What Is Pharmacodynamics?

Pharmacodynamics comprises three different steps: receptor binding, post-receptor effect, and chemical interactions. Find out more here.

Written and verified by el biólogo Samuel Antonio Sánchez Amador.

Last update: 20 June, 2023

Pharmacodynamics is defined as the study of the biochemical, physiological, and molecular effects of medication on the body. We must remember that, from a biological point of view, drugs don’t create functions and structures, but only modify their own processes at a cellular level.

Pharmacodynamics comprises three different steps: receptor binding, post-receptor effect, and chemical interactions. This discipline works together with pharmacokinetics —drug doses and concentrations—to explain the relationship between the dose of a drug and the response of the body.

We live in a world where it’s estimated that 95% of the population has some type of pathology and global spending on medicines rises to more than 12,000 billion dollars annually. These data speak for themselves and, of course, justify the need to know exactly how medicines work in the body.

Pharmacodynamics and pharmacokinetics

To explore the world of pharmacodynamics, we need to clearly differentiate it from its terminological partner, pharmacokinetics. Both are highly interrelated concepts, but they describe different processes and have relatively different utilities.

As experts tell us, pharmacokinetics studies the time course of drug concentrations in the body. This allows specialists to differentiate a potentially toxic drug from a therapeutic one.

The concentration of the drug in the body can be summarized in the LADME mnemonic. This means that the value depends on the Liberation, Absorption, Distribution, Metabolism, and Elimination of the drug in question.

Clinical pharmacokinetics uses these data to choose different variables related to the drug, including the route of administration, the most effective pharmaceutical form, the dose per shot, or the dosing interval. In short, this branch of pharmacology studies the processes that a drug is subjected to in the body, from the time it enters to the time it leaves.

On the other hand, pharmacodynamics takes over when it comes to explaining the actions and effects of drugs within the body, beyond their passage through the body in the form of concentrations and variables. In summary, we can define the differences between both concepts in the following scheme:

1. Drug dose→ 2. Blood concentration→ 3. Pharmacological effect

The pharmacokinetics presents its variability between points 1 and 2, while the pharmacodynamics is expressed between 2 and 3.

The target of pharmacological action

To begin with the pharmacodynamic study of a drug, we first need to know what the target structure is. In general, there are several types and we’ll tell you about them below.

1. Enzymes

The drug can be associated with enzymes. Enzymes are molecules that speed up the reaction speed of cells, so cell metabolism will be modified by this action. The drugs can be the following:

1. Reversible or irreversible inhibitors of the chemical reaction catalyzed by the enzyme in question.
2. False substrates: analogs of the biological substrate of the reaction to make it occur.

2. Transport systems

Drugs can also associate with cell membrane transport systems. These channels allow or inhibit the entry of molecules into the cell. The drug can act in the following ways as far as this method of transportation is concerned:

• It can block some ion channels, such as the sodium channel, thus modifying the flow of ions inside and outside the cell. An example of this mechanism of action is local anesthetics.
• It can be associated with molecules that are transported against the concentration gradient and therefore require energy to enter the cell.

3. Receivers

Most drugs exert their function through this mechanism, that is, by binding to macromolecular components present in the cell membrane, cytoplasm, or nucleus—usually proteins. The selectivity of a drug is defined by the specificity of the adherence of the drug to the target receptor.

A drug that’s going to bind to a receptor is called a ligand, and forms an entity called a “coordination complex” with it. Ligands are classified into two large groups:

• Agonists: The drug binds to the cell receptor and promotes a response similar to that which would cause the original physiological substance. In other words, they’re “activators”.
• Antagonists: Binds to the target receptor, preventing agonists from performing their biological function. They’re inhibitory in nature, and can be further divided into competitive and non-competitive antagonists.

The nature of agonists and antagonists is diverse and complex. For this reason, we’ll limit ourselves to explaining its operation beyond the existing typology, since we still have a lot to explain about the receptors.

The binding rate between the drug-receptor, a very important parameter when talking about receptors and ligands at a pharmacological level, depends on three main characteristics. These are the following:

1. Affinity: The ability of drugs to stably bind to a given receptor and form the drug-receptor complex.
2. Specificity: The ability of the drug to discriminate one molecule from another.
3. Intrinsic activity or efficacy: This is defined as the biological efficacy of the drug-receptor complex to produce a greater or lesser response at the cellular level. This value varies between 0 and 1, with 1 being the maximum possible efficiency.

The binding of the drug to the receptor can be further defined by the following simple equation:

L + R ⇆ L*R

Being L the ligand and R the receptor, this equation shows us that the cellular response is associated with the fraction of receptors bound to their ligands. This fraction of receptors relative to their ligands is known as “occupancy”. The relationship between occupancy and pharmacological response is generally not linear.

Finally, another of the key parameters to quantify the drug-receptor interaction is the relationship of the dose of the drug with the effect on the body. This can be measured by the “50 effective dose”, which represents the dose of the agonist required to cause 50% of its maximum effect (affinity/potency).

Dose-effect curves allow us to quantify the action of a drug on the body.

Effects on the body

Most drugs act by inhibiting or stimulating cells, destroying them, or replacing certain substances of interest within them. Some of the examples of the effects of drugs on the body are as follows.

• Control of ion channels: They increase the permeability of the cell membrane and the conduction of ions through it.
• Formation of second messengers: These form molecules that transduce signals “downstream” in the cell, until inducing a physiological change in the effector. These signals can have multiple functional effects on the cell.
• Enzymatic activity: Drugs can modify the conformational structure of certain proteins, activating or inactivating them.
• Control of transcription: These can modulate the protein transcription that occurs inside the cell, that is, processes related to DNA and RNA.

Drug interactions

Pharmacodynamics is also responsible for describing drug interactions, that is, when two or more drugs interact, increasing or decreasing the action of the other. Pharmacodynamic interactions have to do with the increase or decrease of the pharmacological action and, therefore, of the expected therapeutic effect.

An example of this is synergy, that is, when the joint presence of two or more drugs in the body increases their effects. This synergy can be summation —the resulting effect is the sum of the partials— or potentiation —the effect is more than the sum of its parts.

Describing drug interactions between them is essential, since not all of them are positive for the patient. According to the World Health Organization (WHO), it’s advisable that only one drug be administered for each treatment, although there are clear exceptions to this general rule.

Modifications of drug action

Finally, it’s essential to know that pharmacodynamics also studies the factors that modify the action of the drug. According to professional portals, other disorders or diseases, aging, or interaction with other drugs are parameters that can alter the pharmacodynamic characteristics of a drug.

In general, we can gather all these factors to take into account in the following list:

• Physiological: Age, weight, ethnicity, genetic inheritance, gender, and other normal parameters intrinsic to the individual.
• Pathological: Stress, endocrine factors, kidney or liver failure, and heart disease, for example. Also intrinsic to the individual. Some specific cases may be thyrotoxicosis, certain types of diabetes or myasthenia gravis, since these pathologies clearly disrupt the effect of some medications.
• Pharmacological: Dose and routes of administration or interactions between drugs, for example. In general, this ground is covered in the pharmacokinetic phase.
• Environmental: Weather conditions or presence of toxic compounds in the environment, among others. They’re extrinsic to the individual.

In addition to this, the action of a drug can be modified by the development of tolerance by the patient. This can be slow and progressive —general variant— or present rapidly. In the latter case, the event is called tachyphylaxis.

Final considerations

As a summary, we can affirm that pharmacodynamics is a branch of pharmacology that’s responsible for studying the effects of a drug in the body, from the receptor in which it binds to the interactions with another possible drug. Pharmacokinetics is an essential companion to this discipline, as it describes the passage of the drug through the body.

So, in a world where medical prescriptions and simultaneous treatments are the order of the day, having a tool like pharmacodynamics at our disposal is essential. Undoubtedly, quantifying the effect of drugs on the body is essential to cure diseases.