Introduction: pharmacology 2

In this video, I’ll introduce you to the basic principles of pharmacology. So, before you see what drugs do in the body, it’s important to have an appreciation of what the main targets are for drugs in the body. In this section, you’ll find out what receptors are and the main ways in which drugs can affect receptors. You’ll also see how drugs can effect enzymes, ion channels, and carrier proteins. Receptors are proteins. They are most commonly found on the surface of cells, but can be within a cell. These receptors respond to small molecules in the body. Many drugs can also interact with receptors to produce an effect.

The general principle of how a drug affects a receptor is that a certain portion of the drug molecule selectively combines or interacts with the receptor to produce and affect within the cell. The relationship of a drug to its receptor can be likened to that of the fit of a key in a lock. The drug represents the key and the receptor the lock. Since the receptor, or the lock, is made up of protein, it consists of hundreds of amino acids that interact with each other. Thus, the receptor can have different possible shapes, depending on how the amino acids in the protein are sitting next to each other, like how the levers are sitting inside a lock.

These different shapes can then affect the response produced inside the cell.

Receptors exist in the body so that small molecules can produce effects in cells. What are these small molecules? Neurotransmitters are chemicals that are released from neurons, or nerve cells, that are capable of generating electrical signals. Neurotransmitters then activate receptors that are normally present on other neurons. Receptors are also activated by hormones, which are chemicals that, instead of being released by neurons, like neurotransmitters, are released by cells and then travel in the blood and activate receptors in other parts of the body.

There are a number of different types of receptors that exist in the body. The most common type of receptor that drugs act on are called G protein-coupled receptors or GPCRs. GPCRs are the target of around 50% of drugs currently on the market. This is a diagram of a GPCR on the surface of a cell. They are called G protein-coupled receptors because they interact or couple with protein , called G protein. So, G proteins, shown here in pink, provide the link between the receptor and various substances inside the cell. GPCRs have a binding site for an agonist, such as a neurotransmitter or a hormone, and this is normally the way drugs bind to also.

However, drugs can also bind to other sites on the receptor. Binding of what’s called an agonist to the receptor causes a change in the shape of the receptor, and this changing shape means that the G proteins become activated and then produce a response inside the cell.

Drugs binding to receptors can have effects in two main ways. Drugs can bind to a receptor in order to produce a response in a cell. They’re called agonists. Neurotransmitters and hormones are normally agonists and receptors, and morphine is an example of a drug that is an agonist. Antagonists bind to the receptor, and, instead of producing a response inside the cell, reduce the binding of other molecules in the body. Thus, by decreasing the binding of agonists, they decrease the effect of agonists in a cell. The effect of morphine, for example, can be decreased by giving a person an antagonist called naloxone. Naloxone is used in the case of overdose of drugs such as morphine.

Enzymes, like receptors, are proteins, very important biological catalysts in the body that speed up biological reactions that occur mostly within cells. Drugs that bind to enzymes normally inhibit the activity of the enzyme. They often resemble the structure of what’s called a substrate that normally binds to an enzyme and then gets converted into a product. So the term substrate refers to any molecule on which an enzyme acts. The substrate that normally binds to the enzyme could be a hormone, a neurotransmitter, or another type of small molecule. If enzyme inhibitors resemble a substrate, they are likely to bind to the enzyme just like the substrate would. However, instead of being converted into a product, the enzyme prevents the binding of the substrate.

Later in this course, you will see how the anti-cholesterol drug, Atorvastatin, binds to an enzyme, called HMG-CoA reductase to stop cholesterol being produced.

Competitive enzyme inhibitors, such as Atorvastatin, bind to the same site on the enzyme as the substrate. This means that there’s competition between the competitive inhibitor and the substrate for the same binding sites on the enzyme. Some other inhibitors bind to another site on the enzyme, which then modifies the enzyme activity.

Cell membranes define the outer layer of a cell and the complex structures consisting of mainly lipids and proteins. They regulate the flow of ions in a highly selective manner. Just to recap, ions are charged elements, such as sodium, potassium, and calcium. As this picture shows, ion channels sit in the cell membrane and allow the flow of ions through the membrane. To understand how ion channels work, we need to appreciate differences in concentration of ions on either side of the cell membrane. Within most cells of the body, there is a difference in the number of ions inside the cell compared with outside the cell.

This is caused mainly by carrier proteins or pumps on the membrane surface that continually pump sodium out of and potassium into the cell.

Ion channels are proteins that, when activated, have an opening that allow the flow of ions from an area of high concentration to an area of low concentration, and this is called a concentration gradient. So, when ion channels open, ions flow through the ion channel, down their concentration gradient, either into or out of the cell. For example, because there are more sodium ions outside the cell than inside, when sodium channels open, sodium ions enter the cell, and this activates the cell.

Drugs can affect ion channels in a number of ways. They can bind directly to an ion channel and facilitate the ion channel opening or closing. An example of a drug that closes ion channels is glipizide, a drug used in the treatment of type 2 diabetes. You’ll see more about glipizide later in this course. An example of a drug that opens ion channels is the main active component of tobacco, called nicotine. You’ll learn more about how nicotine causes its effects later in this course. As opposed to ion channels, ions and small molecules can be pumped across a membrane against their concentration gradient through the use of carrier proteins or pumps.

Earlier you saw how ion pumps on the surface of some cells pumped sodium out of and potassium into the cell, and these ion pumps are examples of carrier proteins. Carrier proteins exist on cell membranes in most cells of the body. They’re also very important in the function of neurons. An example you’ll see later in this course is the serotonin, also called 5-hydroxytryptamine or 5-HT reuptake protein. 5-HT is a neurotransmitter, that is a small molecule that is released from 5-HT neurons and activates receptors. The 5-HT reuptake protein transports 5-HT back into the neuron terminal.

So, in this section, you’ve seen how receptors, enzymes, ion channels, and carrier proteins are all targets for drugs in the body. In the next section you’ll see how we measure the potency of drugs and what drug tolerance is.