Exam 2: Inhibitors Of Protein Synthesis 1 Flashcards
What are the types of antibiotics that are inhibitors of protein synthesis? (7)
Macrolides Ketolides Clindamycin Streptogramins Oxazolidinones Aminoglycosides Broad spectrum antibiotics
What are the two inhibitors of protein synthesis that bind to the 30s subunit of the ribosome?
Aminoglycosides and tetracyclines
What are the inhibitors of protein synthesis that bind to the 50s subunit?
Macrolides, chloramphenicol, Lincosamides, Oxaolidinones, and strepogramins
What are the 3 macrolides and what are their routes of administration?
Erythromycin- Oral, IV
Clarithromycin- Oral
Azithromycin (Zithromax) - Oral, IV
What bacteria do the macrolides work best on?
G+
Bacteriostatic, great choice for immune competent person with allergy to pencillins.
How does resistance to macrolides occur?
- Efflux pumps
- Methylation of drug binding site so antibiotic cannot bind.
What is the DOC for chlamydia trachomotis or C pneumoniae?
Macrolides (Erythromycin, Clarithromycin, Azithromycin)
What is the DOC for Mycoplasma pneumoniae and Legionella Species?
Macrolides (Erythromycin, Clarithromycin, Azithromycin)
The majority of G- organisms are resistant to what macrolide?
Erythromycin
What are the main side effects of macrolides?
QT prolongation (torsades), Drug interactions with CYP34A drugs, and GI disturbances (mainly diarrhea)
Which macrolides has the most and which has the least adverse GI effects?
Clarithromycin has the least, erythromycin has the most
Erythrymycin is a potent inhibitor of ***.
CYP34A- this means it inhibits the hepatic metabolism of other drugs that require CYP34A, increasing their serum concentrations and potentially causing toxicity
What kind of drug is Telithromycin and how does it work?
A ketolide- binds tightly to two sites of ribosomal DNA and blocks bacterial protein synthesis
What site of the ribosome does telithromycin bind to?
50s
What bacteria is telihromycin effective against?
Broad spectrum. Bacteriostatic.
Good against respiratory pathogens including erythromycin and penicillin resistant pneumococci.
-Also has activity against intracellular and atypical bacteria
How is telithromycin taken?
Orally
Why was the approval for telithromycin on URIs withdrawn?
Serious hepatotoxicity was reported and the benefits of the medicine no longer supported the risks.
It remains on the marker for CAP, but not the first choice
How is telithromycin metabolized?
Hepatic cytochrome p450 isoenzymes, primarily CYP34A
How is Clindamycin adminstered?
Oral, parenteral, or topically
What bacteria is Clindamycin effective against?
A wide range of aerobic G+ cocci as well as several anaerobic G- and G+ organisms.
Is Clindamycin bactericidal or bacteriostatic?
Either, depending on its concentration at the site of action and the susceptibility of the organism
How is Clindamycin metabolized and excreted?
Metabolized by the liver, minimally excreted by the kidneys
How is toxic shock syndrome treated?
Clindamycin in addition to Vancomycin, Nafcillin, or a first generation cephalosporin
What is used to treat osteomyelitis and why?
Clindamycin because it obtains high concentrations in bones
Clindamycin is a well known cause of what disease?
Pseudomembranous colitis, an overgrowth of C. Diff.
If symptoms of a C. Diff infection arise while patient is taking Clindamycin, what should you do?
Immediately stop Clindamycin use and initiate Vancomycin treatment
What are the two types of Streptogramins?
Dalfopristin and Quinupristin
How does Dalfopristin work?
Binds to the 50s ribosomal particle and inhibits the early phase of protein synthesis
How does Quinupristin work?
Bind to the 50s subunit and inhibits late phase of protein synthesis
What happens wen dalfopristin and Quinupristin are administered together vs alone?
Together, they appear to act synergistically against susceptible bacteria and their effect is bactericidal
Alone they are bacteriostatic.
What bacteria are dalfopristin and Quinupristin effective against?
Aerobic G+ including penicillin resistance S. pneumoniae, MDR streptococci, skin infections due to MSSA or MRSA, and VRE
How are Dalfopristin and Quinupristin administered?
IV infusion
What are the adverse reactions of Dalfopristin and Quinupristin?
Hepatotoxicity, nausea, vomiting, rash
- inhibits the P450 drug metabolizing system
What are the contraindications of Dalfopristin and Quinupristin?
Breast feeeding, children, hepatic disease, pregnancy, and streptogramin sensitivity
What class of drug is Linezolid?
Oxaxolidinones
What bacteria is Linezolid effective against?
Predominately aerobic G+ organisms.
This is not a drug of first resort
What is the MOA of Linezolid?
Prevents to the formation of a functional 70s subunit initiation complex.
- Linezolid is a reversible, nonselective inhibitor of MAO.
- Bacteriostatic, except cidal for streptococci
What can overuse of Linezolid lead to?
It can speed up selection of resistant strains and lead to loss of use for this antibiotic
What infections is Linezolid approved for?
Bacterial PNA, skin and skin structure infections, VRE infections, and MRSA
How is Linezolid administered?
IV infusion or oral (oral bioavailability is 100%)
How is Linezolid metabolized?
Oxidation but the oxidative metabolism of Linezolid is non-enzymatic and does not require the hepatic microsomal oxidative system
What are the adverse reactions of Linezolid?
Diarrhea, headache, N/V, insomnia, constipation, possible superinfection, and the usual side effects and interactions as MAO inhibitors.
What are the contraindications of Linezolid?
Hypersensitivity and pheochromocytoma (tumor in adrenal medulla that can lead to increased EPI, NE, and serotonin)
Who should you never prescribe Linezolid to?
Someone who is on antidepressants such as SSRIs -this can lead to serotonin toxicity
What the is the spectrum of clarithromycin?
Very similar to erythromycin, but clarithromycin is more active against Mycobacterium Adium complex (MAC), Mycobacterium leprae, and toxoplasma Gondii
Out of the 2 macrolides, which is most likely to cause QT prolongation?
Azithromycin
Out of the 3 macrolides, which has the most drug interactions?
Clarithromycin
Are the macrolides bactericidal or bacteriostatic?
Bacteriostatic
