Okay, this is chapter four immune, tetracyclines and macrolides.
We're going to use four drugs to start and then I'm going to add a fifth
later just to stick with the way that we've been doing it. Tetracyclines,
the generic doxycycline, brand Doryx and Periostat. Periostat is a different function,
different dosage, and I'll talk about that in a little bit.
Minocycline is Minocin, and those are both tetracyclines with the '-cycline' stem. The macrolides,
sometimes we call them erythromycin after the original drug in the group.
Azithromycin which comes as a Z-Pack or you may hear it as Zithromax, and then clarithromycin
which is Biaxin. The 'Bi-' comes from
the dosing that's BID or twice daily.
I'll comment on erythromycin in the last two questions.
Before we can get started though, I have to do a little bit of chemistry review, just a tiny bit
about cations, and what divalent means and so forth. The common cations are aluminum, calcium, iron, magnesium.
If you remember from chemistry, you had this Al +3 and
that valence was how many bonds form.
The issue with these
forms is that you can
give something with these cations,
and if someone is on a tetracycline, then they're going to bind and make the tetracycline ineffective.
Let's just look real quick at how a
cation and anion come together.
If we take calcium which is Ca+ 2 and
carbonate which is [CO3 -2, we make calcium carbonate, which is the active ingredient in Tums. It's an antacid.
In questions, you're not going to really see the +3 or +2, that would make it really easy.
You're going to see aluminum as aluminum antacid,
calcium will be hidden even more as milk or dairy.
It might be calcium supplement. Iron, usually you're going to see iron supplement.
And then magnesium as a laxative, but just know that
these cations
are going to be in
word form and a little bit disguised.
Let's go to our first question:
A patient says they works outdoors. Which medication would be of concern?'
What I put here was a lot of information.
A long-acting
tetracycline in my head, and this long-acting tetracycline, is doxycycline is for acne, for dental, peptic ulcer disease,
causes photosensitivity and
chelation.
Minocycline,
same thing except it's second line peptic ulcer disease, but causes acne.
Doesn't have an oral form for dental, photosensitivity and then chelation.
The first macrolide is azithromycin.
I think of respiratory infections, and I've had a bunch, and I've taken erythromycin or azithromycin.
It doesn't affect the cytochrome P450 system, and I'll get into more detail there. The last one clarithromycin is
BID or twice-daily macrolide for peptic ulcer disease affecting cytochrome P450.
The mistake I see students making is that they'll
take all of
the side-effects from
Some kind of reference, make a note card out of it and try to memorize all of that.
What you really want to do is see what
types of questions you see in practice or what types of questions you see on your practice exams or in class and
you go from
the clinical pearls or those that are most common. It's a much better
way to do it because there are just so many side effects to remember
that it's better to go with the ones that are most likely to be on the test.
The answer to the actual question, working outdoors, the two tetracyclines would be of concern.
Let's change these to the drug names and
Patient says they work outdoors which would be of concern?
Doxycycline and minocycline, and we know from the stem '-cycline'.
Now the minocycline does cause a little bit of less photosensitivity. It's actually tough to measure, you can't really do a trial
where you give these two medicines and put people out there and see who burns worse and who burns less,
it's just not ethical, but
from some of the literature I've read minocycline tends to cause a little bit less photosensitivity.
Let's go and make A) correct. Try to find something unique about doxycycline.
'The patient needs an oral medication for periodontal disease'.
The oral medication is what makes A) only right. Doxycycline, it inhibits an enzyme called
collagenase and it saves the gums because
it stops collagenase from basically eating the connective tissue. The way to remember
doxycycline has to do with this dental effect is to just think 'D' for dental.
The minocycline does have a topical form but no oral form and it's for
another dental condition, but not this. Azithromycin and clarithromycin, know these don't have any
periodontal issues.
'A patient needs an oral medication for acne', question number four let's make B) correct.
Well, this is again one of those facts,
and you really don't want to add a
fact to your note card or to your journal or your notebook or whatever you're doing
without having some mnemonic or some way to remember it. If you look in the word tetracycline,
which is the class of doxycycline and Minocycline,
You see that A, C, and E are actually in the word in order,
so that's how I would remember that doxycycline, minocycline,
tetracycline if it's available, all are for acne, A, C, and E.
Question five: 'A patient takes milk or' and what I did here was say
instead of making four questions,
let me just say these are the other ways that you might express the question. 'A patient takes milk or iron supplements or calcium
calcium supplements, or aluminum or magnesium antacid, which medications, if in the chart, would be of concern?' and
it would be the doxycycline and minocycline because both of them chelate
which is that binding that makes the tetracycline inert. If you look in the word
tetracycline if you're a fan of word scrambles, you can find all the letters except the 'h' from chelate in
tetracycline, and I showed that here.
Question six:
'A patient needs a macrolide antibiotic, but is currently on warfarin and again the common other drugs you'll see are carbamazepine
carbamazepine or theophylline, and
which is the best choice?'
Which is the best choice to protect the patient from this? The answer is azithromycin.
Erythromycin came out first, clarithromycin second, and both of those affect the P450 though clarithromycin not as much
as erythromycin but azithromycin the big breakthrough
not only because it has this once daily dosing, but it doesn't affect the P450 system,
specifically the CYP 3A4 isoenzyme. There are five
isoenzymes that are integral to most drug interactions, and that's one of them.
Okay, let's again make C)
correct: 'Which medication makes use of a loading dose twice the regular dose?' Tthat loading dose,
we're trying to get the drug levels up to a certain amount
to kill the bacteria, and
the azithromycin] in the Z-Pak what you find is that you take two tablets on the first day, then one every day thereafter.
What about children's medicines? Well, you might get a little tiny
15 mL bottle or 22.5 or 30 mL bottle and they'll take you know maybe two teaspoonfuls on the first day and then one
teaspoon each day thereafter, but again a double dose on the first day as the loading dose.
Question eight: 'A patient needs an oral therapy for peptic ulcer disease to go with a PPI and second
antibiotic?' Usually we see triple therapy. We might see quad therapy, which is generally better.
But what is, of these you know, which is good for peptic ulcer disease? And the answer is actually all of them.
I've seen that doxycycline, minocycline,
azithromycin, clarithromycin all have been studied.
If you're looking at the one that's most likely to be on some kind of exam
it's going to be the clarithromycin because it's the staple of triple therapy.
There has been some resistance
recently to this clarithromycin,
but I still see it in the most updated literature.
Number nine, we're going to change D)
and we're going to change it from clarithromycin to erythromycin. Why?
because erythromycin, I
see it all the time, and it is one of those drugs that has a lot of interactions,
so it's kind of odder for test banks. 'A patient needs a macrolide antibiotic
but is currently on warfarin or carbamazepine or theophylline, which is of greatest concern?'
Instead of saying which drug do I give them so I don't hurt them,
we're saying which drug would hurt them and should I not give them? The answer erythromycin.
Yes, this macrolide does affect the cytochrome P450 system severely and causes
issues with
metabolism of other drugs.
The warfarin
is
such an issue because we can have bleeding with warfarin or the carbamazepine we would have issues with the seizures and so forth.
Practice question ten: 'Which medication would cause the greatest GI distress?'
That again is erythromycin. It causes severe GI distress. You can take
certain forms of the erythromycin with food,
some you can't. I always remember it as e-rip your stomach, so taking the 'ery' from erythromycin.
Azithromycin is
it's the weirdest thing when it came out. They said no, you can't take it with food and
you'll still see it in many textbooks, don't take azithromycin with food, but then comes out well
it's okay like really? So I'm not really sure about that one,
but azithromycin I still would have somebody taking it on an empty stomach
to make sure that it works the best.
To sum up,
tetracyclines
the macrolides,
there's a lot to them, but there's a lot of consistency with them.
We don't really have the generations like we did with cephalosporins, but if you remember
that doxycycline and minocycline are the long-acting
tetracyclines, and that azithromycin is the newest one so it's the best,
it doesn't have that P450 interaction. The clarithromycin is second to last newest one and that has the peptic ulcer disease
indication and not as bad with P450, and erythromycin was the first one and causes that GI distress and
certainly the issues with P450.