Pharmacokinetics and pharmacodynamics are two pharmacological phenomenon that brings out the effect of the drug when administered in a biological system.
Pharmacokinetics
deals
with the movement of drug administered which is accomplished in different
steps: Absorption, Distribution, Metabolism and Excretion.
Pharmacodynamics deals
with the effect that drug shows when it is administered in the biological system.it is
dependent on factors like Potency, Efficacy, Bio-equivalent and Bio-availability.
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Pharmacokinetics: How Drugs Move Through the Body
Pharmacokinetic is all about the movement of the drug inside the
body as kinetic means movement. Once drugs are inside our body, how do they
move around, and get to where they need to go? Do they stay in the body
indefinitely, or are they eventually removed from the body somehow?
The study of pharmacokinetics deals with precisely these
issues, and in learning about this, we can highlight four main processes. Those
are
- absorption,
- distribution,
- metabolism and,
- excretion.
We want to understand each of these processes, as well as
the ways that interactions with food, drink, other drugs, and additional
factors can have an influence on them, so let’s get a closer look at these now.
As we said, the first step is absorption
Absorption
Generally describes the way the drug moves from its site of administration across one or more membranes, often into the bloodstream, if it was not administered there directly. If a drug is administered topically, this could mean moving through the skin or a mucous membrane, and subsequently through the walls of nearby blood vessels.
If
administered orally, this would mean being absorbed through the lining of the
stomach or intestines, a process which would be slowed by the presence of food.
Some drugs will pass through the cells that comprise these membranes by passive
transport, others by active transport, but one way or another they will make it
through on the way to their destination. In describing this process, it will be
appropriate to review the term “bioavailability”.
This term describes the proportion of a drug that is
successfully absorbed into the systemic circulation.
Bioavailability is a bit confusing with Bioequivalence.
Bio-equivalent
Two or more pharmaceutical product is said to be pharmacologically bioequivalent if their bioavailability after administration is in the same molar doges are similar to such a degree that their biological effect on the recipient is expected to be almost the same.
Similar drug may not always be bioequivalent due to the effect
of the additional component such as a diluent, stabilizing agent, binder, lubricants
etc.
Distribution
Distribution describes its journey through the bloodstream to target cells and specific target molecules within. This is the way that drugs move through the bloodstream, after being absorbed into it, or injected into it. There are many factors that influence this, like the way that the drug interacts with the components of blood, such as plasma proteins.
If the drug binds too tightly to
these proteins, it will not be able to reach its target cells. Sometimes, a
second drug is administered in conjunction with the first that has a higher
affinity for these proteins than the firestone does, thus serving the sole
purpose of displacing the primary drug once bound tithe protein, allowing it to
be delivered to its destination. Beyond these blood elements, there are other
factors that may hinder the movement of a drug. These are anatomical barriers
found in certain organs.
This prevents certain substances from passing out of the
bloodstream into brain tissue. Some drugs will not be able to surpass this
barrier, while others will, such as psychotropic drugs, or those affecting the mind.
There is also the blood-placental barrier, that regulates which substances can
pass from the bloodstream of a pregnant woman into the fetus. There are,
however, a number of substances that are able to pass through this barrier that
can still do harm to the fetus, such as alcohol and certain medications.
And then there is the blood-testicular barrier, which
prevents many substances from reaching the male testes, therefore making
disorders of the testes difficult to treat.
Metabolism
It describes the ways that it eventually gets modified by enzymes and rendered
ineffective. This describes any chemical reactions that the drug may
participate in, often aimed at inactivating it and targeting it for excretion.
If a drug is travelling through the bloodstream, it is highly likely to be
metabolized to some degree. This is when Drug Interaction actually occurs.
For example, if a drug is taken orally, it will be absorbed
through the intestinal wall, and for this reason, the part of the circulatory
system it enters is a collection of blood vessels called the hepatic portal
system. These carry blood directly to the liver, where they will be metabolized
in some manner. This is called the first-pass effect, referring to the first
pass of a drug through the liver, and this will typically greatly reduce the
bioavailability of a drug.
In certain cases, metabolism in the liver actually activates
a drug, but this is less common, and the first pass effect can inactivate over
90 per cent of an orally administered drug before it is able to reach general
circulation. This must be taken into account when determining the appropriate
dosage. Of course, drugs eventually reach their target cells, but even then,
after enough time elapses, they will be metabolized.
There are many different enzymes in the body that perform
these metabolic functions, which are very important because the immune systems
only good at dealing with large biological particles like viruses or bacteria.
It has no defence against small molecules, so this detoxification mechanism
aimed specifically at small molecules had to evolve for life to exist in a
chemical world.
Excretion
It describes the way it then exits the body, typically either through urine or faeces. In excretion, where the drug or its remnants exit the body. This is typically done via exhalation, sweating, urination, or defecation. The kidneys are heavily involved in this process, as they must remove harmful substances from the bloodstream and maintain proper Homeostasis.
Some drugs are metabolized into gaseous form and are thus easily exhaled. Some drugs are excreted through bile, a substance secreted by the liver to aid in digestion, as bile is recirculated back to the liver via enterohepatic recirculation, whereby most of the drug can then be excreted by the kidneys and the rest will exit in the form of faeces.
And as we said,
glands that produce fluids such as saliva and sweat can also promote excretion,
though this method tends to be less effective. And with that, we have traced
the journey of a drug into the body, around the body, and out of the body,
which gives us a basic understanding of pharmacokinetics.
Pharmacodynamics: How Drug act inside the Body
We just learned about pharmacokinetics, which helped us understand how a drug moves through the body. Through absorption and then distribution, a drug will travel through the bloodstream and eventually arrive at its target cells, where it can elicit its intended effect, prior to being metabolized and excreted. But what is this intended effect?
Once a drug reaches
its target, what exactly does it do, and how does this produce a cellular
response? The study of this process is called pharmacodynamics.
So essentially, pharmacokinetics is the study of how our bodies affect a drug, while pharmacodynamics is the study of how a drug affects our bodies. Pharmacodynamics is quite complex, dealing with many advanced concepts in biochemistry.
Far and away, the vast majority of drugs elicit a physiological
response because of the way that they interact with a particular protein. Most
often this will be a receptor protein, which may be embedded in the cell
membrane, or it may be found inside the cell, whether in the cytoplasm or the
nucleus.
Any receptor will have a ligand, which is a molecule that fits into the active site of the receptor, and in essence, turns the receptor on, evoking a conformational change that then propagates the signal in one of several ways. When drugs interact with receptors, there are two main ways that this could go.
A drug could be an agonist for a particular receptor, meaning
that it fits into the active site and mimics the native ligand, eliciting the
typical physiological response.
We can call these facilitators. Or, a drug could be an antagonist for this receptor, meaning that it binds to the active site, but does not activate the receptor, thereby locking it in an inactive state. We can call these inhibitors, or sometimes blockers.
Whichever the case may be, we can
represent binding with this very simple equilibrium, which depicts some ligand,
L, referring to the drug, and R, referring to the receptor, in equilibrium with
LR, which is the receptor-ligand complex, with the ligand bound to the active
site. With that understanding, we must now define two terms, potency and efficacy.
Potency
It refers to the strength of a drug ate particular concentration or dosage, or the amount of a drug that is required to produce a particular effect. And to get more technical, it refers to the concentration or dosage required to produce 50% of the maximal effect that drug can achieve. This can be examined on something called a dose-response curve.
As we can see, drugs of different potencies will require different
doses, or different amounts of the drug being administered, to elicit the drug
response it is capable of achieving. So, if a drug is extremely potent, only a
very small amount of it will need to be administered in order to achieve its
maximum effect.
Efficacy
It deals with the maximum effect that can be achieved by a drug, such that after
this is reached, no higher dose will produce any further effect. Two different
drugs may have similar potencies, meaning that the response increases over the
same increase in dosage, but one will achieve a more significant response than
the other, or a more significant effect, due to its higher efficacy.
And similarly, two drugs can have the same efficacy, but
differ in their potency, since one requires a smaller dosage to achieve its
maximum effect than the other.
If the purpose of the
drug is to bind to the active site of a receptor or enzyme,
- How well, does it bind?
- What is its binding affinity?
If describing binding using this equilibrium from before,
how heavily is the forward reaction favoured, the one that produces the LR complex?
Well in order to answer this question, we have to ask a few
more.
- How well does the drug fit into the active site?
- How many electrostatic interactions are being made, and of what variety?
- Are there hydrogen bonds?
- Perhaps even covalent interactions?
If the drug is acting as an inhibitor, then high binding
affinity will be crucial in order to have reasonable efficacy, because if the
binding affinity is low, then when the native ligand comes along, which is the
molecule that is supposed to go in the active site, it will most likely have a
higher binding affinity than the drug, and will displace it, thus no inhibition
can be achieved.
Sometimes inhibitors will bind irreversibly, meaning that
once they’re in, they’re stuck there, which is often the case if covalent bonds
are formed between the drug and the protein, although covalent bonds are not
necessarily required for binding to be irreversible.
On the other hand, if the drug is acting as an agonist,
again binding affinity will be relevant, and it will also have to have the
right functional groups necessary to promote the same conformational change in
the proteinase the native ligand, so that the protein will produce the same
cellular response.
Now that we understand affinity, we can conceptualize
potency and efficacy in a slightly different way, using receptors as an
example. Potency is the affinity of a drug for a particular receptor. If the
affinity is very high, most of the drug will be bound at any given time, and
thus very little of the drug will be needed to occupy all the receptors.
Efficacy describes the effect the drug has on the receptor
once it is bound or the degree of its ability to act as an agonist or
antagonist. So, potency is related to affinity, whereas efficacy is related to
the clinical effect of the drug.
Summary
Pharmacokinetic it is the movement of the drug inside the body, or how
body react to administered drug.
Pharmacodynamic it is how the drug reacts with the body or simply it is
what drug does to the body.
Both of these phenomenon helps in bringing the full effect of drug administered in human to explore its pathological state and physiological condition.