Macrólidos y Cetólidos

Estructura Química y Farmacodinamia

Estructura química

• Macrólidos: caracterizados por un anillo macrocíclico de lactona
  • Anillo con 14‒16 átomos
  • 1 o más azúcares están unidos mediante enlaces glucosídicos
  • La eritromicina es el medicamento prototipo de la clase.
• Cetólidos (e.g., telitromicina): comparten una estructura similar a los LOS Neisseria macrólidos
  • Anillo de 14 átomos
  • 1 de los LOS Neisseria azúcares es sustituido por un grupo cetónico
  • Derivado de la eritromicina

Mecanismo de acción

General:

• Inhibe la síntesis de proteínas bacterianas al AL Amyloidosis unirse reversiblemente al AL Amyloidosis ARNr 23S de la subunidad ribosomal 50S.
  • Se une cerca del centro de la peptidiltransferasa → impide que la peptidiltransferasa añada aminoácidos a un péptido 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 crecimiento (impide la transpeptidación)
  • También inhibe la formación de la subunidad 50S
• Limita el crecimiento bacteriano → bacteriostático
• Excepción de la fidaxomicina: se une a la subunidad sigma de la ARN polimerasa, lo que impide la transcripción → bactericida contra Clostridioides difficile
• Efectos adicionales:
  • Efecto antiinflamatorio por ↓ interleucinas y factor de necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage tumoral alfa
  • La eritromicina es un agonista del receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors de la motilina 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 las células enterocromafines duodenales → tiene propiedades procinéticas

Fidaxomicina es una excepción:

• Se une a la RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure polimerasa → previene la transcripción del ARNm
• Bactericida

Farmacocinética

Indicaciones

Cobertura antimicrobiana

• Gram-positivos:
  • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
  • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus
  • Clostridioides difficile (fidaxomicin)
• Gram-negativos:
  • Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus y H. ducreyi
  • Moraxella catarrhalis Moraxella catarrhalis Gram-negative aerobic cocci of low virulence that colonize the nasopharynx and occasionally cause meningitis; bacteremia; empyema; pericarditis; and pneumonia. Moraxella
  • Campylobacter jejuni Campylobacter jejuni A species of bacteria that resemble small tightly coiled spirals. Its organisms are known to cause abortion in sheep and fever and enteritis in man and may be associated with enteric diseases of calves, lambs, and other animals. Campylobacter
  • Vibrio cholerae Vibrio cholerae The etiologic agent of cholera. Vibrio
  • Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria (actividad limitada)
  • 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 (claritromicina 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 terapia combinada)
  • Bordetella pertussis Bordetella pertussis A species of gram-negative, aerobic bacteria that is the causative agent of whooping cough. Its cells are minute coccobacilli that are surrounded by a slime sheath. Bordetella
• Atípicos:
  • Mycoplasma pneumoniae Mycoplasma pneumoniae Short filamentous organism of the genus mycoplasma, which binds firmly to the cells of the respiratory epithelium. It is one of the etiologic agents of non-viral primary atypical pneumonia in man. Mycoplasma
  • Chlamydia pneumoniae Chlamydia pneumoniae A species of chlamydophila that causes acute respiratory infection, especially atypical pneumonia, in humans, horses, and koalas. Chlamydia
  • Legionella pneumophila Legionella pneumophila A species of gram-negative, aerobic bacteria that is the causative agent of legionnaires’ disease. It has been isolated from numerous environmental sites as well as from human lung tissue, respiratory secretions, and blood. Legionella/Legionellosis
  • Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema
  • Babesia Babesia Babesiosis is an infection caused by a protozoa belonging to the genus, Babesia. The most common Babesia seen in the United States is B. microti, which is transmitted by the Ixodes tick. The protozoa thrive and replicate within host erythrocytes. Lysis of erythrocytes and the body’s immune response result in clinical symptoms. Babesia/Babesiosis microti
  • Ureaplasma
• Complejo Mycobacterium avium Mycobacterium avium A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the m. avium complex, which infects primarily humans. Mycobacterium

Tipos de infección

• Infecciones respiratorias:
  • Neumonía adquirida 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 comunidad
  • Profilaxis y tratamiento del complejo Mycobacterium avium Mycobacterium avium A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the m. avium complex, which infects primarily humans. Mycobacterium
  • Enfermedad del legionario
  • 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 ferina
  • Faringitis estreptocócica
• Infecciones de transmisión sexual:
  • Gonorrea
  • Clamidia
  • Chancroide
• Infección por H. pylori H. 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 (la claritromicina forma parte de la terapia triple)
• Diarrea asociada a C. difficile (fidaxomicina es monoterapia)
• Infecciones de piel y tejidos blandos: acné

Otras indicaciones

• Exacerbaciones de la enfermedad pulmonar obstructiva crónica y la fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans quística (efecto antiinflamatorio)
• Gastroparesia (eritromicina, efecto procinético)

Indicaciones para los LOS Neisseria cetólidos

• Actividad antimicrobiana similar a la de los LOS Neisseria macrólidos
• La telitromicina se dejó de comercializar 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 Estados Unidos (antes solo estaba indicada para la neumonía adquirida 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 comunidad).

Efectos Secundarios y Contraindicaciones

Macrólidos

• Efectos secundarios:
  • Malestar gastrointestinal (especialmente con el uso de eritromicina y fidaxomicina)
  • Mareo
  • Pérdida auditiva transitoria (relacionada con la dosis, reversible)
  • Hepatotoxicidad:
    • Pruebas de función hepática anormales
    • Hepatitis
    • Ictericia colestática
    • Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage hepática
    • Insuficiencia hepática
  • Prolongación del QT
• Contraindicaciones: antecedentes de insuficiencia hepática o ictericia colestática
• Advertencias:
  • Alteración 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 conducción cardíaca (especialmente aquellos con prolongación del QT y anomalías electrolíticas)
  • Hepatotoxicidad
  • Exacerbación de la miastenia gravis
  • Claritromicina: ↑ potencial de mortalidad 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 pacientes con enfermedad arterial coronaria
• Interacciones medicamentosas (especialmente con eritromicina y claritromicina debido a la inhibición del CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers)):
  • Warfarina: ↑ índice internacional normalizado (INR, por sus siglas 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 inglés)
  • Simvastatina, lovastatina: ↑ riesgo de mialgia y/o rabdomiólisis
  • Midazolam Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at ph less than 4 and lipid-soluble at physiological pH. Benzodiazepines: somnolencia
  • Teofilina: convulsiones
  • ↑ Concentraciones séricas de:
    • Tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants
    • Ciclosporina
    • Alcaloides del ergot
    • Colchicina

Cetólidos

• Efectos secundarios:
  • Malestar gastrointestinal
  • Alteraciones visuales
  • Hepatotoxicidad
  • Síncope
• Contraindicaciones:
  • Hipersensibilidad a los LOS Neisseria macrólidos
  • Miastenia gravis
  • Hepatitis o ictericia
• Advertencias:
  • Hepatotoxicidad
  • Exacerbación de la miastenia gravis
  • Prolongación del QT

Mecanismo de Resistencia

Existen 3 métodos de resistencia a los LOS Neisseria macrólidos:

• Metilación o mutación ribosómica:
  • Evita la unión de los LOS Neisseria macrólidos
  • Puede estar mediada por plásmidos o por cromosomas
• Producción de enzimas inactivadoras de medicamentos:
  • Esterasas
  • Cinasas
• Producción de proteínas de eflujo dependientes de ATP activas:
  • Transportan el medicamento fuera de la célula
  • Los LOS Neisseria cetólidos no se ven afectados por este mecanismo de resistencia → permite su uso 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 algunas cepas resistentes a los LOS Neisseria macrólidos

Comparación de Medicamentos