Abx * Flashcards
Streptomycin
Aminoglycoside
- Binds 30S ribosomal subunit, blocks 3 steps (initiation, translocation, mistranslation)
- Rapidly bacteriocidal v. G-, post antibiotic effect
- 2nd-line therapeutic treatment for TB in combo with another agent (INH)
- Nephrotoxcicity (reversible), Ototoxicity (nonreversible), associated with >5 days of therapy
Tobramycin
Aminoglycoside
- Binds 30S ribosomal subunit, blocks 3 steps (initiation, translocation, mistranslation)
- Rapidly bacteriocidal v. G-, post antibiotic effect
Treatment of serious systemic G- infections, used in combination with B-lactam (synergism)
- Nephrotoxcicity (reversible), Ototoxicity (nonreversible), associated with >5 days of therapy
Gentamycin
Aminoglycoside
- Binds 30S ribosomal subunit, blocks 3 steps (initiation, translocation, mistranslation)
- Rapidly bacteriocidal v. G-, post antibiotic effect
Treatment of serious systemic G- infections, used in combination with B-lactam (synergism)
- Nephrotoxcicity (reversible), Ototoxicity (nonreversible), associated with >5 days of therapy
Amikacin
Aminoglycoside
- Binds 30S ribosomal subunit, blocks 3 steps (initiation, translocation, mistranslation).
- Rapidly bacteriocidal v. G-, post antibiotic effect
Treatment in cases of resistance to tobramycin and gentamycin caused by inactivating enzymes
- Nephrotoxcicity (reversible), Ototoxicity (nonreversible), associated with >5 days of therapy
Neomycin
Aminoglycoside
- Binds 30S ribosomal subunit, blocks 3 steps (initiation, translocation, mistranslation)
- Rapidly bacteriocidal v. G-, post antibiotic effect
Limited to topical use (skin and eyes)
- Nephrotoxcicity (reversible), Ototoxicity (nonreversible), associated with >5 days of therapy
Kanamycin
Aminoglycoside
- Binds 30S ribosomal subunit, blocks 3 steps (initiation, translocation, mistranslation)
- Rapidly bacteriocidal v. G-, post antibiotic effect
Limited to topical use (skin and eyes)
- Nephrotoxcicity (reversible), Ototoxicity (nonreversible), associated with >5 days of therapy
Tetracycline
Tetracyclines
- Bind 50S ribosomal subunit and interfere with protein synthesis by blocking ribosomal translocation
- Generally bacteriostatic v. aerobic Gram+ and some Gram-
Indications:
- Rikettsia (RMSF, typhus, Q)
- STI’s (Chlamydia, etc)
- Respiratory infections
- skin and soft tissue infections (staph, acne)
Contraindications:
GI disturbnces, Teeth and bone issues. Not for children or pregnant women
Oxytetracycline
Tetracyclines
- Bind 50S ribosomal subunit and interfere with protein synthesis by blocking ribosomal translocation
- Generally bacteriostatic v. aerobic Gram+ and some Gram-
Indications:
- Rikettsia (RMSF, typhus, Q)
- STI’s (Chlamydia, etc)
- Respiratory infections
- skin and soft tissue infections (staph, acne)
Contraindications:
GI disturbnces, Teeth and bone issues. Not for children or pregnant women
Demeclocycline
Tetracyclines
- Bind 50S ribosomal subunit and interfere with protein synthesis by blocking ribosomal translocation
- Generally bacteriostatic v. aerobic Gram+ and some Gram-
Indications:
- Rikettsia (RMSF, typhus, Q)
- STI’s (Chlamydia, etc)
- Respiratory infections
- skin and soft tissue infections (staph, acne)
Contraindications:
GI disturbnces, Teeth and bone issues. Not for children or pregnant women
Minocycline
Tetracyclines
- Bind 50S ribosomal subunit and interfere with protein synthesis by blocking ribosomal translocation
- Generally bacteriostatic v. aerobic Gram+ and some Gram-
Indications:
- Rikettsia (RMSF, typhus, Q)
- STI’s (Chlamydia, etc)
- Respiratory infections (community-acquired pneumonia)
- skin and soft tissue infections (staph, acne)
Contraindications:
GI disturbnces, Teeth and bone issues. Not for children or pregnant women
Doxycycline
Tetracyclines
- Bind 50S ribosomal subunit and interfere with protein synthesis by blocking ribosomal translocation
- Generally bacteriostatic v. aerobic Gram+ and some Gram-
Indications:
MDR Bacteria - intra-abdominal, skin, soft-tissue infections, community acquired pneumonia
Contraindications:
GI disturbnces, Teeth and bone issues. Not for children or pregnant women
Tigeclycine (glycylcycline)
Tetracyclines
- Bind 50S ribosomal subunit and interfere with protein synthesis by blocking ribosomal translocation
- Generally bacteriostatic v. aerobic Gram+ and some Gram-
Indications:
Antrhax, malaria, lyme disease
Contraindications:
GI disturbnces, Teeth and bone issues. Not for children or pregnant women
Erythromycin
Macrolide
- Bind 50s ribosomal subunit, interfere with protein synthesis by block ribosomal translocation step
- Generally bacteriostatic v. aerobic G+ and some G- bacteria
Respiratory infections, Acute otitis media, Streptococcal pharyngitis, Chlamydial infections, Diphtheria, Pertussis
Contraindications: GI disturbances and hepatotoxicity
Clarithromycin
Macrolide
- Bind 50s ribosomal subunit, interfere with protein synthesis by block ribosomal translocation step
- Generally bacteriostatic v. aerobic G+ and some G- bacteria
Respiratory infections, Acute otitis media, Streptococcal pharyngitis, Chlamydial infections, Diphtheria, Pertussis
Contraindications: GI disturbances and hepatotoxicity
Azithromycin
Macrolide
- Bind 50s ribosomal subunit, interfere with protein synthesis by block ribosomal translocation step
- Generally bacteriostatic v. aerobic G+ and some G- bacteria
Respiratory infections, Acute otitis media, Streptococcal pharyngitis, Chlamydial infections, Diphtheria, Pertussis
Contraindications: GI disturbances and hepatotoxicity
Telithromycin
Macrolide
- Bind 50s ribosomal subunit, interfere with protein synthesis by block ribosomal translocation step
- Generally bacteriostatic v. aerobic G+ and some G- bacteria
HEPATOTOXICITY –> ONLY APPROVED FOR COMMUNITY-ACQUIRED PNEUMONIA
Contraindications: GI disturbances and hepatotoxicity
Clindamycin
Lincosamide
- Binds 50S Ribosomal subunit and interferes with protein synthesis by blocking ribosomal translocation step.
- Bacteriostatic v. aerobic and anaerobic G+
Skin and soft-tissue infections
Contraindications: Diarrhea, pseudomembranous colitis caused by C. diff, skin rashes
Quinupristin/Dalfopristin
Streptogramins
- Bind 50S ribosomal subunit, interfere with protein synth by blocking ribosomal translocation and inhibiting peptide elongation
- Active v. most G+ bacteria, combination is bacteriocidal v. streptococci, most staph, bacteriostatic vs. enterococci.
Indications:
- treatment of infections caused by VRE, treatment of MSSA
Contraindications: Infusion-related effects of IV only combination, Arthralgias, myalgias
Linezolid
Oxazolidinone
- Binds 50S ribosomal subunit, interferes with protein synthesis by blocking initiation.
- active against aeorobic and anaerobic G+ bacteria.
- Bactericidal v. streptococci, bacteriostatic v. staph and enterococci
Indications: treat MDR G+ bacteria MRSA, VRE, penicillin-resistant streptococci.
Side effects: myelosuppression (leukopenia, pancytopenia, thrombocytopenia) with treatment >2 weeks
Sulfisoxazole
Anti-folate sulfonamide
- Competitive antagonist of dihydropteroate synthase
- bacteriostatic v. many G- and some G+ bacteria
UTI (in combo)
Side Effects: Allergic reactions (fever, rash, photosensitivity, GI), crystalluria, hematuria
Sulfamethoxazole (SMX)
Anti-folate sulfonamide
- Competitive antagonist of dihydropteroate synthase
- bacteriostatic v. many G- and some G+ bacteria
UTI (in combo)
Side Effects: Allergic reactions (fever, rash, photosensitivity, GI), crystalluria, hematuria
Sulfasalazine
Anti-folate sulfonamide
- Competitive antagonist of dihydropteroate synthase
- bacteriostatic v. many G- and some G+ bacteria
Ulcerative colitis and enteritis
Side Effects: Allergic reactions (fever, rash, photosensitivity, GI), crystalluria, hematuria
Trimethoprim/Sulfamethoxazole (TMP-SMX)
Anti-folate TMP-SMX Combo
- TMP is a competitive antagonist of dihydrofolate reductase.
- TMP is bacteriostatic v. many G- and some G+
- SMX Competitive antagonist of dihydropteroate synthase
- SMX bacteriostatic v. many G- and some G+ bacteria
TMP-SMX is bacteriocidal
Indications: UTI, PCP, Shigellosis, Salmonella, prostatitis, acute exacerbations of chronic bronchitis.
Contraindications: 5 days of treatment, megaloblastic anemia, leukopenia
Ciprofloxacin
Fluoroquinolones
- Inhibit TOPO II (DNA gyrase) in G- and inhibit TOPO IV in G+
- Bactericidal v. G-, G+
Indications:
- UTI
- Diarrhea from shigella, salmonella, E. coli
- soft tissue bone and joint infections
- intra-abominal infections
- *anthrax treatment and prevention
Contraindications: generally well tolerated, minor GI disturbances
Lomefloxacin
Fluoroquinolones
- Inhibit TOPO II (DNA gyrase) in G- and inhibit TOPO IV in G+
- Bactericidal v. G-, G+
Indications:
- UTI
- Diarrhea from shigella, salmonella, E. coli
- soft tissue bone and joint infections
- intra-abominal infections
Contraindications: generally well tolerated, minor GI disturbances
Levoflaxin
Fluoroquinolones
- Inhibit TOPO II (DNA gyrase) in G- and inhibit TOPO IV in G+
- Bactericidal v. G-, G+
Indications:
- UTI
- Diarrhea from shigella, salmonella, E. coli
- soft tissue bone and joint infections
- intra-abominal infections
- **Respiratory tract infections
Contraindications: generally well tolerated, minor GI disturbances
Ofloxacin
Fluoroquinolones
- Inhibit TOPO II (DNA gyrase) in G- and inhibit TOPO IV in G+
- Bactericidal v. G-, G+
Indications:
- UTI
- Diarrhea from shigella, salmonella, E. coli
- soft tissue bone and joint infections
- intra-abominal infections
Contraindications: generally well tolerated, minor GI disturbances
Gemifloxacin
Fluoroquinolones
- Inhibit TOPO II (DNA gyrase) in G- and inhibit TOPO IV in G+
- Bactericidal v. G-, G+
Indications:
- UTI
- Diarrhea from shigella, salmonella, E. coli
- soft tissue bone and joint infections
- intra-abominal infections
- ** Resipiratory tract infections
Contraindications: generally well tolerated, minor GI disturbances
Moxifloxacin
Fluoroquinolones
- Inhibit TOPO II (DNA gyrase) in G- and inhibit TOPO IV in G+
- Bactericidal v. G-, G+
Indications:
- UTI
- Diarrhea from shigella, salmonella, E. coli
- soft tissue bone and joint infections
- intra-abominal infections
- ** Resipiratory tract infections
Contraindications: generally well tolerated, minor GI disturbances
Penicillins
penicillin G, cloxacillin, amoxicillin
mimic D-ala-D-ala, blocking peptidoglycan x-link, no more petidoglycan additions to cell wall.
- acid labile, B-lactamase susceptible.
- vs. g+, g- cocci, non-B-lactamase-producing anaerobes
Clavulinic acid
beta-lactamase inhibitor, must be Rx with a beta lactam like penicillan. (sulfbactam and tazobactam are other beta-lactamase inhibitors)
cefazolin
1st generation cephalosporin
- Broad spectrum, best v. G+
- Used for surgical prophylaxis, does not penetrate CNS
cefamandole
2nd generation cephalosporin
- G+, G-
- no allergic cross-reactivity with penicillin
ceftazidime
3rd generation cephalosporin
- more G-, less G+
- some cross to CNS
- vs. inducible B-lactamase production but not constitutive B-lactimase producing strains
cefeprime
4th generation cephalosporin
- True broad spectrum drugs
- penetrate CNS
- more reisistant to chromosomal B-lactamases
- Good against pseudomonas, enterobacteriacae, staph, haemophilus, tessera, most penicillin resistant strep.
ceftaroline
latest generation cephalosporin
- approved against MRSA
- high affinity toward MRSA transpepsidase
- administered IV
- works on G+, G-
aztreonam
monobactam
- no activity toward G+ ( does not bind transpeptidase)
- vs. G- rods, resistant to B-actamases
carbapenem
imipenem
- broad spectrum against g- rods g+ and anaerobes (mixed infections)
- Inactivated by dehydropeptidases in renal tubules so use CILASTATIN to increase t1/2
polymyxins
lipopetides (membrane disruptors)
- large, used topically in neosporin
- perforates G- bacteria by binding lipoplysacc. on membrane
- resistance = lipopolysaccharide structural changes
Inhibitors of peptidoglycan precursors
fosfomycin, bacitracin, D-cycloserine
Oxacillin, cloxacillan, and dicloxacillin
Anti-staphylococcal penicillans
- acid stable, B-lactamase resistant
- vs. B-lactamase-producing staph, penicillan-susceptible strep and pneumonococci.
- NOT for enterococci, anaerobic bacteria, G- occci and rods.
amoxicillan
extended-spectrum penicillans
- acid stable
vs. G- because they penetrate outer membrane - B-lactamase susceptible.
- Use in UTIs, otitis, LRT infections
meropenam
carbapenam, resistant to modification by renal dehydropeptidase
Vancomycin
Non-beta-lactam cell wall synthesis inhibitor
- glycopeptide
- large complicated structure binds D-ala-D-ala in cell wall
- vs. G-
- VRE = D-Ala-D-Lac, reduce binding affinity of Vanco
- Vanco-resistant Staph creates thickened peptidoglycan layer
Daptomycin
lipopeptide pore former
- makes membrane pores__> K+ exists without cell rupture. Bacteria cannot grow.
- v. G+ skin and soft tissue infections involving MRSA
Peptidoglycan precursors assembly steps
- Nag converted to Nam-UDP (Fosfomycin)
- Peptide chains added to Nam-UDP (ala, glu, lys)
- More peptide chains added to Nam-UDP (D-ala, D-ala)
- 1 Lipid phosphotase dephosphorylates a lipid carrier on cell membrane (Bacitracin)
- Nam-UDP added to lipid on lipid membrane with NAG
- Flipped to outside
Fosfomycin
Cell membrane synthesis inhibitor
Inhibits first committed step in cell wall-synthesis; Nag conversion to Nam by MurA
- TB naturally resistant
Bacitracin
Cell membrane synthesis inhibitor
Inhibits lipid phosphotase that dephosphorylates the lipid carrier of Nam and Nag.
- use topically, nephrotoxic
- vs. G+, used with other Abx
D-cycloserine
Cell membrane synthesis inhibitor
- competitively inhibits alanine racemes and D-ala ligase
when d-ALA to be addd to Nam. Looks like D-alanine.
- serious toxicity (Dose related CNS: tremors, convulsions, psychosis)
- 2nd line for TB
Isoniazid (INH)
- bactericidal against extracellular and intramacrophage mycobacteria
- target mycolic acid synthesis in mycobacterial membrane
- Use with other drugs
- TB
- activated by bacterial KatG, compound with NAD
- targets FAS-II multiple enzyme system which makes long chain on mycolic acid
- hepatitis, peripheral neuropathy (looks like B6)
- metabolism depends on fast or slow acetylators (determined by genetics)
Ethambutol (EMB)
- Bacteriostatic mycobacterial drug
- Targets arabinogalactan in mycobacterial membrane
- blocks EmbA and EmbB arabinosyl transferases, weaken cell wall, make TB susceptible to damage
- works bets against fast growing extracellular Mtb
- can cause red-green color blindness, optic neuritis
Pyrazinamide (PZA)
TB/mycobacterial drug that inhibits protein synthesis by targeting ribosomal protein S1 in latent bacteria.
- a stalled ribosome presents danger to cell (incomplete polypeptide) and cell uses RpsA/tmRNA mechanism to recycle the ribosome. PZA interacts with RpsA, to block the ribosome from interacting with tmRNA. Trans-translation is blocked.
Stalled ribosome => depletion of available ribosomes, accumulation of deleterious proteins.
Rifampin (RIF)
First line TB drug
- RNA synthesis inhibitor, inhibits transcription elongation (bacterial nascent RNA gets stuck, cannot depart from gene promotors)
- bacteriacidal to G-, G+, mycobacteria, chlamydia
- complex, semi-synthetic
- induces P450 CYP3A (increased elimination of other drugs)
Rifabutin and Rifapentine
Act like Rifampin but they are more potent, longer t1/2, better membrane permeability, and less CYP3A induction
