Antibiotics Flashcards
Three desired properties of antibiotics
Broad Range (until + diagnosis)
Able to get to body tissues
Selectively Toxic
Give an three examples of a synergistic antibiotic interaction.
SxT will block sequential steps
Cell Wall/Membrane Inhibitors may allow drug entry
One drug may inhibit detox enzymes
Give three reasons for use of multiple antibiotic drugs
Systemic/multiple infections
Delaying resistance to long-term use
Synergisms
Three categories of patients that should be prescribed prophylactic antibiotics.
Known contact with a known agent
Before surgery with high likelihood of complications
Special Cases – ex. predisposed to endocarditis, UTI, immunocompromised
How do new biofilm preventing coatings work?
Implanted devices are coated with a cationic detergent that interacts with the quaternary amine
Over the next several days, hydrolysis occurs and releases dead cells
What is fidaxomicin active against?
Inhibits RNA polymerase
G+
What is Bedaquiline active against?
c Subunit of ATP synthase rotor
Mycobacteria
Why is amoxicillin rarely prescribed alone?
Heightened resistance to the drug
Three primary types of cell wall inhibitors?
beta-lactams
Bacitracin
Glycopeptides (Vancomycin, Telavancin)
How do beta-lactams work?
Inhibit transpeptidation and activate autolysins in the cell wall
How do bacteria resist beta lactams?
beta-lactamases, lack of PBPs, autolysin mutations
What drugs are often given with beta lactams?
Beta lactamase inhibitors (Clavulinic acid, aulbactam, tazobactam)
Which penicilins are natural? Why use them?
Pen G, Pen V
Best vs. Gram + bacteria
Which penicillins are expanded spectrum? (i.e. also good against Gram -)
Ampicillin
Piperacillin
Mezlocillin
Which Penicillins are beta-lactamase resistant? (3)
Nafcillin
Oxacillin
Cloxacillin
Which penicillins are acid resistant?
Amoxycillin
Pen V
Oxacillin
Three most common penicillin +lactamase inhibitor combos
Augmentin = amoxicillin + Clavulanic acid
Ampicillin + Sulbactam
Zosyn/Tazomed = Piperacilin + Tazobactam
Which beta lactam structure provides some natural resistance to beta-lactamase?
Monobactams
beta-lactam with one ring
Three types of beta lactams?
Penicillins
Cephalosporins
Monobactams
Perks of 3rd and 4th generation cephalosporins?
Work on Gram +/-
Can Cross BBB
Examples of 3rd and 4th gen cephalosporins?
Ceftazidime, Cephotaxime, Caphtriaxone
Cefepime
Two downsides to monobactams
Effective vs G- only
Expensive
name a monobactam
Aztreonam
Pro and con of carbapenems?
Broad spectrum Possibly toxic (leads to seizures)
Common problem with beta lactams?
Allergy (Pen>Ceph>Mono)
How does bacitracin work?
Blocks the de-phosphorylation of bactoprenol
When would you use bacitracin?
Topical
Almost only vs. G+
Side effects of bacitracin
Poor absorption
Renal Toxicity
Why is bacitracin so hard to absorb?
Its freakin huge
How do antibiotic glycopeptides (vancomycin, telavancin) work?
Bind to the end of amino acid side chain, blocking transglycosylation and transpeptidation.
What mutation provides bacteria resistance to anti-biotic glycopeptides?
Using Ala-Lactate rather than Ala-Ala
What bacterial subtype are Glycopeptides ineffective against?
G-
Why is oral vancomycin only effective in the GI tract?
Its fuckin huge. Its not getting through to the system.
What is cycloserine?
a D-ala analog that inhibits alanine racemase
Why should you exhibit caution with cycloserine?
Neurotoxic
What four types of drugs are used for Mycobacterium? (4)
Isoniazid/Ethionamine (INH)
Ethambutol (EMB)
Pyrazinamide (PZA)
RMP (Rifampicin)
How do isoniazid, ethionamines work?
Inhibit pyroxidine step in mycolic acid synthesis
How does ethambutol work?
Inhibition of arabinogalactan synthesis
How does pyrazinamide work?
Activated by mycobac enzyme, inhibits trans-translation
Concerns with using INH?
Also blocks your own Vitamin B6 synthesis
Two primary kinds of cell membrane disruptors?
Polymyxins (Colistin)
Daptomycins (Cubicin)
How do polymyxins work?
Dissolve phosphatidylethanolamine (a specialized PL in G- membranes)
When would you use Polymyxins?
As a last resort for resistant bugs
Topically
How does daptomycin work?
Dissolves in the membrane and disrupts potential
When would you use daptomycins?
G+ Cocci (MRSA)
How would you give daptomycins?
IV probably with beta-lactams
Two examples of anti-metabolites?
Sulfonamides (Sulfone) and Trimethoprim
How do anti-metabolites work?
They inhibit individual steps in the pyramidine synthesis pathway
How might bacteria become resistant to antimetabolites?
Overproduction of PABA
Four common nucleic acid inhibitors?
Fluoroquinolones (Ciprofloxacin, moxifloxacin)
Fidaxomycin (Dificid)
Rifamycin (Rifampin, Rifabutin, Rifaximin)
Metronidazole
How how fluoroquinolones work?
Inhibition of DNA gyrase
Important side effects of fluoroquinolones?
Associated with prolonged QT interval
How does fidaxomycin (Dificid) work?
Targets the switch region of RNAP
Prevents interaction of RNAP with DNA
When would you use fidaxomycin?
Its an alternative to vancomycin commonly used in cases of vancomycin resistance.
How does rifamycin (rifampin, rifabutin, rifaximin) work?
Blocks RNA polymerase elongation subunit
When would you use rifamycin?
With Isoniazid to delay mycob. resistance
Meningitis
Poxviruses
Significant side effect of rifamycin?
Can make you sweat and turns urine orange
How does metronidazole work?
Reduced complex with ferredoxin interacts with DNA and breaks DNA strands (Free Radical)
Two targets metronidazole tends to be used against?
Protazoa
Anerobic Bacteria
List five common protein synthesis inhibitors.
Aminoglycosides Tetracycline Chloramphenicol Macrolides Lincosamides
How do aminoglycosides work?
Bind to 30S Ribosome, block initiation by preventing attachment of tRNA(methinonine)
Examples of aminoglycosides?
Streptomycin, Neomycin, Gentamycin, Tobramysin, amikacin
What would you use aminoglycosides for?
G- enterics
Synergy with cephalosporin/penicillin
How does tettacycline work?
Inhibits binding of aa-tRNA to the A-site of 30S ribosome
Examples of tetracyclines?
Doxycycline, tigecycline
How do bacteria become resistant to tetracycline?
Efflux Pumps
What do you use tetracyclines for?
Rickettsia, Chlamydia, Mycoplasmas
Side effects of tetracyclines?
Toxicity, Dissiness, Tinnitus, Fluorescent teeth
Who should you never give tetracycline to?
Pregnant people
How does chloramphenicol work?
Inhibits peptidyl transferase rxn
Why is chloramphenicol use no longer recommended?
Resistance and Toxicity
Examples of macrolides?
Erythromycin, Clarithromycin, Azithromycin
How do macrolides work?
Bind to rRNA and inhibit translocation (50s)
How might bacteria resist macrolides?
Methylation of rRNA
When would you use macrolides?
G+ and some G-
Side effects of macrolides?
Assoc. with prolonged QT
Increased risk of CV death
Example of a lincosamide?
Clindamycin
How do lincosamides work?
bind to rRNA and inhibit tanslocation (50S)
When would you use lincosamides?
Anerobes, Anti-Malarial
Problems with lincosamides?
Can’t get to CNS
One use can cause major disruption of native flora
Long term use allows C diff colonization
When would you use nitrofurantoin?
UTI
When would you use Streptogramins?
VRE and VRSA
What do Mupirosins do? When would you use them?
Inhibit ile-tRNA synthase
G+
When would you use Oxazolidinones?
Treat VRE and MRSA
What do methenamines do? What do you treat with them?
Releases formaldehyde in acidified urine
UTI
What two drugs are used to wake up persister cells?
C10
BF8
