Therapeutic drug monitoring
Encyclopedia
Background
Therapeutic drug monitoring (TDM) is a branch of clinical chemistry and clinical pharmacologyClinical pharmacology
Clinical pharmacology is the science of drugs and their clinical use. It is underpinned by the basic science of pharmacology, with added focus on the application of pharmacological principles and methods in the real world...
that specializes in the measurement of medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
concentrations in blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. Its main focus is on drugs with a narrow therapeutic range, i.e. drugs that can easily be under- or overdosed. TDM aimed at improving patient care by individually adjusting the dose of drugs for which clinical experience or clinical trials have shown it improved outcome in the general or special populations. It can be based on a a priori pharmacogenetic, demographic and clinical information, and/or on the a posteriori measurement of blood concentrations of drugs (pharmacokinetic monitoring) or biological surrogate or end-point markers of effect (pharmacodynamic monitoring).
There are numerous variables that influence the interpretation of drug concentration data: time, route and dose of drug given, time of blood sampling, handling and storage conditions, precision and accuracy of the analytical method, validity of pharmacokinetic models and assumptions, co-medications and, last but not least, clinical status of the patient (i.e. disease, renal/hepatic status, biologic tolerance to drug therapy, etc.).
Many different professionals (physicians, clinical pharmacologists
Clinical pharmacology
Clinical pharmacology is the science of drugs and their clinical use. It is underpinned by the basic science of pharmacology, with added focus on the application of pharmacological principles and methods in the real world...
, clinical pharmacists, nurses, medical laboratory scientists, etc.) are involved with the various elements of drug concentration monitoring, which is a truly multidisciplinary process. Because failure to properly carry out any one of the components can severely affect the usefulness of using drug concentrations to optimize therapy, an organized approach to the overall process is critical.
A priori therapeutic drug monitoring
A posteriori therapeutic drug monitoring
Characteristics of drugs subject to therapeutic drug monitoring
In pharmacotherapyPharmacotherapy
Pharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....
, many medications are used without monitoring of blood levels, as their dosage can generally be varied according to the clinical response that a patient gets to that substance. In a small group of drugs, this is impossible, as insufficient levels will lead to undertreatment or resistance, and excessive levels can lead to toxicity and tissue damage.
Indications for therapeutic drug monitoring include:
- There is an experimentally determined relationship between plasma drug concentration and the pharmacological effect.
- Knowledge of the drug level influences management.
- There is narrow therapeutic windowTherapeutic windowThe Therapeutic window of a drug is the range of drug dosages which can treat disease effectively while staying within the safety range. In other words, it is the dosages of a medication between the amount that gives an effect and the amount that gives more adverse effects than desired effects...
- There are potential patient complianceCompliance (medicine)In medicine, compliance describes the degree to which a patient correctly follows medical advice...
problems. - The drug dose cannot be optimised by clinical observation alone.
Examples of drugs analysed by therapeutic drug monitoring:
- AminoglycosideAminoglycosideAn aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...
antibioticAntibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s (gentamicinGentamicinGentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...
) - Antiepileptics (such as carbamazepineCarbamazepineCarbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, phenytoinPhenytoinPhenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
and valproic acidValproic acidValproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
) - Mood stabilisers, especially lithium citrateLithium citrateLithium citrate is a chemical compound of lithium and citrate that is used as a mood stabilizer in psychiatric treatment of manic states and bipolar disorder. For the medical aspects of lithium citrate, see lithium pharmacology....
- AntipsychoticAntipsychoticAn antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
s (such as pimozidePimozidePimozide is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine . On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome...
and clozapineClozapineClozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
)
Therapeutic drug monitoring can also detect poisoning with above drugs, should the suspicion arise.