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107 Cards in this Set

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Sulfonamides
ANTI-METABOLITES
STRUCTURES:similar to PABA EXAMPLE: Sulfonamide
ACTION:Inhibit synthesis of folic acid; Results in lack of DNA synthesis
BACTERIOSTATIC
BROAD RANGE OF SPECIES
APPLICATION: UTI
Trimethoprim
Anti-metabolites:
Inhibit dihydrofolate reductase (competitive)
(dihydrofolate --> tetrahydrofolate)
Isoniazid
Effective against intracellular pathogen
Inhibit fatty acid elongation by InhA
Synthesis of mycolic acid interfered
Bactrim
Commonly used in combination with trimethoprim
Two main structural components of penicillin
1. Thiazolidine ring
2. beta-lactam ring (4-membered ring)
What are the three weak points of penicillin G?
1. Sensitive to acid hydrolysis
2. Sensitive to penicillinase (aka beta-lactamases)
3. Not effective vs. G-enterics
But penicillin G is still widely used for G+
True or False:
Penicillin V is sensitive to acid hydrolysis but insensitive to beta-lactamases.
False. Pencillin V is NOT sensitive to acid hydrolysis but is sensitive to beta-lactamase.
Name three penicillins that are NOT sensitive to acid hydrolysis.
Penicillin V
Ampicillin
Amoxicillin
All penicillinases we encountered in this class are penicillinase sensitive except...
Methicillin
Oxacillin
Name two penicillins that have extended spectrum
Ticarcillin
Piperacillin
Define "limited spectrum" in the penicillin world.
1. Active only vs G+ and some G-
2. Ineffective vs G-enterics
Define "broader spectrum" in the penicillin world.
1. active vs. G+
2. active vs. G-enterics
Define "extended spectrum" in the penicillin world.
1. active vs a wide variety of G-bacilli including P.aeruginosa
2. less active vs G+ cocci
MRSA
Methicillin resistant Staphylococcus aureus
Penicillin V
Similar to Penicillin G
but it is acid stable
Effective vs G+ bacteria and G-cocci
Ineffective vs G-enterics
Ampicillin
Broader spectrum:
1. Effective vs G-enterics
2. still effectiv vs. G+
Acid stable
Penicillinase sensitive
Amoxicillin
Broader spectrum:
1. Effective vs G-enterics
2. still effective vs G+
Acid stable; Penicillinase sensitive; higher serum levels
Ticarcillin
Extended spectrum:
1. effective against Pseudomonas aeruginosa
2. active vs G-bacilli
3. less effectiv vs G+cocci
Piperacillin
Extended spectrum:
1. most active penicillin against G-enteric bacilli, including Pseudomonas
Methicillin
Resistant to penicillinase
(antistaphylococcal penicillin)
Acid labile
Lower activity against G+ but still effective
Ineffective vs G-
Oxacillin
Resistant to penicillinase
Acid resistant-oral intake
Lower activity against G+ but still effective
Ineffective vs G-
Mechanism of penicillins
B-lactam antibiotics are structural analogs of peptidoglycan pentapeptide.
They bind to and inactivate penicillin-binding proteins.
Crosslinking of bacterial cell wall inhibited
Results in bacterial lysis
Mechanismof cephalosporins
lactam ring + dihydrothiazine ring instead of thiazolidine ring of the penicillins
Interfere with cell wall synthesis
True or false:
Cephalosporins have a broader spectrum action against both G+ and G-bacteria.
True
True or false:
Cephalosporins differ from penicillins in having greater acid stbility and some resistance to penicillinases.
True
True or false:
newer generations of cephalosporins have a better penetration into CSF.
True
Cefazolin
Active vs G+ cocci and some G-enteric baccili
Ineffective vs Pseudomonas
(1st generation: cephalexin, cefaclor, cephalothin)
Cefuroxime
Effective vs G-enterics
Less effective vs G+
Still ineffective vs Pseudomonas
(2nd generation: cefamandole, cefonocid, cefotetan, cefoperazone)
Ceftriaxone, ceftazidime
Improved beta-lactamase stability
Broader G- spectrum
Ceftazidime is effective vs Pseudomonas
Ceftriaxone is good for superior CNS penetration
(3rd generation)
Aztreonam
Monobactam
Mono-cyclic β lactam ring
Resistant to β-lactamases
Minimal cross-immunogenicity with other β-lactams
Effective aerobic G- (Pseudomonas); ineffective vs most G+ and anaerobic bacteria
Imipenem
Broadest antimicrobial spectrum
Resistant to most lactamases
Resistance to MRSA is variable
Susceptible to renal dipeptidase; cilastatin + imipenem = primaxin
Clavulanic acid
beta-lactamase inhibitor in combination with amoxicillin(Augmentin)
Sulbactam
beta-lactamse inhibitor in combination with ampicillin
Vancomycin
Activity restricted to Gram+ organisms
Effective in MRSA and MR Enterococcus A (MREA)
Bind to the peptidoglycan precursor structures (R-D-Ala-D-Ala)
Block peptidoglycan precursor transfer; Permeabilize protoplasts; Inhibit RNA synthesis
VRSA and VREF have been identified
Somewhat toxic
Cycloserine
Secondary TB drug
Toxic
D-Ala analog: Inhibit the conversion of L-Ala to D-Ala and formation of D-Ala-D-Ala
Inhibit the synthesis of pentapeptidase (cytoplasmic)
Bacitracin
Activity restricted to G+
Inhibit regeneration of active carrier lipid (inactivate phosphatase responsible for the regeneration)
Often used with polymyxin B and neomycin; topical therapy only
Not FDA approved; similar to vancomycin
What are possible consequences of combined antibiotic actin? Name three.
Indifference (additive)
Synergistic
Antagonistic
Give an example of potential antagonism
An agent which requires growth (e.g., penicillin) plus a bacteriostatic agent (e.g. tetracycline)
Streptomycin + Chloramphenicol
Give an example of potential synergism
1) An agent which damages the cell wall/ membrane (penicillin/ polymyxin) plus a cidal agent which is taken up poorly by the bacterium (aminoglycoside)
2) Same pathway: sulfonamide + trimethoprim
When would you combine several antibiotics for therapeutic use?
1) EXPECT SYNERGISM
2) REQUIREMENT SUGGESTED BY SUSCEPTIBILITY PATTERNS
3) TOXIC DOSAGE CAN BE DECREASED
4) LESS LIKELY TO DEVELOP BACTERIAL RESISTANCE
5) POLYMICROBIAL INFECTION
What are the disadvantages of combined antibiotic action?
1) SIDE EFFECTS
2) SELECT SUPERINFECTIONS
3) POSSIBLE ANTAGONISM
4) COST
Mechanisms of bacterial resistance (x4)
1) ANTIBIOTIC IS INACTIVATED
2) ANTIBIOTIC CANNOT ENTER; OR IS PUMPED OUT
3) TARGETS ALTERED TO RESIST ACTION
4) SUBSTITUTE PATHWAYS
Give examples of enzymatic inactivation that result in bacterial resistance
1. beta-lactamases cleave the beta-lactam ring
2. aminoglycoside modifying enzyme, generally during transport across the cytoplasmic membrane
3. Chloramphenicol acethyltranserase- acetylation of chloramphenicol
4. Erythromycin esterase- hydrolyzes lactone ring
Give examples of altered membrane permeability that result in bacterial resistance
Outer membrane porins decreased expression result in decreased tranport of beta-lactams, nalidixic acid and chloramphenicol into the cell
Give examples of antibiotic efflux that result in bacterial resistance
TETRACYCLINE OR FLUCONAZOLE EFFLUX MECHANISMS
Give examples of alteration of ribosomal targets that result in bacterial resistance
1. METHYLATE 23S rRNA (ERYTHROMYCIN)
2. ALTER S12 OF 30S SUBUNIT (STREPTOMYCIN)- common
Give examples of alteration of cell wall precursor targets that result in bacterial resistance
ALTER CELL WALL PRECURSORS VANCOMYCIN)
Inducible gene that encodes an enzyme related to D-ala-D-ala ligases. This enzyme makes D-ala-D-lactate which substitute for D-ala-D-ala in PG precursors and is not recognized by vancomycin or teichoplanin
Give examples of alteration of target enzymes that result in bacterial resistance
1. ALTER PBP’S (METHICILLIN)
2. ALTER DHFR (TRIMETHOPRIM)
3. Alter dihydropteroate synthetase (SULFONAMIDE)
Give examples of bypass pathway that result in bacterial resistance
Trimethoprim resistance
- other pathways to form DNA precursors
- plasmid encoding DHFR
Give examples of antifungal polyene compounds.
How do they work?
amphotericin B and Nystatin
Important anti-fungals
Affect membrane permeability
Describe the mechanism by which amphotericin B and Nystatin work.
Affect membrane permeability
BIND STEROLS IN CELL MEMBRANES
SELECTIVE FOR ERGOSTEROL OVER CHOLESTEROL
AMPHOTERICIN IS FUNGICIDAL
Nystatin is fungistatic at clinical doses
NYSTATIN, HOWEVER, IS ONLY FUNGISTATIC AT PHYSIOLOGICALLY ACHIVEABLE CONCENTRATIONS
AMPHO USED SYSTEMICALLY, NYSTAT TOPICAL
Fluconizole
Can be given orally
Risk of hepatotoxicity (0.01% of patients)
Mechanisms:
Inhibition of ergosterol synthesis by inhibition of cytochrome P450 14a-demethylase. This disturbs membrane and cell properties
Hyphae synthesis is inhibited and easily phagocytosed by PMN and macrophages
- Fugistatic
Ketoconazole
a type of azoles that inhibit cell membrane synthesis
Caspofungin
Echinocandins
Inhibitors of glucan synthesis and thereby prevent cell wall synthesis
By inhibiting the activity of 1,3-β-D-glucan synthase
Intravenous infusion
Flucytosine
Can be either fungicidal or static, depending on the fungal isolate
Mechanisms:
1)Inhibit fungal protein synthesis by replacing uracil with 5-flurouracil in fungal RNA
2)Inhibit thymidylate synthetase via 5-fluorodeoxy-uridine monoPi and interfere with fungal DNA synthesis
Describe the resistance mechanism of antifungal drugs
o Resistance is conferred by changes within the fungal genome itself
o NO acquired resistance
o Example: increased expression of normal cellular efflux pumps
Polymyxin B
Give mechanism, effective uses and its route of application
Bacteriocidal-does NOT require cell growth
Positively charged polypeptide antibiotics
Binds to LPS of G- OM and then cytoplasmic membrane phospholipids Effective in G- enteric rods (esp. pseudomonas)
Topical agent
Streptomycin
Inhibitor of protein synthesis
Binds specifically to one 30S protein
Bacteriocidal- not lytic
Describe the mechanism of aminoglycosides
All inhibit 30S ribosomal function
Affect translation:
Binds 30S ribosomal subunit 
Distorts the acceptor site 
Misreading  “Bad proteins”
 Leaky membrane permeability  Uptake of streptomycin 
Higher internal concentration further blocks translation
Why are the uses of streptomycin and gentamicin limited?
Streptomycin easily develops the resistant bacteria.
Gentamicin as well as streptomycin are toxic to CNVIII.
How is streptomycin and gentamicin different in terms of their antibiotic mechanism?
Streptomycin binds to one 30S ribosomal protein, whereas gentamicin binds to more than one 30S proteins.
Tetracycline
Inhibitor of protein synthesis
Bacteriostatic
Blocks binding of aminoacyl-RNA to 30S ribosomal subunit
Doxycycline
a type of tetracycline
Tigecycline
trade name Tygacil
a type of tetracycline
Is tetracycline bacterio-static or -cidal?
Bacteriostatic
Why are tetracyclines used widely?
They are well absorbed orally and hence suited to out-patient treatment
What is a drawback of tetracycline?
its broad spectrum affects the composition of flora and causes diarrhea.
Describe the mechanism of erythromycin
A type of microlide
Inhibitor of 50S ribosomal function
Block chain elongation
Erythromycin is effective against:
G+, some G- and mycoplasma and chlamydia
Azithromycin and erythromycin are related antibiotics. How is azithromycin different from erythromycin?
Azithromycin has a higher activity and a slightly broader spectrum.
It is actively uptaken by phagocytes and thus present in a higher concentration in the inflammatory site.
Mechanism of chloramphenicol
Block polypeptide chain elongation.
Is chloramphenicol a bacteriostatic or bacteiocidal agent?
Bacteriostatic most of time
Bacteriocidal in some bacterial species
True or false:
chloramphenicol is one of the tetracycline that is most widel used.
False. Due to its rare complication of lethal aplastic anemia, it is NOT widely used.
Clindamycin
1. is effective vs...
2. inhibits [ ]
3. is bacteriocidal (T or F)
1. G+ and moderate activity for anaerobes
2. peptidyl transfer
3. False, bacteriostatic like other tetracycline
Is oxazolidinone bacterio-static or -cidal?
Bacteriostatic
Oxazolidinone is highly active vs...
G+ organisms
Name the prototype drug of oxazolidinone.
Linezoid (Zyvox)
T or F:
Oxazolidinone has a potentil to treat VREF, MRSA, VRSA and other multiple-resistant bacteria.
True
True or false:
Zyvox is available for both oral and intravenous routes.
True
VREF
Vancomycin-resistant enterococcus faecalis
What is the proposed mechanism of oxazolidinone?
Inhibit tRNA translocatopm by interacting with ribosomal subunits of 30S and 50S
Streptogramins are newly developed antibiotics. Describe its mechanism.
Binds to 50S subunit
Are streptogramins bacterio-static or -cida?
Bacteriostatic
What is a clinical prototype of streptogramins?
combination of dalfopristin andquinupristin (trade name Synergin)
Is it a possibility to treat MRSA, VREF and other multiply resistant bacteria using streptogramins?
Yes
Dalfopristin
a type of streptogramins
Quinupristin
a type of streptogramins
Describe the mechanism of mupirocin.
Inhibition of translation by binding a specific tRNA synthetase (isoleucyl-tRNA synthetase)
Is mupirocin bacteriostatic or bacteriocidal?
Bacteriostatic at low concetration
Bacteriocidal at high concentration
Mupirocin is effective vs...
MRSA, espcially against nasal carrier state.
Topical treatment of impetigo caused by S. aureus or S. pyogenes
Weaker vs. flora
Quinolones should never never be used in which populations? Why?
pregnant women and children
They damage growing bone.
Give two examples of widely used quinolones.
Ciprofloxacin
Monifloxacin
Quinolones are effective vs.
G- enteric bacilli
Some G+ cocci
Pseudomonas aueruginosa
B. anthracis
Describe the mechanism f quinolone
Inhibit the enzyme DNA gyrase necessary for DNA synthesis
Are quinolones bacteriocidal or bacteriostatic?
Bacteriocidal
True or false:
Quinolone resistance does not arise commonly.
False. Resistance is rapidly emerging, especially for treating MRSA. Therefore, it is no longer recommended for MRSA.
What is unique about metronidazole?
Anaerobic drug- useful against anaerobic bacteria (Bacterioides species)
Its action requires anaerobic condition
True or false:
Metronidazole (nitromidazoles)is used for certain protozoal infections.
True
Describe the mechanism of metronidazole.
Bacterio-cidal or -static?
The activated form binds DNA and fragments it.
Bacteriocidal
Describe the mechanism of rifampin
Inhibitor of RNA synthesis
Inhibit transcription by binding to the beta subunit of bacterial RNA polymerase. This inhibits specific binding to DNA.
Rifampin:
Bacterio-cidal or -static?
Bacteriocidal
True or false:
Rifampin is often used in combination with other antibiotics since resistance develops rapidly when used alone.
True. In combination with isoniazid or pyrazinamide against TB
True or false:
Rimfapin is a useful prophylactic against infectious bacteria that enter via te nasopharyngeal route.
True. It is efficiently secreted in saliva.
Ethambutol:
Bacterio-cidal or -static?
Bacteriostatic
Pyrazinamide:
Bacterio-cidal or -static?
Bacteriocidal
True or false:
ethambutol requires the Mycobacteria amidase to become activated.
False. It's pyrazinamide that requies the Mycobacteria amidase.
What do ethambutol nd pyrazinamide have in common?
They are important TB drugs.