Group 3:

1. List the factors influencing the interpretation of TDM Report.

 Patient demographics

The patient's age, sex, body weight and ethnicity should be considered when interpreting TDM results.
Age, sex, and lean BW are particularly important for renally cleared drugs as knowledge of these allows calculation
of CrCl. Ethnicity may be an important consideration for TDM of some hepatically cleared drugs.

 Patient Clearance

If the concentration of the drug is lower than expected, the possibility of non-compliance should be
considered before a dose increase is recommended. The simplest way to check for non-compliance is to ask the
pt in a non-judgmental way about their compliance.

 Individual capacity to distribute/metabolize/ excrete the drug:

o Absorption

For example, when a patient is given a parenteral, the bioavailability of the drug is 100% therefore the
patient should always be monitored for ADRs because he/she might experience some of this effects and it can
be harmful and should be checked regularly specially that the effects are at its maximum peak.

o Distribution
If the pt has trauma or shock it will cause a decrease in blood flow therefore the distribution of a drug can
be delayed.
o Metabolism
If the patient has a disease which mainly affects the liver and the GI tract, then, the patient may encounter
problems with the metabolism of a drug, whether the drug may be metabolized faster or longer than expected
which can cause a decrease in therapeutic effects or the occurrence of ADRs.
o Excretion
Renal disfunction reduces drug clearance and may contribute to drug accumulation and increased risk of
ADR.

 Concomitant disease, Tropical disease and nutritional deficiencies:

 Ill health is a serious problem impeding progress in most developing countries.
 Some diseases are only prevalent in some or other countries such as infections, diarrhoea, worm infestations,
tuberculosis, neurocysticercosis and nutritional deficiencies, plus a higher proportion of patients with diabetes
and AIDS.
 Nutritional deficiencies are often subclinical and escape detection and they have been shown to affect drug
pharmacokinetics.

 Alternative system of medicine:
 Interaction of alternative medicines with conventional drugs affect drug activity and concentration in the
body.
 A patient with a history of generalized tonic-clonic (GTC) seizures, well controlled and with plasma phenytoin
levels within the therapeutic range, presented with sudden loss of seizure control. History revealed that he
was taking ‘shakhapushpi’ and plasma analysis showed that his phenytoin level had dropped. Experimental
studies showed that this drug had both pharmacokinetic and pharmacodynamic interactions with phenytoin.
 Ethnic differences and extrapolation of the normal range:
 The fact that interpopulation variations in drug pharmacokinetics can result in higher or lower plasma drug
concentrations is well known.
 For example, the metabolism of phenytoin via para-hydroxylation is subject to wide interindividual variation.
It has reported that the effective anticonvulsant dosage may be lower in Indians than in Europeans while other
authors have indicated that ethnic differences may have a significant influence on the plasma clearance of
phenytoin.

 Alcohol & Tobacco use:

 Chronic use of alcohol has been shown to cause non-specific hepatic microsomal enzyme induction, resulting
in increased clearance and decreased serum concentrations of hepatically cleared drugs such as Phenytoin.
 Cigarette smoking increases the hepatic clearance of theophylline and patients who have recently stopped
smoking may have unexpectedly high theophylline concentrations.

 Quality of medication and generic formulation:

Quality of products (drug content, bioavailability) is important especially for drugs with a narrow margin of
safety which is just those drugs for which TDM is relevant. Substandard products or drugs need additional quality
control to have accurate laboratory results. Eg. substandard products by observing low levels of phenytoin in
patients otherwise known to be compliant and previously having levels in the therapeutic range.

 Quality control in drug assays:

For TDM programs, quality control is vitally important and in developing countries there are hardly any
procedures for laboratory accreditation or external quality control. Variations in TDM occur when there are
changes in quality control drug assays.

 Medication or sampling errors:

In cases where the TDM result is incompatible with drug administration records, the possibility of a
medication or sampling error should be considered. For Example, the drug may have been given to the wrong
patient, or blood may have been mistakenly drawn from a patient in a neighboring bed.

 Laboratory errors:
If a laboratory error is suspected, the laboratory should be contacted and asked to repeat the assay.
Alternatively, a new blood sample can be drawn and sent to a different laboratory for assay.
 Cost effectiveness:
Rapid and cost-effective measurement of most drugs for which TDM is indicated can be achieved using
commercial kits run on automated analyzers using a number of different methodologies including fluorescence
polarization immunoassay. Most of the laboratory tests are time- consuming and require highly trained staff.
Most of the laboratory test are also expensive and may cause discomfort to the patient, thus these laboratory
exams should only be done when there is definite need of it and repetitions must be prevented.
2. What would you advise the physician in charge? Provide a clinical explanation to your advice.

We would inform the physician that the patient is hypersensitive to the medication. With that information, we
would advise the physician to lower the dose of Theophylline or prescribe a different drug with the same indication as
Theophylline.

The drug theophylline id an alkaloid related to caffeine. Its major therapeutic effect is bronchodilation which is
the goal for the 25-year-old man. However, within a population there is a wide variance of responses that may be
encountered. Some maybe susceptible while some are resistant.

According to the plasma concentration response relationship of Theophylline, at 20-30 mg/L the patient may
exhibit hypersensitivity reactions such as nausea, vomiting, tremors, palpations, and anxiety. But the patient already
exhibited those reactions at 6mg/L. These indicates that the patient is a sensitive individual that would exhibit maximal
effect even at accepted range of plasma concentration.