Hi, and welcome to the how,
when, and why of the body’s response
to drug dosage and timing.
This is a really important concept
So, let’s get started, first of
all, with a question.
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.
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.
Now, there’s 3 terms I want
you to keep in mind.
First of all, there is the minimum effective
concentration, or the MEC,
that’s the lowest plasma dose
that meets the therapeutic objective.
Now, there’s also a minimum
that’s the plasma level where the patient
starts to have some really negative effects
where those start to occur.
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.
So, that’s what we’re aiming for.
So, keep in mind there’s a direct correlation
to plasma drug concentrations
and the therapeutic effect.
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.
So, just remember half-life
is 50% of the drug left in the plasma.
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.
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.
Now, I want to give you a minute
to kind of get acclimated to it.
The left column talks about the
number of half-lives.
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.
Okay, so if I give a medication, I’ve
got 100% of the drug in the body.
At the 1st half-life, that would be 4 hours,
there should only be 50% of
the drug left in the body.
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%.
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
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.
Okay, so once you understand drug half-life,
it’s going to make the other concepts
much easier to go through.
So, a steady state is a time of plateau
or constant serum drug level.
Now, you’ll never get to steady state if
you just give 1 dose of the medication.
Steady state, or plateau, requires
multiple doses of medication.
So, you’ve got a picture
here to kind of give it,
but I want to walk you through
the steps of this.
Steady state requires repeated
doses of medication,
and the amount of drug given is equal to
the amount of drug that’s eliminated.
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.
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.
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.
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.
Drugs with short half-lives hit that steady
state in a shorter period of time
because they have the shorter half-life.
Drugs with longer half-lives can take days
or weeks to reach steady states.
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.
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.
You can use Depot preparations.
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.
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.
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.
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.
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.
Okay, now the next part we want
to talk about are loading doses.
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.
So, a loading dose is a much bigger
initial dose of the medication
and then you give constant smaller doses.
So, that gives me a big jump in
my serum concentration
and then I kind of maintain
that with smaller doses.
We do this oftentimes with antibiotics,
particularly in the case of
really severe infections.
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.
So, here’s a question for you to consider.
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.
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.
Keep in mind that drugs
with a longer half-life
can remain in the body for
a very long period of time.
Well, that wraps up this section
on talking about
the how, when, and why of drugs
and how they impact the body.