1. Immunology and immunodiagnostics
Lecture 8

2. TDM
Therapeutic drug monitoring is the measurement of specific drugs at timed intervals in order to maintain a relatively constant concentration of the medication in the bloodstream.
To provide information relevant to the diagnosis and management of the patients suspected to have taken overdose.
To screen for the presence of drug of abuse.

3. Need of TDM 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.

4. Drugs should have a narrow "therapeutic index”
Steady state varies from person to person and depends on
Age
General state of health
Genetic makeup
interference of other medications
Various disease states

5. Therapeutic index
a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies).

6. Therapeutic Index High therapeutic index Low therapeutic index NSAIDs
Aspirin
Tylenol
Ibuprofen
Sedative/hypnotics
Benzodiazepines
Most antibiotics
Beta-blockers
Low therapeutic index
Lithium
Neuroleptics
Phenytoin
Phenobarbital
Some antibiotics
Gent/Vanco/Amikacin
Digoxin
Immunosuppressives

7. DO ALL DRUGS NEED TDM? Drugs that do not need TDM:
Drugs used for treating diseases with having end point
BP, HR, cardiac rhythm, blood sugar, blood cholesterol and triglycerides, urine volume, body temperature, inflammation, pain, headache, etc.
Drugs with less complicated pharmacokinetics.
Drugs that used to treat less complicated or not life threatening diseases

8. COMMONLY MONITORED DRUGS
1. Bronchodilators: Theophylline
2. Antibiotics
: Aminoglycosides - Gentamicin, Amikacin
Others - Vancomycin
3. Immunosuppressants: Cyclosporine
4. Anticancers: Methotrexate

9. COMMONLY MONITORED DRUGS (cont’d)
5. Antiepileptics: Phenobarbital, Phenytoin,
Carbamazepine, Valproate
6. Cardiac Drugs : Digoxin*, Procainamide,
Lidocaine
7. Psychoactive Drugs: Lithium, TCA
8. Analgesics: Aspirin, Paracetamol

10. TDM ASSAY METHODOLOGIES
1. EMIT (Enzyme-Multiplied Immunoassay Technique) : highly automated, rapid turnaround, many assays available, homogenous, moderate sensitivity 2. ELISA: highly automated, rapid turnaround, moderate sensitivity but few assays available, heterogenous 3. RIA: high sensitivity but long turnaround,many interferences, heterogenous, radiation hazards

11. TDM ASSAY METHODOLOGIES (cont’d)
4. FPIA (Fluorescence Polarization Immunoassay) highly automated, rapid turnaround, many assays available, stability of reagents and calibration curves, moderate sensitivity, homogenous 5. HPLC: highest sensitivity, most assays available, least expensive but long turnaround, requires highly trained personnel

12. TYPES OF ASSAY REQUIRED
Total drug conc.
Free drug conc.
Metabolites

13. Theophylline Bronchodilator Therapeutic range: 5 - 20 g/mL
Neonates metabolize theophylline to caffeine
Toxic at > 20 g/mL
Nausea, vomiting, diarrhea, stomach pain, headache, insomnia, tachycardia
Seizures, cardiac arrhythmia at > 35 g/mL

14. Gentamycin/Tobramycin
Wide-spectrum aminoglycoside antibiotics
Therapeutic
g/mL (peak); g/mL (trough)
Toxic: g/mL
Ototoxicity
Nephrotoxicity

15. Digoxin Improves cardiac output in CHF patients
Therapeutic range: ng/mL
Toxic levels (> 2.0 ng/mL) produce arrhythmias, GI, CNS symptoms