Inhibitors of bacterial protein synthesis 1 Flashcards
Aminoglycosides
Amikacin Gentamicin Neomycin Streptomycin Tobramycin
Aminoglycosides administration
IV: Amikacin IV or Topical: Gentamicin and Tobramycin IM: Streptomycin Topical or Oral: Neomycin The amino group become protonated and ionized in body fluids, that is why they are poorly absorbed from the gut and must be administered parentally. Occasionally, aminoglycosides are administered orally to treat GI infections such as neonatal necrotizing enterocolitis. They are also administered topically to treat infections of the skin, mucous membranes, and ocular tissues.
Bacterial resistance to aminoglycosides
Primarily caused by inactivation of the drugs by bacterial enzymes that combine the drug with acetate, phosphate, or adenylate Also caused by decreased binding of the drugs to the 30S ribosomal subunit or to decreased uptake of the drugs by porins in bacterial membranes
Aminoglycosides - Advers 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 Hypercholesterolemis
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
Tigecycline - Special consideration
Increased affinity to 30S subunit and decreased susceptibility to resistance Should only be used when other treatments are not suitable because of increased mortality
Routes of administration of tetracyclines
Oral or IV: Doxycyline and Minocycline Oral: Tetracycline IV: Tigecycline
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 Single-dose treatment for uncomplicated chlamydial urethritis (Azithromycin) 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
