Antimicrobials

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Antimicrobials
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2011-03-11 15:55:16
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Antimicrobials
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Antimicrobials
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  1. Bind PCN-binding proteins
    Block transpeptidase cross-linking of cell wall
    Activate autolytic enzymes
    • PCN
    • G+, G- cocci, spirochetes
    • Hypersensitivity, hemolytic anemia
  2. Penicillinase-resistant penicillins
    • Methcillin, nafcillin, dicloxacillin
    • Same mechanism as PCN, but penicillinase resistant
    • S. aureus (not MRSA - altered PBP)
  3. Wider spectrum penicillins
    • Ampicillin, amoxicillin
    • Penicillinase sensitive - combine with clavulanic acid to enhance spectrum
    • G+, HELPS (H flu, E coli, Listeria, Proteus, Salmonelli) and enterococci
    • Can cause pseudomembranous colitis
  4. Antipseudomonals
    • Ticarcillin, piperacillin, carbenicillin
    • Same mechanism as PCN
    • Penicillinase sensitive - use with clavulanic acid
    • Pseudomonas and GNRs
  5. Cephalosporins
    • Beta-lactams, penicillinase resistant
    • First gen (cefazolin, cephalexin): G+ cocci + PEcK (Proteus, E. coli, Klebsiella)
    • Second generation (cefoxitin, cefuroxime): G+ cocci + HEN PEcKS (H flu, Enterobacter, Neisseria + PEcK)
    • Ceftriaxone (3rd gen) for meningitis and gonorrhea
    • Disulfiram-like reaction with alcohol
    • Cross-hypersensitivity with PCN
  6. Aztreonam
    • Monobactam resistant to beta-lactamases
    • Binds PBP3
    • GNRs
    • No cross allergenicity with PCNs
  7. Imipenem/cilastatin
    • Broad-spectrum beta-lactamase resistant carbapenem
    • Given with cilastatin to decrease inactivation in renal tubules (kill is LASTIN' with ciLASTIN)
    • Drug of choice for enterobacter; G+ cocci, GNRs, anaerobes
    • Only used in life-threatening infections (causes seizures)
  8. Vancomycin
    • Inhibits cell wall formation by binding D-ala D-ala
    • Resistance when D-ala -> D-lac
    • Serious G+ MDR organisms (S. aureus, C difficile)
    • "Red man syndrome", Nephrotoxicity, Ototoxicity, Thrombophlebitis (NOT too bad)
    • Treat VRE with linezolid and streptogramins
  9. Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin
    • Aminoglycosides: GNATS
    • Inhibit formation of initiation complex (30S) -> misreading of mRNA
    • Need O2 for uptake - ineffective against anaerobes
    • Severe GNR infections
    • NOT: nephrotoxicity, ototoxicity, teratogen
    • Resistance by 30S modification modification
  10. Tetracyclines
    • Tetracycline, doxycycline
    • Bind 30S subunit, prevent attachment of aminoacyl-tRNA
    • Can't take with milk, antacids, or iron-containing preparations
    • VACUUM: Vibrio cholerae, Acne, Chlamydia, Ureaplasma, Urealyticum, M pneuomoniae + tick diseases (Tularemia, Borrelia, Rickettsia) and H pylori
    • Resistance by decreased uptake or increased transport out of vell
  11. Macrolides
    • Erythromycin, azithromycin, clarithromycin
    • Block translocation (bind 50S subunit); bacteriostatic
    • Contraindicated in pregnancy - discolored teeth and inhibited bone growth
    • Resistance by methylation of rRNA near binding side
  12. Chloramphenicol
    • Binds 50S
    • Aplastic anemia and gray baby syndrome
  13. Clindamycin
    • Blocks peptide bond formation (50S); Bacteriostatic
    • Anaerobiec infections
    • Can cause pseudomembranous colitis
  14. Sulfonamides
    • Sulfamethoxazole
    • PABA antimetabolite, inhibites dihydropteroate synthesis - blocks folate synthesis; bacteriostatic
    • G+, G-, Nocardia, Chlamydia, UTI (with TMP)
    • Hemolysis if G6PD deficient
  15. Trimethoprim
    • Inhibits bacterial dihydrofolate reductase - blocks folate synthesis; bacteriostatic
    • UTIs, Shigella, Salmonella, PCP pneumonia
    • Marrow toxicity
  16. Sulfa drugs w/o "sulfa" in the name
    Thiazides, acetazolamide, furosemide, celecoxib, probenecid
  17. Cipro and other -floxacins
    • Fluroquinolones
    • Inhibit DNA gyrase
    • Don't take with antacids
    • GNRs of urinary and GI tracts
    • Contraindicated in pregnancy, kids (damage to cartilage); tendonitis and tendon rupture in kids
    • Resistance by altered gyrase or reduced uptake
  18. Metronidazole
    • Forms toxic metabolites that damage DNA
    • Bactericidal, antiprotozoal
    • Protozoa + anaerobes
    • Used with bismuth and amoxacillin/tetracycline for H pylori "triple therapy"
    • Disulfuram-like reaction
  19. Polymyxins
    • "Mix up membranes" - act like detergents
    • Resistant G- infections
  20. Anti-TB regimin
    • SPIRE: Streptomycin, Pyrazinamide, Isoniazid, Rifampin, Ethambutol
    • or
    • RIPE: Rifampin, Isoniazid, Pyrazinamide, Ethambutol
    • Ethambutol - optic neuropathy (red-green color blindness)
    • Rest of drugs - hepatotoxicity
  21. Isoniazid
    • Decreased synthesis of mycolid acids
    • TB prophylaxis and treatment
    • Neurotoxicity and hepatotoxicity (INHInjured Neurons and Hepatocytes) - prevent neurotox with B6
  22. Rifampin
    • Inhibits DNA-dependent RNA pol
    • TB treatment, H flu prophylaxis
    • Orange body fluids, P450 inducer
  23. Amphotericin B
    • Binds ergosterol and forms membrane pores
    • Systemic mycoses; does not cross BBB (use intrathecally for fungal meningitis)
    • "Shake and bake", nephrotoxicity (can -> hypomagnesemia and hypokalemia)
  24. Nystatin
    • Binds to ergosterol, disrupting fungal membranes
    • "Swish and swallow" for oral candidiasis; topical for diaper rash or vaginal candidiasis
  25. Azoles
    • Inhibit fungal sterol synthesis
    • Fluconazole for cryptococcal meningitis (crosses BBB) and candida
    • Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida (-> hypercortisolism(
    • Clotrimazole and miconazole for topical infection
    • Gynecomastia, inhibition of P450
  26. Flucytosine
    • Inhibits DNA synthesis by conversion to 5-FU
    • Systemic fungal infections with ampho B
  27. Caspofungin
    • Inhibits cell wall synthesis by inhibiting synthesis of B-glucan
    • Invasive aspergillosis
  28. Terbinagine
    • Inhibits fungal squalene epoxidase
    • Dermatophytoses (esp onychomycosis(
  29. Griseofulvin
    • Interferes with microtubule function -. disrupts mitosis
    • Oral treatment of superficial infections
    • Teratogenic, carcinogenic
  30. Amantadine
    • Blocks viral penetration/uncoating (M2)
    • Prophylaxis and treatment of flu A (90% of strains are resistant)
    • Ataxia, dizziness, slurred speech
  31. Zanamivir, oseltamivir
    • Inhibit flu neuraminidase, decreasing release of progeny virus
    • Flu A and B
  32. Ribavirin
    • Inhibits synthesis of guanine nucleotides by inhibitin IMP dehydrogenase
    • RSV, chronic hepatitis C
    • Hemolytic anemia, teratogenic
  33. Acyclovir
    • Phosphorylated by HSV/VZV thymidine kinase, then by cellular enzymes
    • Guanosine analog
    • Inhibits viral DNA pol by chain termination
    • HSV, VZV, EBV - use famciclovir for herpes zoster
    • Resistance by lack of thymidine kinase
  34. Ganciclovir
    • Phosphorylated by CMV viral kinase, then by cellular kinases
    • Guanosine analog; inhibits viral DNA pol
    • CMV
    • BM and renal tox
    • Resistance by mutated CMV DNA pol or lack of viral kinase
  35. Foscarnet
    • Viral DNA pol inhibitor - binds to pyrophosphate-binding site of enzyme; no activation needed by viral kinase
    • Resistant CMV/HSV
    • Nephrotoxicity
    • Mutated DNA polymerase
  36. HIV protease inhibitors
    • Ritonavir and other -navirs
    • GI intolerance
  37. Nucleoside HIV reverse-transcriptase inhibitors
    • Zidovudine (ZDV/AZT), abacavir
    • BM suppression, peripheral neuropathy, lacic acidosis, megaloblastic anemia
    • Initiated w/protease inhibitor when CD4<500 and in pregnancy
  38. Non-nucleoside HIV reverse transcriptase inhibitors
    • Nevirapine, Efavirez, Delavirdine
    • BM suppression, peripheral neropathy, rash
    • Initiated w/protease inhibitors when CD4 count <500
  39. Enfuvirtide
    • HIV fusion inhibitor
    • Binds viral gp41 subunit
    • Used in HIV refractory to other Tx
  40. Interferons
    • Block viral RNA and DNA synthesis; induce ribonuclease that degrades viral mRNA
    • IFN-alpha - Hep B and C, Kaposi's sarcoma
    • IFN-beta - MS
    • IFN-gamme - NADPH oxidase deficiency

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