Tiêu đề 7. THERAPEUTIC DRUG MONIROTING.pdf ✅

PHARMD GURU Page 1 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.  In other words, TDM refers to the individualization of drug dosage by maintaining plasma or blood drug concentrations within a targeted therapeutic range or window.  Therapeutic drug monitoring involves not only measuring drug concentrations, but also the clinical interpretation of the result.  The goal of this process is to individualize therapeutic regimens for optimal patient benefit.  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.  TDM is based on the principle that for some drugs there is a close relationship between the plasma level of the drug and its clinical effect.  Another assumption is that drug metabolism varies from patient to patient.  When a precise therapeutic end point is difficult to define, monitoring of drug levels may be of considerable therapeutic assistance.  Routine monitoring is however not advocated for most drugs.  Only clinically meaningful tests should be performed.  Therapeutic drug monitoring aims to promote optimum drug treatment by maintaining serum drug concentration within a 'Therapeutic Range'. THERAPEUTIC DRUG MONIROTING
PHARMD GURU Page 2 TDM: HISTORY  The science of Therapeutic Drug Monitoring grew out of the recognition that:  Certain drugs have a narrow therapeutic range.  In concentrations above the upper limit of the range, the drug can be toxic.  In concentrations below the lower limit of the range, the drug can be ineffective.  Not all patients have the same response at similar doses.  These findings led to the development of Clinical Pharmacology departments.  However, not everyone embraced TDM testing. Some believed that TDM testing provided little or no value.  Studies were initiated to determine the clinical value of TDM testing, and in certain instances clear clinical value was demonstrated.  Today there are over 20 therapeutic drugs which are routinely monitored. TDM IN INDIA:  TDM was introduced in India in mid 1980s and last 20 years have seen its growth.  TDM in India exists in mainly 2 settings:  In Large teaching hospitals through Dept. of Clinical Pharmacology.  In Private sector (Biochemistry Labs, dedicated CPU units in Corporate hospitals like Apollo) CRITERIA FOR TDM: 1) An appropriate analytical test for drug and active metabolites must exist. 2) Drug should have a narrow therapeutic range. 3) Patients not showing adequate clinical response to a drug despite being on adequate dose. 4) The therapeutic effect cannot be readily assessed by the clinical observation (e.g. anticonvulsants, anti arrythimcs, antidepressants etc.) 5) Large individual variability in steady state plasma concentration exits at any given dose. There are several classes of drugs commonly monitored to ensure correct blood concentration, including the following:  Antiepileptics (Phenytoin, Valproic acid etc.)  Antiarrythmics (Digitalis, lignocaine etc.)
PHARMD GURU Page 3  Antibiotics (Gentamycin, amikacin, tobramycin)  Antineoplastics (Methotrexate)  Antimanics (Lithium)  Bronchodilators (Theophylline)  Immunosuppressives (Cyclosporine) INDICATIONS FOR TDM: While there may be specific individual circumstances for TDM, most indications can be summarized as follows:  Low therapeutic index.  Poorly defined clinical end point.  Non compliance.  Therapeutic failure.  Drugs with saturable metabolism.  Wide variation in the metabolism of drugs.  For diagnosis of suspected toxicity & determining drug abuse.  Drugs with steep dose response curve (small increase in dose can result in a marked increase in desired/undesired response e.g. theophylline)  When another drug alters the relationship between dose & plasma concentration e.g. plasma concentration of lithium is increased by thiazide.  Renal disease (alters the relationship between dose & the plasma concentration. Important in case of digoxin, lithium & aminoglycoside antibiotics.) TDM IS UNNECESSARY WHEN: 1) Clinical outcome is unrelated either to dose or to plasma concentration. 2) Dosage need not be individualized. 3) The pharmacological effects can be clinically. Quantified (BP, HR, Blood sugar, urine volume etc.) 4) When concentration effect relationship remains unestablished. 5) Drugs with wide therapeutic range such as beta blockers and calcium channel blockers. 6) Hit and run drugs e.g. Omeprazole.
PHARMD GURU Page 4 THE TDM PROCESS: TDM is a multidisciplinary function and requires collaboration and good communication between scientists, clinicians, nurses and pharmacologists. 1) DECISION TO REQUEST DRUG LEVEL: Decision will be based on proper reasons:  Suspected toxicity.  Lack of response/compliance.  To asses therapy following change in dosage.  Change in clinical state of patient.  Potential drug interactions due to concomitant medications. 2) THE BIOLOGICAL SAMPLE:  After decision is made, biological sample is collected for to provide measurement.  Serum or plasma samples are usually collected for TDM.  Serum separator tubes should be avoided as lipophilic drugs can dissolve in gel barrier.  Blood sample should be collected once the drug concentration has attained steady state (SS) (at-least 5 half lives at the current dosage regimen).  Levels approximating SS may be reached earlier if a loading dose has been administered (drugs with long half lives e.g. digoxin).  However, drugs with long half-lives should be monitored before SS is achieved to ensure that individuals with impaired metabolism or renal excretion are not in the risk of developing toxicity at the initial dosage prescribed.  If toxicity is suspected the concentration should be measured as soon as possible.  Immediate assay is required if there is a poor therapeutic control as in atrial fibrillation, when loading dose would be useful.  Blood samples should be collected in elimination phase rather than absorption / distribution phases.  Usually blood samples are collected at the end of the dosage interval (Trough).  For antibiotics given intravenously, Peak concentrations (30 minutes after cessation of i.v. infusion) are also measured.  Usually drug concentrations are monitored in venous blood, serum or plasma and it is important that the appropriate matrix is assayed.