Drug-plasma protein binding plays a key role in drug pharmacokinetics and pharmacodynamics. Proteins, particularly albumin and alpha-1-acid glycoprotein, bind drugs reversibly through mechanisms like hydrogen bonding, hydrophobic interactions, and van der Waals forces. Only the unbound fraction of a drug is active, as protein-bound drug is inert and cannot cross membranes or exert effects. Several factors influence protein binding, including drug properties, protein concentrations, and disease states. The degree of protein binding impacts drug absorption, distribution, metabolism, and elimination.
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 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.
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 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.
Utilization of radioactive isotopes in the investigation of biogenetic studiesMs. Pooja Bhandare
Isotopes: TWO TYPES OF ISOTOPES,Radioactive isotopes.
Stable isotopes, Radiolabelled Tracers ( Radiolabelled compounds), Radiotracer Technique, Steps in Tracer Technique,
Selection of Radioisotopes.
Preparation of Radioisotopes.
Introduction/Insertion of Radiolabelled compound in biological system (Plant part) Seperation and determination of labelled compound in various biochemical reaction, Preparation of labelled compounds : Insertion of Radiolabelled compound in plant part, Root feeding, Stem feeding, Direct Injection, Floating Methods, Spray technique, Separation or Isolation of Radiolabelled compound and detection of radioisotope labelled compound. Detection and assay of Radioactive labelled compound, Detector system used (Analysis of Isotopic content). Method in Tracer Technique,
Precursor – Product sequence
Double and Multiple Labelling
. Competitive Feeding,Sequential Analysis
Applications of Tracer Technique
Neurohumoral transmission in CNS-
The term neurohumoral transmission designates the transfer of a nerve impulse from a presynaptic to a postsynaptic neuron by means of a humoral agent e.g. a biogenic amine, an amino acid or a peptide.
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.
Utilization of radioactive isotopes in the investigation of biogenetic studiesMs. Pooja Bhandare
Isotopes: TWO TYPES OF ISOTOPES,Radioactive isotopes.
Stable isotopes, Radiolabelled Tracers ( Radiolabelled compounds), Radiotracer Technique, Steps in Tracer Technique,
Selection of Radioisotopes.
Preparation of Radioisotopes.
Introduction/Insertion of Radiolabelled compound in biological system (Plant part) Seperation and determination of labelled compound in various biochemical reaction, Preparation of labelled compounds : Insertion of Radiolabelled compound in plant part, Root feeding, Stem feeding, Direct Injection, Floating Methods, Spray technique, Separation or Isolation of Radiolabelled compound and detection of radioisotope labelled compound. Detection and assay of Radioactive labelled compound, Detector system used (Analysis of Isotopic content). Method in Tracer Technique,
Precursor – Product sequence
Double and Multiple Labelling
. Competitive Feeding,Sequential Analysis
Applications of Tracer Technique
Neurohumoral transmission in CNS-
The term neurohumoral transmission designates the transfer of a nerve impulse from a presynaptic to a postsynaptic neuron by means of a humoral agent e.g. a biogenic amine, an amino acid or a peptide.
introduction
mechanisms of protein drug binding
binding of drugs
binding of drugs to blood components
determination of protein drug binding
factors affecting
significance
factors affecting protein drug binding
significance of protein binding
drug related factors
protein related factors
drug interactions
patient related factors
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How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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.
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.
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Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
2. INTRODUCTION
• Drug–plasma-protein binding is critically
involved in drug pharmacokinetics (i.e
ADME) and pharmacodynamics
(pharmacological effects).
• The interacting molecules are generally
the macromolecules such as protein,
DNA or adipose.
3. Protein binding
• The protein are particularly
responsible for such an interaction.
• The phenomenon of complex
formation of drug with protein is
called as protein binding of drug
• Protein + drug ⇌ Protein-drug
complex
4. Protein bound drug- inert
As a protein bound drug is
neither metabolized nor
excreted hence it is
pharmacologically inactive due
to its pharmacokinetic and
Pharmacodynamic inertness.
7. MECHANISMS OF PROTEIN DRUG
BINDING: Reversible Drug Binding
Reversible generally involves weak chemical
bond such as:
1. Hydrogen bonds
2. Hydrophobic bonds
3. Ionic bonds
4. Van der waal’s forces.
8. MECHANISMS OF PROTEIN DRUG
BINDING: Irreversible Drug Binding
Irreversible drug binding,
though rare, arises as a result of
covalent binding and is often a
reason for the carcinogenicity or
tissue toxicity of the drug.
9. Conclusion
The binding of a drug to a
protein can be viewed as a
reversible and rapid
equilibrium process governed
by the law of mass action.
10.
11. Unbound drug
It is commonly stated that unless there is a
specific transport system, only the free drug
molecules are able to cross membrane barriers
and be distributed to tissues to undergo
metabolism and glomerular filtration.
Only the free drug fraction is able to exert
pharmacological and/or toxicological effects
12. BINDING OF DRUG TO BLOOD
COMPONENTS
A. Plasma protein-drug binding:-
Human serum albumin (HSA) and α1-acid
glycoprotein (AGP), are present in relatively
high quantities in plasma are able to bind a
broad variety of drugs with sufficient affinity
to have a significant effect on drug disposition
and action .
Globulins and lipoproteins may also play a
role to a lesser degree
13. B. BINDING OF DRUG TO BLOOD
CELLS
• In blood 40% of blood cells of which major
component is RBC (95%).
• The RBC is 500 times in diameter as the
albumin.
• The rate & extent of entry into RBC is more for
lipophilic drugs.
14. The RBC comprises of 3 components
• Haemoglobin
phenytoin, pentobarbital bind to haemoglobin
• Carbonic anhydrase
acetazolamide & chlorthalidone.
• Cell membrane
Imipramine & chlorpromazine are reported to
bind with the RBC membrane
15. BINDING OF DRUG TO
EXTRAVASCULAR TISSUE PROTEIN
It increases apparent volume of
distribution of drug.
Localization of a drug at a specific
site in body.
Binding order: Liver › Kidney › Lung ›
Muscles
16. Tissue Binding of
• Kidney
Metallothionin protein binds to Heavy metals &
results in Renal accumulation and toxicity.
• Skin
Chloroquine & Phenothiazine binds to Melanin.
• Eye
Chloroquine & Phenothiazine also binds to Eye
Melanin & results in Retinopathy.
17. Tissue Binding of
• Hairs
Arsenicals, Chloroquine, & Phenothiazine.
• Bones
Tetracycline(yellow discoloration of teeth), Lead-
(replaces Ca & cause brittleness)
• Fats
Lipophilic drugs (thiopental), Pesticides (DDT)
• Nucleic Acid
Chloroquine & Quinacrine
18. FACTORS AFFECTING PROTEIN DRUG
BINDING
• 1. Drug-related factors
a. Physicochemical characteristics of the drug:-
Protein binding is directly related to the
lipophilicity of drug. An increase in lipophilicity
increases the extent of binding.
b. Concentration of drug in the body:-
Alteration in the concentration of drug substance
as well as the protein molecules or surfaces
subsequently brings alteration in the protein
binding process.
19. FACTORS AFFECTING PROTEIN DRUG
BINDING
c. Affinity of a drug for a particular binding
component:-
This factor entirely depends upon the degree
of attraction or affinity the protein molecule
or tissues have towards drug moieties.
For Digoxin has more affinity for cardiac
muscles proteins as compared to that of
proteins of skeletal muscles or those in the
plasma like HSA.
20. 2. Protein/ tissue related factors:
a. Physicochemical characteristics of protein or
binding agent:
Lipoproteins & adipose tissue tend to bind
lipophilic drug by dissolving them in their lipid
core.
The physiological pH determines the presence
of active anionic & cationic groups on the
albumin to bind a variety of drug
21. b. Concentration of protein or binding
component:
Among the plasma protein , binding
predominantly occurs with albumin, as it is
present in high concentration in comparison
to other plasma protein.
The amount of several proteins and tissue
components available for binding, changes
during disease state.
22. 3. Drug interactions
• a. Competition between drugs for the binding
sites[ Displacement interactions]:-
• e.g. Administration of phenylbutazone to a
patient on Warfarin therapy results in
Hemorrhagic reaction.
• b. Competition between drug & normal body
constituents:-
• The free fatty acids are known to interact with a
no. of drugs that binds primarily to HSA. the free
fatty acid level increase in physiological,
pathological condition.
23. c. Allosteric changes in protein
molecule:-
The process involves alteration of the
protein structure by the drug or it’s
metabolite thereby modifying its binding
capacity.
e.g. aspirin acetylates lysine fraction of
albumin thereby modifying its capacity to
bind NSAIDs like phenylbutazone.
24. 4. Patient-related factors
a. Age:
1.Neonates: Low albumin content: More free
drug.
2.Young infants: High dose of Digoxin due to
large renal clearance.
3.Elderly:Low albumin: So more free drug.
25. • b. Intersubject variability: Due to genetics &
environmental factors.
• c. Disease states:-
• Renal failure – disease condition
• ↓ Albumin content – influence on plasma
protein
• ↓ binding of acidic drugs; neutral and basic
drugs are un affected-Influence on protein
drug binding
26. SIGNIFICANCE OF PROTEIN/TISSUE
BINDING OF DRUG
a. Absorption-
As we know the conventional dosage form follow
first order kinetics. So when there is more protein
binding then it disturbs the absorption equilibrium.
b. Distribution-
A protein bound drug in particular does not cross
the BBB, the placental barrier and the glomerulus.
Thus protein binding decreases the distribution of
drugs
27. c. Metabolism-
Protein binding decreases the metabolism of drugs
& enhances the biological half life. Only unbound
fraction get metabolized.
e.g. Phenylbutazone & Sulfonamide.
d. Elimination
Only the unbound drug is capable of being
eliminated.
Protein binding prevent the entry of drug to the
metabolizing organ (liver ) & to glomerulus
filtration.
e.g. Tetracycline is eliminated mainly by glomerular
filtration.
28. e. Systemic solubility of drug
Lipoprotein act as vehicle for hydrophobic drugs
like steroids, heparin, oil soluble vitamin.
f. Drug action-
Protein binding inactivates the drugs because
sufficient concentration of drug can not be build
up in the receptor site for action.
e.g. Naphthoquinone
29. g. Sustain release-
The complex of drug protein in the blood act as
a reservoir & continuously supply the free drug.
e.g. Suramin sodium-protein binding for
antitrypanosomal action.
h. Diagnosis-
The chlorine atom of chloroquine replaced with
radiolabeled I-131 can be used to visualize-
melanomas of eye & disorders of thyroid gland.
30. REFERENCES
• 1. Brahmankar D.M. and Jaiswal S.B.(2009)
Biopharamaceutics and pharmacokinetics: A Treatise ,2nd ed.
,Vallabh Prakashan ,p.116-136.
• 2. Shargel L.& Andrew B.C.(2005) Applied
Biopharamaceutics and pharmacokinetics ,5th ed. ,Mc Graw
Hill company ,p. 267-298.
• 3. Tripati K.D. Essential of Medical pharmacology ,6th ed. ,
Jaypee brothers Medical publisher Ltd. ,p. 20-23.
• 4. Barar F.S.K. Essential of pharmacotherapeutices ,5th ed.
,S.Chand and Company Ltd. ,p. 43-48.