Pharmacodynamics: Nursing pharmacology

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

Now, medications bind to receptors, which are specialized proteins found inside the cell or on its surface, to cause a change in the cell’s activity that ultimately creates a physiological effect. When a medication binds a receptor and mimics the body’s own chemical messengers, like hormones and neurotransmitters, to produce a desired response, it's called an agonist. So, an agonist is like a key that fits into a lock, causing it to open. There are also medications that are partial agonists. Like agonists, they fit into the lock, but not as well, so they produce a weaker response. Lastly, there are antagonists, which bind to a receptor and block it so it can’t be bound to and activated by other medications or the body’s own chemical messengers. So, it’s like a key that can’t turn the lock, and may even get stuck in the lock.

An example of an agonist is morphine, which primarily binds to mu receptors, and less so kappa receptors, to mimic the body’s endogenous opioid peptides, to produce an analgesic effect. In contrast, pentazocine is a partial agonist, so it produces a less powerful analgesic effect. On the other end of the spectrum, naloxone is an opioid antagonist that blocks the effects of opioid peptides.

Now, after a medication binds to a receptor, there are additional factors that determine how the body will respond, including the dose of the medication, its efficacy, and its potency. So, let’s draw a graph, to show the relationship between the dose, on the x axis, and the response on the y axis. What we get is an S-shaped curve, called the dose-response curve, which has three phases. At first, in phase 1, the curve is more or less flat; that’s because the dose of the medication is too low, so not enough receptors bind to the medication to cause a significant response. As the dose increases, in phase 2, more receptors are occupied by the medication until just enough is present in the body to produce an effect. This is called the minimum effective concentration, or MEC. As the dose continues to increase, so does the response; but eventually, in phase 3, we reach a point where all the receptors are occupied, and the curve starts to flatten out. This is where the maximal efficacy of the medication is achieved, and at this point, increasing the dose will not produce a stronger effect. Lastly, is the medication’s potency, which determines the amount of medication needed to elicit an effect; so medications with a high potency can produce an effect at a lower dose, while medications with a low potency produce an effect at a higher dose.

Okay, let’s switch gears and look at how we measure the safety of medications. To do this, we can compare the dose that’s effective in 50% of the population for a particular medication, referred to as the effective dose or ED50, with the dose that toxic side effects occur in 50 percent of the population, called the toxic dose TD50. Now, the ED50 to TD50 ratio is the therapeutic index, or TI, which is a measure of a medication’s safety. So, the closer this ratio is to 1, the greater the danger of toxicity. In other words, medications with a large or wide therapeutic index are safer, since their toxic dose is much higher than their effective dose. On the flip side, medications with a small or narrow therapeutic index are more dangerous, since their toxic and effective doses are close to each other. For example, if a medication’s ED50 is 10 and the TD50 is 100, the therapeutic index would be 10, which means the medication is relatively safe. In contrast, if a medication’s ED50 is 10 and the TD50 is 30, the therapeutic index is 3, which means the medication is much less safe.