1. The document discusses drug distribution between blood and tissues, factors affecting it like lipid solubility, and implications of volume of distribution, plasma protein binding, redistribution, and barriers like the blood-brain and placental barriers.
2. Apparent volume of distribution describes the fluid volume required to contain the entire drug dose at the same concentration as plasma, and is affected by factors like lipid solubility and plasma protein binding.
3. Plasma protein binding influences drug availability and can cause drug interactions through displacement, while barriers like the blood-brain and placental barriers control drug passage into sensitive tissues and the fetus.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
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.
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.
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).
Once a drug has gained access to the bloodstream,
it gets distributed to other tissues that initially
had no drug, concentration gradient being in the
direction of plasma to tissues. T
Definition Of Drug Distribution.
Factors affecting drug distribution.
Volume Of Distribution.
Binding of Drug with PlasmaA process by which drug reversibly leaves blood stream & enters interstitium and/or cells of tissues like muscle, fat & brain tissue .
proteins.
At the end of this e-learning session you are able to…
A. Explain factor affecting drug distribution.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
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Pharmacokinetics of Drug_Pharmacology Course_Muhammad Kamal Hossain.pptxMuhammad Kamal Hossain
Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism and excretion (ADME) and their relationship with the pharmacological, therapeutic or toxicological response in man and animals.
Health informathics part passive reabsorption2.pptxMelakeselamGedamu
passive reabsorption Occurs by simple diffusion.
Drugs should be in their non-ionized form to undergo passive reabsorption.
Hence, polar drugs are more readily excreted through the kidneys.
When the urine is acidic, the degree of
ionization of basic drug increase and their reabsorption decreases.
When the urine is more alkaline, the degree of ionization of acidic drug increases and the
reabsorption decreases.
Immunosupressants and Immunostimulants their pharmacology, uses etc. Basics of immunology, innate immune response, acquired immune response, role of complement in innate immune response. Major histocompatibility complex, antibody structure. classification of immunosupressants, their mechanism of action, uses and adverse effects.
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
Antileprosy drugs have been described with their pharmacology also this topic covers Multidrug treatment for leprosy including paucibacillary and multibacillary leprosy and lepra reactions
Pharmacology of cephalosporins, monobactums and carbapenums including their mechanism of action, indications, adverse effects.
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Drugs for treatment of Diabetes MellitusNaser Tadvi
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Introduction to Autonomic Nervous systemNaser Tadvi
Lecture intends to give a brief overview of autonomic nervous system.
it includes the anatomical distribution of ANS, Neurohumoral transmission, co-transmission, receptors for ANS and synthesis of the neurotransmitters, Acetylcholine and Catecholamines
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Lecture includes definition of bioassay, Types of Assay and Bioassay , Indications, principles, advantages of bioassay. Example of a Bioassay with calculations. This lecture will be of help for postgraduate pharmacology students as well as undergraduates
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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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!
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
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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.
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
2. Objectives
1. Overview of drug distribution
2. Explain apparent volume of distribution
with clinical implications
3Discuss drug binding to plasma proteins and
tissues with clinical implications
4. Explain redistribution
5. Discuss blood brain barrier and Placental
barrier
3. 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).
4. DRUG ADMINISTRATION
May get distributed
to…..
Vascular compartment
Total body water
Interstitial fluid compartment
Extracellular space
Intracellular compartments
Body fat
Bones
Placenta
Brain
Plasma proteins
Liver
Many more organs !!!
6. Volume of distribution
• Fluid volume that is required to contain the entire
drug in the body at the same concentration
measured in the plasma.
• Calculated by dividing the dose that ultimately gets
into the systemic circulation by the plasma
concentration at time zero (C0)
7. Which means
• If 500 mg of drug reaches circulation…(total amount of drug )
• And if plasma concentration is 0.5 mg/ml
• Vd will be 500/0.5 = 1000 ml.
• Which means you require 1000 ml of fluid to accommodate total 500 mg
of drug at concentration of 0.5 mg/ml.
• At times it can be larger than total blood volume. (when drug
has been stored in peripheral tissues so lower blood concentration).
• At times it can be smaller than or equal to total blood
volume( when drug remains in vascular compartment).
8. Vd(L) =
Total amount administered
Plasma concentration
Total amount administered
Plasma concentration
Vd(L) =
When plasma
concentration
is high….
Vd is low….
9. Vd(L) =
Total amount administered
Plasma concentration
When plasma
concentration
is low….
Vd is high….
10. Distribution into the water
compartments of body
• Plasma compartment:
– Drugs having high molecular weight or extensively
plasma protein bound like heparin Vd= 4L
• Extracellular fluid:
– Low molecular weight but hydrophilic drugs
– Aminoglycosides Vd=14L
• Total body water:
– low molecular weight and lipophilic,
– E.g Ethanol Vd=42 L
11.
12. Apparent Volume of distribution
• A drug rarely associates exclusively with only one
of the water compartments of the body.
• Vast majority of drugs distribute into several
compartments, often avidly binding cellular
components, such as lipids, proteins, and nucleic
acids.
• Thus, the volume into which drugs distribute is
called the apparent volume of distribution (Vd).
13. Plasma protein binding
• Most drugs posses physicochemical affinity for
plasma proteins
– Acidic drugs bind to plasma albumin, basic drugs
bind to 1 acid glycoprotein
– Reversible manner
– Extensive binding serves as a circulating drug
reservoir
– Other proteins to which drugs can bind: globulins,
transferrin, ceruloplasmin, tissue proteins &
nucleoproteins
14. Clinical implications of plasma protein
binding
1. Highly plasma protein bound drugs does not
cross membranes so largely restricted to
vascular compartments (smaller Vd).
2. Temporary storage of the drug which is not
available for any action.
3. High degree of protein binding generally
makes the drug long acting
4. Plasma concentrations of the drug refer to
bound as well as free drug.
15. 5. One drug can bind to many sites on the albumin molecule.
Conversely, more than one drug can bind to the same site.
6. Displacement reactions- (Drug interactions)
– Salicylates displace sulfonylureas & methotrexate.
– Indomethacin, phenytoin displace warfarin.
– Sulfonamides and vit K displace bilirubin(kernicterus in neonates) .
7. In hypoalbuminemia, reduced binding leads to high
concentrations of free drug e.g. phenytoin and furosemide.
8. Other diseases: e.g. phenytoin and pethidine binding is
reduced in uraemia;
Clinical implications of plasma protein
binding
17. Clinical implications of volume of distribution
• Dialysis is not very useful for drugs with high
Vd e.g digoxin, imipramine
• It helps in estimating the total amount of drug
at any time
amount of drug = Vd X plasma conc of drug at
certain time
• Vd is important to determine the loading dose
Loading dose = Vd X desired concentration
18. Drugs concentrated in body tissues
• Digoxin, emetine: Skeletal muscles, heart,
liver, kidney
• Chloroquine: retina and liver
• Iodine: Thyroid
• Chlorpromazine: eye
• Atropine: iris
• Tetracyclines: Bone and teeth
• Thiopentone , DDT: Adipose tissue
19. Redistribution
• Highly lipid-soluble drugs get initially distributed to organs
with high blood flow ( brain, heart, kidney) & later into bulky
less vascular tissues (muscle, fat)
• So plasma concentration falls and the drug is withdrawn from
these sites
• If the site of action of drug is one of highly perfused organs,
redistribution may result in termination of drug action.
• Greater the lipid solubility faster is the redistribution of drug.
• Anaesthetic action of thiopentone sod. injected i.v. is
terminated in few minutes due to redistribution.
• To overcome , give continous infusion
20.
21. PLASMA HALF LIFE
• It is the time taken for the plasma concentration or amount of the drug
present in the body to reduce to 50% of previous level.
PLASMACONC
TIME
ALPHA = DISTRIBUTION PHASE
BETA = ELIIMINATION PHASE
Clinically t ½ that is
calculated from BETA
ELIMINATION PHASE is
considered as t ½ of
drug.
22. At peak blood concentration will be 100 %
After 1 half life blood concentration will be 50 %
After 2 half lives blood concentration will be 25 %
After 3 half lives blood concentration will be 12.5 %
After 4 half lives blood concentration will be 6.25 %
After 5 half lives blood concentration will be 3.125 %
So after 4-5 half lives
drug will be almost
completely eliminated
from the body
If you administer a
drug before that
there will be
accumulation of
the drug in the
body.
24. Functions and Properties of the BBB
• Protects the brain from "foreign substances"
in the blood that may injure the brain.
• Protects the brain from hormones and
neurotransmitters in the rest of the body.
• Maintains a constant environment for the
brain.
25. Properties of drugs that can cross BBB
• low molecular weight
• High degree of lipid solubility
• Non ionized
• Tertiary structure and
• Free drug
26. Placental Barrier
• Lipoidal and allows free passage of lipophilic
drugs
• P Glycoprotein limits exposure to maternally
administered drugs
• Also placenta is site of metabolism- lowers
exposure to drugs
• Incomplete barrier
• Congenital anomalies
27. Summary
1. Overview of drug distribution
2. Apparent volume of distribution with clinical
implications
3 Drug binding to plasma proteins and tissues
with clinical implications
4. Redistribution
5. BBB and Placental barrier
Editor's Notes
For drugs administered IV, absorption is not a factor, and the initial phase (from immediately after administration through the rapid fall inconcentration) represents the distribution phase, during which the drug rapidly leaves the circulation and enters the tissues
The distribution of a drug from the plasma to the interstitium depends on cardiac output and local blood flow, capillary permeability, the tissue volume,the degree of binding of the drug to plasma and tissue proteins, and therelative lipophilicity of the drug.
Volume of distribution is the measure of the apparent space in the body available to contain the drug. Volume of distribution (V) relates the amount of drug in the bodyto the concentration of drug (C) in blood or plasma:
Drugs with very high volumes of distributionhave much higher concentrations in extravascular tissue than inthe vascular compartment, ie, they are not homogeneously distributed.
The apparent volume of distribution reflects a balance betweenbinding to tissues, which decreases plasma concentration andmakes the apparent volume larger, and binding to plasma proteins, which increases plasma concentration and makes the apparent volume smaller.Changes in either tissue or plasma bindingcan change the apparent volume of distribution determined fromplasma concentration measurements. Older people have a relativedecrease in skeletal muscle mass and tend to have a smaller apparent volume of distribution of digoxin (which binds to muscleproteins). The volume of distribution may be overestimated inobese patients if based on body weight and the drug does not enterfatty tissues well, as is the case with digoxin. In contrast, theophylline has a volume of distribution similar to that of total bodywater. Adipose tissue has almost as much water in it as other tissues, so that the apparent total volume of distribution of theophylline is proportional to body weight even in obese patients.Abnormal accumulation of fluid—edema, ascites, pleuraleffusion—can markedly increase the volume of distribution ofdrugs such as gentamicin that are hydrophilic and have small volumes of distribution
Plasma compartment: If a drug has a high molecular weight or is extensively protein bound, it is too large to pass through the slit junctions of the capillaries and, thus, is effectively trapped within the plasma (vascular) compartment. As a result, it has a low Vd that approximates the plasma volume or about 4 L in a 70-kg individual. Heparin shows this type of distribution.
lipids (abundant in adipocytes and cell membranes), proteins (abundantin plasma and cells), and nucleic acids (abundant in cell nuclei).
unless it is actively extracted by liver or kidney tubules.
Equilibrium (drug movement will continue till the equilibrium is reached
Redistribution depends upon regional blood flow & diffusibility of drug