The Body’s Response to Drug Dosage and Timing (Nursing)

by Rhonda Lawes, PhD, RN

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    00:01 Hi, and welcome to the how, when, and why of the body’s response to drug dosage and timing.

    00:07 This is a really important concept in pharmacology.

    00:10 So, let’s get started, first of all, with a question.

    00:13 The blood stream is not usually the site of action for drugs, so why not measure the concentration at the target site or the cell? Well, here’s why, because there is a direct correlation to the plasma drug concentrations and the therapeutic or toxic effect.

    00:31 So, because we really can’t measure the concentration of the drug right at the site, we use the blood stream as a way to look for risk of therapeutic or toxic effect.

    00:41 Now, there’s 3 terms I want you to keep in mind.

    00:43 First of all, there is the minimum effective concentration, or the MEC, that’s the lowest plasma dose that meets the therapeutic objective.

    00:52 Now, there’s also a minimum toxic concentration— that’s the plasma level where the patient starts to have some really negative effects where those start to occur.

    01:01 Now, we really don’t want to be at either end; we want to be right in the middle of, what I like to call, “The Sweet Spot.” This is the therapeutic range. It’s in between the MEC and the MTC, and this is where the patient is going to get the most benefit, the therapeutic range, they’re going to get the most benefit with the least risk for toxicity.

    01:21 So, that’s what we’re aiming for.

    01:23 So, keep in mind there’s a direct correlation to plasma drug concentrations and the therapeutic effect.

    01:30 Drug half-life plays a really big role in making sure that we can hit that “sweet spot.” Drug half-life is the amount of time it takes for the amount of the drug to decrease by 50% in the plasma.

    01:42 So, just remember half-life is 50% of the drug left in the plasma.

    01:48 Okay, so I’m going to talk about this chart in just a second, but I want to talk a little bit more about drug half-life because drug half-life can range from minutes to up to a week, so that’s a long time for a drug to hang around in your body.

    02:02 But if a drug’s half-life is 4 hours, then every 4 hours the level of the drug that’s present in the body will decrease by 50%, so drugs with shorter half-life must be given more frequently than ones with longer half-lives, but let’s take a look at that chart.

    02:18 Now, I want to give you a minute to kind of get acclimated to it.

    02:21 The left column talks about the number of half-lives.

    02:24 Then, the next column talks about the time of administration of the medication if the half-life was equal to 4 hours, and that 3rd column is drugs remaining in the body.

    02:35 Okay, so if I give a medication, I’ve got 100% of the drug in the body.

    02:40 At the 1st half-life, that would be 4 hours, there should only be 50% of the drug left in the body.

    02:46 Now, as you follow that chart all the way down, you can see at 8 hours, that would be 2 half-lives, we’re down to 25%; at 3 half-lives, 12.5%; 5 half-lives, we’re down to 3.125%; and 6, we’re all the way down to 1.56%.

    03:02 So, what I want you to take away from this slide is just you clearly understand 1 half-life means that 50% of the drug that was present in the bloodstream is decreased.

    03:13 So, this would be an example where we only gave the medication 1 time, and that’s how you end up 6 half-lives later, or 24 hours, with a tiniest bit of that drug in their bloodstream.

    03:25 Okay, so once you understand drug half-life, it’s going to make the other concepts much easier to go through.

    03:31 So, a steady state is a time of plateau or constant serum drug level.

    03:36 Now, you’ll never get to steady state if you just give 1 dose of the medication.

    03:41 Steady state, or plateau, requires multiple doses of medication.

    03:46 So, you’ve got a picture here to kind of give it, but I want to walk you through the steps of this.

    03:51 Steady state requires repeated doses of medication, and the amount of drug given is equal to the amount of drug that’s eliminated.

    03:59 So, you can look at those doses, and usually based on the half-life, it’s usually about after the 4th dose, the steady state is reached as long as you’ve given equal doses each time.

    04:12 So, when I’m starting a patient on a new medication, I know that it’s going to take us several doses to get that patient at a steady state.

    04:20 So, if we give the same dose of medication at every time, it should take around the 4th dose for the patient to arrive at the steady state.

    04:29 Now, why do we care about the steady state? Because that should be “The Sweet Spot,” the therapeutic range where a patient is going to get the most benefit from that medication.

    04:41 Drugs with short half-lives hit that steady state in a shorter period of time because they have the shorter half-life.

    04:47 Drugs with longer half-lives can take days or weeks to reach steady states.

    04:53 So, if we want to impact the serum drug levels, I want to talk to you about some of the things that you can do to kind of keep those elevated.

    04:59 If you start with a constant IV infusion, that way you don’t have different doses, they’re just getting a constant IV infusion of that medication in their body all the time.

    05:10 You can use Depot preparations.

    05:11 So, we talked about those in some of the other videos, but those drugs are IM or subcu and they release slowly over extended periods of time.

    05:21 Now, if I want to reduce the interval in between doses and the individual doses of the medication that will also impact the serum levels.

    05:28 Okay, so for example, if you take the total daily dose remains the same; okay, so I’m going to give 100 mg every day.

    05:36 If I want to impact the serum drug level, I could break that up into two 50 mg doses a day or four 25 mg doses a day.

    05:45 So, instead of getting 100 mg and then every half-life, it gets less if I break that dose up and I give it multiple times during the day, I’m going to definitely impact the serum drug level.

    05:59 Okay, now the next part we want to talk about are loading doses.

    06:03 So, we talked about, you want that “sweet spot,” right in the middle of therapeutic range, we talked about half-life and how that impacts plateauing, and multiple doses. Now, we’re going to talk about serum drug levels and how they’re impacted by loading doses.

    06:19 So, a loading dose is a much bigger initial dose of the medication and then you give constant smaller doses.

    06:26 So, that gives me a big jump in my serum concentration and then I kind of maintain that with smaller doses.

    06:32 We do this oftentimes with antibiotics, particularly in the case of really severe infections.

    06:37 So, we’ll get to that steady state— remember that’s the therapeutic range— we’ll get to that steady state for most drugs with a lot shorter time.

    06:47 So, here’s a question for you to consider.

    06:49 How long does it take for a drug to leave the body once we’ve discontinued the medication? Well, after the medication is discontinued, it takes about 4 half-lives for 94%, so the majority of the drug to leave the body.

    07:04 Now, the cool part about that is that should be easy to remember, because remember it took about 4 doses to reach that steady state, or that “Sweet Spot”—that therapeutic range— and it also takes about 4 half-lives for the majority of that drug to be gone from the body.

    07:20 Keep in mind that drugs with a longer half-life can remain in the body for a very long period of time.

    07:26 Well, that wraps up this section on talking about the how, when, and why of drugs and how they impact the body.

    About the Lecture

    The lecture The Body’s Response to Drug Dosage and Timing (Nursing) by Rhonda Lawes, PhD, RN is from the course Pharmacology and Implications for Nursing.

    Included Quiz Questions

    1. The plasma level where harmful effects start to occur
    2. The medication dosage that causes negative outcomes
    3. Any plasma level outside of the therapeutic range
    4. The lowest plasma dose that produces therapeutic effects
    1. 5mg
    2. 15mg
    3. 10mg
    4. 4mg
    1. Using depot preparations
    2. Administering instant release formulations
    3. Administering a daily IV dose
    4. Giving the daily dose in a single administration
    1. Achieves a quicker steady state
    2. Reduces the minimum toxic concentration
    3. Increases the minimum effective concentration
    4. Prolongs the medication half-life

    Author of lecture The Body’s Response to Drug Dosage and Timing (Nursing)

     Rhonda Lawes, PhD, RN

    Rhonda Lawes, PhD, RN

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