Therapeutic drug monitoring (TDM) involves measuring drug concentrations in patients to optimize drug therapy and avoid toxicity. TDM emerged in the 1960s with pharmacokinetic studies linking drug levels to outcomes. Pioneers in the 1970s demonstrated that constructing therapeutic ranges could reduce adverse reactions to drugs like digoxin. TDM utilizes pharmacokinetics and pharmacodynamics to assess medication efficacy and safety. It aims to individualize treatment and tailor it to each patient's needs. Factors like genetics, disease states, and drug interactions cause vast inter-patient variability in how drugs are absorbed, distributed, and eliminated.
Therapeutic drug monitoring (TDM) is a process in clinical pharmacology that specializes in measuring the concentration of certain drugs in the body fluids and clinically interpreting it to obtain useful and often lifesaving information. It is defined as “the use of drug concentration measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease”. TDM is done only for a few selected drugs with a narrow therapeutic range where the challenge is to avoid both sub-therapeutic and overtly toxic doses.
In this document, there is all the information about TDM and its relation with pharmacogenetics and pharmacokinetics
TDM can be looked at as a new area in pharmacokinetics that will lead to better patient's outcomes.
Hope you enjoy it.
Therapeutic drug monitoring (TDM) is a process in clinical pharmacology that specializes in measuring the concentration of certain drugs in the body fluids and clinically interpreting it to obtain useful and often lifesaving information. It is defined as “the use of drug concentration measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease”. TDM is done only for a few selected drugs with a narrow therapeutic range where the challenge is to avoid both sub-therapeutic and overtly toxic doses.
In this document, there is all the information about TDM and its relation with pharmacogenetics and pharmacokinetics
TDM can be looked at as a new area in pharmacokinetics that will lead to better patient's outcomes.
Hope you enjoy it.
Indications for therapeutic drug monitoringChandra Lekha
TDM Indications ('why do it'):
Drug assays are costly, so the reason for monitoring and the additional information to be gained (if any) should be carefully considered.
For some drugs, therapeutic drug monitoring helps to increase efficacy (vancomycin), to decrease toxicity (paracetamol) and to assist diagnosis (salicylates).
Routine monitoring is not advocated for most drugs.
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)
Only clinically meaningful tests should be performed
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).
The target concentration may depend on the indication. For example, the recommended concentration for digoxin depends on whether it is being used to treat atrial fibrillation or congestive heart failure.
an experimentally determined relationship between plasma drug concentration and the pharmacological effect.
• Knowledge of the drug level influences management.
Therapeutic drug monitoring (TDM) is a process in clinical pharmacology which specializes in measuring the concentration of certain drugs in the body fluids and clinically interpreting it to obtain useful and often lifesaving information. It is defined as “the use of drug concentration measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease”. TDM is done only for a few selected drugs with a narrow therapeutic range where the challenge is to avoid both sub-therapeutic and overtly toxic doses.
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. 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 is increasingly being used in clinical practice in order to improve the therapeutic outcome and reducing the toxicity in HIV infection.
The use of TDM requires certain criteria in order to interpret the plasma concentrations appropriately.
Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drug at designated intervals to maintain a constant concentration in a patients blood stream, thereby optimizing individual dosage regimen.
Indications for therapeutic drug monitoringChandra Lekha
TDM Indications ('why do it'):
Drug assays are costly, so the reason for monitoring and the additional information to be gained (if any) should be carefully considered.
For some drugs, therapeutic drug monitoring helps to increase efficacy (vancomycin), to decrease toxicity (paracetamol) and to assist diagnosis (salicylates).
Routine monitoring is not advocated for most drugs.
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)
Only clinically meaningful tests should be performed
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).
The target concentration may depend on the indication. For example, the recommended concentration for digoxin depends on whether it is being used to treat atrial fibrillation or congestive heart failure.
an experimentally determined relationship between plasma drug concentration and the pharmacological effect.
• Knowledge of the drug level influences management.
Therapeutic drug monitoring (TDM) is a process in clinical pharmacology which specializes in measuring the concentration of certain drugs in the body fluids and clinically interpreting it to obtain useful and often lifesaving information. It is defined as “the use of drug concentration measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease”. TDM is done only for a few selected drugs with a narrow therapeutic range where the challenge is to avoid both sub-therapeutic and overtly toxic doses.
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. 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 is increasingly being used in clinical practice in order to improve the therapeutic outcome and reducing the toxicity in HIV infection.
The use of TDM requires certain criteria in order to interpret the plasma concentrations appropriately.
Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drug at designated intervals to maintain a constant concentration in a patients blood stream, thereby optimizing individual dosage regimen.
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
Epidemiology is the study of occurrence, distribution and determinants of health and
diseases or disorders in man and its application in controlling health problems.
Epidemiology has by tradition two major areas.
First is the study of infectious diseases that spread to large populations, i.e., epidemics.
The second is the study of chronic diseases.
Epidemiological studies help to solve such health problems and provide a basis for
improving living conditions of the people.
During its progress and development, epidemiology has made available precise and
strict methodologies for the study of diseases.
Pharmacology is the study of the effects of drugs.
Clinical Pharmacology is the study of the effects of drugs in humans, It is traditionally
divided into two basic areas namely:
1. Pharmacokinetics
2. Pharmacodynamics.
Pharmacokinetics is the study of the relationship between dose administered of a drug
and the serum or blood level achieved, it deals with absorption, distribution, metabolism
and excretion.
Epidemiology is the study of the distribution and determinants of diseases in
populations.
Epidemics is the study of chronic/ infectious diseases in large populations.
Pharmacoepidemiology is the study of the use of and the effects of drugs in large
number of people.
It involves the examination of a single individual or large groups of people followed for
many years.
It involves gathering & analysis of information in order to identify possible causation &
related factors, that can be applied in clinical practice to group of people & also to
individuals undergoing treatment.
“ Bioavailability-
means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action."
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
3. • The science of TDM introduced a new aspect of clinical practice in the 1960s with the publication
of initial pharmacokinetic studies linking mathematical theories to patient outcomes. From there,
clinical pharmacokinetics emerged as a discipline in the late 1960s and early 1970s.
• Pioneers of drug monitoring in the 1970s focused on adverse drug reactions. They
demonstrated clearly that by constructing therapeutic ranges, the incidence of toxicity to drugs
such as digoxin, phenytoin, lithium, and theophylline could be reduced.
since
When the journey began?
History
4. • Therapeutic Drug Monitoring (TDM) is
identified as clinical laboratory
measurement of chemical parameters
that, along with reasonable medical
interpretation, can directly affect the
procedures for prescribing drugs.
• TDM can also refer to the individualization
of drug dosage by preserving a plasma or
blood drug concentration within a targeted
therapeutic range.
Definition
5. SLIDE
A C
B
TDM as
multidisciplinary
approach
• To attain accurate and clinically
meaningful blood drug level or
concentration requires a
harmonizing collaboration by the
TDM team.
• TDM team is usually comprised of
scientists, clinicians, nurses, and
pharmacists.
• Excellent communication among the
TDM team member is necessary to
ensure that best practices in TDM
being achieved.
7. 2. TDM is used
for detecting
under treatment
of an
established
condition.
4. The indication for drug
monitoring has widened to
include
1. TDM must be considered if
the dosage regimen must be
altered for any reason at a
any stage of treatment.
3. TDM helps in achieving
particular plasma
concentrations in case of
prophylactic drug usage. 1. Efficacy,
2. Compliance,
3. Drug-drug interaction,
4. Toxicity avoidance
5. Therapy cessation
monitoring.
Indication (When to do?)
Sunday, March 21, 2021 Orcipathologia.com 7
8. Drug concentration is
determined
Patient
assessments
are performed
A pharmacokinetic
model is applied, and
clinical judgment is
used
The dosage schedule
is designed to reach
a target plasma
concentration
A drug is
selected
Initially, a
diagnosis has to
be made
01 06
02 05
03 04
Application
Cycle
Sunday, March 21, 2021 Orcipathologia.com 8
9. The GOAL of this process is to individualize therapeutic
regimens for optimal patient benefit, in addition to tailoring
the treatment to the patient's physiological needs.
Goal
10. Criteria that is
required in drug to
undergo TDM
1. Difficulty in interpreting
clinical evidence of
therapeutic or toxic effects
4. Dose does not
metabolize to
important active
metabolites.
2. A good relationship
between the plasma drug
concentration and the
therapeutic or toxic effect
or both.
3. A low toxic – to -
therapeutic ratio
TDM Drug Criteria
Sunday, March 21, 2021 10
11. Suppose a given drug
administration leads to active
metabolite formation. In that case,
both the parent drug and the
metabolites must be measured to
provide a comprehensive picture
of the relationship between the
active compound's total plasma
concentration and the clinical
effect.
Drug and Active Metabolites
Be aware…!
12. • TDM depends upon
the blood drug
concentration.
However, plasma/
serum
concentration may
not correlate with
the tissue
concentration in
this setting.
• Other medications
can also interact
with the TDM
medications, giving
displacement
feature, causing
either increase or
• Example1: amiodarone
administration along with digoxin
requires digoxin dose to be reduced
to avoid toxicity.
• Example2: co-administration of
rifampicin with cyclosporine will
require cyclosporine measurement
to avoid under treatment.
Drug displacement issues
Be aware…!
14. Accuracy, precision, and specificity
confirmation are mandatory for clinical
laboratory used assays to ensure correct
measured serum drug concentration.
Sunday, March 21, 2021 Orcipathologia.com 14
Analytical Issue
15. 01 02 03
Enzyme-
Multiplied
Immunoassa
y Technique
(EMIT)
Fluorescence
polarization
immunoassay
(FPIA)
Enzyme-Linked
Immunosorbent
Assay (ELISA)
04
Magnetic
particle,
Magnetic
immunoassay
(MIA)
Most commonly used procedures for
measuring drug concentration include:
Analytical Issue
16. Peak
Peak is the measurement of blood drug
concentration after administration by 1 to 2
hours for deterring the highest
concentration.
However, factors such as slow or delay
absorption significantly delay the peak
serum concentration.
Note:
For antibiotics administrated intravenously,
peak concentrations are also measured at
30 min following infusion cessation.
Analytical Issue
17. Trough
Trough is the amount of drug blood
level that is measured before the next
dose.
Trough levels are less likely to be
influenced by absorption and
distribution problems.
Note:
Due to variable absorption upon oral
administration, blood samples should
be collected in the elimination phase
rather than in the absorption or
distribution phase.
Analytical Issue
18. Steady-State
Steady-State describes the situation where the
drug and its metabolite have been accumulated in
the body to a level that led to the amount being
given is equal to the amount being eliminated or
become at an equilibrium.
To reach a steady state depending on the drug's
half-life alone, it requires five half-lives to
accumulate over 95% of the body's drug reaching
a steady-state.
Note 1:
Drug steady-state level can be reached earlier if a
loading dose has been administrated.
Note 2:
Drugs with long half-lives should be monitored
before steady state is achieved to ensure that
individuals with impaired metabolism or renal
excretion are not at risk of developing toxicity at
the initial dosage regimen prescribed.
Analytical Issue
19. Clinical Laboratories Responsibilities
Practical Issues
01 Ensure that specimen
information is accurate and
complete, besides obtaining any
missing information from the
drug assay request that may be
needed for appropriate clinical
interpretation of the results, such
as dosage regimen, time of
blood sampling, etc.
Information Accuracy
02 Ensure that accuracy,
precision, sensitivity, and
specificity of each assay are
documented and assessed
regularly.
Test Accuracy
03 Ensure that assay performance
has been evaluated using an
external quality assurance
program. This external test
should provide a rapid turn-
around time for results and
comprehensive feedback on the
assay performance along with a
large peer group number.
Performance
Assurance
04 The TDM assay results should
be available quickly, as the
most important uses of the
measurements are during
dosage adjustments and in
diagnosing toxicity when rapid
decisions must be made.
Timely Analysis
20. Situations that can
modify TDM:
These are some factors that modify the effect of
the parent drug for a given drug plasma
concentration if total drug concentration is
measured.
acid-base balance
electrolyte balance
Drug interaction bacterial resistance
age protein binding
Clinical Laboratories Responsibilities
Practical Issues
21. "Patient demographic
characteristics are critically
important so that the
contribution of age, disease
state, ethnicity, and other
variables to inter-individual
variation in
pharmacokinetics and
pharmacodynamics can be
considered."
To interpret a blood plasma
concentration properly, the
TDM team must be informed
as to when a plasma sample
was obtained concerning the
last dose administered and
when the drug regimen was
initiated.
Data allocation
Practical Issues
22. "If a given dose of a drug produced the same plasma
concentration in all patients, there would be no need to
measure the plasma concentration of the drug!"
Why consider TDM for drugs?
Why consider TDM for drugs?
23. .
Patient genetic variation,
.
Drug formulations,
.
Underlying disease,
• TDM is required because people
vary vastly in how their bodies
absorbion, distribution, and
elimination of drugs. It is found that
up to ten-fold or even higher
differences in steady-state plasma
concentration have been found
among patients treated with the
same doses of essential drugs such
as digoxin, phenytoin, and warfarin.
• These vast differences arise from
the fact that large differences are
found in:
.
Environmental effects
.
Drug-drug interactions.
Why consider TDM for drugs?
25. A toxicology screen is a test used to
determine if an individual has been exposed
to certain legal or illegal drugs.
Toxicology screens are usually ordered to
see if a patient has taken drugs that could
endanger his or her health.
What is The Toxicology Screening?
Definition
26. • It is a fact that most screen tests provide
limited information about how frequently or
the amount a patient has taken the drug.
• If a test screening results come positive,
the requesting doctor or the laboratory
specialist can order a more specific test.
This test will show exactly how much of
the drug is present in the patient's system.
It is Just a Screening Test!
27. Among drugs of abuse, each class of drug may contain a variety of chemically similar substances. Legal substances
that are chemically similar to illegal ones can produce a positive screening result. Therefore, screening tests that
are positive for one or more classes of drugs are frequently confirmed with a secondary test that identifies the
exact substance present using a very sensitive and specific method, such as gas chromatography/ mass
spectrometry (GC/MS)
Why consider TDBe Aware of the Confounding Effects
Be Aware of the Confounding Effects
28. • Alcohol (including ethanol and
methanol)
• Amphetamines
• Barbiturates
• Benzodiazepines
• Methadone
• Cocaine
• Opiates
• Phencyclidine
• Tetrahydrocannabinol
• Etc.
What is being tested?
(Common Tests)
29. Toxicology is being used for drugs of abuse is primarily focused on determining what drugs or
combinations of drugs aperson may have taken so that the person can receive proper
treatment.
However, drugs' overall effect on aparticular person depends on the :
01 02 03
Quantity being taken
Person's body's
response to the
substance
Drugs’ combination taken When it was taken.
04
Medical screening… Why!
Why to screen for drug and what factors affects drug effect?
30. 01
02
03
Acute Health Problem
Has injuries from an
accident that an
emergency room
physician suspects are
due to drugs or alcohol
Accident
Is suspected of drug use
or is known to use legal
or illegal drugs.
Susception
04
05
06
Transplantation
If pregnant, especially if
she is thought to be at
risk for drug abuse.
Pregnancy
Is on pain medication to
ensure that the person is
taking the medication as
prescribed.
Pain Medication
Has acute health
problems that may be
drug-related or shows
signs of intoxication like;
unconsciousness,
nausea, delirium, panic,
paranoia, increased
temperature, etc.
If a candidate is to
receive an organ
transplant
Ahealth practitioner may order drug testing for
medical reasons if an individual :
I. Clinical practice surveillance
Request! Who and When?
31. Drug testing for legal purposes primarily
aims to detect illegal or banned drug use
in various situations.
• Sample collection procedures for
this type of testing are strictly
controlled and documented to
maintain a legal "chain-of-custody."
• The donor provides a sample that is
closed and secured with a
tamperproof seal in his or her
presence.
II. Legal or forensic:
Request! Who and When?
32. 01 02 03
Before employment, On a random basis Following an accident
04
If the employer has a
reasonable suspicion
that an employee is
using illegal drugs.
Ahealth practitioner may order drug testing
for medical reasons if an individual
Request! Who and When?
III. Employment Drug Testing
33. While conventional drug testing is
performed on competitive athletes,
the primary focus is on doping, the
use of drugs or supplements
intended to promote muscle
growth or improve strength and
endurance.
IV. Sports/ Athletics Screening
Request! Who and When?
34. A positive initial drug screening means that the
person tested has a substance in his or her body
that falls into one of the drug classes and is above
the established cutoff level.
If secondary testing confirms a positive result, it
means that the person has indeed taken this drug.
Note:
In some cases, this result indicates a window of
time in which the person took the substance and its
approximate quantity, but that information is not
necessary for most circumstances.
What if positive?
Sample
Report
Analyze
Results interpretation
35. Interpretation of when and how much drug was consumed can be
challenging because the concentration of many drugs varies, as do people's
metabolism.
Why consider TDBe Aware of the Confounding Effects
Is it time informative?
36. If testing reveals no drugs or drugs in amounts
below the established cutoffs, the results are usually
reported as "not detected" or "none detected."
A negative result does not necessarily mean that
the person did not take a drug at some point.
Note:
Causes of negative results may include:
1. The drug may be present, but below the
established cutoff.
2. the drug may have been already metabolized
and eliminated from the body.
3. the test method does not detect the particular
drug present in the sample.
What if negative?
Analyze
Report
Sample
Results interpretation