This document discusses drug receptor interactions, including definitions of key terms like drug, receptor, antagonist, and pA2 value. It describes how drugs bind to receptors and can act as agonists or antagonists. Quantitative aspects of drug-receptor interactions are covered, including dose-response curves, potency, and therapeutic indices. Factors that contribute to variability in individual responses are also summarized. Binding studies and docking simulations are introduced as methods to study these interactions.
Receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased agonism
SAR versus QSAR, History and development of QSAR, Types of physicochemical
parameters, experimental and theoretical approaches for the determination of
physicochemical parameters such as Partition coefficient, Hammet’s substituent
constant and Taft’s steric constant. Hansch analysis, Free Wilson analysis, 3D-QSAR
approaches like COMFA and COMSIA.
Receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased agonism
SAR versus QSAR, History and development of QSAR, Types of physicochemical
parameters, experimental and theoretical approaches for the determination of
physicochemical parameters such as Partition coefficient, Hammet’s substituent
constant and Taft’s steric constant. Hansch analysis, Free Wilson analysis, 3D-QSAR
approaches like COMFA and COMSIA.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
In this slide I covered the detailed about hansch analysis, Free-Wilson analysis, and Mixed approach. I also gave a detailed application for each points.
Definition
Classification and description of each class.
Description of individual receptor.
Forces affecting the drug receptor binding.
Binding of drug receptor affect drug action.
Agonist and antagonist.
Disease due to malfunctioning of receptors.
New drug design based on structure of receptors
Receptor as target for drug discovery.
Drug action not mediated by receptor.
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
In this slide I covered the detailed about hansch analysis, Free-Wilson analysis, and Mixed approach. I also gave a detailed application for each points.
Definition
Classification and description of each class.
Description of individual receptor.
Forces affecting the drug receptor binding.
Binding of drug receptor affect drug action.
Agonist and antagonist.
Disease due to malfunctioning of receptors.
New drug design based on structure of receptors
Receptor as target for drug discovery.
Drug action not mediated by receptor.
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
THIS PPT INCLUDE PHARMACODYNAMICS AND THIS PPT IS VERY USEFUL FOR (MBBS,BDS ) STUDENTS ,POSTGRADUATE STUDENT (MD,MDS,Phd) STUDENTS TO UNDERSTAND PHARMACODYNAMICS.
Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanisms of action. Pharmacodynamics is often referred to as “what the drug does to the body”.
In order to exert their effects, drugs usually interact in a structurally specific way with a protein receptor or act on physiological processes within the body. This activates a secondary messenger system that produces a physiological effect. Drugs do not create new action but they can only modify (alter) the functions of cells or tissues in body. The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cell by a process called signal transduction.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
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
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.
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.
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
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
2. DRUG:
The WHO (1966) defined it as -
"Drug is any substance or product that is used
or is intended to be used to modify or explore
physiological systems or pathological states
for the benefit of the recipient."
3. RECEPTOR:
It describes protein molecules whose
function is to recognise and respond to
endogenous chemical signals.
Other macromolecules with which drugs
interact to produce their effects are known
as drug targets.
8. pA2:
A pA2 value determines the important relationship
between two drugs "competing" for effect on the same
receptor.
The two drugs are "competitive" if increasing or reducing
one drug decreases or increases the effect of the other,
respectively.
The pA2 value indicates the concentration of antagonist
when double the agonist is required to have the same
effect on the receptor as when no antagonist is present.
9. Defined as: The negative logarithm to base 10 of the
molar concentration of an antagonist that makes it
necessary to double the concentration of the agonist
needed to elicit the original submaximal response
obtained in the absence of antagonist.
10.
11. DRUG SPECIFICITY:
The strength of the reversible interaction between a drug
and its receptor.
It is defined as the affinity of one for the other.
A drug that interacts with a single type of receptor that is
expressed on only a limited number of differentiated cells
will exhibit high specificity.
12. If, however, a receptor is expressed ubiquitously
on a variety of cells throughout the body, drugs
acting on such a widely expressed receptor will
exhibit widespread effects, and could produce
serious side effects or toxicities if the receptor
serves important functions in multiple tissues.
13. The pharmacological properties of many drugs
differ depending upon whether the drug is used
acutely or chronically.
In some cases, chronic administration of a drug
causes a down-regulation or desensitization of
receptors that can require dose adjustments to
maintain adequate therapy.
14. Quantitative Aspects of Drug
Interactions with Receptors
The basic currency of receptor pharmacology is
the dose-response (or concentration-response)
curve.
The drug effects can be measured for
quantitative assessment of its safety and efficacy.
17. Thus, measuring agonist potency by comparison
of EC50 values is one method of measuring the
capability of different agonists to induce a
response in a test system and for predicting
comparable activity in another.
18. Pharmacodynamic Variability: Individual and
Population Pharmacodynamics
Individuals vary in the magnitude of their response to the
same concentration of a single drug or to similar drugs,
and a given individual may not always respond in the
same way to the same drug concentration.
Attempts have been made to define and measure
individual "sensitivity" (or "resistance") to drugs in the
clinical setting, and progress has been made in
understanding some of the determinants of sensitivity to
drugs that act at specific receptors.
19. Drug responsiveness may change because of
disease or because of previous drug
administration.
Receptors are dynamic, and their concentration
and function may be up- or down-regulated by
endogenous and exogenous factors.
The variability in pharmacodynamic response in
the population may be analyzed by constructing
a quantal concentration-effect curve.
20. The dose of a drug required to produce a
specified effect in 50% of the population is the
median effective dose ED50
In preclinical studies of drugs, the median lethal
dose (LD50) is determined in experimental animals.
The LD50/ED50 ratio is an indication of the
therapeutic index, which is a statement of how
selective the drug is in producing its desired
effects versus its adverse effects.
21.
22. The binding of drugs to receptors :
The binding of drugs to receptors can often be
measured directly by the use of drug molecules
(agonists or antagonists) labelled with one or
more radioactive atoms (usually 3H, 14C or 125I).
23. The usual procedure is to incubate samples of the
tissue (or membrane fragments) with various
concentrations of radioactive drug until
equilibrium is reached.
The bound radioactivity is measured after
removal of the supernatant.
24. The amount of non-specific binding is estimated
by measuring the radioactivity taken up in the
presence of a saturating concentration of a (non-
radioactive) ligand that inhibits completely the
binding of the radioactive drug to the receptors,
leaving behind the non-specific component.
This is then subtracted from the total binding to
give an estimate of specific binding .
25.
26. The binding curve defines the relationship
between concentration and the amount of drug
bound (B), allowing the affinity of the drug for the
receptors to be estimated, as well as the binding
capacity (Bmax), representing the density of
receptors in the tissue.
27.
28. It has also been shown, in skeletal muscle and
other tissues, that denervation leads to an
increase in the number of receptors in the target
cell, a finding that accounts, at least in part, for
the phenomenon of denervation supersensitivity.
29. Non-invasive imaging techniques, such as
positron emission tomography (PET), can also be
used to investigate the distribution of receptors in
structures such as the living human brain.
30. Docking studies:
Docking is a method which predicts the preferred orientation
of one ligand when bound in an active site to form a stable
complex.
The ligand is docked onto the receptor and the interactions are
checked. The scoring function generates score, depending on
which the best fit ligand is selected.
31. Types:
Rigid Docking (Lock and Key)
In rigid docking, the internal geometry of both the receptor
and ligand are treated as rigid. In the rigid molecule docking ,
we relate to the molecules as rigid objects that cannot change
their spatial shape during the docking process.
Flexible Docking (Induced fit)
An enumeration on the rotations of one of the molecules
(usually smaller one) is performed. Every rotation the energy is
calculated; later the most optimum pose is selected.
The Schild plot is a pharmacological method of receptor classification. To construct a Schild plot, the dose-effect curve for an agonist is determined in the presence of various concentrations of a competitive antagonist. From this experiment the pA2 is determined which is a measure of affinity of the antagonist for its receptor (i.e., the equilibrium dissociation constant). As such, the Schild Plot is sometimes referred to as pA2 analysis. Once the actual experiments are completed a series of dose ratios (DR) are calculated for a given effect. For example the ratio of the dose of agonist (A') to produce a specific effect (e.g., half maximal effect) in the presence of the antagonist (B) to the dose required in the absence of the antagonist (A) is calculated. This is determined for several doses of antagonist and then log ((A'/A) -1) versus the negative log B is plotted (this can also be plotted versus log B, but negative log B is more convenient). If the regression of log ((A'/A) -1) on -log B is linear with a slope of -1, then this indicates that the antagonism is competitive and by definition the agonist and antagonist act at the same recognition sites.