling time for Teicoplanin?
Trough
Time to steady state for Teicoplanin?
14 days or more
Phenytoin has ___(linear/non-linear) pharmacokinetics?
Non-linear pharmacokinetics
Non-linear pharmacokinetics means:
Dose-dependent
What can affect the pharmacokinetics of Phenytoin?
Concurrent renal or hepatic disease
What can affect the distribution of Phenytoin?
Pregnancy
Which lab value is necessary for
appropriate interpretation of Phenytoin concentration?
Serum albumin concentration
What is the optimum sampling time for Phenytoin/Fosphenytoin?
1) If steady state: Any (long half-life)
2) If short-term (Fosphenytoin): Trough
Time to steady state for Phenytoin/Fosphenytoin?
2-6 days
What is the optimum sampling time for Carbamazepine?
Trough
Time to steady state for Carbamazepine?
2-6 days
What is the optimum sampling time for Ethosuximide?
Trough
Time to steady state for Ethosuximide?
5-15 days
What is the optimum sampling time for Lamotrigine?
Trough
Time to steady state for Lamotrigine?
5-7 days
What is the elimination half-life of Lamotrigine?
20-35hrs
Is the elimination half-life of Lamotrigine longer or shorter in children?
Shorter
What is the elimination half-life of Lamotrigine when given with enzyme inducers?
15hrs
What is the elimination half-life of Lamotrigine when given with Valproate?
60hrs
What is the optimum sampling time for Valproate?
Trough
Time to steady state for Valproate?
3-7 days
Protein binding for valproate is normally:
95%
If you increase the dose of valproate, protein binding will become:
80%
What is the optimum sampling time for Zonisamide?
1) Any (long half-life)
2) Trough (advised)
Time to steady state for Zonisamide?
2 weeks
Plasma concentration of Methotrexate is an important predictor of:
Toxicity
What should be given with Methotrexate to avoid toxicity?
Folinic acid
What is the optimum sampling time for Methotrexate?
24, 48, and 72hrs post high-dose therapy
Time to steady state for Methotrexate?
1-2 days of chronic low dosing
What are some immunosuppressants?
1) Cyclosporine
2) Sirolimus
3) Tacrolimus
4) Mycophenolate
What is a common problem in children taking Cyclosporine?
Compliance
Deterioration in post-transplant renal function in patients taking Cyclosporine can reflect either:
1) Graft rejection due to
inadequate cyclosporine concentration
2) Toxicity from excessive concentrations
Sirolimus use should be monitored, especially when:
1) Used with Cyclosporine
2) There is hepatic impairment
3) During or after treatment with inducers or inhibitors of drug metabolism
What is the optimum sampling time for Cyclosporine?
1) Trough
2) 2hrs post-dose
Time to steady state for Cyclosporine?
2-6 days
What is the optimum sampling time for Sirolimus?
Trough
Time to steady state for Sirolimus?
5-7 days
What is the optimum sampling time for Tacrolimus?
Trough
Time to steady state for Tacrolimus?
2-5 days
What is the optimum sampling time for Mycophenolate?
Trough
