At the end of this e-learning session you are able to…
1. Discuss How drug is excreted from blood circulation?
2. Explain different factor affecting excretion.
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Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
At the end of this e-learning session you are able to…
1. Discuss How drug is excreted from blood circulation?
2. Explain different factor affecting excretion.
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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For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
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Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
Pharmacokinetics variations in Disease States.Faizan Akram
The biggest issue in PK/PD and drug therapy is variability in
response. Variability factors that affect pharmacokinetics and pharmacodynamics influence clinical trials and dose regimen designs.
The Provision Of Written And/Or Verbal Information About Drugs And Drug Therapy In Response To A Request From Other Healthcare Providing Organizations, Committees, Patients, And Public Community
Pharmacokinetics variations in Disease States.Faizan Akram
The biggest issue in PK/PD and drug therapy is variability in
response. Variability factors that affect pharmacokinetics and pharmacodynamics influence clinical trials and dose regimen designs.
The Provision Of Written And/Or Verbal Information About Drugs And Drug Therapy In Response To A Request From Other Healthcare Providing Organizations, Committees, Patients, And Public Community
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.
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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For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
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For 2+ video lecture series on Therapeutic drug monitoring refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
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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.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
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Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
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Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
21. THE DISTRIBUTION OF DRUG DEPENDS
ON
• Differences in regional blood flow,
determine the rate of uptake of drug
• Capillary permeability & Special
Barriers ---- BBB, placental barrier
• Drug structure - lipid solubility,
ionization
• Binding of drugs to
macromolecules
22. BLOOD FLOW AND DRUG DISTRIBUTION
• The initial rate of distribution of a drug depends heavily on blood flow to
various organs
• Brain, liver, kidney > muscle, skin > fat, bone
• At equilibrium, or steady state, the amount of drug in an organ is related to
mass of the organ and its properties, as well as to the properties of the
specific drug
23. BLOOD FLOW AND DRUG DISTRIBUTION
• Size of the organ – and concentration gradient
• Skeletal muscle –blood tissue gradient remains high even after a relatively
large amount of the drug has been transferred
• Brain – blood tissue gradient reduced to zero on distribution of a smaller
amount of drug, preventing further uptake of drug.
24. DRUG REDISTRIBUTION
• The relative distribution of a drug in the body changes with time
• This is seen with highly lipophilic drugs such as thiopental
• I/v thiopental produce short duration of hypnosis
• GA in 10-20seconds, effect stops 5-15 minutes due to redistribution
• – initial high concentration achieved in brain (blood flow + lipid solubility of
drug)--- then slow distribution to skeletal muscle and adipose tissue
(redistribution)
25. Permeability and Special Barriers to drug distribution
BBB, placental barrier
Drug structure --- lipid solubility, ionization
26.
27. BBB
• BBB may not be fully developed at birth
• Inflammation, such as that result
from meningitis, may increase the
ability of ionized, poorly soluble
drugs to cross the BBB
30. PLACENTAL BARRIER
• Lipid soluble drugs cross the placental barrier more easily than polar drugs;
drugs with a molecular weight of less than 600 pass the placental better
than larger molecule
• The possibility that drug administered to the mother may cross the placenta
and reach the fetus is an important consideration in therapy
• Drug transporter e.g., P-glycoprotein transporter transfer drugs out of the
fetus
31. CAPILLARY PERMEABILITY --LIVER &
SPLEEN
• large, discontinuous capillaries
through which large plasma
proteins can pass
• Drugs exchange freely between
blood and interstitium in the liver
32.
33. BINDING OF DRUGS
TO PROTEINS
INERT BINDING
(DRUG +
NONREGULATORY
MOLECULES --- NO
EFFECT)
34. THE DRUGS EXISTS IN PLASMA IN THE FREE
FORM OR BOUND TO PLASMA PROTEINS
D + S DS
Free binding complex
drug site
• Extent of binding is highly variable --- 0% to 99
• The free drug is maintained as a constant fraction
of the total drug
• When the free drug levels fall, the bound drug is
releases
35. • Only the free drug diffuses through the capillary
walls
• Drug bound to proteins is a nondiffusible form–
it serves as a store (reservoir) & the drug is
released when the free drug levels fall
• Only free drug is available for pharmacological
action, metabolism, and excretion
• It is the free drug in the interstitial fluid that
exerts a pharmacological effect
36. • The amount of a drug that is bound to
protein depends upon
• The concentration of free drug
• Its affinity for binding site
• The concentration of protein
• Saturable binding sometimes leads to non-
linear relation between dose and free
(active) drug concentration
37. • Plasma albumin is most important; β globulin and acid glycoprotein also
bind some drugs
• Plasma albumin binds mainly acidic drugs
• 2 molecules per albumin molecule.
• Warfarin, NSAIDS, Sufonamides
• Basic drugs may be bound by β globulin & acid glycoprotein-- Quinine
38. CLINICAL SIGNIFICANCE OF PLASMA
PROTEIN BINDING
• Extensive protein binding
• Prolongs duration of action of the drug
• Slows drug elimination(metabolism and / or elimination)
• CRF and CLD results in hypoalbuminemia with ↓ binding of
drugs
• Drug interaction
• Many drugs may compete the same binding sites.
• Thus one drug may displace another from the binding
sites resulting in toxicity
• indomethacin displaces warfarin from protein binding
sites leading to increase warfarin levels
• Tolubutamide (95% bound) displaced by a sulphonamide
• Chloroquine strongly bounds to extravascular tissue protein
39. DISTRIBUTION -- WHERE THE DRUG
GOES?
• The drug is distributed to
various fluid compartments of
the body
-Volumes of distribution
-Apparent spaces
41. Total body fluid (42 liters)
Hydrophobic small molecule --- ethanol
42. Total body fluid (42 liters)
Hydrophobic small molecule --- ethanol
Hydrophilic
low molecular weight
---Aminoglycoside
---Gentamicin
43. Total body fluid (42 liters)
Hydrophobic small molecule --- ethanol
Hydrophilic
low molecular weight
---Aminoglycoside
---Gentamicin
Protein bound molecules
Very large molecules --- heparin
45. Plasma compartment
Very high molecular weight drugs, or
drugs that bind to plasma proteins
excessively
Example: heparin 4L (3-5)
46. Fat (0.2-0.35 L/Kg) ---
highly lipid soluble molecules --- DDT
Bone (0.07 L/Kg)
certain ions --- lead, fluoride
47. Vd equal to or higher than total body water
Diffusion to intracelullar fluid .
Vd equal to total body water.
Ethanol 38 L (34-41)
Drug that binds strongly to tissues.
Vd higher than total body water.
Fentanyl: 280 L
Propofol: 560 L
Digoxin : 385 L
49. Vd = amount of drug in the body(dose)
plasma concentration
Vd is expressed as in units of volume
50. APPARENT VOLUME OF DISTRIBUTION
(VD)
• Most drugs distribute unevenly in several compartments
• Apparent volume of distribution assumes that the drug distributes uniformly
in a single compartment
• In most cases , the “initial” plasma concentration, C0, is determined by extrapolation
from the elimination phase
51. FEATURES OF VD
• The higher the Vd, the lower the
plasma concentration and vice
versa.
• A very low Vd value may indicate
extensive plasma protein binding
of the drug.
52. FEATURES OF VD
• A very high Vd value may indicate
that the drug is extensively bound to
the tissue sites
• An exceptional large Vd indicate
considerable sequestration of the
drug in some organ or the
compartment
54. Vd equal to or higher than total body water
Diffusion to intracelullar fluid .
Vd equal to total body water.
Ethanol 38 L (34-41)
Drug that binds strongly to tissues.
Vd higher than total body water.
Fentanyl: 280 L
Propofol: 560 L
Digoxin : 385 L
55. SIGNIFICANCE OF VD
• To calculate the loading dose of a drug
• Drug displacement, Vd & drug
interaction
• Vd and half life of a drug
• Vd can be used to calculate the amount
of drug needed to achieve a desired
plasma concentration
56. VD AND DRUG DOSAGE
• To calculate the loading dose of a drug -------Drugs with large Vd need a
loading dose to achieve the desired plasma concentration
• Vd can be used to calculate the amount of drug needed to achieve a desired
plasma concentration
• (Vd ) (C1) = amount of drug initially in the body
• (Vd ) (C2) = amount of drug needed to achieve the desired plasma drug
concentration
• Additional dose needed = Vd (C2 – C1)
57. DRUG DISPLACEMENT, VD &
DRUG INTERACTION
• A very low Vd value indicate extensive plasma protein binding of the drug.
• Displacement of drug from albumin --- ↑in the “free” drug
• If the therapeutic index of the drug is small. An ↑ in free drug concentration
may lead to
• ↑ therapeutic effects
• ↑ toxic effects
• Tolubutamide (95% bound) displaced by a sulphonamide
58. EFFECT OF A LARGE VD ON HALF LIFE OF
A DRUG
• A very large Vd indicate that most
of the drug is in the extraplasmic
space and is unavailable to
excretory organs. --- the longer is
half life and the duration of
action of the drug
59. • Vd may be influenced by age, sex, weight, and disease processes – edema,
ascities
• The Vd is altered by diseases
• For drugs that are normally bound to plasma protein
• Liver disease – through reduce protein synthesis
• Kidney disease – through urinary protein loss
• An exceptional large Vd
• For drugs that avidly bound in peripheral tissues, the drug’s concentration in plasma may drop
to very low values even though the total amount in the body is very large
• Vd is 50,000 liters for quinacrine
60. DRUG DISTRIBUTION
• Blood flow
• Capillary permeability
• Binding of drugs to plasma proteins and tissues
• Binding to plasma proteins
• Binding to tisssue proteins
• Hydrophobicity
• Volume of distribution