Pharmacdynamics

This is different from pharmacodynamics, which studies what the drug does to the body - the actual biological effects and mechanisms of action.

Pharmacodynamics is the study of how drugs affect the body.¹

- Pharmacodynamics emphasizes the relationship between drug concentration and effect.

This relationship helps determine the optimal dose that maximizes therapeutic effects while minimizing adverse effects [1][4].

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The fundamental pharmacodynamic concepts are captured in the relationship between exposure to a drug and physiological response to the drug, often called the dose–response or concentration–response relationship.

As the amount of a drug in the body increases, the drug’s effect usually increases as well, up to a maximum level. This relationship is shown by a graph with drug exposure (such as dose or concentration) on the x-axis and the body’s response on the y-axis. Exposure can be plotted on a linear or logarithmic scale, while the response can be shown as the actual measured effect or as a percentage of the baseline or maximum effect. In pharmacodynamics, concentration is commonly used to describe exposure, but other measures (such as dose or area under the curve) can also be used.

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It involves the concepts of potency, efficacy, and therapeutic window.

 

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### Key Concepts in Pharmacodynamics

1. **Drug-Receptor Interactions**:
- Drugs exert their effects by binding to specific biological targets, such as receptors, enzymes, or other proteins. This binding can activate or inhibit the target, leading to a physiological response [1][2].
- The interaction between a drug and its receptor is often modeled by the equation $$ {\ce {L + R <=> LR}} $$, where $$L$$ represents the ligand (drug), $$R$$ the receptor, and $$LR$$ the ligand-receptor complex [4].

 

3. **Mechanisms of Action**:
- Drugs can produce their effects through various mechanisms, such as binding to an active site of an enzyme, interacting with cell surface signaling proteins, or binding to molecules like tumor necrosis factor (TNF) [1][5].
- Examples include aspirin inhibiting platelet aggregation, ACE inhibitors reducing blood pressure, and insulin lowering blood glucose levels [1].

4. **Factors Affecting Pharmacodynamics**:
- Physiological changes due to disorders, aging, or the presence of other drugs can affect pharmacodynamic responses. These changes can alter receptor binding, binding protein levels, or receptor sensitivity [2].

5. **Agonists and Antagonists**:
- Drugs can act as agonists, which bind to receptors and produce a desired effect, or as antagonists, which block the action of other molecules at receptor sites [5].

### Clinical Relevance

Pharmacodynamics is crucial in understanding how drugs work and in designing effective treatment regimens. It helps healthcare practitioners tailor drug therapy to individual patients, aiming to treat the underlying condition rather than just the symptoms or lab values [1].

### Conclusion

Pharmacodynamics provides essential insights into the actions of drugs at the molecular level, the resulting physiological effects, and the factors influencing these interactions. It is a foundational concept in pharmacology, complementing pharmacokinetics, which studies how the body affects a drug [1][2][4].

Citations:
[1] https://www.ncbi.nlm.nih.gov/books/NBK507791/
[2] https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacodynamics/overview-of-pharmacodynamics
[3] https://www.sciencedirect.com/topics/medicine-and-dentistry/pharmacodynamics
[4] https://en.wikipedia.org/wiki/Pharmacodynamics
[5] https://www.ncbi.nlm.nih.gov/books/NBK595006/

 

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Most drugs are small molecules that interact with macromolecular entities, or drug targets, intrinsic to the body or to pathogens. Drug targets include receptors for endocrine and paracrine factors, enzymes, voltage-gated ion channels, membrane transporters, and, for pathogens chiefly, structures relevant to cell viability and replication. As such, targets can be located anywhere on or within a cell, including the cell-surface membrane, cytosol, and nucleus, or entirely in the extracellular compartment. In keeping with the nature of these targets, drugs almost always alter the rate or magnitude of intrinsic cellular or physiological processes rather than create biologically novel phenomena.

 

 

Of the new drugs approved by the FDA (U.S. Food and Drug Administration), a growing percentage, averaging approximately 25% over the past 5 years (Figure 1–7), are therapeutic biological products. These are defined by the FDA (in the Therapeutic Biologics Applications) as:

• Monoclonal antibodies for in vivo use

• Cytokines, growth factors, enzymes, immunomodulators, and thrombolytics

• Proteins intended for therapeutic use that are extracted from animals or microorganisms, including recombinant versions of these products and other nonvaccine therapeutic immunotherapies

A distinction is commonly made between these products, which are often proteins, and the much larger number of small-molecule drugs. Targets in the case of monoclonal antibodies and certain recombinant proteins include inflammatory mediators, immunological checkpoint inhibitors, and cell-surface molecules (Chapters 39, 42, 44, and 72). Genetically modified viruses, for example oncolytic viruses, and microbes, too, are considered biological products and are actively investigated as recombinant vectors for candidate vaccines (Chapter 40).

Another important dimension to pharmacodynamics is gene therapy. Gene therapy uses viruses as vectors to replace defective genes that cause debilitating or lethal diseases, or it can introduce other genes altogether. Recently approved examples of gene therapy include the treatments of a congenital form of retinoblastoma and of spinal muscular atrophy with proteins (RPE65 [retinal epithelium-specific 65-kDa protein] and SMN1 [survival motor neuron 1], respectively) introduced by means of adeno-associated virus (AAV) vectors. The insertion of an anti-CD19 chimeric antigen receptor into T cells for the treatment of B-cell acute lymphoblastic leukemia makes use of a lentiviral vector (Chapter 72). Gene therapy also has the capacity for gene silencing, for example, in the treatment of hereditary transthyretin-mediated amyloidosis with patisiran and inotersen, two transthyretin-directed short interfering RNAs (siRNAs). Exon skipping represents another facet of gene therapy, as exemplified in the treatment of certain forms of Duchenne muscular dystrophy with the antisense oligonucleotide eteplirsen. The CRISPR-Cas9 (clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9) genome-editing system holds considerable potential in providing highly targeted forms of editing. Drugs can also act by influencing epigenetic regulation. For example, tazemetostat, used in the treatment of epithelioid carcinoma, is a recently approved inhibitor of histone methyltransferase EZH2. Clearly, the boundaries among pharmacology, immunology, and genetics overlap.

Quarterly updated eChapters in Section X of the online version of this textbook can provide the reader with reviews of new and noteworthy FDA approvals, including first-in-class drugs and breakthrough therapies (see AccessMedicine.com or AccessPharmacy.com; select Goodman & Gilman).

Rational Dosing & the Time Course of Drug Action

The goal of therapeutics is to achieve a desired beneficial effect with minimal adverse effects.

When a medicine has been selected for a patient, the clinician must determine the dose that most closely achieves this goal.

A rational approach to this objective combines the principles of pharmacokinetics with pharmacodynamics to understand the dose-effect relationship

 

Pharmacodynamics governs the concentration-effect part of the relationship, whereas pharmacokinetics deals with the dose-concentration part (Holford & Sheiner, 1981).

The pharmacodynamic concepts of maximum response and sensitivity determine the magnitude of the effect at a particular concentration.

The pharmacokinetic processes of input, distribution, and elimination determine how rapidly and for how long the target organ will be exposed to the drug.

 

References

1. Pharmacological Principles. In: Butterworth IV JF, Mackey DC, Wasnick JD. eds. Morgan & Mikhail’s Clinical Anesthesiology, 7e. McGraw-Hill Education; 2022. Accessed December 23, 2025. https://accessmedicine.mhmedical.com/content.aspx?bookid=3194&sectionid=266517902