Therapeutic drug monitoring (TDM) involves measuring drug concentrations in patients' blood to optimize drug therapy. TDM is useful for drugs with a narrow therapeutic index, high inter-individual variability, or when the relationship between concentration and clinical effects is well established. The TDM process includes requesting the test with relevant clinical information, collecting a proper blood sample, measuring drug levels in the laboratory, interpreting the results clinically, and adjusting drug dosing regimen accordingly to maintain concentrations within the therapeutic range. TDM aims to maximize drug effectiveness while minimizing toxicity.
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
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
Therapeutic drug monitoring (TDM) of drugs used in seizure disordersAbel C. Mathew
Therapeutic drug monitoring (TDM) of drugs used in seizure disorders- Phenytoin, Valproic acid, Carbamazepine are major drugs used in epilepsy disorders. These drug need TDM to ensure their proper usage.
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.
Therapeutic drug monitoring (TDM) of drugs used in seizure disordersAbel C. Mathew
Therapeutic drug monitoring (TDM) of drugs used in seizure disorders- Phenytoin, Valproic acid, Carbamazepine are major drugs used in epilepsy disorders. These drug need TDM to ensure their proper usage.
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.
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.
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.
Definition of social pharmacy, social pharmacy as a discipline, scope of social pharmacy and role of pharmacist in public health, National Health Mission, National rural health mission, National urban health mission
Organization and objectives of ICH, expedited reporting, ICSR, PSURs, post approval expedited reporting, pharmacovigilance Planning, good clinical practices
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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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.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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.
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
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This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
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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
6. •Therapeutic range is the plasma concentration
range that is effective and safe in treating
specific diseases.
•Therapeutic Index is a ratio between minimum
effective concentrations to the minimum toxic
concentration.
THERAPEUTIC WINDOW/RANGE
7. NARROW THERAPEUTIC INDEX DRUGS
• Therapeutic index of the drug is ≤ 3
• Higher inter-individual variability (CV > 20%)
8. MONITORING OF DRUG THERAPY
1. Pharmacokinetic Measures using TDM
2. Pharmacodynamics Measures using Surrogate Markers
3. Therapeutic Outcomes using Clinical End Points
9. PHARMACOKINETIC MEASURES
It includes measurement of drug concentrations in the blood
or plasma i.e. by Therapeutic Drug Monitoring (TDM).
Is the drug getting
to the site of
action ?
10. PHARMACODYNAMICS MEASURES
For many drugs there are no readily available measure of effect or it is
insufficiently sensitive.
Clinician routinely monitor drug pharmacodynamics by directly
measuring physiological indices (Surrogate Markers) of therapeutic
response.
Is it producing
required
pharmacological
effect ?
11. Surrogate Marker is defined as an endpoint that is measured
in place of true end point and that relates in someway to
the primary end point.
Surrogate markers are cheaper and easier to measure than
true end point and can be measured quickly.
Eg: Clotting time in patient on warfarin anticoagulation
therapy, Glucose level in diabetic patient using insulin
products, etc.
12. THERAPEUTIC OUTCOMES
Monitoring therapeutic outcomes in patient/individual:
Reduced frequency of asthma attacks - Bronchodilators
Decreased frequency of seizure – Anti-epileptic drugs
Reduced swelling - Diuretics
13. Prescribed Dosing
Regimen
Drug at Site of
Action
Drug Effects
Pharmacokinetic Variability
a) Compliance
b) Dosing or medication Error
c) Tissue and body fluid mass and
volume
d) Drug interactions
e) Elimination
Pharmacodynamic Variability
a) Drug receptor status
b) Genetic factors
c) Drug interactions
d) Tolerance
PHARMACOKINETICS PHARMACODYNAMIC
15. INTRODUCTION
• Therapeutic drug monitoring is the individualization
of drug dosage by maintaining plasma or blood
drug concentrations within a targeted therapeutic
range or window.
• Commonly known as TDM
• It involves measuring serum drug concentration at
designated intervals to maintain constant
concentration in a patient bloodstream.
16. •TDM Aims to promote optimum drug therapy
by maintaining serum drug concentration within
a therapeutic Range/Window.
•Therapeutic monitoring of plasma drug
concentrations is valuable only if a relationship
exists between the plasma drug concentration
and the desired clinical effect or between the
plasma drug concentration and an adverse
effect.
17. •Therapeutic drug monitoring blends knowledge
of therapeutics, pharmacology, pharmacokinetics,
laboratory technology and clinical medicine and
applies it to certain drugs that require
determination of patient specific dosage
regimens to maximize therapeutic
effectiveness while minimizing toxicity.
18. TDM WILL BE USEFUL IN FOLLOWINGS:
1) Narrow therapeutic indexed drugs
2) Direct relationship exists between the drug or drug
metabolite levels in plasma and the pharmacological or
toxic effects.
3) Therapeutic effect can’t assessed by the clinical
observation.
4) Large individual variability in steady state plasma
concentration exists at any dose.
5) Appropriate analytical techniques are available to determine
the drug and metabolite levels
19. TDM IS NOT USEFUL IF
Clinical outcome is unrelated either to dose or to
plasma concentration.
Dosage need not be individualized
Pharmacological effect can be clinically quantified
Concentration effect relationship remains
unestablished
Drugs having wide therapeutic range such as
calcium channel blockers or beta blockers
20. TDM PROCESS
1. Reasons for Requesting TDM
2. The Biological Sample
3. The Request
4. Laboratory Measurement
5. Communication of the Results by Laboratory
6. Clinical Interpretation
7. Therapeutic Management
21. 1. Reasons for Requesting TDM
Narrow Therapeutic Index
Therapeutic failure
Poorly defined End point
Non compliance
Wide variation in the metabolism of the drugs
Prevention of Adverse drug effects
Toxicity suspected
Assess therapy
Potential drug interaction due to change in co-medication
22. 2. The Biological Sample
It is important that biological sample collected should provide
a clinically meaningful measurement.
Blood sample should be collected once the drug concentration
have reached steady state (at least 5 half lives at the current
dosage regimen)
Steady state may be reached earlier if a loading dose has been
administered (drugs with long half lives).
However, drugs with long half lives should be monitored
before steady state to ensure that individuals with impaired
metabolism or renal excretion are not in the risk of developing
toxicity.
23. If toxicity suspected – concentration should be
measured as soon as possible.
Absorption is variable after oral dosing so blood
sample should be collected in elimination phase rather
than absorption/distribution phases.
Generally blood samples are collected at the end of
the dosage interval i.e. trough concentration.
For antibiotics given intravenously, peak
concentrations are also measured.
24. • Usually drug concentration are monitored in venous
blood, serum or plasma.
• In general serum or plasma concentration are
comparable.
• Whole blood must be sampled for few drugs like
cyclosporine A, that distributes between plasma and
erythrocytes.
• In infants, capillary blood may be collected for TDM.
• Utility of saliva measurements and other biological
fluids are not routinely sampled.
25. 3. The Request
Patient demographics such as age, disease state,
ethnicity etc. are critically important to know the
variation in Pharmacokinetic and pharmacodynamics.
So these details should be effectively communicated
to the members of TDM team with a drug assay
request.
When a drug which is commonly measured for TDM
is suspected of causing toxicity, it is important for
requesting clinicians to clearly communicate the
expectation of a high concentration and need for a
rapid feedback of results.
26. 4. Laboratory Measurement
Drug assay must be performed within a clinically
useful timeframe.
The assay procedure should be validated.(accuracy,
precision, sensitivity, specificity, limit detection)
If possible the assay procedure should be evaluated
with an external quality assurance program.
Senior laboratory staff should verify the assay results.
27. Commercial kits can be used wherever possible and
found economical. However, kits are not available for
all the drugs.
The analytical methodology used should ideally:
•Detect small amount of drugs.
•Differentiate between compounds of similar
structure, unchanged drug and metabolite.
•Simple enough to use as routinely.
28. Various analytical techniques available for TDM are:
•Thin Layer Chromatography
•Mass Spectrophotometry
•HPLC and HPTLC
•GC
•Radio Immuno assay
•Enzyme Immuno assay
•Least Count Mass Spectrometry
29. 5. Communication of the Results
by Laboratory
The assay results should be communicated as quickly
as possible once it is verified by the senior laboratory
personnel.
The drug concentrations measured are generally
reported in mass or molar units.
To relate concentration back to dose, mass units are
preferable.
30. The result should clearly state the therapeutic
concentration range for the drug assayed.
It must be understood that different indications for
therapy, age or ethnic differences in PK and PD could
results in different therapeutic ranges being
appropriate for different population groups.
Therefore, critical assessment of the original
literatures and consensus recommendations for
therapeutic ranges should be encouraged.
31. 6. Clinical Interpretation
Clinical interpretation can add value and convert
therapeutic measurement service into therapeutic drug
monitoring service.
The information required to interpret the drug
concentration include:
o Time of blood sampling
o Time at which dose is given
o Dosage regimen (Dose, Duration, Dosage form)
o Patient demographics (age, gender, concomitant
diseases)
o Indication for monitoring
o PK and therapeutic range of the drug
32. Serum concentration lower than anticipated
Patient non compliance
Error in dosage regimen
Wrong drug product
Poor bioavailability
Rapid elimination
Increased plasma protein binding
Enlarge apparent volume of distribution
Timing of blood sample
Steady state not reached
33. Serum concentration higher than anticipated
Patient compliance
Error in dosage regimen
Increased bioavailability
Decreased elimination
Decreased plasma protein binding
Drug interaction due to inhibition of elimination
Smaller apparent volume of distribution
34. Serum concentration within range but patient
does not respond to therapy
Altered Receptor Sensitivity (Intolerance)
Drug interaction at Receptor site
35. 7. Therapeutic Management
The Clinician will modify a drug dosage regimen
with respect to information available.
Dose Adjustment:
For drugs with linear kinetics:
New Dose = 𝑜𝑙𝑑 𝑑𝑜𝑠𝑒 𝑥
𝐷𝑒𝑠𝑖𝑟𝑒𝑑 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
old drug concentration
36. Limitations of TDM Process
1) Scientific accuracy of the drug assays
2) Laboratory variability in reporting
3) Validity of suggested target ranges
4) Lack of training and skills
5) Cost involved
6) Limited infrastructure facilities