El documento describe la historia y clasificación de los agentes quimioterapéuticos, incluyendo los primeros antimicrobianos como la penicilina descubierta por Alexander Fleming, y cómo funcionan diferentes tipos como bacteriostáticos, bactericidas y bacteriolíticos. También cubre mecanismos de acción, estructuras representativas y la resistencia a los antibióticos.
5. Salvarsan (arsénico), Ehrlich, 1900. Prontosil (sulfonamida), Gerard Domag, 1930. Se establece el primer mecanismo de acción, Woods, 1935. Penicilina, Alexander Fleming, 1939. Florey, 1941. Optimización del cultivo y producción
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7. antimicrobianos Son elementos químicos naturales o sintéticos que pueden reducir o eliminar (matar) el desarrollo de los microorganismos. Tiempo número de células Viables Totales Tiempo número de células Viables Totales Tiempo número de células Viables Totales
8. antimicrobianos Bacteriostático Tiempo número de células Tiempo número de células Tiempo número de células Viables Totales Viables Totales Viables Totales
14. La lisis celular puede ser observada por un cambio en la turbidez del medio de cultivo. Tiempo (hrs) 0 1 2 3 4 No expuesto a ampicilina Expuesto a ampicilina
15. CUANTIFICACIÓN DE LA ACTIVIDAD ANTIMICROBIANA Concentración Mínima Inhibitoria (CIM) Método de difusión en agar con discos de celulosa Concentración del químico Incubación 0 50 75 100 0 50 75 100
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19. Agentes Quimioterapéuticos Agentes químicos sintéticos o naturales destinados a usarse internamente en el cuerpo humano para el control de microorganismos causantes de infecciones.
20. antimicrobianos Son elementos químicos naturales o sintéticos que pueden reducir o eliminar (matar) el desarrollo de los microorganismos. Independiente de donde se utilicen. Tiempo número de células Viables Totales Tiempo número de células Viables Totales Tiempo número de células Viables Totales
21. Agentes Quimioterapéuticos Agentes químicos sintéticos o naturales destinados a usarse internamente en el cuerpo humano para el control de microorganismos causantes de infecciones.
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23. Agentes Quimioterapéuticos Se clasifican según ESTRUCTURA MECANISMO DE ACCIÓN Sintéticos Naturales (Antibióticos) ORÍGEN Carbohidratos Lactosas macrocíclicas Quinonas Aminoácidos Heterocíclicos N, O Aliciclos Aromáticos Alifáticos Quinolonas Oxazolidinona Síntesis de pared celular Análogos de factores de crecimiento Estructura de la MB plasmática Síntesis de DNA Transcripción Traducción
27. Síntesis de pared celular Cicloserina Vancomicina Bacitarcina Penicilina Cefalosporina Monobactamas Carbapenemas Metabolismo del ácido fólico Trimetropina Sulfonamidas PABA MEMBRANA Estructuras de la membrana Polimixina PARED Elongación de mRNA Actinomicina DNA girasa Trasncripción Rifampicina Estreptovaricinas Síntesis protéica 50S Eritromicina Cloranfenicol Clindamicina Lincomicina Síntesis protéica 30S Tetraciclina Espectinomicina Gentamicina Kanamicina Nitrofuranos Síntesis protéica tRNA Mupirocina Puromicina Ac. Nalidixico Ciprofloxaxin Novobiocin Quinolonas
28. Macrólidos e interferencia con la síntesis protéica. Bloqueo de la peptidil transferasa Eritromicina Azitromicina Inhibición del traspaso del peptidil tRNA al sitio P
31. Orígen Sintéticos Naturales Análogos de factores de crecimiento Sulfamidas, Isoniazina, Mycobacterium tuberculosis Quinolonas Interacción con DNA girasa. Ácido nalidixico. Norfloxacino, ciprofloxacino. Antibióticos -lactámicos Penicilinas y Cefalosporina De origen procariota Aminoglicósidos Macrólidos Tetraciclinas
36. Resistencia a los antibióticos Capacidad presente en una población bacteriana que es seleccionada por la presencia del antibiótico Está presente habitualmente en genes que son transmitidos horizontalmente a otros microorganismos.
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41. Diseminación de la resistencia Uso inadecuado excesivo en la práctica clínica Uso inadecuado de dosis y duración de tratamientos Falta de seguimiento terapéutico
68. Amoxicilina Claritromicina Ceftriaxona Clasificación Penicilinas (β- lactam) Macrólido Cefalosporina (β- lactam) Mecanismo de acción Inh. Síntesis pared celular: Unión a transpeptidasas (PBPs). Inh. Síntesis proteíca: Unión a subunidad 50S Inh. Síntesis pared celular: Unión a PBPs. Dosis adulto 500 mg/12h 1g/24 h 250-500 mg/12h 1-2 g/24h Presentación Comprimidos Jarabe Comprimidos Sol. EV Solución EV Vías de adm. Oral Oral y EV EV Nombre comercial Abiolex, Amobiotic, Amoval Clarimax, Infex, Euromicina Acantex
69. Trimetoprim+Sulfametoxazol Ciprofloxacino Clasificación Dihidropirimidina/Sulfonamida Quinolona Mecanismo de acción Inh. De la síntesis de ácido fólico. Inh dihidro folato reductasa/ Análogo de PABA Inh. DNA girasa Dosis adulto 800/160 mg cada 12 h 125-250 mg/12h Presentación Comprimidos, PSO Comprimidos, Solución Oftálmica Vías de administración Oral Oral, Ocular Nombre Comercial Cotrimoxazol,Bacterol, Septrin Baycip, Ciproval, Ciprodex (ocular)
Editor's Notes
Figure: 20-14-01UN Caption: Salvarsan
Figure: 20-10 Caption: Antibiotic assay by tube dilution, permitting detection of the minimum inhibitory concentration (MIC). A series of increasing concentrations of antibiotic is prepared in the culture medium. Each tube is inoculated, and incubation is allowed to proceed. Growth (turbidity) occurs in those tubes with antibiotic concentrations below the MIC.
Figure: 20-11 Caption: Agar diffusion method for assaying antibiotic activity.
Figure: 20-14 Caption: Annual worldwide production and use of antibiotics. Each year more than 500 metric tons of chemotherapeutic agents are manufactured.
Figure: 20-12a Caption: Classification of antibacterial chemotherapeutic agents according to chemical structure. A representative example is shown for each group.
Figure: 20-12b Caption: Classification of antibacterial chemotherapeutic agents according to chemical structure. A representative example is shown for each group.
Figure: 20-12c Caption: Classification of antibacterial chemotherapeutic agents according to chemical structure. A representative example is shown for each group.
Figure: 20-15 Caption: Antimicrobial spectrum of action for selected chemotherapeutic agents.
Figure: 20-16 Caption: (a) The simplest sulfa drug, sulfanilamide. (b) Sulfanilamide is an analog of p-aminobenzoic acid, which itself is part of (c) the growth factor folic acid (Section 5.1 discusses growth factors).
Figure: 20-17 Caption: Growth factors and structurally similar analogs.
Figure: 20-18 Caption: The structure of ciprofloxacin, a quinolone. Fluorinated derivatives of nalidixic acid (Figure 20.12) are more soluble than nalidixic acid and reach clinically therapeutic levels in blood and tissues. Ciprofloxacin is used to treat urinary tract infections and anthrax caused by penicillin-resistant Bacillus anthracis.
Figure: 20-25 Caption: The emergence of antimicrobial drug-resistant bacteria. (a) Relationship between antibiotic use and the percentage of bacteria isolated from diarrheal patients resistant to the antibiotic. Those agents that have been used in the largest amounts, as indicated by the amount produced commercially, are those for which drug-resistant strains are most frequent. (b) Percentage of reported cases of gonorrhea caused by drug-resistant strains. The actual number of reported drug-resistant cases in 1985 was 9000. This number rose to 59,000 in 1990. Greater than 95% of the reported drug-resistant cases are due to penicillinase-producing strains of Neisseria gonorrhoeae . Since 1990, penicillin has not been recommended for treatment of gonorrhea because of emerging drug resistance. (Source: Centers for Disease Control, Atlanta, GA).
Figure: 20-26 Caption: The appearance of antimicrobial drug resistance in some human pathogens. The *symbol indicates that some multi-drug resistant strains of these organisms are now untreatable with known antimicrobial drugs.
Figure: 20-27ab Caption: Computer-generated antiviral drugs. (a) The HIV protease homodimer. Individual polypeptide chains are shown in green and blue. A peptide (yellow) is bound by the catalytic site. This protease cleaves an HIV precursor protein, a necessary step in virus maturation (Section 16.14). Blocking of the protease site by the peptide shown inhibits precursor processing and HIV maturation. This structure is derived from information in the Protein Data Bank. (b) These anti-HIV drugs are peptide analogs that were designed by computer to block the active site of HIV protease. The areas highlighted in orange show the regions analogous to peptide bonds. Binding of these compounds by the HIV protease prevents HIV precursor processing and virus maturation. These compounds are representative of a class of therapeutic drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTI). The concentration of these compounds in HIV-infected cells, coupled with their strong affinity for HIV reverse transcriptase, makes them very potent competitive inhibitors for the active sites of the transcriptase and prevents viral replication. These protease inhibitors are widely used for treatment of HIV infection (see Table 20.5 and Section 26.14).
Figure: 20-17 Caption: Growth factors and structurally similar analogs.
Figure: 20-19 Caption: The structures of some important penicillins. The red arrow (top panel) is the site of action for most b-lactamases.
Figure: 20-20 Caption: Structure of kanamycin, an aminoglycoside antibiotic. The amino sugars are in yellow. The site of modification by an N -acetyltransferase, encoded by a resistance plasmid, is indicated.
Figure: 20-21 Caption: Structure of erythromycin, a macrolide antibiotic.
Figure: 20-22 Caption: Structure of tetracycline and important semisynthetic analog
Figure: 20-24 Caption: Sites at which antibiotics are attacked by enzymes encoded by R plasmid genes. In aminoglycoside antibiotics related to streptomycin, those with a free amino group may be inactivated by N -acetylation (see also Figure 20.20).