Aminoglycosides – Bacterial Protein Synthesis Inhibitors (Antibiotics)

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.