Folic Acid Inhibitors, DNA/RNA, and Antimycobacterials Flashcards
What drug inhibits the first step of folic acid synthesis?
Sulfonamides
What do sulfa drugs compete with to inhibit folic acid synthesis?
para-amniobenzoic acid
What drug is highly protein bound?
What’s the significance of that?
Sulfa drugs
Adverse effects with drugs like warfarin and NSAIDs
When are sulfa drugs contraindicated?
IN pregnant women near term and neonates under 2mo because drugs displace bilirubin from protein binding sites, which can cause kernicterus (CNS disorder)
How do bacteria develop resistance to sulfa drugs?
- reduced uptake of drug
- develop alternate way to synthesize folic acid
- produce excessive amounts of para aminobenzoic acid
- alterations or mutations in dihydropteroate synthase (rate limiting step)
How are sulfa drugs metabolized?
Hepatically by acetylation, oxidation, or glucoronidation. If slow acetylator, then increased risk for hypersensitivity
After hepatic biotransformation of sulfa drugs, how are they excreted?
Renally
WHat is responsible for most of the adverse effects assoc with sulfa drug?
oxidation
What is trimethoprim’s MOA?
Inhibits DHF, last step of folic acid synthesis
What are the resistance mechanisms for trimethoprim?
reduced uptake, alterations or mutations in DHF, or overproduction of DHF
What drugs are part of the Fluoroquinolones?
drugs ending in -floxacin
DNA synthesis
What do Fluoroquinolones inhibit?
DNA gyrase or topoisomerase IV.
Gemifloxacin is good at inhibiting both enzymes.
What can impair absorption of Fluoroquinolones?
Food or cations like Ca, FE, Al, Mg, and Zn. Also sucralfate
Where do Fluoroquinolones distribute?
Nearly all compartments in the body, but CNS is minimal
Lipopeptides include what drug?
Daptomycin
What is Daptomycin’s MOA?
Bind bacterial mbs causing rapid depolarization of of the cell. B/c is has a unique MOA, cross resistance has not been observed
How is Daptomycin excreted
In the urine, primarily unchanged
What is Metronidazole’s MOA
selectively absorbed by anaerobic bacteria. Reduced by reacting with pyruvate/ferropdoxcin which causes production of toxic metabolites
Nitazoxanide MOA
Interferes with pyruvate/ferropdoxcin oxidoreductase
Tinidazole MOA
Cytotoxic by damaging DNA and inhibiting further DNA synthesis
When are Tinidazole and Metronidazole contraindicated?
1st trimester of preganancy
Where can Metronidazole distribute in the body?
CNS. Absorption through skin or mucus mbs is low
Rifaximin MOA
Rifampin derivative that inhibits bacterial RNA synthesis by binding to RNA polymerase
PK properties of Rifaximin
Not absorbed from GI tract, therefore most of it is excreted unchanged in the feces. Does not interfere with P450s
Why are mycobacterial infections hard to treat?
- Grow slowly
- Can lie dormant
- Cell walls are thick and impermeable
- Can reside within host cells
- Become resistant to antibiotics very quickly
Very basically, how would you treat a mycobacterial infection
For long periods of time and with severel different antibiotics so that you prevent resistant strains from emerging
Isoniazid MOA
inhibits synthesis of mycolic acids, which are essential components of mycobacterial cell walls
Isoniazid distribution
Everywhere including CNS
Isoniazid metabolism
Acetylation. If fact acetylators, then Isoniazid may not reach therapeutic levels. If slow acetylator, have greater risk for toxicity
Rifampin MOA
inhibits bacterial RNA polymerase, which prevents transcription by suppressing initiation of RNA chain formation
Does Rifampin have drug interaction concerns?
Yes. It’s a potent inducer of drug metabolism and alters plasma levels of many drugs (digitoxin, warfarin, etc)
Pyrazinamide MOA
MOA unclear. Possible that it lowers the pH in the tubercle cavity and inhibits growth of mycobacterium
Ethambutol MOA
inhibits RNA synthesis and decreases replication of tubercle bacilli
Clofazimine MOA
bind’s DNA and inhibits RNA plymerase actions. The bacteriocidal activities of this drug are very slow and pt’s are treated for a min of 2 yrs and possibly life
What are mycobacteria?
rodlike gram -pos. aerobic bacteria that can for filamentous branching structures
What drugs are possibly carcinogenic and/ or mutagenic because of their actions?
Metronidazole, nitazoxanide, and tinidazole
Retapamulin structure?
Available as a Topical ointment, it’s structurally considered to be a pleuromutilin antibiotic.
Retapamulin MOA
inhibit protein synthesis by interfering with peptidyl transferase. Binds a unique site on 50s subunit and blocks P site interactions
Mupirocin MOA
inhibits tRNA that transports ILE. No cross resistance b/c of unique MOA
-available as topical cream and ointment
Lineziod MOA
interferes with protein synthesis by binding unique site on 50s subunit, preventing formation of fnc 70s complex
What drrugs are in streptogramins?
Quinupristin and dalfopristin
Streptogramin MOA
acts at bacterial ribosome and interferes with protein synthesis. Quinupristin irreversibly blocks ribosomes and inhibits late phase of protein synthesis. Dalfopristin inhibits early phase. Used for vancomycin resistance MRSA
