Pharmacology
Mechanism of action
Amikacin irreversibly binds to 16S rRNA and the RNA-binding S12 protein of the 30S subunit of prokaryotic ribosome and inhibits protein synthesis by changing the ribosomes shape so that it cannot read the mRNA codons correctly. It also interferes with the region that interacts with the wobble base of the tRNA anticodon. It works in a concentration-dependent manner, and has better action in an alkaline environment.At normal doses, amikacin-sensitive bacteria respond within 24–48 hours. Resistance
Amikacin evades attacks by all antibiotic-inactivating enzymes that are responsible for antibiotic resistance in bacteria, except for aminoacetyltransferase and nucleotidyltransferase. This is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA) moiety attached to N-1 (compare to kanamycin, which simply has a hydrogen), which blocks the access and decreases the affinity of aminoglycoside-inactivating enzymes. Amikacin ends up with only one site where these enzymes can attack, while gentamicin and tobramycin have six.Bacteria that are resistant to streptomycin and capreomycin are still susceptible to amikacin; bacteria that are resistant to kanamycin have varying susceptibility to amikacin. Resistance to amikacin also confers resistance to kanamycin and capreomycin.Resistance to amikacin and kanamycin in Mycobacterium, the causative agent of tuberculosis, is due to a mutation in the rrs gene, which codes for the 16S rRNA. Mutations such as these reduce the binding affinity of amikacin to the bacterias ribosome.
Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations.Associated autoimmune diseases (e.g., systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population. Although uncommon, insulin resistance increases cardiovascular risk. Susceptibility to bacterial infections probably results from a C3 deficiency (due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial killing. Epidemiology
Around 250 cases have been reported since the recognition of this syndrome. It is a rare syndrome with no known prevalence, although it is more common than the generalized form of acquired lipodystrophy (Lawrence syndrome). Race: No clear relationship exists between incidence and race in this syndrome; however, most reported patients have been of European descent. Age: The median age of onset of lipodystrophy has been reported to be around seven years; however, onset occurring as late as the fourth or fifth decade of life also has been reported. The median age at presentation has been about 25 years, and women have been found to present later than men (age 28 for women, age 18 for men). Sex:  Analysis of the pooled data revealed female patients were affected about four times more often than males. See also
Lipodystrophy
Laminopathy
List of cutaneous conditions

References


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