Protein synthesis inhibitors

Tetracyclines
 Binds 30s and prevents T-RNA binding (Reversible)
 Can cover atypical (doesn’t need cell wall)
 Efflux pump are resistance mechanism (Mg++ mediated by TetA)
 Enzymatic modifications are resistance mechanisms
 Good absorption, except with milk and 2 and 3 valency metals
 Binds Ca++ containing tissues – Bone, Teeth
 Minocycline Enters CSF
 Meningococcal carrier state eradication
 Doxycycline administered parenterally
 Doxycycline excreted in bile
 RMSF, Lyme, Chlamydia, Yersinia, Tick-born, h. pylori, mycoplasma
 Covers MRSA, Acne, Legionella
 Side effects:
o Damages gastric/ esophageal mucosa
o Take with food
o Hepatotoxicity with high dose
o Photoxicity (Classic)
o Vertigo, pseudotumor cerebri (IC hypertension)
o Headache, N/V
o Fanconi syndrome – Expired tetracyclines
 Type II RTA, can’t secrete H+/Reabsorb HCO3-
 Anion gap doesn’t change (diarrhea also causes)
o Deposits in Bone and teeth
o Superinfections, Vaginal Candida and Clostridium Difficile
o Contraindicated in pregnancy and childhood
 o Inhibits bone growth and enamel formation
 Discoloration of teeth

Tigecycline
 MRSA, VRSA, VRE, ESBL producing GNRS
 Doesn’t cover Pseudomonas well
 Excreted in bile
 Hepatotoxic

Aminoglycosides
 Large, very polar compounds

 Need channels to cross membranes/cell wall

 O2 – dependent (ineffective against anaerobes)

 30S subunit and cause code misreading (Bactericidal)

 PAE – Continues killing After Levels less than MIC (minimal inhibitory capacity)

 GNRs - Pseudomonas, E. coli, Enterobacter, klebsiella, Serratia, Enterococcus (beta-

lactams)

 Ampicillin + gentamycin = Strep agalactia, enterococcus

 Gentamicin, Streptomycin, tobramycin, amikacin, neomycin

 IV or IM

 Efflux pumps raise resistance

 Neomycin used for skin infections (topical), toxic when systemic

o Oral prophylaxis before surgery

 Excreted renally except of Neomycin

 Adverse effects:
o Nephrotoxicity

o Ototoxicity

o Sensorineural hearing loss, vertigo

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 o Lowers NMT activity

o Flaccid paralysis, dose dependent

o Higher with combination with NMJ blockers

o CI with myasthenia gravis and LEMS and Mg2+

o teratogenic

Fidaxomicin
 Blocks Sigma Subunit of RNA polymerase (bacterial)

 Narrow spectrum (Gram-positives)

 Mostly used with gram positive anaerobes (C. difficile or vancomycin)

 Low systemic absorption

 N/V, GI discomfort, Thrombocytopenia

Macrolides
 Binds 50S
 Inhibits translocation
 Erythromycin, Azithromycin, Clarithromycin
 Similar coverage to penicillin + intracellular
 h. pylori
 Intracellular/atypical
 Pharmacokinetics: well, absorbed orally
 Inhibitors of P450
 Azithromycin – bile
 Clarithromycin - renal
 Side effects:
o GI upset -abdominal cramps, diarrhea
o Gastroparesis and Post-op ileus
o Cholestasis – jaundice, liver failure
o Reversible ototoxicity
o QTc prolongation – increased risk of TDP
 Resistance:

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 o Uptake decreased
o Efflux pump
o Enzymatic modification

Chloramphenicol
o Binds 50S
o Inhibits Peptidyl transferase
o Not as selective for prokaryotic ribosomes
o Active against intracellular, N. meningitidis
o Enzyme modifications
o Liver metabolism, renal excretion
o Crosses placenta and is in breast milk
o Adverse effects:
o Bone marrow suppression
o G6PD deficiency – hemolysis
o Grey baby syndrome (because trans glucuronidation is
impaired) increased mitochondrial toxicity -> grey baby
o Cytochrome inhibitor

Clindamycin
o similar to macrolides
o activity in GP (MRSA) coverage, anaerobes
o C. diff is resistant
o High risk of C. diff colitis
o Anaerobic abscess, skin infections, Acne, Bacterial vaginosis
o Adverse effects:
o Rash
o Diarrhea
o Pseudomembranous colitis

Quinepristin-Dalfopristin
o 50S subunit
o Treats VRE. Faecium/ not Faecalis
o Resistance enzymatic modifications
o Bile metabolism
o CYP inhibitor

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 o Irritates peripheral veins
o Arthralgia myalgia
o Bilirubinemia

Linezolid
o Inhibits assembly of initiation complex
o Gram positive coverage
o MRSA, VRE
o Gi upset
o Thrombocytopenia > 10 days
o MAO inhibitor – serotonin syndrome with SSRI, SNRI,
tramadol
o Hypertensive Crisis – Tyramine
o Irreversible peripheral and optic neuropathy >28 days