Antibacterial Agents Targeting Protein Synthesis

Question 1

What is the Post-Antibiotic effect (PAE)?

Answer 1

If a drug has PAE it means that even after the bacteria has been exposed it will continue to kill it off.

Concentration of the drug is going down but you still get effects of that drug

Question 2

Which drugs bind at the 50s at the beginning of protein synthesis?

Answer 2

Oxazolidinones

Linazoid (Zyvox)

Tediozide (Sivextro)

Question 3

Where do tetracycline bind>

Answer 3

On 30s which block tRNA binding

Doxycycline

Minocycline

Tigecycline

Eravacycline

Omdacycline

Question 4

Where does chloramphenicol bind ?

Answer 4

It binds at the 50s and blocks peptide chain transfer

Question 5

Where does Clindamycin and macrolides bind?

Answer 5

50s at the end and block translocation

Question 6

Where do aminoglycosides bind?

Answer 6

30s at the end

Blocks translocation

Question 7

What to know about clindamycin

Answer 7

Good oral bio = 90%

Lincosamide

No PAE

Bacterodies activity, CA MRSA, Aspiration pneumonia, Skin and soft tissue, acne, bacterial vaginosis

Cleared in RENAL and bile

No CYP3A4

Question 8

What are the Macrolides?

Answer 8

Azithromycin (Zithromax)

Clarithromycin (Biaxin)

Not so good oral bioavailability

LIVER CYP3A4!!!!! Very big inhibitors have to watch for drug interactions (clarithromycin)

has PAE effects

Works on Atypicals

Has really big ring structure

Question 9

What is important to note about clindamycin and drug resistance

Answer 9

It can create its own drug resistance

You must do the D-TEST which uses erythromycin to see if it is isolated to CA MRSA

Positive = can not use clindamycin

Negative = you can use

Question 10

What is erythromycin used for when you see it in pharmacy?

Answer 10

Typically it will not be as an antibiotic but will be used in order to induce diarrhea

Question 11

What is important to note about the half-life of azithromycin?

Answer 11

It is very long!

Serum = 60-70 hours

Intracelluar = 2-3 weeks!

Question 12

What are the side effects of Clindamycin?

Answer 12

GI= N/V

BIG IN DIARRHEA and CDAD!!!!

Hepatotoxic

Question 13

What are the side effects of Azithromycin and clarithroymcin

Answer 13

GI= N/V

Does cause moderate diarrhea (not as bad as clindamycin)

Does does CDAD but not near as bad as clindamycin

Hepatotoxic

These give QTc prolongation!!!! Clari is worse

Also have to watch for CYP3A4 interactions!!!! (They are inhibitors)

Clarithromycin is really bad at this!!!

Question 14

What are the uses for Macrolides?

Answer 14

Azithromycin (Zithromax)

Clarithromycin (Biaxin)

Atypicals

CA acquired pneumonia

COPD exacerbation

Sinusitis

Some mycobacterial infections

Azithromycin = travelers diarrhea

H. pylori = clarithromycin

Question 15

What is the route for the aminoglycosides?

Answer 15

They are only given IV

Tobramcyin

Gentamicin

Amikacin

Question 16

How is the distribution of the aminoglycosides?

Answer 16

It’s poor, DOES NOT get into the CNS and the lungs!

Also it does have a PAE effect where it works even after the concentration has fallen off

***when given n the hospital the pharmacist will also choose the dose that is needed for the pt

Question 17

What do Aminoglycosides work against?

Answer 17

ONLY WORKS FOR GRAM NEGATIVE AEROBES!!!

** includes PSEUDOMONAS and ACINETOBACTER

Gentamicin**
Can be good with beta lactam or Vanco for MRSA and MSSA for endocarditis

Question 18

What are the side effects for Aminoglycosides?

Answer 18

Gentamycin

Tobramycin

Amikacin

Nephrotoxicity

Ototoxicity

Question 19

What is the clinical pearl when using this drugs (when would you use these) Aminoglycosides?

Answer 19

You would use gentamicin and tobramycin first

But they are already later choice drugs that are only brought out if resistance is a problem!!

Amikacin would be you last chance drug if the bacteria is resistant to genta and tobramycin

Question 20

What are the tetracycline and what is their MOA?

Answer 20

Minocycline (minocin)

Doxycycline

It binds to the 30s subunit and prevents tRNA from binding

The structure has 4 rings back to back

Question 21

What are the new agents of tetracyclines?

Answer 21

Omadacycline

Eravacycline

Tigecycline

**these drugs are used held off on because these you only use when a bacteria has MDR. So you must avoid it unless really needed

Question 22

What are the pharmacokinetic considerations when it comes to the tetracyclines?

Answer 22

Doxycycline and Minocycline

Very good oral, has good distribution EXPECT the CNS

Metabolism is in the liver (none-CYP3A4)

Eliminated in the bile and thro feces

New agents:

Same as above but the oral bioavailability for omadacycline is really poor. Around 35%

Question 23

What are some drug interactions when it comes to the tetracyclines

Answer 23

Doxycycline, minocycline, omadacycline, tigecycline, eravacycline

Have to watch for cations of magnesium and calcium (milk, and antacids)

**these will cause it to bind and form participates which effect the absorption of the drug

Question 24

What are the clinical uses for Doxycycline and Minocycline?

Answer 24

Atypical bacteria

• CA pneumonia
• STD - Chlamydia

COPD exacerbation

Sinusitis

Skin and soft-tissue infection (cellulitis)

Acne

Spirochete diseases

Bioterrorism

Malaria prophylaxis

Question 25

When would you use the new type of tetracyclines?

Answer 25

They are not first line agents and will only be used if there is a MDR bacteria that you needed to work on

Question 26

What are the warnings / adverse effects of Doxycyline and minocycline? And the new ones!

Answer 26

1. GI upset 2. Esophageal irritation- drink with H20!! 3. N/V 4. Diarrhea 5. CDAD 6. Pancreatitis and Liver toxicity!!!!!!!! 7. Tissue and bone discoveration as well as inhibitor of bone growth (CAN NOT GIVE TO CHILDREN)!! (It can sit inside the bones and cause issues later on in life for kids) 8. Photosensitivity - watch out for sun exposure these two are quite prone for this 7. Psuedotumor cerebri (increased intracranial pressure (rare)) 8. Infection site rxn/ phebilitis (buring in veins) The new ones cause increase in N/V and infusion rxns

Question 27

What are the oxazolidinones and their MOA?

Answer 27

Linezolid (Zyvox) Tedizolid (Sivextro) MOA: they block the 50s subunit at the start of the process and prevent the two from binding together

Question 28

What are the Pharmacokinetics of the Oxazolidinones?

Answer 28

Linezolid (Zyvox) and Tedizolid (Sivextro) They have good bioavailability (90-100%) ***********HAVE MAO-INHIBITOR ACTIVITY!!! Linezolid more so than tedizolid but must watch for interaction of these when taking antipsychotics!!!!

Question 29

What are the clinical uses for Oxazolidinones?

Answer 29

Linezolid (Zyvox) and Tedizolid (Sivextro) Used for gram (+) bacterial infections!!! Can be used for everything!!! Including up to VRE!!!!! CAN NOT BE USED FOR BACTERMIA ( infection of the blood)!! **these will be used for gram (+) that has MDR

Question 30

What are the adverse effects for the Oxazolidinones?

Answer 30

Linezolid (Zyvox) and Tedizolid (Sivextro) generally well-tolerated But can cause Bone marrow suppression - thrombocytopenia Also when used for a long time must watch for Peripheral Neurophathy!!!! (When used for months!!!!!!) WATCH FOR MAO-INHIBITORS!!!!!!! - do not use for those things!!!

Question 31

What is Chloramphenicol (include MOA and pharmacokinetics)

Answer 31

It is not used in the US MOA: Block peptide chain transfer by binding to the 50s subunit of the bacterial ribosome Pharmacokinetics: Good bioavailability (75-90) Gets excreted not thro kidney and non-fecal

Question 32

What are the chloramphenicol adverse effects?

Answer 32

1. Hypersensitivity rxn (rash, hives (urticaria) and anaphylaxis 2. Aplastic anemia - Agranulocytosis (loss of granulocytes, macro neutrophils) 3. Gray baby syndrome (in newborns) 4. Altered mental status 5. Leukemia These bad effects are why this drug is not used in the US.