Term
| What is the MoA of sulfonamides? |
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Definition
Competition with PABA for synthase, inhibiting the synthesis of folic acid OR makes false metabolite
**Resistance: make more PABA or folic acid uptake from environment |
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Term
| What is the MoA of trimethoprim? |
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Definition
Inhibits the 2nd step of the PABA pathway by inhibiting reductase
**Binds away from active site - selective for bacteria |
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Term
| How does sulfa antibiotic resistance occur? |
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Definition
- Lower affinity for synthase
- PABA synthesis increases, salvage pathways |
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Term
| How does ionization affect sulfonamide metabolism? |
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Definition
| The ionized form is the active form - must be in a pKa lower than it (10.5) |
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Term
| What is the biggest AE of sulfonamides? |
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Definition
crystal urea! Comes from unionized form in the urine. Drink LOTS of water
**Get out of the kidney by reducing the pKA/more basic - sodium bicarb |
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Term
| How is sulfadiazine different from it's parent? |
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Definition
| The pKa is lower, so it is more ionized at the body's pH and in the urine. Less concentration needed for an effect. |
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Term
| What is triple sulfa used for? |
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Definition
Sulfadiazine/Sulfamerazine/Sulfamethazine
For UTI (gram -), dosed with Na-bicarb to increase ionization |
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Term
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Definition
| Silver sulfadiazene/Silvadene inhibits growth when used topically - for burns |
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Term
| What agents are sulfa antibiotics? |
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Definition
- Sulfisoxazole/Gantrisin - UTI and otitis media
- Sulfisoxazole and Phenazopyradine/ Azo-gantrisin
- Sulfisoxazole Acetyl/Pediazole - combo w/ E.E.S
- Sulfamethoxazole/Gantanol - does not cover MRSA by itself. Broad spectrum
- Sulfacetamide |
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Term
| How do sulfa allergies work? |
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Definition
| The allergy is to the sulfonamide + arylamine groups. Also a depletion in glutathione --> hapten formation |
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Term
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Definition
| Sulfamethoxazole/Trimethoprim are synergistic - very wide spectrum to include MRSA, P. aerug, and toxoplasma gondii |
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Term
| What are the AEs of sulfonamides? |
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Definition
- Crystaluria - prevention by raising pH, drinking water, lowering pKa of compound
- Hypersensitivity
- Trimethoprim - Hyperkalemia |
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Term
|
Definition
| inhibition of DNA gyrase (topo 2) and topo 4 (opens replication fork, decatenation) - Inhibition of DNA replication |
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Term
| What leads to resistance in FQNs? |
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Definition
- Gram(-) gyrase mutations lead to low or high
- gram(+) topo 4 mutations |
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Term
| What agent is the only quinolone? |
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Definition
| Nalidixic Acid/Negram - for gram(-), but P. aerug is resistant |
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Term
| What agents are 2nd gen FQNs? |
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Definition
- Norfloxacin/Noroxin - Broad gram(-) spectrum including P. aerug
- Ciprofloxacin/Cipro - Broader spectrum, including better P. aerug, Legionella, Rickettsia, B. anthracis, Klebsiella, H. influenzae, cholera, and enterococci. **Crosses CSF
- Ofloxacin/Floxin - racemic
- Levofloxacin/Levaquin - better gram(+) coverage - MSSE, mycoplasma |
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Term
| What are the major side effects of FQNs? |
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Definition
- Displacement of GABA leading to CNS excitation - due to piperazine
- Tendon rupture
- Proconvulsant
- Chelates cations
- QT prolongation |
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Term
| What are properties of 2nd gen FQNs? |
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Definition
- Good for systemic infections
- Broad spectrum, especially against gram (-) including P. aerug
- Does NOT work against anaerobes
- Weak gram(+) activity |
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Term
| What are 3rd generation FQNs? |
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Definition
S. pneumoniae coverage, better gram(+)
- Gatifloxacin/Zymar - only opth |
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Term
| What are 4th generation FQNs? |
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Definition
- Moxifloxacin/Avelox - better against bacteria that live inside cells and anaerobes like bacteroides, S. pneumoniae. Loss of gram(-) activity
- Gemifloxacin/Factive - most gram(+) and gram (-) coverage, lowest resistance |
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Term
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Definition
Methenamine and Hippuric Acid/Hiprex - for UTI, a disinfectant that creates ammonia and formaldehyde.
**Proteus are resistant |
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Term
| What are the differences in Furantin forms? |
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Definition
- Furadantin - Original, most N/V
- Macrodantin - macrocrystals
- Macrobid - mix of crystals and gel
**reduce flavoproteins, produce reactive intermediates to stop DNA and RNA. ONLY for E. coli and Enterococci |
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