-
Bind PCN-binding proteins
Block transpeptidase cross-linking of cell wall
Activate autolytic enzymes
- PCN
- G+, G- cocci, spirochetes
- Hypersensitivity, hemolytic anemia
-
Penicillinase-resistant penicillins
- Methcillin, nafcillin, dicloxacillin
- Same mechanism as PCN, but penicillinase resistant
- S. aureus (not MRSA - altered PBP)
-
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
-
Antipseudomonals
- Ticarcillin, piperacillin, carbenicillin
- Same mechanism as PCN
- Penicillinase sensitive - use with clavulanic acid
- Pseudomonas and GNRs
-
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
-
Aztreonam
- Monobactam resistant to beta-lactamases
- Binds PBP3
- GNRs
- No cross allergenicity with PCNs
-
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)
-
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
-
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
-
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
-
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
-
Chloramphenicol
- Binds 50S
- Aplastic anemia and gray baby syndrome
-
Clindamycin
- Blocks peptide bond formation (50S); Bacteriostatic
- Anaerobiec infections
- Can cause pseudomembranous colitis
-
Sulfonamides
- Sulfamethoxazole
- PABA antimetabolite, inhibites dihydropteroate synthesis - blocks folate synthesis; bacteriostatic
- G+, G-, Nocardia, Chlamydia, UTI (with TMP)
- Hemolysis if G6PD deficient
-
Trimethoprim
- Inhibits bacterial dihydrofolate reductase - blocks folate synthesis; bacteriostatic
- UTIs, Shigella, Salmonella, PCP pneumonia
- Marrow toxicity
-
Sulfa drugs w/o "sulfa" in the name
Thiazides, acetazolamide, furosemide, celecoxib, probenecid
-
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
-
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
-
Polymyxins
- "Mix up membranes" - act like detergents
- Resistant G- infections
-
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
-
Isoniazid
- Decreased synthesis of mycolid acids
- TB prophylaxis and treatment
- Neurotoxicity and hepatotoxicity (INHInjured Neurons and Hepatocytes) - prevent neurotox with B6
-
Rifampin
- Inhibits DNA-dependent RNA pol
- TB treatment, H flu prophylaxis
- Orange body fluids, P450 inducer
-
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)
-
Nystatin
- Binds to ergosterol, disrupting fungal membranes
- "Swish and swallow" for oral candidiasis; topical for diaper rash or vaginal candidiasis
-
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
-
Flucytosine
- Inhibits DNA synthesis by conversion to 5-FU
- Systemic fungal infections with ampho B
-
Caspofungin
- Inhibits cell wall synthesis by inhibiting synthesis of B-glucan
- Invasive aspergillosis
-
Terbinagine
- Inhibits fungal squalene epoxidase
- Dermatophytoses (esp onychomycosis(
-
Griseofulvin
- Interferes with microtubule function -. disrupts mitosis
- Oral treatment of superficial infections
- Teratogenic, carcinogenic
-
Amantadine
- Blocks viral penetration/uncoating (M2)
- Prophylaxis and treatment of flu A (90% of strains are resistant)
- Ataxia, dizziness, slurred speech
-
Zanamivir, oseltamivir
- Inhibit flu neuraminidase, decreasing release of progeny virus
- Flu A and B
-
Ribavirin
- Inhibits synthesis of guanine nucleotides by inhibitin IMP dehydrogenase
- RSV, chronic hepatitis C
- Hemolytic anemia, teratogenic
-
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
-
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
-
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
-
HIV protease inhibitors
- Ritonavir and other -navirs
- GI intolerance
-
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
-
Non-nucleoside HIV reverse transcriptase inhibitors
- Nevirapine, Efavirez, Delavirdine
- BM suppression, peripheral neropathy, rash
- Initiated w/protease inhibitors when CD4 count <500
-
Enfuvirtide
- HIV fusion inhibitor
- Binds viral gp41 subunit
- Used in HIV refractory to other Tx
-
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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