ADVANCED BLOOD SCIENCE
DR. WALSH
THERAPEUTIC DRUG MONITRING
Definition:
Use of drug measurements in body fluids as an aid to management of patients receiving drug
therapy for the cure, alleviation or prevention of disease, whilst minimising the risk of
toxicity.
The primary determinant of clinical response is concentration achieved at site of action.
There are certain criteria for TDM:
1) Narrow therapeutic range (window)
2) Overdose symptoms are similar to disease being treated
3) Drug produces abnormalities in hepatic/renal clearance
a. Because liver and kidney are main sites for clearance and metabolism of
drugs.
4) Drug absorption varies with dose
TDM due to clinical problems:
1) Establishing/changing dose regime
a. The patient may require different drug, different dose and it is important to
monitor those changes
2) Failure to achieve therapeutic control
3) Loss of control in previously stabilised patient
4) Check for toxicity
DOSAGE:
Suboptimal (subtherapeutic) – low [plasma]
o Just below the therapeutic window
Above therapeutic threshold, drug clinically effective
Above toxic threshold, adverse effects
Therapeutic window, [plasma] between therapeutic & toxic thresholds
,Y-axis = plasma concentration It takes time for some drugs to establish the
correct plasma levels – antidepressants,
X-axis = time antibiotics
After several similar doses – steady state (usually 4-5 half-lives)
It oscillates between peaks and troughs
Stable relationship between dose and effect is the key purpose of TDM
SAMPLING
, Take measurements immediately pre-dose (trough concentration) – as they are most
reproducible
Peaks are more relevant to diagnosis of toxicity
Should always take note of time of sampling and last date.
INTERPRETATION
If the concentration is lower than expected – the most likely cause could be non-
compliance (patient not sticking to the instructions)
If the concentration is higher than expected – the possible causes are hepatic or renal
failures – they cant metabolise and transport waste properly. Also, the change in other
drug therapy could cause increase in plasma concentrations of a drug.
It is important to remember that therapeutic range is just a rough guide and not
decisive test.
INTER-INDIVIDUAL VARIATION
This is another important aspect of drug monitoring. Each individual will react differently to
the drug and his body will deal differently with the drug. It is important to take notice of that
, when prescribing the medication/therapy. There are two main distinctions within the
variation:
1) Pharmacokinetics – what body does to the drug
2) Pharmacodynamics – what drugs do to body
Non-compliance is a very common source of serious complications associated with drug
therapy monitoring. Essentially the patient is responsible for taking the prescribed drug. This
is especially important in remission or prophylactic (epilepsy).
Non-compliance is also easily detected – by blood tests (low or non-present plasma levels of
the drug)
Variable compliance is more difficult to detect and deal with – this happens when patient
takes the drug, then stops for few days, then take double dosage etc.
PHARMACOKINETIC FACTORS (BIOAVAILABILITY)
This refers to amount of drug reaching the circulation
There is a considerable variation in % absorbed – this is known as bioavailability (F)
dose reaching circulation
F=
dose administered
This varies between drugs, individuals and dosage forms (the pill, powder, IV
injection all will react differently)
Bioavailability depends on number of factors including:
1) Dissolution properties
DR. WALSH
THERAPEUTIC DRUG MONITRING
Definition:
Use of drug measurements in body fluids as an aid to management of patients receiving drug
therapy for the cure, alleviation or prevention of disease, whilst minimising the risk of
toxicity.
The primary determinant of clinical response is concentration achieved at site of action.
There are certain criteria for TDM:
1) Narrow therapeutic range (window)
2) Overdose symptoms are similar to disease being treated
3) Drug produces abnormalities in hepatic/renal clearance
a. Because liver and kidney are main sites for clearance and metabolism of
drugs.
4) Drug absorption varies with dose
TDM due to clinical problems:
1) Establishing/changing dose regime
a. The patient may require different drug, different dose and it is important to
monitor those changes
2) Failure to achieve therapeutic control
3) Loss of control in previously stabilised patient
4) Check for toxicity
DOSAGE:
Suboptimal (subtherapeutic) – low [plasma]
o Just below the therapeutic window
Above therapeutic threshold, drug clinically effective
Above toxic threshold, adverse effects
Therapeutic window, [plasma] between therapeutic & toxic thresholds
,Y-axis = plasma concentration It takes time for some drugs to establish the
correct plasma levels – antidepressants,
X-axis = time antibiotics
After several similar doses – steady state (usually 4-5 half-lives)
It oscillates between peaks and troughs
Stable relationship between dose and effect is the key purpose of TDM
SAMPLING
, Take measurements immediately pre-dose (trough concentration) – as they are most
reproducible
Peaks are more relevant to diagnosis of toxicity
Should always take note of time of sampling and last date.
INTERPRETATION
If the concentration is lower than expected – the most likely cause could be non-
compliance (patient not sticking to the instructions)
If the concentration is higher than expected – the possible causes are hepatic or renal
failures – they cant metabolise and transport waste properly. Also, the change in other
drug therapy could cause increase in plasma concentrations of a drug.
It is important to remember that therapeutic range is just a rough guide and not
decisive test.
INTER-INDIVIDUAL VARIATION
This is another important aspect of drug monitoring. Each individual will react differently to
the drug and his body will deal differently with the drug. It is important to take notice of that
, when prescribing the medication/therapy. There are two main distinctions within the
variation:
1) Pharmacokinetics – what body does to the drug
2) Pharmacodynamics – what drugs do to body
Non-compliance is a very common source of serious complications associated with drug
therapy monitoring. Essentially the patient is responsible for taking the prescribed drug. This
is especially important in remission or prophylactic (epilepsy).
Non-compliance is also easily detected – by blood tests (low or non-present plasma levels of
the drug)
Variable compliance is more difficult to detect and deal with – this happens when patient
takes the drug, then stops for few days, then take double dosage etc.
PHARMACOKINETIC FACTORS (BIOAVAILABILITY)
This refers to amount of drug reaching the circulation
There is a considerable variation in % absorbed – this is known as bioavailability (F)
dose reaching circulation
F=
dose administered
This varies between drugs, individuals and dosage forms (the pill, powder, IV
injection all will react differently)
Bioavailability depends on number of factors including:
1) Dissolution properties
