What Is Pharmacodynamics?

Pharmacodynamics, referred to as pharmacodynamics, is a study of the effects of drugs on the body and its laws, and clarifies the mechanism of drugs in preventing and treating diseases. At the same time that the drug treats the disease, it also produces untoward reactions or adverse reactions, including side effects, toxic reactions, allergy reactions, and secondary reactions. ) Residual Effect, Teratogenesis, etc. ^[1]

Pharmacodynamics

First, the nature and mode of drug action

Drug effect refers to the initial effect caused by the interaction between drugs and biological macromolecules. Pharmacological effects are the secondary changes in the physiological and biochemical functions of the body caused by drugs, and are the specific manifestations of the body's response. Usually pharmacological effects and drug effects are common to each other, but when the two are used together, the order should be reflected.

Pharmacological effects are changes in the original level of function of the body's organs. Enhanced function is called excitement; weakened function is called inhibition.

The mode of drug action is divided into local action and absorption action according to the site of drug action. Local effect refers to the effect on the part of the medication, with little drug absorption. Absorptive effect, also known as systemic effect, means that the drug is absorbed into the blood and distributed to the relevant parts of the body before it functions.

Second, the therapeutic effect of drugs

The therapeutic effect of drugs refers to the effects caused by patients following medication, which are consistent with the purpose of medication, and are conducive to changing the patient's physiology, biochemical function or pathological process and returning the body to normal. According to the therapeutic effect achieved by the drug, it is divided into symptomatic treatment and symptomatic treatment.

Third, adverse drug reactions

Any reaction that does not meet the purpose of the medication and brings discomfort or pain to the patient is collectively referred to as an adverse drug reaction. According to the purpose of treatment, the dose size or severity of adverse reactions is divided into:

1. Side effects: refers to uncomfortable reactions that are not related to the purpose of treatment when the drug is in a therapeutic dose.

2. Toxic reactions: reactions that are harmful to the body when the drug dose is too large or the body accumulates too much, which are generally more serious. It is divided into acute toxicity and chronic toxicity.

3. Allergic reaction: refers to the abnormal immune response that occurs when the body is stimulated by drugs, which can cause physiological dysfunction or tissue damage, also known as allergic reactions.

4. Aftereffects: Pharmacological effects that remain after the plasma concentration has dropped below the minimum effective concentration after discontinuation.

5. Secondary reaction: Refers to the adverse consequences caused by the therapeutic effect of the drug.

6. Withdrawal response: refers to the exacerbation of the original disease after taking certain drugs for a long time, and it is also called rebound reaction.

7. Idiopathic reactions: refers to certain drugs that can cause a small number of patients to have idiosyncratic adverse reactions, which are related to heredity and belong to hereditary biochemical defects.

First, the concept of dose

The amount of medicine used is called the dose. The minimum dose required for the efficacy to appear is called the minimum effective amount; the minimum dose for the onset of a toxic reaction is called the minimum poisoning amount; the dose that produces the desired effect between the minimum effective amount and the minimum poisoning amount but is not easily poisoned is called The amount of treatment; the extreme amount is the dose that has reached the maximum therapeutic effect but has not yet caused a toxic reaction; the dose that causes a toxic reaction beyond the minimum poisoning amount is called the poisoning amount; the dose that causes half of the animal poisoning is called half the poisoning amount; causing half of the animal death The dose is called the half lethal dose.

Second, the dose-response relationship and the dose-response curve

The strength of the drug effect has a certain relationship with the dose size or concentration of the drug, that is, the dose-response relationship, referred to as the dose-response relationship. It can be expressed by the dose-response curve, see the figure on the right.

The relationship between the chemical structure of a drug and its pharmacological activity or toxicity is called structure activity relationship (SAR), and it is one of the main research contents of medicinal chemistry. Changes in the chemical structure of a drug, including its basic skeleton, side chain length, stereoisomerism, and geometrical isomerism, can affect the physicochemical properties of the drug, and then affect the drug's in vivo process, efficacy, and even toxicity. Understanding the structure-activity relationship of drugs is not only conducive to in-depth understanding of the role of drugs, guiding the rational use of drugs in the clinic, but also of great significance in the design of targeted drug structures and research and development of new drugs.

Quantitative structure-activity relationship (QSAR) developed in the 1960s is a quantitative study of the interaction between small organic molecules and biological macromolecules by mathematical or statistical means using the physical and chemical properties or structural parameters of molecules. And methods for the absorption, distribution, metabolism, and excretion of small organic molecules in the body. This method is widely used in the rational design of bioactive molecules such as drugs, pesticides, and chemical agents. Quantitative structure-activity relationship methods dominated early drug design.

Since the 1990s, with the improvement of computer computing capabilities and accurate determination of the three-dimensional structure of many biological macromolecules, molecular shape analysis (MSA) distance geometry (DG) and comparative molecular force field analysis (comparative) have been used. Molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and other methods, analyze the relationship between the three-dimensional structure of the drug molecule and the role of the receptor, and deeply reveal the mechanism of drug-receptor interaction . The three-dimensional quantitative structure-activity relationship based on molecular structure has gradually replaced the dominance of quantitative structure-activity relationship in the field of drug design, and it has become the basic means and analysis method of computer-aided drug design. ^[2]

The mechanism of action of the drug mainly explores how the drug causes the body to function. The drug effect is the result of the interaction between the small drug molecules and the biological macromolecules of the body, and it is the change of the original functional level of the body's cells. Therefore, it is necessary to explore from the cell level. Most drugs act on receptors to exert pharmacological effects. Enzymes are the main targets of drug effects. Drugs act on cell membrane ion channels, affect nucleic acid metabolism, participate in or interfere with cell metabolism, change the physical and chemical properties of the cell environment, and affect physiologically active substances and Its transport affects immune function.

First, concepts and characteristics

Receptors are a class of functional proteins that mediate cell signal transduction. They can recognize certain trace chemical substances in the surrounding environment, first bind to them, and pass through an intermediate information amplification system, such as the amplification and differentiation of the second messenger in the cell. Integrate and trigger subsequent pharmacological effects or physiological responses. A true receptor has the following characteristics: 1, saturation; 2, specificity; 3, reversibility; 4, high sensitivity; 5, diversity.

Second, the type of receptor

According to the characteristics of receptor protein structure, information transduction process, effect properties, and receptor location, it can be divided into four categories:

1. Ion channel receptors (ligand-gated channel receptors). This family is a membrane receptor that is directly connected to ion channels. It exists on the membrane of fast-responding cells and consists of several subunits. .

2, G protein-coupled receptors, a family of membrane receptors that connect the intracellular effector system through G proteins.

3. Receptors with tyrosine kinase activity. This family is a membrane receptor that binds to intracellular protein kinases, typically tyrosine kinases.

4. Membrane receptors that regulate gene expression.

Third, the drugs acting on the receptor

Drugs have an effect after binding to the receptor. First, the drug should have affinity, that is, the drug can bind to the receptor; second, it should have intrinsic activity to excite the receptor and produce an effect. The drug has a high affinity and intrinsic activity with the receptor, and produces the largest effect after binding to the receptor, which is called a full agonist. Partial agonist means that the drug has a strong affinity for the receptor, but its internal activity is not strong. Even if the dose is increased, the maximum effect cannot be achieved. Although receptor antagonists have strong affinity, but lack intrinsic activity, they cannot produce effects, but because they occupy a certain number of receptors, they can antagonize the effect of agonists, and are divided into competitive antagonists and non-competitive Sex antagonists.

Fourth, the regulation of receptors

Receptor regulation is an important factor in maintaining the stability of the body's environment. There are two types of regulation: desensitization and sensitization.

Receptor desensitization refers to the phenomenon that the sensitivity or reactivity of tissues or cells to agonist drugs decreases after long-term use of an agonist drug. According to different generation mechanisms, it is divided into homologous desensitization and heterologous desensitization. Homologous desensitization refers to a decrease in the reactivity to agonists of only one type of receptor, while the reactivity to other types of agonists remains unchanged. Heterogeneous desensitization means that the receptor is desensitized to one type of agonist and not sensitive to other types of receptor agonists.

Receptor sensitization, the opposite of receptor desensitization, can be caused by reduced levels of receptor agonists or long-term use of antagonists.