CNS Infections Review Drugs Flashcards
Ceftriaxone
(3rd generation cephalosporin)
• Cell wall inhibitor, binds to penicillin binding proteins, good CNS penetration
• N. gonorrhoeae conjunctivitis
• Empiric treatment of bacterial meningitis: Ceftriaxone + vancomycin
• Definitive, Prophylactic treatment of Neisseria meningitis
• Empiric treatment of brain abscess: Ceftriaxone + metronidazole
Penicillin
- Cell wall inhibitor, binds to penicillin binding proteins
- High levels of beta-lactam antibiotics in CNS block binding of GABA to receptors. The tissue becomes more excitable and prone to seizures.
- Gram positive only, intrapartum prophylaxis for Streptococcus agalactiae (Strep B)
Amoxicillin, Ampicillin
- Cell wall inhibitor, binds to penicillin binding proteins
- Add clavulanate to inactivate enzymatic degradation by Beta-lactamases
- Otitis media and sinusitis: Amoxicillin
- Listeria monocytogenes meningitis: Ampicillin + Gentamicin (unless pregnant)
Aztreonam
- Cell wall inhibitor, binds to penicillin binding proteins
* Empiric treatment of meningitis if beta-lactam allergy: Aztreonam + Vancomycin
Vancomycin
- Cell wall inhibitor, binds to the D-ala-D-ala shielding it from the transpeptidation reaction
- Gram positives including MRSA, Empiric treatment of meningitis with ceftriaxone
Rifampin
- inhibits DNA-dependent RNA polymerase, increases P-450 levels decreasing activity of other drugs
- Meningococcal prophylaxis for H. influenza type B, Mycobacterium tuberulcolosis
Gentamicin, Amikacin (Aminoglycosides)
- Protein synthesis inhibitor, binds 30S ribosomal subunit, ototoxicity
- Listeria monocytogenes meningitis: Gentamicin + Ampicillin
Acyclovir, Gancyclovir
guanosine analog
• Prodrugs must be phosphorylated by viral thymidine kinase leading to its selectivity
• Inhibits viral DNA polymerase and leads to chain termination
• Not effective against latent virus
• HSV-1, HSV-2(Acyclovir), CMV(Gancyclovir)
Foscarnet
- Phosphonoformate binds viral DNA and RNA polymerases
- Nephrotoxic
- CMV and gancyclovir-resistant strains
Trifluridine
- Prodrug must be phosphorylated by cellular kinases leading to its toxicity
- Inhibits viral DNA polymerase and leads to chain termination
- Topical use for HSV keratoconjunctivitis
Amphotericin B
- Disrupts the plasma membranes allowing the leakage of electrolytes,
- Liposomal form enters CNS
- Nephrotoxic
- Also used for visceral leishmaniasis
Flucytosine (5-FC)
- DNA synthesis inhibitor conversion to 5-fluorouracil
* Combined with amphotericin B to treat Cryptococcus, Candida infections
Fluconazole
- Decreases ergosterol synthesis
* Used to treat fungal otitis externa caused by Candida
Antimycobacteria
Combine the following 4 drugs for the treatment of Mycobacterium tuberculosis
• Rifampin- inhibits DNA-dependent RNA polymerase
• Isoniazid- mycolic acid inhibitor, difference in drug half-life depending on if the individual is a fast or slow acetylator
• Pyrazinamide- Unknown
• Ethambutol- cell wall inhibitor, binds arabinosyl transferase
Pentamidine
Pentamidine
• Binds DNA minor groove, mitochondrial as well as nuclear genome replication is affected
• Trypanosoma brucei