Tiêu đề 9. INDICATIONS FOR TDM. PROTOCOL FOR TDM.pdf ✅

PHARMD GURU Page 1 INDICATIONS FOR TDM: INDICATIONS WHERE TDM IS IMPORTANT: 1) Drug efficacy difficult to establish clinically (phenytoin). 2) Suspected toxicity. 3) Inadequate therapeutic response. 4) Compliance concerns 5) Dosage change 6) Change in patients clinical state 7) Change in co-medications (Quinidine decreases digoxin clearance) 8) Manifestations of toxicity and disease state are similar (Theophyllin). INDICATIONS FOR TDM EXAMPLE PURPOSE A. PHARMACOKINETIC CONSIDERATIONS: Drugs with narrow therapeutic range. Lithium, Digoxin, Phenytoin, Gentamicin, valproic acid. To avoid dose related toxicity. Drugs showing conc- dependent kinetics within therapeutic range. Phenytoin, Antibiotics. Subtle adjustment of dose. To check bioavailability. - To explain non attainments of therapeutic outcome (or) Unanticipated dose related toxicity following administration of standard dose of drug. B. PHARMACODYNAMIC CONSIDERATIONS: Drugs showing wide inter- individual variation in metabolism. Tri-cyclic anti depressants (20 to 30 fold difference in anti- arrhythmics) To maintain plasma concentration within acceptable, therapeutic range. INDICATIONS FOR TDM. PROTOCOL FOR TDM
PHARMD GURU Page 2 Drugs used for prophylactic purpose. Tri-cyclic antidepressants (in endogenous depression, anti- arrhyythmics) To replace biochemical and clinical endpoints. Drugs used in patients at risk (renal failure, liver disease, metabolic disorders, compromised cardiovascular function). Amino glycoside antibiotics, Theophyllin and other bronchodilators, cardiovascular drugs. To compensate for disease mediated changes in T1/2 & clearance C. TOXICOLOGICAL AND OTHER CONSIDERATIONS: To distinguish between drugs related adverse effect from disease symptoms. Digoxin. To assist in differential diagnosis. Suspected drug-drug interaction. Quinidine-digoxin interaction (increased Digoxin concentration) To avoid toxicity. To check patient compliance. - To explain therapeutic failure with standard doses of the drug. INDICATIONS WHERE TDM IS LESS VALUE: 1) Drugs which show tolerance in their effect on continuous administration, do not demonstrate predictable concentration-efficacy relationship, like opiates, barbiturates, etc. 2) Fairly safe drugs like penicillin do not require plasma concentration measurement for purpose of dosage adjustment. 3) In situation where therapeutic effect can be easily monitored, like blood pressure, pulse rate, blood sugar, etc, the cost effectiveness of plasma measurement does not work. 4) For drugs with plasma concentrations does not correlate with the drug effect. Ex: Reserpine, MAOI. These drugs are known as ‘Hit and Run’ drugs, since their biological effective half-life outlasts their plasma Half-life.
PHARMD GURU Page 3 5) Drugs, which have better correlation of dose-effect relationship than concentration-effect relationship does not require estimation of plasma concentration. Ex: Sodium valproate 6) For drugs with an active metabolite (or) a pro drug, it is difficult to interpret plasma concentration versus effect relationship. Ex: Procainamide, Lidocaine etc. PROTOCOL FOR TDM: 1. DECISION TO REQUEST:  Any toxicity.  Lack of response.  Assessment of compliance.  Assess therapy after regimen change.  Potential drug interactions.  Chronic administration needs. 2. PATIENT DEMOGRAPHICS:  Patient information: age, address, occupation.  Indications for TDM.  Etiology, other illness.  Treatments (past, present)  Other investigations. 3. TIME OF SAMPLE WITHDRAWAL:  Proper selection of sampling time is of vital importance in obtaining an effective TDM.  The dosing interval and the deviation of dosing are the factors which influence the variation in drug concentration, reaching the steady state concentration.  The collection of sample for drugs, having shorter half-life is done at pre-dose, while for drugs having longer half-life, the collection of sample can be done at any point after the distributive phase.
PHARMD GURU Page 4 4. COLLECTION OF BIOLOGICAL SAMPLE:  Biological sample should be obtained in such a manner that, it permits significant analysis of the drug concentration in biological fluids.  Biological samples should be withdrawn after the drug reaches the steady state.  For most of the drugs (given without a loading dose) steady state concentration is raised at least after five biological half-lifes.  However, under certain conditions, TDM can be conducted prior to the attainment of steady state concentration. Ex: In case of suspected toxicity. 5. LABORATORY MEASUREMENT: SPECIFIC METHODS: 1) Colorimetry 2) UV-spectrometry 3) Fluorescence spectrometry 4) Chromatography a) Gas chromatography b) HPLC c) HPTLC d) SFC 5) Capillary electrophoresis. 6) Immunoassay: a) RIA b) Enzyme Immunoassay:  ELISA: Enzyme linked immunoassay.  EMIT: Enzyme multiplies immune-technique.  FPIA: Fluorescence polarization.  NIIA: Nephelometric inhibition. 7) LC-MS: Least count mass spectrometry. 6. STUDY PROTOCOL FOR TDM: 1) Title of the study / project 2) Investigators  Chief investigator.  Joint investigator.