"Therapeutic - Drug - Monitoring"

THERAPEUTIC DRUG MONITORING

Therapeutic drug monitoring

 

INTRODUCTION:

Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient’s bloodstream, thereby optimizing individual dosage regimens. It is unnecessary to employ TDM for the majority of medications, and it is used mainly for monitoring drugs with narrow therapeutic ranges, drugs with marked pharmacokinetic variability, medications for which target concentrations are difficult to monitor, and drugs known to cause therapeutic and adverse effects. The process of TDM is predicated on the assumption that there is a definable relationship between dose and plasma or blood drug concentration, and between concentration and therapeutic effects. TDM begins when the drug is first prescribed, and involves determining an initial dosage regimen appropriate for the clinical condition and such patient characteristics as age, weight, organ function, and concomitant drug therapy. When interpretingconcentration measurements, factors that need to be consideredinclude the sampling time in relation to drug dose, dosage history,patient response, and the desired medicinal targets.The goal of TDM is to use appropriate concentrations of difficultto-manage medications to optimize clinical outcomes in patientsin various clinical situations.

Therapeutic drug monitoring (TDM) is generally defined as the clinical laboratory measurement of a chemical parameter that, with appropriate medical interpretation, will directly influence drug prescribing procedures. Otherwise, TDM refers to the individualization of drug dosage by maintaining plasma or blood drug concentrations within a targeted therapeutic range or window. By combining knowledge of pharmaceutics, pharmacokinetics, and pharmacodynamics, TDM enables the assessment of the efficacy and safety of a particular medication in a variety of clinical settings . The goal of this process is to individualize therapeutic regimens for optimal patient benefit. Traditionally, TDM involves measuring drug concentrations in various biological fluids and interpreting these concentrations in terms of relevant clinical parameters. Clinical pharmacists and pharmacologists use pharmacokinetic principles to assess these interpretations.

OBJECTIVES:

 To attain rapid and safe concentration of drug in plasma within the desired therapeutic range in order to provide the safest approach to optimal drug therapy.

 To coordinate clinical pharmacology, pathology, chemistry, toxicology, analytical chemistry and medicine.

 To remove empirical trial and error approach.

PURPOSE OF THERAPEUTIC DRUG MONITORING :

Performing TDM requires a multidisciplinary approach. Accurate and clinically meaningful drug concentrations are attainable only by complete collaboration by a TDM team, typically comprised of scientists, clinicians, nurses, and pharmacists. Excellent communication among team members is necessary to ensure that best practices in TDM are achieved The indications for drug monitoring have widened to include efficacy, compliance, drug-drug interactions, toxicity avoidance, and therapy cessation monitoring Plasma drug concentration measurements alone may be helpful in several circumstances, although each indication may not apply equally to every drug Measuring plasma concentrations may be helpful, however, as a low measurement reflects either poor recent compliance or under treatment. Poor compliance is implicated if the patient is prescribed a dose that is unlikely to be associated with a measured low concentration or if a previous measurement suggested that the plasma concentration should be higher for the given dose. When initiating drug therapy, the physician may find it useful to measure the plasma drug concentration and tailor the dosage to the individual. This directive applies to all drugs, although it is most important for those with narrow therapeutic ranges such as lithium, cyclosporine, and aminoglycoside antibiotics.

The appropriate indications for therapeutic drug monitoring (and examples) include:

 Toxicity

 - diagnosing toxicity when the clinical syndrome is undifferentiated (unexplained nausea in a patient taking digoxin)

 - avoiding toxicity (aminoglycosides, cyclosporin)

 Dosing

 - after dose adjustment (usually after reaching a steady state)

 - assessment of adequate loading dose (after starting phenytoin treatment)

 - dose forecasting to help predict a patient's dose requirements1 (aminoglycosides)

 Monitoring

 - assessing compliance (anticonvulsant concentrations in patients having frequent seizures)

 - diagnosing under treatment (particularly important for prophylactic drugs such as anticonvulsants, immunosuppressants)

 - diagnosing failed therapy (therapeutic drug monitoring can help distinguish between ineffective drug treatment, non-compliance and adverse effects that mimic the underlying disease).

INDIVIDUALIZATION OF DOSAGE REGIMEN

 Dosage Regimen - Dosage regimen is defined as the manner in which the drug is taken.

 For some drugs like analgesics single dose is efficient for optimal therapeutic effect however the duration of most illnesses are longer than the therapeutic effect produced by a single dose, In such cases drugs are required to be taken on a repetitive bases over a period of time depending upon the nature of illness.

 An optimal multiple dosage regimen is the one in which the drug is administered in suitable doses with sufficient frequency that ensures maintenance of plasma conc. Within the therapeutic window for entire duration of therapy.

INDIVIDUALIZATION

 Rational drug therapy requires Individualization of Dosage regimen to fit a particular patient’s needs. The application of Pharmacokinetic principles in the dosage regimen design for the safe and effective management of illness in individual patient is called as Clinical Pharmacokinetics.

 Same dose of drug may produce large differences in pharmacologic response in different individuals; this is called as Intersubject variability. In other words it means that the dose required to produce a certain response varies from individual to individual.

BIOLOGICAL FACTORS:

1. Age:

 The factors that affect drug absorption, including gastric pH, gastric emptying, intestinal motility , and blood flow change with age.

 Thus, in the neonate a condition of achlorhydria persists for the first week of life, and only after 3 years of age gastric acid secretion approaches the adult value

 Gastric emptying is also prolonged and peristalsis is irregular during the early months of life

 Skeletal muscle mass is also much reduced, and muscle contractions, which tend to promote both blood flow and spreading of an intramuscularly administered drug, are relatively feeble

 An elevated gastric pH, a delay in gastric emptying, and both diminished intestinal motility and blood flow are also seen in the elderly

 Differences in drug absorption among adults, the very young and the elderly, are therefore expected

 Generally, changes in rate rather than in extent of absorption are found

 These changes tend to be less apparent in the elderly than in the very young

 Children often appear to absorb drugs as completely and, if anything, more rapidly than adults

 Accordingly, in subsequent calculations of dosage, extent of absorption is assumed not to vary with age

 A major exception is for some first-pass drugs given to the elderly, where oral bioavailability increase with age

 The half life is shortest around 1 year of age; it is longest in both newborn and elderly patients

 In premature newborns, the urinary excretion is even more depressed per kilogram of body weight than in full-term neonates

 Metabolic activity may take months to mature, the time required for full maturation varies with the enzyme system

 A decrease in unbound metabolic clearance in the elderly patient has been demonstrated for an increasing number of drugs, especially, those principally by oxidation

 These changes may be associated in part, with the decrease in the size of the liver, as a proportion of body weight, from 2.5 % in the young adult to 1.6 % at 90 years of age

2. Body Weight:

 One aspect of aging is body weight

 Weight, 3.5 kg at birth, increases rapidly in childhood and adolescence and then declines slowly in the elderly

 As body water spaces, muscle mass, organ blood flow, and organ function are related to body weight, the volume of distribution, clearance and hence dosage regimens of drugs also depend on body weight.

For more information on TDM, Pls go through this link and read the exciting information provided by World Health Organisation (WHO)

Therapeutic drug monitoring