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In this article we will discuss about:- 1. Introduction to Therapeutic Drug Monitoring (TDM) 2. Drugs Analyzed by Therapeutic Drug Monitoring (TDM) 3. Process 4. Clinical Utility.
Introduction to Therapeutic Drug Monitoring (TDM):
Therapeutic drug monitoring is a branch of clinical chemistry that specializes in the measurement of medication levels in blood. It is a process of using drug serum concentration measurement in determining drug dosage adjustment to maximize efficacy and safety of drug use.
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The aim of drug monitoring is to ensure the medication dose is at therapeutic range and not toxic. The medication dosage differs between each patient based on metabolic process. Drug monitoring has been established on the principle that the concentration correlates better than the dose with the drug effect.
The purpose of TDM is:
i. To confirm effective concentrations.
ii. To investigate unexpected lack of efficacy.
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iii. To check compliance.
iv. To avoid or anticipate toxic concentrations.
v. Limited role in toxicology.
Its main focus is on drugs with a narrow therapeutic range i.e., drugs that can easily be under- or overdosed. In pharmacology many medications are used without monitoring of blood levels, as their dosage can generally be varied according to clinical response that a patient gets to that substance.
In a small group of drugs, this is impossible, as insufficient levels will lead to under treatment or resistance and excessive levels can lead to toxicity and tissue damage. TDM offers a scientific rather than empirical approach in selecting a drug regimen to optimize therapy.
Drugs Analyzed by Therapeutic Drug Monitoring (TDM):
i. Antibacterial Agents:
a. Aminoglycoside antibiotics (gentamicin),
b. Vancomycin, and
c. Amikacin.
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ii. Antiepileptic Drugs:
a. Carbamazepine,
b. Phenytoin,
c. Valporic acid, and
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d. Phenobarbital.
iii. Immunosuppressive Drugs:
a. Cyclosporin.
b. Tacrolimus.
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iv. Mood Stabilizers Especially Lithium Citrate (Bipolar Disorder).
v. Anti-Seizure Drugs:
a. Dilantin.
b. Tegretol.
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c. Depakane.
vi. Cardioactive Medications:
a. Digoxin
vii. Anti-Cancer (Neoplastic) Drugs:
a. Methotrexate
viii. Antidepressants:
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a. Tricyclic antidepressants
ix. Bronchodilators:
a. Theophylline
x. Therapeutic drug monitoring can also detect poisoning with above drugs.
Pharmacokinetics (PK):
Study of what the body does to the drugs, i.e., drug absorption, distribution, metabolism and elimination.
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Pharmacodynamics (PD):
Study of what the drugs do to the body i.e., drug efficacy, toxicity and/or possible side effects.
Therapeutic range for drug concentration:
i. Sub-Optimal Levels:
Associated with low therapeutic effects with possible future resistance.
ii. Therapeutic Effect:
Reduction of the infected organism (HIV RNA), increase of CD4 cells and consequent decrease in opportunistic infections.
iii. Therapeutic Range:
Level of drug that causes a therapeutic effect versus a toxic effect.
iv. Toxic Effect:
Speaks for itself.
A drug is effective when it binds to a specific receptor in the target tissue. TDM assumes that serum levels are proportional to the intercellular tissue bind capacity of the drug.
Drug utilization in the body is influenced by:
i. Absorption.
ii. Distribution.
iii. Metabolism.
iv. Excretion.
i. Absorption:
There are three routes of administration for drugs to go through absorption.
a. Orally:
The drug is absorbed by the GI tract. The drugs are formulated to withstand acid pH in the stomach so that the medication can be absorbed in the intestine.
b. Rectally:
The drug is absorbed within and the lining of the lower intestine.
c. IV/IM:
The drug is directly administered into the venous flow and absorbed into the tissue.
ii. Distribution of Drug:
Once the drug enters the circulation, it is quickly distributed based on its solubility. Some drugs are water-soluble whereas some are water insoluble which need protein carriers e.g., albumin and Alpha1-scid glycoprotein.
iii. Metabolism:
Drugs are absorbed, distributed and then excreted in urine or as waste product. The liver metabolizes the lipid insoluble drugs into more H2O soluble form. Enzymes in hepatocytes help in the conversion of soluble gluconoride, sulfate and phosphate.
iv. Excretion:
Kidneys are the primary excretory organ. In renal disease- other excretory organs or pathway become involved such as biliary tract, lungs and sweat glands. H2O soluble drugs are excreted faster than insoluble drugs. pH of urine is based on the acidic or basic nature of the drug.
Process of Therapeutic Drug Monitoring (TDM):
Clinical Utility of Therapeutic Drug Monitoring (TDM):
1. Noncompliance can be recognized. Patients with chronic diseases require prolonged drug therapy. Non-compliance leads to exacerbation of the existing disorder and failure of the treatment. Values of the drug concentration give a positive feedback to physicians.
2. Individual’s metabolism and clinical condition of patients very from one other and also change within a patient during treatment. Therefore, drug deposition parameters change, requiring frequent dose and dosing interval adjustment, guided by TDM.
3. During periods of continuous physiological changes, therapeutic drug regimens can be adjusted. For example, during pregnancy, aging, etc.
