00:00
Let's move on to
the aminoglycoside antibiotics.
00:04
So the aminoglycoside
antibiotics are incorporated
into the bacteria through
an oxygen dependent process.
00:10
Therefore, these medications
don't work that well against
anaerobic bacteria.
00:16
The aminoglycoside seen in
the red triangle there,
binds to the 30S subunit
of the ribosome.
00:23
Now how it works is it
inteferes with protein synthesis
by preventing the initiations
complex from forming.
00:31
So that's when the bottom
of the ham burger bun,
the top of the ham burger bun and the cheese
which is the mRNA which all
come together.
00:38
The aminoglycosides prevent that
entire initiation complex from
coming together.
00:43
It can also cause misread
errors on the messengerRNA.
00:49
So the messengerRNA is now
prone to making mistakes.
00:53
So instead of putting in amino
acid number 5,
it will put in amino acid
number 11 for example.
00:59
The other thing that happens as
well is that it does cause some
inhibition of translocation
which is another potential
mechanism that these drugs use.
01:09
They are highly dependent
upon concentration.
01:13
So aminoglycosides are
concentration dependent
antibiotics.
01:19
These medications actually
work better when given
intermittently.
01:24
So your better off having a high
peak and a trough then you're
having steady state level.
01:30
This is what makes these
medications unique.
01:33
They are concentration killers
as opposed to time killers.
01:36
So we like to have an
intermittent on off exposure
to these medications.
01:43
As I said before concentration
dependent killing action.
01:46
They also have a very strong
post antibiotic activity.
01:50
Which is why we can afford to
have low levels or trough levels
when we give these medications.
01:55
Remember that aminoglycosides
are really polar so they must
be given IV or IM.
02:02
They are not given orally.
02:03
They are excreted through
the kidney or renally.
02:07
So renal function will
determine the dose.
02:11
So a lot times in patients with
renal failure, will actually do
what's called "Peak and Trough
Levels."
So monitoring drug levels
is a big issue.
02:19
The other thing I want to
mention is that these drugs
do not cross the blood
brain barrier.
02:25
They do better as large,
single doses
than as multidose regimens.
02:31
Because like I said like
the peak and trough.
02:33
And the toxicity of these
medications limits the peak
concentration.
02:38
So that's what
limits our top level.
02:42
Now the broad spectrum agent
active across many classes
of bacteria is very typical
of aminoglycoside activity
whether it's gentamicin
or whatever.
02:54
E.coli, Haemophilus influenzae,
Klebsiella, Moraxella species,
Proteus species, Serratia
species, Shigella species.
03:03
These are all very susceptible
to this class of drugs.
03:07
They are almost always used in
combination with the penicillin.
03:11
So there's kind of like this
pairing, this husband and wife
kind of team that we like.
03:16
So ampicillin always seems
to go with gentamicin.
03:19
And piperacillin seems
to go with tobramycin.
03:21
They work very well together.
03:23
Ampicillin is more
about broad spectrum.
03:26
Gentamicin is more
broad spectrum.
03:28
So we use that in more
of a broad spectrum
kind of situation.
03:33
Pip/Tobra is used more
in gram negative disease.
03:36
And the reason why these two
combinations work so well is
because of something called
antibacterial synergy.
03:45
So what's that mean?
If you think about it, the
ampicillin or the piperacillin
their job is to open
up the cell wall.
03:55
That allows the gentamicin
or the tobramicin
to get into the cell.
04:00
And now their concentration near
the ribosome is much greater.
04:04
So the ampicillin
knocks down the door.
04:08
And the gentamicin goes through
in the door and does the job.
04:11
So that's why these two drugs
seem to work so well together.
04:15
Whether they are
Amp/Gent or Pip/Tobra.
04:20
Gentamicin is the prototypical
drug.
04:23
Tobramicin also has activity
against Pseudomonas
and it's used more in
gram-negative disease.
04:29
There are whole list of
those gentamycin antibiotics.
04:32
And streptomycin is one
of them and it's certainly
a very effective class.
04:38
Now toxicity is going
to be a big concern
with aminoglycosides.
04:43
Ototoxicity.
04:45
So a lot of people
get ototoxicity.
04:46
This is on exams.
04:48
And it is also something
important for clinical practice.
04:51
You need to be aware of this; auditory symptoms,
or amikacin, vestibular symptoms
or gentamycin and tobramycin.
04:58
So, although both are working on the inner ear,
there's a slight difference between the two.
05:03
So vestibular symptoms are gent and tobra,
auditory symptoms are amikacin.
05:10
Other toxicity includes neuromuscular blockade.
05:13
There's a curare like illness and you
treat it with calcium and neostigmine.
05:18
Finally, there are some skin reactions,
mostly with neomycin that you have to be aware of.