This document discusses factors that contribute to variability in individual drug responses and the need to individualize drug dosing regimens. It outlines several key sources of variability, including age, body weight, gender, genetics, disease conditions, and drug interactions. For each factor, it provides examples of how that factor can influence the pharmacokinetics and pharmacodynamics of drugs and necessitate dosage adjustments tailored to the individual patient. The goal is to achieve effective therapy while avoiding toxicity by understanding and accounting for variability between patients.
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
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.
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Individualisation and optimization of drug dosing regimenJyoti Nautiyal
Drug dosing regimen, dosing frequency, individualisation, Steps Involved in Individualization of Dosage Regimen, optimization, variability, Clinical experience with individualization and optimization based on plasma drug levels.
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
various measures for the measurement of outcome such as incidence prevalence and other drug us measures are briefly discussed here with suitable examples and equations
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
THIS SLIDE GIVES AN INSIGHT TO THE DIFFERENT METHODS THAT COULD BE USED FOR THE DOSAGE ADJUSTMENT IN PATIENTS WITH RENAL DISEASE.
RENAL FUNCTION OF THE PATIENT IS ASSESSED TO DETERMINE THE DOSAGE ADJUSTMENT
breif notes on what is pharmacoepidemiology, why do we need pharmacoepidemiology, whats is its aim and its main applications, advantages and disadvantages
In this presentation i have tried to explain in detail about the measurements of the outcomes which are used in epidemiology such as prevalence, incidence, fatality rate, crude death rate etc.
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.
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Individualisation and optimization of drug dosing regimenJyoti Nautiyal
Drug dosing regimen, dosing frequency, individualisation, Steps Involved in Individualization of Dosage Regimen, optimization, variability, Clinical experience with individualization and optimization based on plasma drug levels.
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
various measures for the measurement of outcome such as incidence prevalence and other drug us measures are briefly discussed here with suitable examples and equations
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
THIS SLIDE GIVES AN INSIGHT TO THE DIFFERENT METHODS THAT COULD BE USED FOR THE DOSAGE ADJUSTMENT IN PATIENTS WITH RENAL DISEASE.
RENAL FUNCTION OF THE PATIENT IS ASSESSED TO DETERMINE THE DOSAGE ADJUSTMENT
breif notes on what is pharmacoepidemiology, why do we need pharmacoepidemiology, whats is its aim and its main applications, advantages and disadvantages
In this presentation i have tried to explain in detail about the measurements of the outcomes which are used in epidemiology such as prevalence, incidence, fatality rate, crude death rate etc.
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
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
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.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
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.
Stay informed, stay safe, and get your flu shot today!
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
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
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.
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Individualization of drug dosage regimen
1. INDIVIDUALIZATION OF
DRUG DOSAGE REGIMEN
DR. RAMESH BHANDARI
ASST. PROFESSOR
DEPARTMENT OF PHARMACY PRACTICE,
KLE COLLEGE OF PHARMACY, BELAGAVI
2. INTRODUCTION
• All Peoples are alike - True only as a Species.
• Human are reasonably homogenous but differences
among people exist including their responsiveness to
drugs.
• Accordingly, there is a frequent need to tailor drug
administration to the individual patient.
• A failure to do so lead to ineffective therapy in some
patients and toxicity in others.
• Therefore, the main challenge in designing a ‘standard’
drug dosage regimen is the variability in drug handling
3. INTRODUCTION
• Understanding the sources of this variability and adjusting drug doses
accordingly is an area in which pharmacists can make a major impact on risk
management and patient care.
• Average data are useful as a guide; but ultimately, information pertaining to
the individual patient is important – interindividual variability.
• Intraindividual variability is generally much smaller than interindividual
variability.
• There are three main sources of variability in pharmacokinetics of drugs and
consequently patient’s response to drugs.
5. 1. Age:
Aging characterized by periods of growth and
development, is an additional source of variability in
drug response.
Hence the usual adult dosage regimen need to be
modified, particularly in the young and old patients.
The life of a human is commonly divided into various
stages i.e. Neonate, Infant, child, adolescent, adult, and
elder.
6. 1. Age:
Drug absorption doesnot appear to change dramatically with
age but the factors that affect drug absorption, including
gastric pH, gastric emptying, intestinal motility, and blood
flow change with age.
Thus, in the neonate a condition of relative achlorhydria
persists for the first week of life, and only after 3 years of age
gastric acid secretion approaches the adult value.
Gastric emptying is also prolonged and peristalsis is
irregular during the early months of life.
7. 1. Age:
Skeletal muscle mass is also much reduced, and muscle
contractions, which tend to promote both blood flow and
spreading of an intramuscularly administered drug, are
relatively slow.
An elevated gastric pH, a delay in gastric emptying, and both
diminished intestinal motility and blood flow are also seen in
the elderly.
Differences in drug absorption among adults, the very young
and the elderly, are therefore expected.
Generally, changes in rate rather than in extent of absorption
are found.
8. 1. Age:
These changes tend to be less apparent in the elderly
than in the very young.
Children often appear to absorb drugs as completely
and, if anything, more rapidly than adults.
Accordingly, in subsequent calculations of dosage,
extent of absorption is assumed not to vary with age.
A major exception is for some first-pass drugs given
to the elderly, where oral bioavailability increases with
age.
9. 1.Age:
Generally, plasma binding is lower in neonates than adults
During adulthood the value of fu (fraction of unbound drug
in plasma) remains unchanged or tends to raise for those
drugs bound to albumin, the concentration of which falls
slightly with advancing years
The change in binding is generally too small, to warrant
any consideration of dose adjustment.
10. 1. Age:
Clearance, if normalized for body weight, is depressed
in the neonate, but increases rapidly to reach a
maximum value at 6 months, when it is almost twice
that in the adult
Therefore, weight –normalized clearance falls but still
remains, throughout childhood, considerably above the
adult value.
11. 1. Age:
The half life is shortest around 1 year of age; it is longest in
both newborn and elderly patients
In premature newborns, the urinary excretion is even more
depressed per kilogram of body weight than in full-term
neonates
Metabolic activity may take months to mature, the time
required for full maturation varies with the enzyme system
12. 1. Age:
A decrease in unbound metabolic clearance in the elderly
patient has been demonstrated for an increasing number of
drugs, especially, those principally by oxidation.
These changes may be associated in part, with the decrease
in the size of the liver, as a proportion of body weight, from
2.5 % in the young adult to 1.6 % at 90 years of age.
13. 2. BODY WEIGHT:
One aspect of aging is body weight
Weight, 3.5 kg at birth, increases rapidly in childhood and
adolescence and then declines slowly in the elderly
Because, body water spaces, muscle mass, organ blood
flow, and organ function are related to body weight. So too
volume of distribution, clearance and hence dosage
regimens of drugs also depend on body weight
14. 2. BODY WEIGHT:
However, a weight adjustment is generally thought
necessary only if the weight of an individual differs
by more than 30% from the average adult weight (70
kg).
In practice, adjustments for weight are made only
for the child and for the adult who is small, thin, big,
or obese.
15. 2. BODY WEIGHT:
A dose correction must be considered for thin and obese
patients.
The difference in loading dose may not be as great as
anticipated from body weight alone.
Because, distribution get age-related changes and much
depends on the physicochemical properties of the drug.
16. 2. BODY WEIGHT:
For example, digoxin and other polar drugs (water soluble)
show better correlation between unbound volume of
distribution (Vu) with lean body mass, which is similar in
obese and average persons of the same height and frame,
than with total body weight.
In contrast, total body weight may be more relevant for a
drug that is highly lipid soluble.
17. 2. BODY WEIGHT:
Though renal and hepatic functions are related to body size, obesity
may not produce a corresponding increase in hepatic function
Consequently, the use of total body weight to determine a drug dosage
regimen could result in toxic effects if the patient is grossly obese
Thus, though many drug doses are based on the body weight of the
patient (expressed as mg/kg), the influence of obesity or
malnourishments is not always considered.
18. 2. BODY WEIGHT:
Child Maintenance
Dose =
Typical
Adult
Maintenanc
e dose
70 Kg[Weight of the child
(Kg)
[1.4 XX
0.7
19. 3. GENDER:
Genetic and physiological differences between male
and female can have effect on pharmacokinetic and
pharmacodynamics of the drugs.
For example, many genes on the Y chromosome,
which are expressed only in males, have no
counterpart on the X chromosome
The Y chromosome has genes involved in basic
cellular function and some genes on the X
chromosome are expressed at higher levels in
females.
20. 3. GENDER:
Gene expression and regulation are likely to be
influenced by hormonal differences between males
and females.
Genomic imprinting, body size, organ size, body fat,
ADME can also affect pharmacological outcome.
Other factors such as gastrointestinal transit time,
liver enzyme function and urinary creatinine
clearance are influenced by both age and sex.
21. 3. GENDER
Across the path of a woman’s life it is necessary to consider the
stages of ovarian function to appreciate the potential for drug, sex,
and age interactions as they influence rational drug therapy
Use of oral contraceptives and hormonal changes which occur
throughout the menstrual cycle influence pharmacological results
Necessary considerations during pregnancy are alterations in body
composition, cardiac output, pulmonary and renal function as well
as changes in immune and gastrointestinal systems
22. 3. GENDER
In menopause, the ovaries, uterus, urinary tract, hypothalamus,
cardiovascular systems, and liver are some of the tissues, organs or
systems which are altered by the loss of estrogens, androgens, and
progesterons.
These hormonal changes are also associated with the expression of
different diseases after menopause.
Sex differences include the observation that in many developed countries
women take more medications, creating the potential for adverse effects
based on drug interactions, they appear more sensitive to adverse events,
and may be overdosed more frequently.
23. 4. GENETICS
Genetic polymorphism that lead to the production of isoenzyme with reduced or no
activity of to multiple copies of an enzyme with high activity make a major contribution
to the variability in the dose requirements of drugs that eliminated by hepatic
metabolism.
Cytochrome P450 (CYP 450) enzymes, P – glycoproteins are increasingly being
recognized for their importance to pharmacokinetic variability.
Most of these genetic differences are complex and are difficult to determine with any
degree of certainty; but a few genetic differences are well documented (oxidation, S-
methylation, and acetylation).
In future, genetic screening (phenotyping) may be done to individual patients to design
the dose of a drug.
25. 5. DISEASE CONDITIONS
Disease is a major source of variability in drug response
The PK and PD of some drugs have been shown to be influenced
by the presence of concurrent diseases other than the one for
which a drug is used
There are also occasions when the pharmacokinetics of a drug is
altered in the disease for which it is used
Diseases of the kidney, liver, cardio vascular system, respiratory
system, gastrointestinal system and endocrine system are the
major cause that warrant individualized drug therapy.
26. CONDITION DRUG OBSERVATION VARIATION IN COMMENTS
PK PD
HEPATIC DISEASES
Cirrhosis Theophylline Slower fall in
plasma
concentration
+ - Clearance reduced.
Reduce the dosage
to avoid toxicity
Acute viral
hepatitis
Warfarin Excessive
anticoagulant
response
- + Reduce dosage to
lessen risk of
hemorrhage
RENAL DISEASES
Uremia Gentamycin Increased toxicity
with usual dosage
+ - Renal clearance
diminished; reduce
dosage to lessen risk
of toxicity
Thiopental Prolonged
anesthesia
+/- + Reduce dose to
avoid excessive
sleeping time
27. CONDITION DRUG OBSERVATION VARIATION IN COMMENTS
PK PD
CARDIOVASCULAR DISEASE
Congestive
Cardiac Failure
lidocaine Elevated plasma
concentration after
usual dosage
+ - Clearance and Vd
reduced. Reduce the
dosage to lessen
toxicity
GASTROINTESTINAL DISEASES
Celiac Disease Fusidic Acid Elevated plasma
concentration after
usual dosage
+ - BA increased and /
Clearance
diminished
Crohn’s Disease Propranolol Elevated plasma
concentration after
an oral dose
+ NS Increased plasma
binding, elevated
alpha – 1 acid
glycoprotein
suspected cause;
observed only in
active phase
28. CONDITION DRUG OBSERVATION VARIATION IN COMMENTS
PK PD
RESPIRATORY DISEASES
Asthma Tolbutamide More rapid fall in
plasma concentration
+ - Therapeutic
consequences
uncertain
Emphysema Morphine Increased sensitivity
to respiratory
depressant effect
NS NS Reduce dose to
diminish risk of
respiratory
complications
Cystic fibrosis Dicloxacillin Reduced AUC + - Renal clearance
increased
Pneumonia Theophylline Elevated plasma
concentration
+ - Metabolic clearance
decreased; reduce
dose to lessen risk
of toxicity
29. CONDITION DRUG OBSERVATION VARIATION IN COMMENTS
PK PD
ENDOCRINE DISEASE
Thyroid disease Digoxin Diminished response in
hyper thyroidism;
increased response in
myxedema
- + Adjust dosage
according to thyroid
activity
OTHER
Fever Quinine Plasma concentration of
drug elevated, of
metabolite depressed,
after usual dosage
+ NS Impaired
metabolism
suspected; may
need to reduce
doses in severe
febrile states
+, Established source of Variability
-, No evidence that variability is increased due to disease
NS, Not Studied
30. 1. DRUG INTERACTIONS:
Many of the clinically significant interactions between drugs are pharmacokinetic in origin, often
due to induction and inhibition of metabolizing enzymes or transporter proteins.
However, interactions can also occur between drugs and food supplements or herbal remedies.
Interactions involving competitive inhibition often occur within two to three days whereas
induction may take anything form hours to weeks.
If the interacting drug has a long elimination half life, the interaction may persist for some time
after it has been discontinued.
31. 1. DRUG INTERACTIONS:
Absorption:
Studies have demonstrated the importance of intestinal CYP3A4 and P – glycoprotein in drug
absorption.
Induction of these mechanisms by rifampicin and by St John’s wort have been shown to reduce
the BA of Digoxin.
Absorption can also be altered by drug interactions within the gut that result from binding to
other drugs, such as cholestyramine or antacids, or to enteral feeds, as in the case of Phenytoin.
32. 1. DRUG INTERACTIONS:
Distribution:
Drug distribution can be altered by interactions that cause displacement from plasma protein
binding.
But, these do not normally alter maintenance dose requirements unless there is also a reduction in
the clearance of unbound drug.
Metabolism:
Metabolism can be altered by enzyme induction or inhibition.
Due to wide variability in enzyme activity, the clinical significance of an interaction is often difficult
to predict on an individual basis.
33. 1. DRUG INTERACTIONS:
Metabolism…
These interactions are often dose-dependent and the timescale of the offset and onset of the effect
depends not only on the PK of two (or more) drugs concerned, but also the isoenzyme(s)
responsible for their metabolism.
Excretion:
Probenecid reduces the renal excretion of many antibiotics by competing for anion secretion
transport mechanism.
Changes in biliary secretion and entero-hepatic circulation can also play a role.
For example, Penicillins can impair the recirculation of oral contraceptives by altering the bacterial
flora of the gut.