Nitroimidazoles

Estructura Química y Farmacodinamia

Estructura química

Los LOS Neisseria nitroimidazoles Nitroimidazoles Nitroimidazoles are prodrugs composed of an imidazole ring with an attached nitro group. Nitroimidazoles are reduced within susceptible microorganisms, leading to free radical formation and disruption of DNA integrity. Nitroimidazoles están compuestos por un anillo de imidazol unido a un grupo nitro.

Mecanismo de acción

• Los LOS Neisseria nitroimidazoles Nitroimidazoles Nitroimidazoles are prodrugs composed of an imidazole ring with an attached nitro group. Nitroimidazoles are reduced within susceptible microorganisms, leading to free radical formation and disruption of DNA integrity. Nitroimidazoles se difunden de manera pasiva hacia la célula microbiana.
• Nitrorreductasas (producidas por los LOS Neisseria organismos susceptibles) → reducen el grupo nitro de la molécula y por ende, activándola
• Resultan en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la producción de:
  • Radicales libres
  • Metabolitos citotóxicos → interactúan con el ADN de la bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology → rotura de hebras y desestabilización
• Se produce la muerte celular.
• Efecto:
  • Bactericida contra bacterias anaerobias
  • Antiprotozoo

Farmacocinética

Lo siguiente describe la farmacocinética del metronidazol (medicamento prototipo de la clase) y del tinidazol.

Absorción

• Se absorbe casi completamente cuando se administra por vía oral
• Biodisponibilidad > 90%

Distribución

• Se distribuye ampliamente en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum los LOS Neisseria tejidos
• Baja unión a proteínas (< 20%)
• Atraviesa la barrera hematoencefálic

Metabolismo y excreción

• Se metaboliza ampliamente en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el hígado
• Se excreta principalmente en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la orina

Indicaciones

Cobertura antimicrobiana

• Bacterias anaerobias:
  • Helicobacter pylori Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter
  • Bacteroides Bacteroides Bacteroides is a genus of opportunistic, anaerobic, gram-negative bacilli. Bacteroides fragilis is the most common species involved in human disease and is part of the normal flora of the large intestine. Bacteroides
  • Clostridium (incluyendo C. difficile)
  • Gardnerella Gardnerella A genus of bacteria found in the human genital and urinary tract. It is considered to be a major cause of bacterial vaginosis. Nitroimidazoles
• Protozoos:
  • Giardia Giardia A genus of flagellate intestinal eukaryotes parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. Nitroimidazoles
  • Entamoeba Entamoeba A genus of ameboid protozoa characterized by the presence of beaded chromatin on the inner surface of the nuclear membrane. Its organisms are parasitic in invertebrates and vertebrates, including humans. Nitroimidazoles
  • Trichomonas Trichomonas A genus of parasitic flagellate eukaryotes distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. Nitroimidazoles

Tipos de infecciones

• Colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis pseudomembranosa
• Infecciones ginecológicas (incluida la vaginosis bacteriana)
• Amebiasis Amebiasis Amebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis
• Uretritis no gonocócica
• Infecciones intraabdominales
• Abscesos intracraneales

Efectos Secundarios y Contraindicaciones

Efectos secundarios

• Malestar gastrointestinal
• Reacción tipo disulfiram con el alcohol (debido a la inhibición del aldehído deshidrogenasa)
• Disgeusia (sabor metálico)
• Neuropatía periférica
• Cefalea
• Mareo
• Convulsiones
• Decoloración de la orina (color rojo-marrón)

Contraindicaciones

• Embarazo (1er trimestre)
• Lactancia materna
• Deterioro hepático severo

Interacciones medicamentosas

• Preparaciones que contengan etanol:
  • Jarabes para la tos TOS Thoracic outlet syndrome (TOS) is a broad term used for a spectrum of syndromes related to the general region of the thoracic outlet, which involves the compression or irritation of elements of the brachial plexus, subclavian artery, or subclavian vein. Thoracic Outlet Syndrome
  • Trimetroprim-sulfametoxazol intravenoso
• Disulfiram: puede causar psicosis aguda
• ↓ Eliminación de:
  • Litio
  • Ergotamina
• ↓ Metabolismo hepático de:
  • Fenitoína
  • Warfarina
  • Carbamazepina

Mecanismo de Resistencia

La resistencia al AL Amyloidosis metronidazol es rara, pero puede ocurrir por:

• ↓ Tasa de reducción del metronidazol en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el interior de los LOS Neisseria anaerobios
• ↓ La captación del medicamento
• ↑ Eflujo del medicamento de la célula
• ↑ Actividad de la lactato deshidrogenasa
• ↑ Actividad de las enzimas de reparación del ADN
• ↑ Capacidad de eliminación del oxígeno

Comparación de Antibióticos

La siguiente tabla compara varias clases de antibióticos con cobertura anaeróbica: