Inhibitors of Bacterial Protein Synthesis Flashcards
Aminoglycosides
Amikacin Gentamicin Neomycin Streptomycin Tobramycin
Aminoglycosides - Adverse effects
Most serious: Nephrotoxicity and Ototoxicity (vestibular and cochlear)
Vestibular toxicity manifestations: Dizziness, impaired vision, nystagmus, vertigo, nausea, vomiting, and problems with postural balance and walking
Cochlear toxicity manifestations: Tinnitus and hearing impairment and can lead to irreversible deafness
Drug-induced renal failure (acute tubular necrosis, when they accumulate in proximal tubule cells)
Glomerular toxicity
High dose: respiratory paralysis (cuarare-like effect with neuromuscular blockade). Reversible by calcium gluconate or neostigmine.
Hypersensitivity (infrequently)
Aminoglycosides tendency to cause cochlear or vestibular toxicity
Amikacin produces more cochlear toxicity (deafness),
Gentamicin and streptomycin cause more vestibular toxicity.
Tobramycin appears to cause similar degrees of cochlear and vestibular toxicity.
Most nephrotoxic aminoglycosides
Neomycin, Tobramycin and Gentamicin
Aminoglycosides - MoA
Bind 30S ribosomal subunit, interfering with initiation of protein synthesis and cause misreading of the genetic code
Breakup of polysomes into nonfunctional monosomes
Amikacin - Clinical use
Strains of Proteus, Pseudomonas, Enterobacter, and Serratia
Joint infections Intra-abdominal infections Meningitis Pneumonia Sepsis Urinary tract infections
Strains of multidrug-resistant Mycobacterium tuberculosis, including streptomycin-resistant strains
Gentamicin - Clinical use
Mainly in severe infections (eg, sepsis and pneumonia) caused by gram-negative bacteria that are likely to be resistant to other drugs
E. coli, Klebsiella, Enterobacteriae P. aeruginosa Serratia marcescens Proteus Acinetobacter
In combination with a penicillin to treat serious enterococcal, staphylococcal, or viridans group streptococcal infections such as endocarditis
Tobramycin - Clinical use
The most active aminoglycoside against many strains of Pseudomonas aeruginosa
Enterococcus faecalis
Streptomycin - Clinical use
Tuberculosis and infections caused by Yersinia pestis (plague) and Francisella tularensis (tularemia)
Sometimes brucellosis
Penicillin plus streptomycin is effective for enterococcal endocarditis and 2-week therapy of viridans streptococcal endocarditis.
Neomycin - Clinical use
Gram-positive and gram-negative and some mycobacteria
Superficial infections
Prevents Hepatic encephalopathy and Hypercholesterolemia
Paromomycin - Clincal use
has recently been shown to be effective against visceral leishmaniasis when given parenterally
Drugs that have similar properties as Neomycin
Kanamycin and Paromomycin
Tetracylines - MoA
Binds to 30 S ribosomal subunit, prevents addition of new amino acid to the nascent polypeptide chain. Bacteriostatic
Tetracyclines
Doxycycline
Minocycline
Tetracycline
Tigecycline
Tetracylines - Clinical use
Lyme disease Rocky Mountain spotted fever Relapsing fever Ehrlichiosis Granuloma inguinale Brucellosis Cholera Peptic ulcer disease Gonorrhea (doxycycline in combination with ceftriaxone) Community acquired pneumonia Leptospirosis (leptospira) Nontuberculous mycobacterial infections (Mycobacterium marinum)
Prophylaxis of protozoal infections (plasmodium falciparum)
H. pylori Chlamydia trachomatis Rickettsiae Acne vulgaris MRSA Spirochetes Mycoplasmas Protozoa Borrelia burgdorferi Borrelia recurrentis Klebsiella granulomatis Vibrio cholerae
Good penetration of skin –> Acne treatment (Minocycline)
Tetracyclines - Adverse effect
Discoloration of teeth and hypoplasia of the enamel in pregnant women and children under 8 years
Nephrotoxicity and Hepatotoxicity (increased risk in pregnant women) (Fatty degeneration)
Photosensitivity (Increased incidence in Doxycycline)
Erythema, sunburn
Dose-related nausea and vomiting (Tigecycline)
Nausea, vomiting, anorexia
Intestinal functional disturbances, anal pruritus, vaginal/oral candidiasis, Clostridium difficile associated colitis.
Renal tubular acidosis and other renal injury leads to nitrogen retention (outdated prepatarions)
IV: venous thrombosis
IM: local pain
Tetracyclines - Interactions
Binds divalent and trivalent cations, including calcium, aluminium, and iron. For this reason, their oral bioavailability is reduced if they are taken with foods containing these ions.
Tigecycline - Clinical use
Skin and soft tissue infections caused by MSSA and MRSA, E. coli,
Community-aquired pneumonia and complicated intraabdominal infections caused by various gram-positive and gram-negative organisms
Enterococcus fecalis, various streptococci, and Bacteroides fragilis
Multidrug-resistant strains of Acinetobacter,
Rickettsiae, Chlamydia sp., Legionella pneumophila, rapidly growing mycobacteria
Azithromycin, Clarithromycin - Clinical use
Respiratory infections by erythromycin sensitive bacteria, H. influenzae, M. catarrhalis,
Mycobacterium avium-intracellulare in patients with AIDS
Gonorrhea in combination with ceftriaxone
Toxoplasma gondii Chlamydia Sinusitis Otitis media Bronchitis
Azithromycin: campylobacter jejuni
Single-dose treatment for uncomplicated chlamydial urethritis (Clarithromycin)
Mycobacterium laprae (Clarithromycin) Peptic ulcer disease from H. pylori (Clarithomycin)
Azithromycin - Special considerations
Administered 1 h before or 2 h after meals
Aluminium and magnesium antacids delay absorption and reduce peak serum concentration
Macrolides: Adverse effects
Stomatitis Heart burn Uncoordinated peristalsis Nausea Anorexia Abdominal discomfort Diarrhea
Erythomycin:
Tinnitus & impaired hearing
Thrombophlebitis
QT prolongation
Estolate: acute cholestatic hepatitis (fever, jaundice, impaired liver function). Allergic reactions (eosinophilia, rashes)
Tetracyclines - Contraindications
Contraindicated for pregnant women and children <8 y
Macrolides, Ketolides and Aminosugar - MoA
Binds to 50S ribosomal subunit and prevents peptide elongation and translocation from acceptor site to peptidyl site
Macrolides
Azitromycin
Clarithromycin
Erythromycin (Base, stearate, estolate)
Erythromycin - Clinical use
Gram-positive:
Corynebacterial infections (diphteria, erythrasma)
Sepsis
Resp., Neonatal, ocular, genital chlamydial infections and Community acquired pneumonia by pneumococcus
L. pneumophila, M. pneumoniae, Chlamydia pneumoniae
Mycobacteria (ex. Mycobacterium kansasii)
Gram-negative:
Neiserria sp, Rickettsia sp, Treponema pallidum, Campylobacter
Penicillin allergic patients (staph, strep. Pneumo)
Prophylaxis against endocarditis during dental procedures in patients with valvular heart disease
campylobacter jejuni
Macrolides interactions
Erythromycin and clarithromycin inhibit cytochrome P450 3A4 and can elevate the plasma concentration of a large number of drugs metabolized by this isozyme. For example, concurrent administration of erythromycin or clarithromycin with carbamazepine can lead to life-threatening carbamazepine toxicity, and this combination should be avoided.
Erythomycin and clarithromycin also inhibit metabolism of lovastatin and simvastatin, and concurrent use of these statin drugs can lead to elevated statin levels and rhabdomyolysis.
Ketolide
Telithromycin
Telithromycin - Clinical use
Active in vitro against: Streptococcus pyogenes S pneumoniae S aureus H influenzae Moraxella catarrhalis Mycoplasma sp L pneumophila Chlamydia sp H pylori Neisseria gonorrhoeae Bacteroides fragilis Toxoplasma gondii certain nontuberculosis mycobacteria
Telithromycin - Contraindications
Contraindicated for myasthenia gravis and for driving
Telithromycin - Adverse effects
Diarrhea Nausea Elevated liver enzymes Severe liver toxicity (very rare) Prolongation of QT Resp failure in myasthenia gravis Visual disturbances Loss of conciousness
Aminosugar antibiotic
Clindamycin
Clindamycin - Clincal use
Bacteroides fragilis Clostridium perfringes (the cause of gas gangrene).
MRSA and penicillin-resistant streptococci, including necrotizing fascittis
Skin and soft-tissue infections
Prophylaxis of endocarditis in patients with valvular heart disease
Pneumocystis jiroveci pneumonia in AIDS patients with primaquine
AIDS-related toxoplasmosis with pyrimethamine
Acne vulgaris
Clindamycin - Adverse effects
Higher incidence of superinfections (clostridium) than other antibiotics
Severe diarrhea
Psuedomembranous colitis
Impaired liver function
Neutropenia
Nitrobenzene antibiotic
Chloramphenicol
Chloramphenicol - MoA
It binds reversibly to the 50S subunit of the bacterial ribosome and inhibits peptide bond formation
Chloramphenicol - Clinical use
Broad-spectrum antibiotic that is active against pathogens causing meningitis, including pneumococci, meningococci, and H. influenzae
Salmonella
Bacteroides
Brain abcess
Rickettsiae (typhus, rocky mountain spotted fever)
Neiserria meningitidis
Chloramphenicol - Special considerations
High concentrations in CNS
Lipophilic, well absorbed from gut
Partly metabolized by glucoronate conjugation (neonates obs)
Chloramphenicol - Adverse effects
Gray baby syndrome characterized by cyanosis, weakness, respiratory depression, and shock
Reversible, dose-dependent anemia caused by blockade of iron incorporation into heme
Aplastic anemia (rare)
Nausea, vomiting, diarrhea,
Oral/vaginal candidiasis
Streptogramin antibiotic
Quinupristin-Dalfopristin
Quinupristin-Dalfopristin - MoA
Binds to 50S ribosomal subunit. Inhibits tRNA synthesis + inhibits peptidyl transferase
Inhibits protein synthesis when administered in 30:70.
Quinupristin-Dalfopristin - Clinical use
Bactericidal against susceptible strains of staphylococci and streptococci but bacteriostatic against Enterococcus faecium
Active against many gram-postitive bacteria, including multidrug-resistant straphylococci, penicillin-resistant pneumococci, and vancomycin-resistant E. faecium, but not E. fecalis
Bacteremia Pneumonia Skin and soft tissue infections Peritonitis Endocarditis Aortic graft infections
Quinupristin-Dalfopristin - Adverse effects
Infusion site reactions Arthralgia Myalgia Diarrhea Nausea
Linezolid - MoA
Binds to 23S ribosomal RNA of the 50S subunit, preventing formation of 70S initiation complex
Linezolid - Clinical use
Active against aerobic gram-positive bacteria
Bactericidal against most strains of streptococci
Bacteriostatic against enterococci and staphylococci
Vancomycin-resistant E. faecium; pneumonia caused by methicillin-sensitive S. aureus and MRSA; and skin and soft tissue infections caused by methicillin-sensitive or methicillin-resistant staphylococci and Streptococcus pyogenes, or Steptococcus agalactiae
Given IV for serious infections such as necrotizing fasciits and pneumonia
Orally for mild to moderate skin and soft tissue infections
Linezolid - Adverse effects
serotonin toxicity with fluoxetine
Thrombocytopenia
Anemia
Neutropenia in patients with renal insufficiency or during prolonged therapy
Mupirocin - MoA
Competetive inhibition of isoleucine, preventing addition of isoleucine to protein
Mupirocin - Clinical use
Active against gram-positive cocci, including most strains of methicillin-resistant staphylococci
Impetigo by streptococci and staphylococci
Nasal colonization of methicillin-resistant staphylococci
