Antibacterial Protein and Nucleic Acid Synthesis Inhibitors Flashcards
- Name the classes of antimicrobial drugs that act by inhibiting protein synthesis.
oxazolidinones amino glycosides tetracyclines macrolides clindamycin streptogramins chloramphemicol
- Site examples of the each of the classes of antimicrobial drugs the inhibit proteins synthesis.
oxazolidinones: linezolid
amino glycosides: gentamicin, tobramycin, amikacin
tetracyclines: doxycycline, minocyline [Glycycyclines: tigecycline]
macrolides: erythromycin, azithromycin
clindamycin
streptogramins
chloramphemicol
- Name the classes of antimicrobial drugs that act by inhibiting nucleic acid synthesis.
quinolones rifampin metroniadzole trimethoprim sulfonamides
- Cite examples of the major drugs in the quinolone and sulfonamide classes.
quinolones: ciprofloxacin, moxifloxacin
Sulfonamides-trimethoprim, silver sulfadiazine
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: aminoglycosides.
natural: (gentamicin, tobramycin) semisynthetic: amikacin
susceptibility: Enterobacteriaceae and Staphylococci, Pseudomonas aeruginosa; water soluble with good CNS penetration
can be used in combo with B-lactam, concentration dependent killing (8x10 the MIC), effects prolonged after dose
resistance: inactivating enzymes (major amikacin addresses), enhanced efflux (pseudamonas), and chromosomal mutation (TB)
adverse effects: nephrotoxicity (reversible) through binding to megalin of BM and ototoxicity (irreversible) damage to hair cells; best avoided with once daily dosing
clinical use: complicated UTI cut to gram neg bacilli, oral bowel prep, 2nd line mycobacteria and in combo for serious staph, strep and enterococci
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: tetracyclines.
doxycycline, minocyline [Glycycyclines: tigecycline]
susceptibility (broad): gram pos., gram neg, mycoplasma, chlamydia, rickettsia, spirochetes, malaria (EXCEPT enterococci or pseudomonas)
mostly bacteriostatic, bactericidal is not concentration dependent, persistent effects, good oral absorption with extensive tissue distribution
resistance primarily to enhanced drug efflux or ribosomal mutations with extensive cross resistance among tetracyclines
adverse reactions: discoloration of bones and teeth (avoid preg- 8yo); gastrointestinal intolerance, over growth of candididasis (superinfection)
clinical use: STI, tick infections, alt. CAP, Rickettsial, malaria, anthrax prophylaxis, SSTI
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: chloramphenicol.
chloramphenicol
primarily bacteriostatic
susceptibility: broad activity (poor activity against Pseudomonas and Legionella; excellent oral bioavailability and tissue distribution
resistance due to plasma-mediated production of chloramphenicol acetyl transferase (CAT)- acetylates the nitro group
adverse effects: reversible bone marrow depression, non-reversible aplastic anemia; Gray syndrome in newborns
clinical uses: (cheap) Typhoid fever in developing countries, bacterial meningitis in B lactam allergy, CNS anaerobic infections
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: macrolides.
natural: erythromycin; semisynthetic: clarithromycin, azithromycin
susceptibility: gram pos. bacteria (mostly strep, pneumo), legionella, mycoplasma, chlamydia, H. pylori, some atypical mycobacteria (weak H. flu because of efflux pump); acid labile, high concentrations in epithelial lining fluid in lung
resistance via methylation of 23s ribosome (Erm gens in Europe) and enhanced efflux pump (Mef gene in US), 50S mutation and drug inactivation by esterase
adverse effects: GI intolerance, hepatitis in pregnancy, reversible ototoxicity with IV high dose
clinical use: respiratory infections (DOC for outpatient CAP), strep in pen. allergic patients, atypical mycobacteria (MAC), H. pylori in combo, azith. can reduce biofilms used on combo to treat pseudomonas (no direct effect)
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: oxazolidinone.
linezolid (IV and oral), tedizolid (oral) binding 50S ribosome inhibits formation of 70S initiation complex
susceptibility: gram pos- staph (MRSA), strep, pneumo, enteroccoci (VRE); considered bacteriostatic because kills bacteria slowly; good oral bioavailability, intra/extracellular concentration, CSF penetration
resistance: E. Faecium, very rare in S. aureus (increasing) due to mutations of binding site
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: nitrofurantoin.
MOA: drug is reduced to derivatives to bind proteins involved in protein synthesis
susceptibility: E. coli, eneterococci and group B strep (some Eneterobacter and Klebsiella species); oral absorption, rapid enzymatic degradation (adequate concentrations in the urine)
clinical use: tx and prophylaxis of UTI (renal function 50%+
resistance due to reduced nitorfuran reductase activity
adverse effects: GI and pulmonary hypersensitivity
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: quinolones.
MOA inhibits DNA gyrase (topoisomerase II) and topoisomerase IV; bactericidal
susceptibility: cipro- excellent aerobic gram negative bacilli, and only oral against Pseudomonas; moxifloxicin increased against gram positive cocci (except MRSA), atypical reparatory pathogens and myobacteria; very good serum and tissue concentrations
resistance: mutation in DNA gyrase or topoisomerase IV, decreased permeability, enhanced efflux pumps (staph, pneumo, Psuedomonas and gram neg. bacilli)
clinical use: serious gram neg, including Pseudomonas, enteric infections (salmonella, shigella, E.coli, campylobacter; respiratory infections, mycobacterial infections, UTI, prostatitis and anthrax prophylaxis
adverse effects: cartilage damage (Mg deficiency) and achilles tendon rupture in adults, others removed for photo toxicity, hepatitis, QTc prolongation, dizziness, dysglycemias
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: rifamycin.
rifampin: inhibits DNA dependent RNA polymerase; bactericidal
susceptibility (broad): MRSA, myobacteria primary uses; lipid soluble, excellent extracellular and intracellular distribution
resistance: rapid emergence due to B-subunit, must be used in combo with other drugs
clinical uses: myobacterial, staph in combo with B lactams, vancomycin or daptomycin (eliminate intracellular or slow growing staph in osteomyelitis etc.) active in biofilms; travelers diarrhea or relapsing C. diff.
adverse effects: hepatitis (1st mo), stimulates p450 enzyme (enhance clearance), orange discoloration
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: metronidazole.
metronidaxole: convered to active metabolite by reduction of nitrogroup which bind and damage DNA
susceptibility: anaerobic - Bacteroides fragilis and C. diff. and protozoan parasites (Entameoba histolytica, Giardia lamblia and Trichomonas vaginalis); lipid soluble
clinical use: anaerobic infections below the diaphragm. C. diff. diarrhea or pseudomembranous collitis, protozoan infections
resistance in organisms that lack nitro reductase activity
adverse effects: peripheral neuritis, vomiting if taken with alcohol
3,4,5,6. Identify the major bacterial species susceptibility, major clinical use, major resistance and major adverse reactions: trimethoprim/sulfamthoxazole.
sulfonamide-trimethoprim: inhibit folic acid synthesis in two independent parts of pathway; mostly lipid soluble
susceptibility: Sulfonamides-(broad) nocardia, toxoplasma and Pneumocystis jiroveci; Trimethoprim- gram neg bacilli ( Ecoli, Klebsiella but not Pseudomonas), staphylococci, pnemococci, and Pneumocystis jiroveci
clinical use: UTI, respiratory tract, Pneumocystis, Typhoid fever or enteric infection, oral therapy, MRSA oral treatment, nocardia, toxoplasmosis, burns topical antiseptic
adverse effects: rash or hypersensitivity, crystals in urine at high concentrations (sulfa); folate deficiency (anemia, leukopenia) (trim)
- Be able to list Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, bactericides fragilis and Chlamydia species.
pseudomonas: amikacin, ciprofloxin, aminoglycocides, macrolides in combo
Staph: TMP sulfa, clindamycin, linezolid, quinolones, and rifamycin (combo), amino glycosides (combo)
E coli: nitrofurantoin, quinolones
B. fragilis: metronidazole, clindamycin
Chlymidia: clindamycin, tetracycline, macrolide
