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96 Cards in this Set
- Front
- Back
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What are the bacteriostatic protein synthesis inhibiting antibacterial drugs?
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TCECTCL
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What is TCECTCL?
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-tetracyclines
-Chloramphenicol -Erythromycin -Clarithromycin -Telithromycin -Clindamycin -Linezolid |
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What are the 2 Tetracyclines to know?
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-Doxycycline
-Minocycline |
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What is the mechanism of action of the Tetracyclines? (2 steps)
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1. Transported into cells by protein-carrier system
2. Bind 30S ribosome and prevent attachment of incoming aminoacyl tRNA |
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How is the protein carrier system that transports Tetracyclines into the cell different from that for aminoglycosides?
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It does not require energy
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How are the bacteriostatic protein inhibitors different from all the other antibacterials we've talked about so far?
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All the previous ones were bacteriocidal!
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What is the most common mechanism of resistance to the Tetracyclines?
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Drug efflux pumps that are specific for tetracyclines!
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What happens if a bacterial strain develops resistance to one Tetracycline?
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It develops resistance to them all!
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What has happened to the resistance to Tetracyclines over time?
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It has increased dramatically!
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What are the Tetracyclines mainly used for now?
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Oddball bugs
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What are 5 oddball bugs for which the tetracyclines are given?
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-Lyme's disease
-Chlamydia -Rickettsia -Ureaplasma -Mycoplasma |
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What are the 3 advantages of Doxycycline and Minocycline over the other tetracyclines?
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-Semisynthetic
-Longer half lives -Reduced toxicity |
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For what patients is Doxycycline mainly used as a treatment for the oddball bugs?
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Patients with impaired renal function
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Why is Doxycycline especially useful for patients with renal impairment?
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Because Doxycycline is largely handled by the LIVER not the kidney.
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What is a specific use of Minocycline and why?
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Prophylaxis of Neisseria meningitis - bc it is highly lipophilic (like Rifampin).
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What disease can be treated with Minocycline in patients that are allergic to Penicillin G?
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Syphilis
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What serum ion do all of the tetracyclines bind to?
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Calcium
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Which tetracycline has the least, in between, and most affinity for calcium?
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Least = Doxycycline
In btwn = Minocycline Most = Tetracycline |
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Why is the tetracycline's calcium binding noteworthy?
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It inhibits tetracycline absorption from the GI tract.
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How can we get around the decreased absorption of tetracyclines due to Ca binding?
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Give it parenterally or avoid high-Ca foods/antacids
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What are the 4 side effects of tetracyclines to know?
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-GI Disturbances/Enterocolitis
-Candida superinfection in colon -Photosensitive rash -Tooth discoloration/bone deposition |
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In what patients should you avoid giving tetracycline?
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Those 8 yrs old or younger
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When WOULD you give an 8yr old tetracycline? Which one?
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For Rickettsial infections - Doxycycline - it has the least calcium binding.
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And what should patients avoid taking with tetracyclines?
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Ca-rich foods, Milk, and Antacids.
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What drug was developed to bring back sensitivity in some of the bugs that became resistant to Tetracyclines?
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Tigecycline
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What is Tigecycline's mechanism?
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Like the tetracyclines but binds to additional unique sites in the ribosomes.
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What does the fact that Tigecycline binds to different ribosome sites have for its use?
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Resistance to tetracyclines does NOT mean resistance to Tigecycline! There is no cross resistance.
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What bugs can be treated with Tigecycline?
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Many - GN, GP, and Anaerobes
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What types of infections has Tigecycline been used to treat so far? (it's new on the mrket)
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-Skin infections
-Complicated intrabdominal infections |
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How is Tigecycline administered?
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By IV only
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What are 3 side effects of Tigecycline?
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-Nausea
-Vomiting -Calcium binding (like the tetracyclines) |
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What is a major difference between Tetracyclines and most of the other protein synthesis inhibitors?
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Tetracyclines bind the 30S ribosomal subunit; the others bind to the 50S ribosomal subunit.
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What are 2 things included in Chloramphenicol's mechanism of action?
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1. Binds to 50S ribosome subunit and inhibits incoming tRNA's from binding
2. Inhibits peptide bond formation |
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What is the main resistance mechanism to Chloramphenicol?
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Chloramphenicol transacetylase
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What has happened to Chloramphenicol resistance? Why?
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It has increased dramatically bc it was used indiscriminately in the 1950s
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What is the sensitivity of bacteria to Chloramphenicol like today?
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Quite variable
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What is Chloramphenicol used for?
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Only very serious infections for which no other agents are suitable
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Why is Chloramphenicol's use so restricted?
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It has very serious side effects
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What are 5 types of infections for which Chloramphenicol is currently indicated when no other suitable agent is available?
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-CNS - meningitis/brain abscess
-Intra-abdominal abscesses -Bacterial ophthalmitis -Chronic granulomatous disease -Severe disseminated infections |
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What pathogens is Chloramphenicol effective against?
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-Neisseria meningitidis
-Anaerobes -Rickettsia -Salmonella typhi/others -Haemophilus influenza |
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Where does Chloramphenicol fall in agents for treating Rickettsia?
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2nd
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What is the 1st choice for Rickettsial infections?
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Tetracyclines
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Though chloramphenicol is Bacteriostatic, for what bugs can it be cidal?
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-H. flu
-N. meningitid -Strep pneu |
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What would you probably want to treat meningitis in children with before falling back on Chloramphenicol?
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3rd-generation cephalosporins
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What is the most common side effect of Chloramphenicol? What increases the risk of it developing?
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Bone marrow depression - DOSE related
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What can the BM depression caused by Chloramphenicol progress to?
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Aplastic anemia that is fatal and not dose related
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What does Chloramphenicol cause in infants?
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Grey baby syndrome
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What is the cause of grey baby syndrome in infants?
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Their lack of liver enzymes to metabolize the Chloramphenicol so that it accumulates to high levels.
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What is teh result in 50% of Gray baby syndromes?
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Rapid fatality in only a few hours
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What are 2 other adverse reactions to Chloramphenicol, though less feared in general than the BM depression and Gray baby syndrome?
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-Optic neuritis
-Blindness |
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Why can Chloramphenicol be used for treating meningitis?
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It penetrates the CSF quite well
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What are the macrolides?
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-Clarithromycin
-Erythromycin |
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How often are the macrolides used compared to Chloramphenicol?
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Much more often!
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What is the mechanism of action of the Macrolides?
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-Bind to 50S ribosome
-Block translocation along ribosomes |
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What are 5 main bugs for which Erythromycin is effective in treating?
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-Streptococci
-Staphs (except MRSA) in patients allergic to penicillin -Oddballs - Chlamydia, Mycoplasma, Legionella |
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What is a major side effect of Erythromycin according to our classmate Denise Babin?
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Enhanced GI motility - cramps and diarrhea, n/v
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What are 2 other side effects of Erythromycin in addition to increasing GI motility?
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-Inhibits CYP3A
-Increases the risk of arrythmias and cardiac arrest on 2X its own, and 5X with other drugs that inhibit Cyp3A too |
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What are 4 examples of drugs that inhibit Cyp3A4?
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CCBs: Verapimil, Diltiazem
Clarithromycin Fungals: Flu/Itraconazole Anti-HIV protease inhibitors |
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What is the newer, more expensive macrolide related to erythromycin?
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Clarithromycin
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What is the mechanism of Clarithromycin?
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Similar to erythromycin - binds 50S ribosome, blocks translocation.
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What are 3 differences in Clarithromycin compared to Erythromycin?
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-Better kinetics, less freq dose
-Less GI upset -Broader antibacterial spectrum |
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What are 5 treatment indications (bugs) for Clarithromycin, in addition to those for Erythromycin?
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-H. flu
-Moraxella -Penicillin resistnt S. pneumo -Atypical mycobacteria -H. pylori combination therapy |
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How does the efficacy against Staphs/streps compare between Clarithromycin and Erythromycin?
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Clarithromycin has better efficacy
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What 3 infection sites are well treated by Clarithromycin based on its distribution?
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-Pharyngitis
-Respiratory/sinusitis -Soft tissue infections |
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What are the 2 FDA-approved treatments for H. pylori eradication?
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1. Clarithromycin + Amoxicillin + Omeprazole (PPI)
2. Metronidazole + Tetracycline + Bismuth subsalicylate + PPI |
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What do you have to keep track of when treating H. pylori?
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Resistance trends in your area.
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What are the Ketolides?
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Drugs with similar structure to the macrolides but with significant modifications.
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What is the Ketolide to know of?
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Telithromycin
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What is Telithromycin's mechanism of action?
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Similar to the macrolides - inhibits translocation, but binds 23S rRNA, at a DISTINCTLY different site than erythromycin!
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What does the fact that Telithromycin binds the 23s rRNA at a different site to inhibit translocation have for its use?
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Telithromycin is STILL EFFECTIVE in strains that are MACROLIDE RESISTANT!
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How does Macrolide resistance usually occur?
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By plasmid-mediated methylation of the ribosome so that the drug can't bind the ribosome.
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Does ribosomal methylation affect Telithromycin's mechanism of action?
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No
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What are the main types of pathogens Telithromycin is used for treating?
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Respiratory pathogens including those resistant to macrolides.
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What are 3 specific organisms Telithromycin can be used to treat?
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-Strep pneumo (even MDR)
-Haemoph. influenzae- -Mycoplasma |
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What indication has Telithromycin been approved for?
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Community-acquired pneumonia - not less severe URI because of its potential for toxic side effects.
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What are 3 side effects to be aware of wit Telithromycin?
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-Visual disturbances
-Strong inhibition of CYP3A4 -Severe hepatotoxicity |
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What is Clindamycin?
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NOT a macrolide or ketolide
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What is Clindamycin's mechanism of action?
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Binds to 50S ribosomal subunit, blocks translocation along ribosomes.
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What is a major side effect of Clindamycin?
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Significant C. difficile antibiotic induced Enterocolitis!!
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What are 2 types of bugs for which Clindamycin is used?
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-Most gram pos cocci
-Many anaerobes including B. fragilis |
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What GPC is Clindamycin NOT for?
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MRSA - hospital acquired strains of staph
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What GPC IS Clindamycin useful against?
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Flesh-eating streptococci
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What limits the use of Clindamycin to serious infections where other agents are inappropriate?
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Its SERIOUS colitis
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Which anaerobe is Clindamycin NOT effective in treating?
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C. difficile
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What site of infection is Clindamycin not effective in treating?
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Brain abscesses - its CSF penetration is low
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What drug was invented to treat vancomycin-resistant enterococci?
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Linezolid
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What is the mechanism of Linezolid?
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Binds the 50S ribosomal subunit; interferes w/ formation of the 70S INITIATION complex. This interferes w/ translation.
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What are the 2 organisms for which Linezolid is bacteriostatic?
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Staph and Enterococcus
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What types of Staph can Linezolid treat?
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MRSA or MSSA
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What type of Enterococcus can Linezolid treat?
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Vancomycin resistant VRE!
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What other organisms can Linezolid treat?
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-Strep grps A/B
-Strep pneumo |
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What is an advantage in terms of administration of Linezolid?
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It has high bioavailability and can be given IV or ORAL
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What 2 types of infections is Linezolid used for treating?
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-Skin structure infections with VRE/Staph/Streps grp A/B
-Nosocomial pneumonia w/ Strep pneumo or Staphs |
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What is the most important side effect of Linezolid to remember?
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Non-selective inhibitor of MAO so can cause drug interactions and avoid foods with tyramine
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What are some side effects in addition to the nonselective MAOI action of Linezolid?
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-Diarrhea/N/V/Headache
-BM suppression |
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What should not be done with Linezolid?
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Don't mix it with other drugs in vitro - its very reactive.
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