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Publication
Farmacologia dos antibióticos aminoglicosídeos
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| PPG_31032 | 2.09 MB | Adobe PDF |
Advisor(s)
Abstract(s)
Os aminoglicosídeos pertencem a uma das classes de antibióticos mais antigos. A
primeira molécula a ser obtida foi a estreptomicina, em 1944, por Waksman, e, nos anos
que se seguiram, outras moléculas similares, produzidas quer por microrganismos quer
por processos semissintéticos, foram surgindo. Atualmente, na prática clínica, destacamse
cinco antibióticos pertencentes a esta classe, designadamente a estreptomicina, a
gentamicina, a netilmicina, a tobramicina e a amicacina.
Os aminoglicosídeos são antibióticos constituídos por dois ou mais açúcares aminados
unidos a um anel aminociclitol através de ligações glicosídicas, apresentando um grande
número de radicais NH2 e OH, caracterizando-se, por isso, pela sua natureza
policatiónica. Exibem um extenso espectro de ação, apresentando grande atividade sobre
bactérias aeróbias de Gram negativo, sendo moderadamente ativos contra bactérias
aeróbias de Gram positivo, não apresentando, no entanto, atividade sobre bactérias
anaeróbias estritas.
Os antibióticos aminoglicosídeos ligam-se ao ribossoma bacteriano, inibindo
irreversivelmente a síntese proteica, e, a par do seu amplo espectro de ação antibacteriana,
têm como vantagens terapêuticas a sua atividade bactericida, o seu efeito pós-antibiótico,
uma farmacocinética relativamente previsível e o sinergismo com outros antibióticos,
nomeadamente β-lactâmicos.
Todavia, os aminoglicosídeos caracterizam-se pelo seu potencial de toxicidade. A
nefrotoxicidade é dose dependente e é geralmente reversível, enquanto a ototoxicidade se
destaca pela capacidade de causar danos ao nível vestibular e/ou coclear irreversíveis. O
estudo e a compreensão dos diversos parâmetros farmacocinéticos podem, todavia,
ampliar a probabilidade de sucesso terapêutico, bem como reduzir a ocorrência de efeitos
tóxicos associados a esta classe de antibióticos.
The aminoglycosides belong to one of the oldest classes of antibiotics. The first molecule obtained, in 1944 by Waksman, was streptomycin, and in the following years, other similar molecules, produced by microorganisms or by semi-synthetic processes, emerged. Currently, in clinical practice, five antibiotics belonging to this class stands out: streptomycin, gentamicin, netilmicin, tobramycin and amikacin. The aminoglycosides have two or more amino sugars attached to an aminocyclitol ring through glycosidic bonds, having a large number of NH2 and OH radicals, being therefore characterized by its polycationic nature. They exhibit a broad spectrum of action, showing great activity on Gram negative aerobic bacteria, being moderately active against Gram positive aerobic bacteria, but they don’t have activity on strict anaerobic bacteria. The minoglycoside antibiotics bind to the bacterial ribosome and inhibit protein synthesis, and, along with their broad spectrum of antibacterial action, they have other therapeutic advantages, such as their bactericidal activity, their post-antibiotic effect, relatively predictable pharmacokinetics and the synergism with other antibiotics, namely β-lactams. However, the aminoglycosides are characterized by their toxicity potential. The nephrotoxicity is dose dependent and it is generally reversible, while the ototoxicity is notable for its ability to cause irreversible vestibular and/or cochlear damage. The study and understanding of the various pharmacokinetic parameters may increase the likelihood of therapeutic success, as well as less occurrence of toxic effects associated with this class of antibiotics.
The aminoglycosides belong to one of the oldest classes of antibiotics. The first molecule obtained, in 1944 by Waksman, was streptomycin, and in the following years, other similar molecules, produced by microorganisms or by semi-synthetic processes, emerged. Currently, in clinical practice, five antibiotics belonging to this class stands out: streptomycin, gentamicin, netilmicin, tobramycin and amikacin. The aminoglycosides have two or more amino sugars attached to an aminocyclitol ring through glycosidic bonds, having a large number of NH2 and OH radicals, being therefore characterized by its polycationic nature. They exhibit a broad spectrum of action, showing great activity on Gram negative aerobic bacteria, being moderately active against Gram positive aerobic bacteria, but they don’t have activity on strict anaerobic bacteria. The minoglycoside antibiotics bind to the bacterial ribosome and inhibit protein synthesis, and, along with their broad spectrum of antibacterial action, they have other therapeutic advantages, such as their bactericidal activity, their post-antibiotic effect, relatively predictable pharmacokinetics and the synergism with other antibiotics, namely β-lactams. However, the aminoglycosides are characterized by their toxicity potential. The nephrotoxicity is dose dependent and it is generally reversible, while the ototoxicity is notable for its ability to cause irreversible vestibular and/or cochlear damage. The study and understanding of the various pharmacokinetic parameters may increase the likelihood of therapeutic success, as well as less occurrence of toxic effects associated with this class of antibiotics.
Description
Keywords
Aminoglicosídeos Antibióticos Bactérias de gram negativo Parâmetros farmacocinéticos Nefrotoxicidade Ototoxicidade Aminoglycosides Antibiotics Gram-negative bacteria Pharmacokinetics Nephrotoxicity Ototoxicity