L30 - Drugs Flashcards
Name the 2 drugs that block folate synthesis
Sulfonamides
Trimethoprim
TMP-SMX combo
What enzyme do sulfonamides target?
Dihydro-pteroate synthetase
We don’t have this enzyme so no side-effects to humans in taking this
What enzymes does trimethoprim target?
Dihydrofolate reductase
Drug has MUCH higher affinity for the bacterial version of this enzyme - small side effects for humans
Sulfonamides are rarely used alone. What are they given with? Why?
Trimethoprim + sulfamethoxazole (TMP-SMX)
- Enhanced activity via synergy
- Broad spectrum bactericidal action
- Less resistance
TMP-SMX use
Gram - S. aureus (g+) Some protozoa & fungi Pseudo & enterococci resistant * Urinary, respiratory, GI infections*
How are folate antagonists given
Oral/IV
What are the adverse effects for folate antagonists
Rash, GI = common Severe: - SJS - Toxic epidermal necrolysis - Amenias and thrombocytopenia
What can happen with TMP-SMX during pregnancy?
Kernicterus = high bilirubin
Brain dysfxn in the baby
Trimethoprim resistance
Plasmid w/ dhfr gene
Transposon (Tn7) of integrons
Sulfonamide resistance
Plasmid that made TMP resistance/changes coding of dihydropteroate synthetase
Chromosomal mutation
What are the 3 DNA inhibitors
Quinolones
Furoquinolones
Nitrofurantoin
Quinolones mechanism
Double strand breaks to stabalizes topo-DNA complex
No DNA replication or RNA transcription
Chromosome fragmentation –> bactericidal (!)
What are quinolones used against
Gram - by inhibiting topo2
Gram + by inhibiting topo4
Atypicals & mycobacteria
How are quinolones given?
Oral
BUT poor absorption w/ divalent cations
Drug primarily targets topo2 and has good [ ] in urine. Not gets vs Step
Ciprofloxacin
Drug primarily targets topo4 and good vs Step
Levofloxacin
Quniolone that has strong g + and anaerobic activity
Moxifloxacin
What causes fluroquinolone resistance
gyrA or parC mutations
Efflux pumps
Quinolone adverse effects
Prolonged OT
Tendon rupture
What quinolone are you using to treat UTIs
Nitrofurantoin
Good against gram-/+ uropathogens
PO - poor serum but good urine [ ]
Might see nausea & pulm fibrosis
What are the 2 RNA inhibitors?
Rifamycins
Fidaxomicin
Rifamycin mechanism
Binds B subunit of RNA polymerase
X transcription
BacterioSTATIC
Rifamycin metabolism. What are the 3 forms of rifamycin?
Cp450 3A4 metabolism
Rifampin - induces this enzymes
Rifabutin
Rifaximin - not absorbed so for GI infections
Rifamycin use
In combos!
Prophylasis of N.meningitidis & S.aureus
GI as rifaximin - traveler’s diarrhea
