MODIBBO ADAMA UNIVERSITY,
YOLA
CENTER FOR DISTANCE
LEARNING
DEPARTMENT OF COMMUNITY HEALTH
COURSE CODE: HC 208
COURSE TITLE: INTRODUCTION TO
PHARMACOLOGY
ID NO: DL/HC/23D/1477
ASSIGNMENT QUESTION
1. PHARMACOLOGY DEFINE THE FOLLOWING TERMINOLOGIES
PHARMACOLOGY, AFFINITY FOR BINDING SITE, EFFICACY, BINDING,
ACTIVATION, AGONIST AND ANTAGONIST.
2. WITH THE AID OF DIAGRAM, EXPLAIN THE EVOLUTION OF
PHARMACOLOGY FROM 19TH CENTURY TO DATE.
3. WRITE A SHORT NOTE ON RESEMBLANCE THEORY
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PHARMACOLOGY
Pharmacology is the scientific study of the effects of drugs and chemicals on living organisms
where a drug can be broadly defined as any chemical substance, natural or synthetic which
affects a biological system. Pharmacology may involve how organisms handle drugs,
identification and validation of new targets for drug action, and the design and development of
new drugs to prevent, treat and cure disease. Pharmacology research is also a critical component
in the development of modern 'personalized medicine'. There are many sub-specialties within the
general discipline of pharmacology. Pharmacodynamics is the study of the effects of drugs on
biological systems and specifically addresses the chemical properties and physiological and
behavioral effects of drugs arising from their interaction with molecular targets such as receptor
proteins or enzyme systems. In contrast, pharmacokinetics is the study of what biological
systems do to the drug and encompasses investigations of drug absorption, distribution,
biotransformation and excretion, essential information for the design of drug treatment schedules
in different patient populations and experimental animals, and for the prediction of drug-drug
interactions that may enhance or compromise the effectiveness and safety of therapeutic agents.
While pharmacologists are trained as laboratory researchers, pharmacists usually work in a
hospital or retail pharmacy and are concerned with the preparation, dispensing, dosage, and the
safe and effective use of therapeutic agents.
Binding Affinity
Binding affinity is the strength of the binding interaction between a single biomolecule (e.g., a
protein or DNA) to its ligand or binding partner (e.g., a drug or inhibitor). Binding affinity is
typically measured and reported by the equilibrium dissociation constant (KD), which is used to
evaluate and rank order strengths of bimolecular interactions. The smaller the K D value, the greater
the binding affinity of the ligand for its target. The larger the K D value, the more weakly the target
molecule and ligand are attracted to and bind to one another.
Binding affinity is influenced by non-covalent intermolecular interactions such as hydrogen
bonding, electrostatic interactions, and hydrophobic and van der Waals forces between the two
molecules. In addition, binding affinity between a ligand and its target molecule may be affected by
the presence of other molecules.
Efficacy
The efficacy of a binding site is the ability of a drug-bound receptor to produce a response. In
other words, it's the degree to which a ligand activates receptors and leads to a cellular response.
Here are some other related concepts:
Affinity: The probability of a drug occupying a receptor at any given time.
Potency: The agonist concentration at which signaling reaches the half-maximal response.
Selectivity: The extent to which a drug molecule exhibits high affinity for only one
receptor. Drugs with high affinity and efficacy require less drug to activate receptors, and have a
lower potential for nonselective actions.
The binding site for a drug can be the same as or different from that of an endogenous
agonist. Agonists activate receptors to produce a desired response, while antagonists prevent
receptor activation
Binding Site
A binding site is a region on a molecule or cell surface where chemical substances combine. In
biochemistry and molecular biology, binding sites are cavities or pockets on a macromolecule,
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like a protein, where a ligand molecule binds. The binding event is often reversible and non-
covalent, but can also be covalent reversible or irreversible.
Binding sites are important for: Drug designing, In silico studies, and Understanding the nature
and affinity of interactions for a substrate or ligand.
Here are some things to know about binding sites:
Ligands
The binding partner of the macromolecule is often called a ligand. Ligands can include other
proteins, enzyme substrates, second messengers, hormones, or allosteric modulators.
Specificity
The arrangement of a protein's amino acid chain determines the specificity of its ligand-
binding site. This arrangement gives the area its shape and chemical reactivity.
Prediction
Binding sites can be predicted using 3D structures of protein-protein complexes, computational
methods, and web servers.
Energy-based methods
Energy-based methods calculate the interaction energy between probes placed on the grid
points around the target surface.
Allosteric interactions
Binding of a drug to one site may increase binding and transport of a drug from a different
site.
ACTIVATION
The activation of a binding site can occur in a number of ways, including:
Binding of a ligand or drug molecule
A ligand or drug molecule binds to a target protein's binding site, which is a cavity or pocket
on the protein's surface. This binding can cause a conformational change in the protein, which
can activate or inhibit its function.
Binding of a substrate to an enzyme
A substrate binds to an enzyme's active site, which is where a chemical reaction takes
place. The substrate is oriented for catalysis by the active site.
Mechanical stretching
Mechanical stretching of a protein can enhance its binding to another protein. For example,
stretching the N-terminal region of the talin rod enhances its binding to vinculin.
Activation by agonists
Agonists activate receptors to produce a desired response. Conventional agonists increase the
proportion of activated receptors.
Prevention of activation by antagonists
Antagonists can prevent receptor activation, which can have various effects on cellular
function.
Identifying the binding site of a target protein is a crucial first step in designing a drug that can
interact with it.
Agonists
Agonists and antagonists are two terms commonly used in pharmacology. They refer to drugs or
chemical agents that work in opposite ways in terms of how they function and produce
effects. The main difference between agonists and antagonists is that an agonist produces a
response by binding to a receptor on the cell. An antagonist opposes the action by binding to the
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receptor, i.e., it blocks these receptors and renders them ineffective. In other words, the agonists
turn the receptors on, and the antagonists turn them off. Natural agonists are hormones or
neurotransmitters. Artificial agonists are drugs that are made to resemble natural agonists. These
drugs contain molecules that bind to specific receptors on cells and cause them to become
active. For instance, let’s take opioid receptors in the brain. Endorphins are the natural agonists
for opioid receptors. They bind to opioid receptors and produce the effect of pain relief.
Therefore, endorphins are natural pain relievers. The pain medication morphine (and the illegal
drug heroin) are artificial agonists of opioid receptors. They produce pain relief or a “high” by
mimicking the action of the natural agonist.
Agonist drugs are structurally similar to the natural agonists in the human body. They mimic the
natural agonists and trigger the receptors, producing the desired response, or in some cases, a
much stronger action.
TYPES OF AGONIST DRUGS
There are three main types of agonist drugs:
Complete Agonists
Also called direct binding agonist drugs, they bind directly to the receptor at the same binding
site where natural ligands bind. These drugs, therefore, bring about a faster response. Examples
of direct agonists include morphine and nicotine. Methadone, which is used to treat opioid
addiction, is a full opioid agonist.
Partial Agonists
Also called indirect binding agonist drugs, they promote the binding of the natural ligand to the
receptor site. These drugs produce a delayed response. Sometimes, a partial agonist can act as an
antagonist by competing for the same receptors as a full agonist. An example is Buprenorphine,
a medication used to treat drug addiction to opioids.
Inverse Agonists
An inverse agonist is a drug that produces the opposite effect by binding to a receptor. In other
words, an agonist increases the activity of the receptor, whereas an inverse agonist decreases the
receptor’s activity below the baseline. For example, an antihistamine medication, an H1 receptor
antagonist, has some inverse agonist activity.
ANTAGONIST DRUGS
An antagonist inhibits or opposes the action of an agonist. In other words, an antagonist works
by blocking the activity of an agonist. Using the lock and key analogy once more, an antagonist
binds to a cell and makes it unable for the agonists to bind to the cell receptor appropriately. As a
result, the agonists are rendered ineffective.
To demonstrate how antagonist drugs inhibit the regular action of a receptor, let’s come back to
opioid receptors in the brain. As mentioned, heroin is an agonist for the opioid receptor. If
someone has taken a potentially fatal heroin overdose, naloxone (an opioid receptor antagonist)
can reverse the effects. Naloxone (brand name Narcan) works by blocking or occupying all the
opioid receptors, preventing morphine or heroin from binding and activating them. An overdose
victim who is unconscious and near death can become fully conscious quite dramatically within
seconds of receiving naloxone.
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TYPES OF ANTAGONIST DRUGS
There are three main types of antagonist drugs:
Competitive Antagonists
These are drugs that bind at the same binding site of the receptor and prevent the natural ligand
from binding. The shape of a competitive antagonist mimics the natural ligand. However, if the
concentration of the natural ligand increases, it can suppress the effect of a competitive
antagonist. Naloxone is a competitive antagonist for the opioid receptor, and it prevents a natural
ligand like morphine or heroin from binding to the receptor. Another good example of a
competitive antagonist is naltrexone, which is also used to treat opioid addiction.
Noncompetitive Antagonists
A non-competitive antagonist binds at an allosteric site (a site other than the true binding site).
The binding of the non-competitive antagonist causes a conformational change (change in shape)
of the receptor, which prevents the natural ligand from binding. Ketamine, an anesthetic drug, is
a non-competitive antagonist for the NDMA receptor. The difference between competitive and
non-competitive antagonists is that the action of the non-competitive antagonist cannot be
overcome by the amount of agonist present.
Irreversible Antagonists
Irreversible antagonist drugs bind strongly to the receptor through covalent bonds and cannot be
displaced or washed out. They permanently modify the receptor and prevent the binding of the
natural ligand.
2. WITH THE AID OF DIAGRAM, EXPLAIN THE EVOLUTION OF
PHARMACOLOGY FROM 19TH CENTURY TO DATE.
The rapid growth of data in medical and life sciences has fostered the development of
interdisciplinary fields like systems biology, bioinformatics, and computational biology,
including network pharmacology. Initially proposed by Chinese scholar Li in 1999, network
pharmacology examines how pharmaceuticals interact with multiple targets within biomolecular
networks. This approach has gained traction over the years, with numerous studies exploring the
effects of traditional Chinese medicine (TCM) on complex diseases through these networks.
Research has shown that TCM prescriptions can influence gene networks, leading to potential
therapeutic effects for various conditions, such as cardiovascular diseases and diabetes.
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Techniques like reverse molecular docking and protein-protein interaction networks have been
employed to identify active ingredients and their targets, facilitating the understanding of
mechanisms underlying the efficacy of TCM formulations.
Recent methodologies in network pharmacology emphasize the study of compound drugs rather
than single-component drugs, reflecting the complexity of TCM. General steps in research
include identifying active ingredients, extracting disease-related targets from various databases,
and analyzing the interactions between these targets. Enrichment analyses help elucidate the
biological pathways involved, while molecular docking validates the interactions at a structural
level.
Overall, the integration of network pharmacology into TCM research offers new opportunities
for understanding and developing effective treatments by mapping the relationships between
active ingredients, their targets, and the corresponding biological pathways.
3. WRITE A SHORT NOTE ON RESEMBLANCE THEORY
In "Resemblance and Representation," author Ben Blumson examines the relationship between
depiction and resemblance, arguing against philosophical objections to the idea that depiction
depends on the resemblance between a representation and what it represents. Blumson begins by
defending the "platitude" that authorship and resemblance are inherently connected, asserting
that this view is often dismissed by philosophers despite its intuitive nature. He explores the
analogy between depictive and descriptive representation, positing that both share a contingent
relationship with their respective subjects. Blumson's work aims to reconcile the perceived
opposition between these two views by highlighting their shared characteristics as forms of
representation, while acknowledging their differences: description relies on convention, whereas
depiction is based on resemblance.
Blumson extends the Gricean analysis of speaker meaning to encompass depiction, suggesting
that both forms of representation involve intentions. He emphasizes that understanding a
depiction requires recognizing its resemblance to the subject, which informs the creator's
intentions. Throughout the book, he defends this view while addressing various objections,
reinforcing the notion that both depiction and description involve a recognition of intentions but
differ in their mediating factors. The work is interdisciplinary, drawing on insights from
philosophy of language and metaphysics, and Blumson argues that depiction can be understood
as a symbolic system, similar to language. He addresses various media for depiction, including
painting, sculpture, and photography, while intentionally excluding abstract art from his analysis.
In the latter chapters, Blumson tackles complex issues, such as the compositional nature of
depiction and its implications for understanding new representations. He also engages with the
challenges of attributing intentions to historical artworks, suggesting that recognizing
resemblance remains crucial despite potential shifts in audience interpretation. While Blumson's
analysis is rich and thought-provoking, it also raises questions about the reliance on intentions
and the subjective nature of resemblance, particularly when different audiences perceive
representations differently. Ultimately, he seeks to create a framework that clarifies the nature of
representation, inviting further exploration of its implications and challenges.
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Li, S., & Zhang, B. (2013). Network pharmacology: A new approach to understanding the
mechanisms of traditional Chinese medicine. Molecules, 18(2), 1562-1581.
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Blumson, B. (2018). Resemblance and Representation. Oxford University Press.
Abell, C. (2019). Representation and resemblance: Analyzing the relationship in art and
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