It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
Drug Distribution & Factors Affecting DistributionVijay Kevlani
To have the full content of slide, kindly download it and convert it to ppt form.
Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues.
Presentation covers the basics of pharmacokinetic. Mechanism for the transport of drug molecule. Absorption, factors affecting on absorption of drugs. Concept of bioavailability. Distribution, plasma protein binding, tissue binding, barriers.
The study of the disposition of a drug
It includes the processes of ADME
Absorption
Distribution
Metabolism
Excretion
Toxicity
Patients may suffer
Toxic drugs may accumulate
Useful drugs may have no benefit because doses are too small to establish therapeutic efficacy
A drug can be rapidly metabolized
Absorption is the process by which a drug enters the bloodstream without being chemically altered
Factors which influence the rate of absorption
types of transport
the physicochemical properties of the drug
protein binding
routes of administration
dosage forms
circulation at the site of absorption
concentration of the drug
Physiological barriers to diffusion of drugsLokesh Patil
Drug distribution is greatly hampered by physiological barriers to drug diffusion, including cell membranes, the blood-brain barrier (BBB), blood-testis barrier (BTB), placental barrier, gastrointestinal tract barrier, and mucosal barrier. Whereas the BBB prevents most medications from reaching the central nervous system, cell membranes preferentially allow lipophilic medications to pass. The testes and fetus are similarly denied medication access by the placental barrier and the BTB, respectively. Through different pH levels and first-pass metabolism, the GI tract barrier influences medication absorption; mucosal barriers trap compounds in mucus and expose them to enzymatic breakdown. To improve medication penetration and effectiveness, these obstacles are overcome by means of techniques including chemical changes, nanoparticle formulations, and direct delivery techniques.
Drug distibution, significance, steps in Drug distribution, Factors affecting,physiochemical properties of drug, volume of distribution,protein binding, mechanism of protein drug binding
CNS Introduction, Neurons, Type of Neurons and functions, Neuroglia and types, Receptors and their types, Synapse, Neurotransmitters and their functions
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
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.
- 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
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.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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
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.
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.
3. Disposition
Once a drug has gained access to the blood
stream, the drug is subjected to a number of
processes called as Disposition Processes
that tend to lower the plasma concentration.
1. Distribution which involves reversible
transfer of a drug between compartments.
2. Elimination which involves irreversible loss of
drug from the body. It comprises of
metabolism and excretion.
MIHS 3
4. Drug Distribution refers to the
Reversible Transfer of a Drug between the
Blood and the Extra Vascular Fluids and
Tissues of the body
(for example, fat, muscle, and brain tissue).
MIHS 4
5. •The Process
occurs by the
Diffusion of
Free Drug
until
equilibrium is
established.
Distribution is a
Passive Process,
for which the
driving force is the
Conc. Gradient
between the blood
and Extravascular
Tissues
MIHS 5
7. MIHS 7
Distribution of a drug is not Uniform
throughout the body because different
tissues receive the drug from plasma at
different rates and to different extents.
9. Following factors affect distribution of drugs.
1. Regional blood flow
2. Capillary permeability
3. The degree of binding of drug to plasma and
tissue proteins.
MIHS 9
10. A. BLOOD FLOW
Depends upon cardiac output
Varies widely due to unequal distribution of cardiac
output to various organs.
Blood flow to brain, liver and kidney is greater
>then skeletal muscle>then adipose tissue, skin
and viscera.
MIHS 10
11. B.CAPILLARY PERMEABILITY
CAPILLARY PERMEABILITY DEPENDS UPON:
1.CAPILLARY STRUCTURE
2.CHEMICAL NATURE OF THE DRUG
Capillary structure
The basement membrane of the capillary wall is
fractioned by slit junctions between endothelial
cells.
Greater the slit junctions, greater the passage of
drug molecules.
liver and spleen have more slit junctions
In brain capillaries ,there are no slit junctions so to
enter the brain the drug must pass through the
endothelial cells of the capillaries or be actively
transported.
MIHS 11
12. Chemical nature of the drug
Ionized or polar drugs fail to enter the CNS because
they are unable to pass through endothelial cells.
Hydrophilic drugs by contrast do not readily
penetrate cell membranes and must pass through
the slit junctions.
The lipid soluble drugs readily penetrate the CNS
because they can penetrate the endothelial cells of
capillaries.
Hydrophobic drugs readily cross the biological
membranes and dissolve in the lipid membranes so
the major factor influencing the hydrophobic drug
distribution is the blood flow to the area.
MIHS 12
14. C.BINDING OF DRUG TO PROTEINS
THIS INCLUDE:
1) BINDING TO PLASMA PROTEINS
2) BINDIND TO TISSUE PROTEINS
MIHS 14
15. 1)BINDING TO PLASMA PROTEINS
Reversible binding to plasma proteins sequesters
drugs in a non diffusible form and slows their
transfer out of the vascular compartments.
Major proteins are albumin and globulin.
Plasma proteins also act as drug reservoirs that is
when the concentration of free drug decreases
due to metabolism or excretion then the bound
drug dissociates from the protein.
MIHS 15
16. 2)BINDING TO TISSUE PROTEINS
Drugs may accumulate as a result of binding to
lipids, proteins and nucleic acids.
Act as tissue reservoirs
Some times cause local drug toxicity e.g.
ACROLEIN the metabolite of
CYCLOPHOSPHAMIDE is toxic to kidney as it
accumulates in the renal cells.
MIHS 16
17. D. VOLUME OF DISTRIBUTION
The Volume of distribution (VD), also known as Apparent
volume of distribution, is used to quantify the distribution of a
drug between plasma and the rest of the body after oral or
parenteral dosing.
It is called as Apparent Volume because all parts of the body
equilibrated with the drug do not have equal concentration.
It is calculated by dividing the dose that ultimately gets into the
systemic circulation by the plasma concentration at time zero
(C0).
MIHS 17
18. Redistribution
Highly lipid soluble drugs when given by i.v. or by
inhalation initially get distributed to organs with high
blood flow, e.g. brain, heart, kidney etc.
Later, less vascular but more bulky tissues (muscles,
fat) take up the drug and plasma concentration falls
and drug is withdrawn from these sites Which have
more drug concentration like heart, brain, kidney etc.
Greater the lipid solubility of the drug, faster is its
redistribution.
MIHS 18
20. DRUG RESERVOIRS
Drug reservoirs are the water compartments in the
body as well as the other storage sites .
Water compartments
1. PLASMA VOLUME
2. EXTRACELLULAR FLUID
3. TOTAL BODY WATER
Storage sites
1. Adipose
2. Bone
3. Muscle
4. Organs
MIHS 20
21. Water compartments
Plasma compartment:
If a drug has a very large molecular weight or
binds extensively to plasma proteins, it is too
large to move out through the endothelial slit
junctions of the capillaries and, thus, is
effectively trapped within the plasma (vascular)
compartment (4L).
Heparin shows this type of distribution.
MIHS 21
22. Water compartments
Extracellular fluid:
If a drug has a low molecular weight but is
hydrophilic, it can move through the endothelial slit
junctions of the capillaries into the interstitial fluid.
However, these hydrophilic drugs cannot move
across the lipid membranes of cells to enter the
water phase inside the cell.
Therefore, these drugs distribute into a volume that
is the sum of the plasma water and the interstitial
fluid, which together constitute the extracellular fluid
(14L).
Aminoglycoside antibiotic is an example.
22
23. Water compartments
Total body water:
If a drug has a low molecular weight and is
hydrophobic, not only can it move into the
interstitium through the slit junctions, but it can
also move through the cell membranes into the
intracellular fluid (42L).
Ethanol exhibits this type of volume of
distribution.
MIHS 23
24. Storage sites
ADIPOSE
For lipid soluble drugs, fat deposits throughout the
body serve as a considerable reservoir .
Drugs stored in adipose tissue remain there for long
periods because of low metabolic rate and poor blood
perfusion of fat tissues.
Example ;- barbiturate anaesthetic like THIOPENTAL
Inhalational anesthetics like HALOTHANE.
BONE
Storage site for several toxic agents especially heavy
metals like lead.
Example ; TETRACYCLINE 24
25. Storage sites
Muscle
long term storage
Example; antimalarial drug QUININE.
ORGANS
like Liver and kidneys
Example; Antimicrobial aminoglycoside agents such
as GENTAMICIN and STREPTOMYCIN that is stored
in renal proximal tubular cells.
MIHS 25