Flashcards in Protein Synthesis Inhibitors Deck (53):
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
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!
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
Protein synthesis inhibitors exert their antimicrobial effects by what?
targeting the bacterial ribosome (within the cell, NOT the cell wall!)
The bacterial ribosome is composed of what subuntis?
50S and 30S subunits (as opposed to 60S and 40S subunits in humans)
What are the protein synthesis inhibitors?
Which kind of antibiotics inhibit 30s ribsome?2
Which kind of antibiotics inhibit the 50s ribsome?4
Buy AT 30
CELL at 50
What are the tetracyclines?
***Doxycycline: by far the most important one you need to understand in this class!!
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
Antibacterial Spectrum for tetracyclines?
Broad spectrum antibiotics, active against many gram positive and gram negative organisms including anaerobes
How do bacteria become resistant to tetracyclines?
Can a bacteria be resistant to one tetracycline and not another?
Cell develops efflux pumps
Forms ribosomal protection proteins
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
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)
but does not cross the BBB
How are tetracyclines eliminated?
Concentration in Liver
Released in the Bile
Reabsorbed in Intestine and enter urine via glomerular Filtration
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
Common Adverse Effects
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
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
Contraindications for tetracyclines?
*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
Tetracycline Routes of Administration?
IM injection not recommended because of pain and inflammation at injection site
When you think tetracycline what is the first thing you should think of?
Doxycycline (100mg BID)
What are tetracyclines useful in treating?
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
What should we never use a tetracycline for?
Never used for skin infections because of decreased activity against staphylococcus aureus(resistance)
What will tetracycline use in kids under 8 always cause?
What is Doxycycline the drug of choice for?
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
Minocycline is often used for what?
Demeclocycline is often used for what?
because of its inhibiting action of ADH in the renal tubule is used in the treatment of SIADH
What are the three macrolides?
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
What kinds of bacteria does erythromycin work against?
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
How is Clarithromycin (Biaxin) different from erythromycin?
similar to erythromycin but also effective against Haemophilus influenzae
How is Azithromycin (Zithromax) different from the other macrolides?
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
Most strains of staphylococci in hospital isolates are resistant to which macrolide?
Why is this bad for other macrolides?
Clarithromycin and azithromycin show cross resistance with erythromycin
How do bacteria become resistant to macrolides?
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
Describe the absorption of macrolides?
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
Describe the distribution of macrolides?
Widely distributed in tissues except for CSF-azithro is the best
Describe the metabolism of macrolides?
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
A- Not many interactions
Describe the excretion of Macrolides?
Erythromycin and azithromycin:
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
Common Adverse Effects
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
Azithromycin is much easier to use than erythromycin and clarithromycin for several reasons. What are they?
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)
What are no macrolides good with?
no good for staphylococcal disease
Macrolides are first line alternative for what?
streptococcal pharyngitis (strep throat)
What are macrolides first line treatment for?
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
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!!
MOA for Chloramphenicol?
Binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction
Antimicrobial spectrum for Chloramphenicol?
Who is it not effective against?
Very broad including excellent activity against anaerobes. Not effective against Pseudomonas or Chlamydiae
Bioavailability of Chloramphenicol?
Completely absorbed orally
Readily enters CSF
Adverse affects of Chloramphenicol?
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)
MOA for clindamycin?
Same as the macrolides
What kind of bacteria does clindamycin have great coverage against?
Great coverage against ***anaerobic bacteria but also significantly active against many gram-positive cocci
Describe the bioavailability of clindamycin?
Well absorbed orally
Distributes well into all body fluids EXCEPT the CSF
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
When you think about common medications used against anaerobes, you typically think either?2
Clindamycin or Metronidazole (Flagyl)
What specifically is Clinda great at treating?
Excellent in treating infections of the gut
Used to treat penetrating wounds of abdomen and gut