Pharmacodynamics refers to the mechanisms and effects of medications within the body. Or more simply, it’s what medications do to the body and how they do it.

In order to have an effect, most medications have to reach their target cells and bind to a receptor. Receptors are specialized proteins both inside the cell and on the cell membrane that can bind to a ligand and get triggered to alter their shape or activity. This gives rise to a signal cascade of intracellular molecules, known as the second messengers, which, ultimately, results in some change in the cell’s function.

Intracellular receptors are typically located in the cytoplasm or nucleus of the cell and recognize small, hydrophobic, meaning water- hating, ligands. These include molecules like steroids, which are happy to diffuse across the phospholipid membrane. Once bound to their ligand, the receptor- ligand complex attaches to specific DNA sequences that activate or inhibit specific genes.

On the cell membrane are cell-surface receptors, which are embedded into the plasma membrane and bind to ligands too large or hydrophilic to pass through. Based on their structure and properties, cell- surface receptors fall into three main types: ligand-gated ion channels, enzyme coupled receptors, and G-protein coupled receptors.

Starting with ligand-gated ion channels, also known as the ionotropic receptors, these form channels or pores that are generally closed. Once they bind a specific ligand, they open up and allow ions like chloride, calcium, sodium, and potassium to passively flow through the membrane, down their gradient, and trigger the signaling pathway.

Next are enzyme-coupled receptors, which are usually single-pass transmembrane proteins, meaning that they have only one transmembrane segment. The extracellular end of these receptors binds to medications, and their intracellular end has enzyme activity. The enzymatic domain is usually a protein kinase known as the tyrosine kinase, which phosphorylates other molecules. When a ligand binds, it triggers a conformational change in the enzymatic domain to form high-affinity binding sites for the second messengers. These second messengers get phosphorylated by the tyrosine kinases before heading off to activate other proteins in the signal pathway.

Finally, there are the G-protein coupled receptors, also known as seven-pass transmembrane receptors, which means they are really long proteins that have one end that sits outside the cell, and then the snake-like protein dips in and out of the cell membrane seven times, and finally ends on the inside of the cell. A ligand binds to the end sitting outside the cell, and the end of the protein that’s within the cell activates guanine nucleotide-binding proteins or G proteins, which contain an alpha, beta, and gamma subunit. Normally, the alpha subunit binds to a guanosine diphosphate or GDP molecule and the G protein is inactive. When a ligand binds to the receptor, the G protein changes shape, causing the alpha subunit to release the GDP and allowing a guanosine triphosphate or GTP, to bind. This causes the alpha subunit to detach and trigger other proteins in the signalling pathway.

Video - Pharmacodynamics: Drug-receptor interactions

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