Inhibitors of Nucleic Acid Synthesis
Drug
Spectrum
Mechanism
Sulfonamides – static
Broad G+/-
Inhibits Dihydropteroic acid synthesis in folic acid
synthesis pathway
Resistance
Clincial
Toxic
UTI, malaria, prophylactic
Dose related: crystalurria,
kerncterus (encephalopathy)
Dose unrelated: hypersensitivity,
Stevens-Johnson
Trimethoprim – static
Broad, G+/-
Rifampin
M. tuberculosis, some staph and Inhibits bacterial wall synth (blocks RNAPol)
chlamydiae
Inhibits dihydrofolate reductase in folic acid
synthesis pathway.
Often with sulfaxonamzole
(TMP/SMZ); UTI, RTI
Slight blood dysearasias
Anemia in patient w/ low folate
Primary TB (w/ isoniazid,
pyrazinamide, ethambutol)
Prophylactic, meningitis
Incr liver P450  clear HIV drugs
faster
Liver damage, GI, headache, dizzy
Resistance
Clincial
Toxic
Alter gyrase/topoisomerase
UTI, RTI, gonorrhea,
pseudomonas
Dose related: crystalurria,
kerncterus (encephalopathy)
Alter the DHFR protein
Attacks bacterial DHFR stronger than mammal
DNA Damaging Agents
Drug
Quinolones
eg: ciproflaxin
--Levofloxacin, ofloxacin,
norfloxacin, moxifloxacin,
gatifloxacin
Spectrum
Mechanism
Gram +/-; not some G- w/ pores Strand breaks by inhibition of DNA gyrase and/or
DNA topoisomerase IV
Better vs G+ (CAP)
Incr efflux pores
Dose unrelated: hypersensitivity,
Stevens-Johnson
Nitrofuratoin – static
Gram +/- NOT PSEUDOMON
Oxygen radical induced DNA Damage
Metronidazole
Anaerobic and parasites
Nitro reduction activates drug (metabolite) which
binds to and causes DNA damage (ROS)
Anaerobic and parasites
Mild: headache, nausea, vomit,
~disulfiram
Hydrolyzes to form formaldehyde which damages
DNA and alkylates proteins (cage like)
Good co-drug, acidify urine
Gastric distress, bladder irritation,
crystalluria
Clincial
Toxic
Good vs pseudomonal
Nephrotoxicity related to dose
VRE, MRSA
Little, REV SM enzyme changes
Chronic toxic; REV pulmonary
fibrosis
NOT aerobic/facultative
Methenamine
Lower UTI, G-
Inhibitors of Cell Membrane Function
Drug
Spectrum
Mechanism
Polymyxins (colisitin)
G- ONLY, topical bc bad GI
uptake
Acts as cationic detergent to disrupt cell membranes
(holes in membrane)
Daptomycin (newer version)
G+, VRE, MRSA
Lipopeptide binds to cell membrane, disrupts
function
Resistance
None Identified
Inhibitors of Cell Wall Synthesis
Penicillins – mostly vs G+, good when used with clavulanic acid (prevents B-lactamases by preferentially binding)
Drug
Spectrum
Mechanism
Resistance
Natural penicillin (G, V (acid
resist))
Strep and few G-
Prevents crosslinking of cell wall by titrating out
PBP
B-lactamases
Clincial
Toxic
Hypersensitive
MRSA/MRSE – make PBP with altered,
low affinity
Same
NOT E. Coli or Klebsiella
Methicillin
cloxacillin, naficillin
Staph and strep
Same
Amino-penicillin
ampicillin, amoxicillin
Strep, enterococci, some G-
Same
Same
Strep, many G-; enterobacteriae, Same
pseudomonas, S. pneumoniae,
H. influenza, n. gonorrhea,
treponema, UTI
same
NOT pseudomon
Anti-pseudomonal pen
piperacillin, ticarcillin
Cephalosporins-resistant B-lactamases, but new cephalosporinases
Drug
Spectrum
Mechanism
1st Gen: cephaxlein (Keflex)
G+, some E. coli
Same
2nd Gen: cefammdole
(Mandol)
G+, more G-
3rd / 4th gen: cefepime
(maxipime) IV!!
G+, more G-, pseudomonas
Resistance
Clincial
Toxic
Cross-hypersens w/ pen.
Proximal renal tubular necrosis
~disulfiram
Resist B-lactamases even better
Broader, more G-, incr antipseudomonas
Carbapenams (imipenem, IV)- stable towards B-lactamase, new carbapenamase
Extensive vs G-, some G+
Binds PBP1/2 of G-, especially pseudomonas!
RESERVED serious nonsocomial
Cilistatin increases effectiveness by preventing renal elimination
Monobactams (aztreconam)- G-, stable toward B-lactamase
RESTRICTED to serious nonsocomial, pseudomonal
Others- non B-lactams
Drug
Spectrum
Mechanism
Resistance
Vancomycin
G+, staph, strep, MRSA
Binds to D-ala-D-ala peptide preventing
polymerization of linear peptidoglycan
D-ala-D-ser
Bacitracin
G+ cocci, some G-
Binds to lipid carrier of peptidoglycans preventing
delivery for cell wall synthesis
Clincial
Toxic
Hearing loss ~ dose (often
underlying kidney problem)
Skin infection (Neosporin)
IV can lead to severe renal damage
Inhibitors of Protein Synthesis
Drug
Spectrum
Mechanism
Resistance
Clincial
Toxic
Tetracycline -static
(Doxycycline)
BROAD, will preferentially
conc in proky over euky cells
Acts by binding 30S ribosomal subunit
Decr ribosome binding affinity,
2nd line to resistant bacteria
Bone sequestration: yellow/brown
teeth
Incr efflux pumps
Acne, vanco alternate
tigecycline (less effectd by
resistance mech)
Eg. Ricksettiae, mycoplasma,
chlamydiae
Aminoglycosides
G-, some G+
30s, Aminoglycosides can also bind to 50S
ribosomal subunits
Chloramphenicol-static
Broad
50S ribosomal subunit
Acetylation of drug
Rickettsiae when tetracycline fails ***Aplastic anemia
Gray Baby Syn (fail to
glucorunoidate chlor)
Macrolides- static
(erythromycin)
now: Clarithromycin,
azithromycin
G+
50S ribosomal subunit
50S methylation, incr efflux
Staph when Penicillin
hypersens/2nd line if pen reistant
Mycoplasma, legionairres,
Chlamydia
Fanconi Sx (renal dysfunction)
Photosensitivity
Pseudomonal, S. aureus
Ototoxicity IRR degen auditory nerve
*Nephrotoxicity: proximal tubular
Watch PAE (trough below toxicity as cell accumulation
drug is dose-dependent)
Neuromuscular blockade: SM weak
Streptomycin
Gentimicin (endocarditis)
neomycin (burns)
Ketolides (type of macro)
telithromycin
Fairly safe, mild GI, REV hearing
loss
RTI, CAP
S. pneumoniae, S. aureus, H.
influenza
Clindamycin –static
G+ and anaerobes
50S
Pen resistant stuff, acne
S. pyogenes
Pseudomembranous colitis from C.
Dificile  tx w/ metronidazole
Synercid
(quinupristin/dalfopristin)
G+
50S, dalfo enhances action of quino
VRE, VISA (s. aurues) MRSA
Phlebitis, myalgia
Linezolid RESERVED –
static
G+
50s
VRE, MRSA
Mild myelosuppression
NOT G-/anaerobes