Antibacterials - Nucleic Acid Synthesis inhibitors Flashcards
Streptogramins, MOA, Spectrum, CA, PK
Quinupristin and Dalfopristin
MOA: bind to 50S bacterial ribosome
Spectrum: gram-positive cocci, and multidrug resistant bacteria
CA: treatment of infections caused by drug resistant Staphylococci or VRE
PK: Inhibition of CYP 34A
Linezolid MOA, Spectrum, CA, PK, AE
MOA: inhibits formation of 70S initiation complex (binds 23S ribosomal RNA of 50S subunit)
Spectrum: gram positive incluing MRSA and VRE
CA: treatment of multi-drug resistant infections
PK: weak reversible inhibitor of MAO (potential interaction with adrenergic and serotonergic drugs
AE: long term administration causes bone marrow suppression, optic/peripheral neuropathy, lactic acidosis, and serotonin syndrome
Fidaxomicin MOA, CA
MOA: binding to RNA polymerase to inhibit bacterial protein synthesis
CA: treatment of C. difficile colitis
Mupirocin MOA, CA
MOA: binds to bacterial isoleucyl transfer-RNA synthetase
CA: Intranasal (eradication of nasal colincation with MRSA), Topically (impetigo or secondary infected traumatic skin lesions)
What are the drugs that affect nucleic acid synthesis?
- Fluoroquinolones
- Sulfonamides
- Trimethoprim
What are the 4 generations of Fluoroquinolones and MOA?
1st: Nalidixic Acid (quinolone)
2nd: Ciprofloxacin
3rd: Levofloxacin
4th: Gemifloxacin, Moxifloxacin
MOA: interference of topoisomerase II (DNA gyrase)
Fluoroquinolones Spectrum
Nalidixic acid: moderate gram negative activity
Ciprofloxacin: synergistic with beta-lactams
Levofloxacin: excellent activity against S. pneumoniae
Moxifloxacin, Gemifloxacin: improved gram positive acitivity and anaerobic activity
Fluoroquinolones clinical applications
Nalidixic acid: uncomplicated UTI’s
Ciprofloxacin: travelers diarrhea, prophylaxis for meningitis
Levofloxacin: community acquired PNA
Moxifloxacin, Gemifloxacin: community acquired PNA
What are the respiratory Fluoroquinolones and when are they used?
Levofloxacin, Moxifloxacin, Gemifloxacin
Treatment for PNA when:
- First line agents have failed
- Presence of comorbidities
- Inpatient
What are the AE, interactions, and contraindications of Fluoroquinolones?
AE: connectice tissue problems (BBW), peripheral neuropathy, QT prolongation, superinfections
Interactions: Theophylline/NSAIDS/corticosteroids enchance toxicity; 3/4th generation raise serum warfarin/caffeine/cyclosporine
Contraindications: Pregnancy/nursing mother, children under 18
What are the sulfonamide drugs and structure?
Sulfamethoxazole, Sulfadiazine, Sulfasalazine
- structural analogs of p-aminobenzoic acid (PABA)
Sulfonamides MOA, CA, AE
MOA: compete with PABA to inhibit bacterial folic acid synthesis
CA: topical agents (ocular, burns), oral agents (UTIs), ulceratic colitis/enteritis/IBD (Sulfasalazine)
AE: crystalluria (nephrotoxicity), hypersensitivity reactions, hematopoietic disturbances, kernicterus (new borns and infants)
Trimethoprim MOA, CA, AE
MOA: inhibitor of bacterial dihydrofolate reductase
CA: UTI’s, bacterial prostatitis, bacterial vaginitis
AE: antifolate effects (contraindicated in pregnancy), skin rash, pruritus
What is Cotrimoxazole and what is its MOA, CA, and AE
Combination of trimethoprim and sulfamethoxazole
MOA: synergistic inhibition of sequential steps in tetrahydrofolic acid synthesis
CA: uncomplicated UTIs (DOC), opporunistic infections (in immunocompromised)
AE: dermatologic, GI, hematologic, AIDS pts, contraindicated in pregnancy
Metronidazole MOA, CA, AE
MOA: anaerobic conditions are vital for optimal activity
CA: pseudomembranous colitis, anaerobic or mixed intra-abdominal infection, vaginitis, brain abcesses, H. pylori eradication
AE: disulfiram like effedt, headache/dark coloration of urine/metallic taste, not advised for 1st trimester
