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Flashcards in Protein Synthesis Inhibitors Deck (53):
1

Streptococcus pneumoniae (the most common agent that causes classic community-acquired pneumonia) as well as atypical pathogens such as mycoplasma pneumoniae what is the best treatment choice?

Protein synthesis inhibitors

2

Why is Methicillin Resistant Staphylococcus Aureus (MRSA)?

if something is resistant to methicillin it can be very dangerous because it means it is resistant to something that typically works against bugs that are resistant!

3

An organism such as Mycoplasma Pneumoniae is resistant to penicillins and cephalosporins. Why?

NOT because it produces beta-lactamase, but because it lacks a peptidoglycan cell wall

4

Protein synthesis inhibitors exert their antimicrobial effects by what?

targeting the bacterial ribosome (within the cell, NOT the cell wall!)

5

The bacterial ribosome is composed of what subuntis?

50S and 30S subunits (as opposed to 60S and 40S subunits in humans)

6

What are the protein synthesis inhibitors?
4

Tetracyclines
Macrolides
Chloramphenicol
Clindamycin

7

Which kind of antibiotics inhibit 30s ribsome?2

Which kind of antibiotics inhibit the 50s ribsome?4

Buy AT 30
Amnoglycosides
Tetracyclines

CELL at 50
Chloramphenicol,
erythromycin,
lincomycin,
clinamycin

8

What are the tetracyclines?
4

Tetracycline
***Doxycycline: by far the most important one you need to understand in this class!!
Minocycline
Demeclocycline

9

MOA for tetracylcines?

Binds to 30S subunit of the bacterial ribosome and is believed to block access of the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site, thus inhibiting bacterial protein synthesis

Binds to 30s and blocks tRNA from binding to the mRNA= inhibiting protein synthesis

10

Antibacterial Spectrum for tetracyclines?
3

Broad spectrum antibiotics, active against many gram positive and gram negative organisms including anaerobes

11

How do bacteria become resistant to tetracyclines?
2

Can a bacteria be resistant to one tetracycline and not another?

Cell develops efflux pumps
Forms ribosomal protection proteins

no

12

How would you describe the bioavilablity of tetracyclines?

What helps with absorption?

All tetracyclines adequately but incompletely absorbed after oral ingestion

Taking concomitantly with dairy foods decreases absorption (less of a problem with doxycycline which is important to understand)
DONT take with dairy

13

How would you describe the distribution of tetracyclines?

Concentrate in liver, kidney, spleen, and skin and bind to tissues undergoing calcification (for example, ***teeth and bones)
HIGH
but does not cross the BBB

14

How are tetracyclines eliminated?
4

Concentration in Liver
then
Metabolized and
Conjugated
then
Released in the Bile
then
Reabsorbed in Intestine and enter urine via glomerular Filtration

15

What is the exception to the rule with tetracyclines being excreted renaly?


Why is this important?

Doxycycline is an exception at this stage as its metabolite is preferentially excreted via the bile into the feces

Because of this, doxycycline CAN BE employed in treating infections in renally compromised patients

16

Common Adverse Effects
of tetracyclines?
4

1. Effects on calcified tissues: Deposition in the bone and primary dentition occurs during calcification in growing children which causes discoloration and hypoplasia of the teeth and a temporary stunting of bones for growth
TEETH STAINING
2. Gastric discomfort: controlled if taken with foods other than dairy products- (doxy)cant take others with food or absorption will go way down
3. *Phototoxicity: severe sunburn can occur when the patient taking a tetracycline is exposed to sun or ultraviolet rays
4. Vestibular problems: dizziness, nausea,and vomiting occur with minocycline

17

Contraindications for tetracyclines?
3 absolute
3 precautions

*Pregnant women-D
*Breast-feeding women. unsafe
*Children under 8 years of age
Caution if impaired renal function (except which one again?)Doxy
Caution if impaired liver function
Caution in SLE (Lupus) - monoclycine

*absolute contraindications

18

Tetracycline Routes of Administration?

Oral
IV
IM injection not recommended because of pain and inflammation at injection site

19

When you think tetracycline what is the first thing you should think of?

Doxycycline (100mg BID)

20

What are tetracyclines useful in treating?
5
4 first line uses
2 alternative uses

1. sexually transmitted diseases, 2. atypical pneumonia,
3. exacerbations of chronic bronchitis,
4. acne vulgaris, and
5. great alternative for sinusitis and acute prostatitis

21

What should we never use a tetracycline for?

Never used for skin infections because of decreased activity against staphylococcus aureus(resistance)

22

What will tetracycline use in kids under 8 always cause?

TEETH STAINING

23

What is Doxycycline the drug of choice for?
4

1. mycoplasma pneumoniae,
2. chlamydiae (which can be responsible for a variety of STIs), 3. rickettsiae (Rocky Mountain Spotted Fever), and excellent for 4. Lyme Disease

24

Minocycline is often used for what?

acne vulgaris

25

Demeclocycline is often used for what?

because of its inhibiting action of ADH in the renal tubule is used in the treatment of SIADH

26

What are the three macrolides?

Erythromycin
Azithromycin (Zithromax)
Clarithromycin (Biaxin)

27

Whats the MOA for macrolides?

Bacteriostatic or Bacteriocidal?

Bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis

Bacteriostatic

28

What kinds of bacteria does erythromycin work against?
4

effective against the same organisms as penicillin G and therefore used in patients allergic to the penicillins. Also effective against

chlamydial species and mycoplasma pneumoniae and legionella pneumophila

29

How is Clarithromycin (Biaxin) different from erythromycin?

similar to erythromycin but also effective against Haemophilus influenzae

30

How is Azithromycin (Zithromax) different from the other macrolides?
3

1. less active against streptococci and staphylococci than erythomycin but
2. more active against respiratory infections due to Haemophilus influenzae and Moraxella catarrhalis.
3. Excellent for urethritis caused by Chlamydia trachomatis

31

Most strains of staphylococci in hospital isolates are resistant to which macrolide?

Why is this bad for other macrolides?

erythromycin

Clarithromycin and azithromycin show cross resistance with erythromycin

32

How do bacteria become resistant to macrolides?
3

1. Alteration in the binding site of the ribosome
2. Manifestation of an efflux pump to get the drug out of the cell
3. Enzymatic inactivation

33

Describe the absorption of macrolides?
Erythromycin:
Clarithromycin and Azithromycin:

Erythromycin base destroyed by gastric acid and therefore enteric coated tablet is required; is adequately absorbed on oral administration

stable to stomach acid and readily absorbed

34

Describe the distribution of macrolides?

Widely distributed in tissues except for CSF-azithro is the best

35

Describe the metabolism of macrolides?
3

1. Erythromycin is a cytochrome P450 drug (lots of interaction)
2. Clarithromycin metabolized by liver and may also interfere with other drugs
3. Azithromycin is NOT a P450 drug and tends to have very few interactions with other medications

E- most interactions
C-moderate interactions
A- Not many interactions

36

Describe the excretion of Macrolides?

Erythromycin and azithromycin:
Clarithromycin:

Erythromycin and azithromycin primarily concentrated in the bile

Clarithromycin and its metabolites however, are eliminated by the kidney as well as the liver and it is recommended that the dosage be adjusted in patients with compromised renal function

37

Common Adverse Effects
for macrolides?
3

1. GI distress including diarrhea especially a problem with erythromycin
-A and C are much better tolerated than E with GI
2. Ototoxic- erythromycin
3. Prolonged QT with C and E

38

Azithromycin is much easier to use than erythromycin and clarithromycin for several reasons. What are they?
4

1. Fewer adverse effects
2. Fewer drug interactions
3. For the most part you don’t have to worry about adjustment in patients with kidney and liver disease unless extremely severe
4. Because of it’s long half life it’s exceptionally easy to use and patients are more compliant with it (once daily dosing versus twice daily with clarithromycin and up to qid dosing with erythomycin)

39

What are no macrolides good with?

no good for staphylococcal disease

40

Macrolides are first line alternative for what?

streptococcal pharyngitis (strep throat)

41

What are macrolides first line treatment for?
3

1. chlamydial cervicitis and urethritis STIs
2. Excellent for broad spectrum coverage of both typical and atypical pneumonias
3. Used all the time for exacerbations of chronic bronchitis in the patient with COPD

42

What’s the most important thing you need to know about Chloramphenicol?

Well, even though it is active against a wide range of gram-positive and gram negative organisms, because of its high toxicity, its use is restricted to life-threatening infections in which there are no alternatives!!

43

MOA for Chloramphenicol?

Binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction

44

Antimicrobial spectrum for Chloramphenicol?

Who is it not effective against?
2

Very broad including excellent activity against anaerobes. Not effective against Pseudomonas or Chlamydiae

45

Bioavailability of Chloramphenicol?

Distribution?

Completely absorbed orally

Readily enters CSF

46

Adverse affects of Chloramphenicol?
4

1. Hemolytic Anemia
2. Aplastic Anemia (which is usually idiosyncratic and usually fatal, this occurs independent of dose and may occur after therapy has ceased!)
3. Gray Baby Syndrome – because of interference with human mitochondrial ribosomes, can lead to poor feeding, depressed breathing, cardiovascular collapse, cyanosis, and death
4. Can interfere with a number of other drugs (phenytoin and warfarin)

47

MOA for clindamycin?

Same as the macrolides

48

What kind of bacteria does clindamycin have great coverage against?
2

Great coverage against ***anaerobic bacteria but also significantly active against many gram-positive cocci

49

Describe the bioavailability of clindamycin?

Distrbution?

Well absorbed orally

Distributes well into all body fluids EXCEPT the CSF

50

What do we always have to remember about Clinda?

Very Important Fact: Clostridium difficile is ALWAYS resistant to clindamycin
Note: Clostridium difficile is a bug that hangs out in the gut and typically causes zero problems. However, with administration of Clindamycin you can potentially have overgrowth of Clostridium difficile which can lead to a potentially fatal disease referred to as pseudomembranous colitis

51

When you think about common medications used against anaerobes, you typically think either?2

Clindamycin or Metronidazole (Flagyl)

52

What specifically is Clinda great at treating?

Excellent in treating infections of the gut
Used to treat penetrating wounds of abdomen and gut

53

Always remember, when you think anaerobic you are thinking what?2

gut flora (or female genital tract flora)