Inibidores de Microtúbulos e de Topoisomerases

Descrição Geral

Inibidores de microtúbulos

• Agentes quimioterápicos que interferem com o sistema de microtúbulos, afetando a mitose celular e perturbando a forma e a motilidade celular.
• Sistema microtubular:
  • Os microtúbulos são parte do citoesqueleto em células eucarióticas e têm várias funções:
    • Estruturas dinâmicas que ancoram no centríolo perto ao núcleo
    • Crescimento direcional: adição e subtração de subunidades de tubulina
    • “Autoestradas” para o transporte dentro da célula por motores moleculares
    • Montam e fornecem uma estrutura para o movimento de cromossomas durante a divisão celular ou mitose
  • A alfa- e a beta-tubulina são os componentes primários dos microtúbulos.
• Agentes antineoplásicos nesta classe:
  • Taxanos
  • Alcaloides da vinca

Inibidores de topoisomerases

• Agentes que exercem a sua atividade antineoplásica ao enfraquecer as enzimas que facilitam o desenrolamento e a ligação das cadeias de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure, impedindo, em última instância, a replicação
• Topoisomerases:
  • Enzimas que ajudam a desenrolar e a selar novamente a cadeia de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
  • A replicação ocorre ao longo da estrutura do DNA em “coiled-coil” → o DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure enrola-se à volta de si mesmo
    • A topoisomerase alivia isto ao cortar o esqueleto de fosfatos.
    • Após o esqueleto de fosfato ser cortado (1 ou ambas as cadeias de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure), o DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure pode ser desenrolado.
    • Quando o enrolamento é aliviado, o DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure é novamente selado, ou religado.
  • Tipos:
    • Topoisomerase tipo I: introduz quebras de cadeias simples
    • Topoisomerase tipo II: faz quebras de cadeia dupla
• Vários fármacos previnem a atividade da topoisomerase, o que acaba por levar à morte celular.
  • Os antibióticos de fluoroquinolona inibem a atividade da topoisomerase bacteriana.
  • Este mecanismo também é uma ferramenta em fármacos anticancerígenos.
• Os agentes quimioterápicos desta classe:
  • Inibidores da topoisomerase I:
    • Irinotecano
    • Topotecano
  • Inibidores da topoisomerase II Topoisomerase II DNA topoisomerases that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. Fluoroquinolones:
    • Etoposido
    • Teniposido
    • Antraciclinas (por exemplo, doxorrubicina)

Taxanos

Descrição

• Os agentes antineoplásicos foram originalmente isolados da casca de uma árvore de teixo (Taxus brevifolia); os agentes mais MAIS Androgen Insensitivity Syndrome recentes foram posteriormente derivados semissinteticamente.
• Farmacodinâmica:
  • Os taxanos perturbam o funcionamento dos microtúbulos.
  • Os microtúbulos são partes essenciais dos fusos mitóticos e das estruturas axonais dos nervos.
  • Assim, o efeito inclui a inibição da mitose, mas também leva adversamente a danos axonais (neuropatia).
  • Os taxanos são considerados fármacos radiossensibilizantes.
• Farmacocinética:
  • Cerca de 90% ligado a proteínas
  • Metabolismo: sistema P450 hepático
  • Excreção: via hepatobiliar eventualmente excretados nas fezes
• Fármacos nesta classe:
  • Paclitaxel Paclitaxel A cyclodecane isolated from the bark of the pacific yew tree, taxus brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. Microtubule and Topoisomerase Inhibitors (produto natural)
  • Docetaxel Docetaxel A semisynthetic analog of paclitaxel used in the treatment of locally advanced or metastatic breast neoplasms and non-small cell lung cancer. Microtubule and Topoisomerase Inhibitors (análogo semissintético)
  • Cabazitaxel Cabazitaxel Microtubule and Topoisomerase Inhibitors (análogo semissintético)

Paclitaxel Paclitaxel A cyclodecane isolated from the bark of the pacific yew tree, taxus brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. Microtubule and Topoisomerase Inhibitors

• Indicações:
  • Cancro do ovário
  • Cancro da mama
  • Cancro do pulmão de células não pequenas
  • Sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions
• Efeitos adversos:
  • Mielossupressão
  • Hipersensibilidade
  • Neuropatia periférica
  • Reações cutâneas e alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia
  • Hipertensão ou hipotensão relacionada com a infusão, bradicardia
  • Toxicidade GI: vómitos, diarreia
  • Deficiência hepática: aumento de enzimas hepáticas, bilirrubina
  • Extravasamento

Docetaxel Docetaxel A semisynthetic analog of paclitaxel used in the treatment of locally advanced or metastatic breast neoplasms and non-small cell lung cancer. Microtubule and Topoisomerase Inhibitors

• Indicações:
  • Cancro da mama
  • Adenocarcinoma gástrico
  • Cancro da cabeça e do pescoço
  • Cancro do pulmão de não pequenas células
  • Cancro da próstata
• Efeitos adversos:
  • Mielossupressão
  • Retenção de fluidos: como derrame pleural, ascite, tamponamento cardíaco
  • Hipersensibilidade
  • Toxicidade miocárdica ou agravamento de disfunção cardíaca
  • Neuropatia periférica
  • Toxicidade GI: colite
  • Oculares: como o edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema macular cistoide
  • Malignidade secundária
  • Síndrome de lise tumoral

Cabazitaxel Cabazitaxel Microtubule and Topoisomerase Inhibitors

• Indicação: cancro da próstata metastásico resistente à castração (tratamento prévio com docetaxel Docetaxel A semisynthetic analog of paclitaxel used in the treatment of locally advanced or metastatic breast neoplasms and non-small cell lung cancer. Microtubule and Topoisomerase Inhibitors)
• Efeitos adversos:
  • Mielossupressão
  • Toxicidade GI: vómitos, diarreia
  • Neuropatia periférica
  • Deficiência hepática: ↑ enzimas hepáticas, bilirrubina
  • Toxicidade pulmonar
  • Urinários: hematúria, cistite
  • Insuficiência renal

Contraindicações e interações medicamentosas

• Contraindicações:
  • Neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia:
    • Contagem de neutrófilos < 1500/mm³
    • No sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions: contagem de neutrófilos < 1000/mm³
  • Reação de hipersensibilidade prévia
• Interações medicamentosas:
  • Antraciclinas: Aumenta a cardiotoxicidade
  • Os inibidores do CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) (↑ níveis de taxanos) incluem:
    • Cetoconazol
    • Eritromicina
    • Claritromicina
    • Diltiazem Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of calcium ion on membrane functions. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
  • ↓ Efeitos terapêuticos das vacinas (vivas e inativas)
  • ↑ Efeitos tóxicos das vacinas vivas

Alcaloides da Vinca

Descrição

• Agentes que inibem a mitose ao interromper a montagem de microtúbulos
• Derivado da planta pervinca Catharanthus roseus
• Farmacodinâmica:
  • Inibem a polimerização da tubulina
    • Suprimem o movimento dos microtúbulos em baixas concentrações
    • Reduzem a massa polimérica dos microtúbulos em concentrações mais MAIS Androgen Insensitivity Syndrome elevadas
    • Em qualquer concentração, levam a uma paragem mitótica na metáfase.
  • Previnem a divisão de células cancerígenas
• Farmacocinética:
  • Metabolismo: hepático, através do CYP3A
  • Má penetração na barreira hematoencefálica
  • Excreção: sistema hepatobiliar (fezes)
• Fármacos nesta classe:
  • Vimblastina
  • Vincristina
  • Vinorelbina

Vimblastina

• Indicações:
  • Linfoma de Hodgkin e não Hodgkin
  • Sarcoma de Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions
  • Cancro do testículo
  • Histiocitose de células de Langerhans
• Efeitos adversos:
  • Mielossupressão
  • Neurotoxicidade: ↓ reflexos profundos dos tendões, parestesias, vertigens, neurite periférica
  • Cardiovasculares: hipertensão arterial, isquemia miocárdica, angina
  • Dermatológicos: alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia, dermatite
  • Extravasamento
  • Toxicidade pulmonar: broncoespasmo
  • Toxicidade GI: dor abdominal, diarreia, náuseas, vómitos, estomatite
  • SIADH SIADH Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of impaired water excretion due to the inability to suppress the secretion of antidiuretic hormone (ADH). SIADH is characterized by impaired water excretion leading to dilutional hyponatremia, which is mainly asymptomatic but may cause neurologic symptoms. S Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Vincristina

• Indicações:
  • Leucemia Linfocítica Aguda (LLA)
  • Linfoma de Hodgkin e não Hodgkin
  • Neuroblastoma Neuroblastoma Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma
  • Rabdomiossarcoma
  • Tumor Tumor Inflammation de Wilms
• Efeitos adversos:
  • Mielossupressão
  • Neurotoxicidade: neuropatia periférica
  • Alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia
  • Toxicidade pulmonar: broncoespasmo
  • Extravasamento
  • Toxicidade GI: íleo paralítico, vómitos, diarreia, cãibras abdominais
  • SIADH SIADH Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of impaired water excretion due to the inability to suppress the secretion of antidiuretic hormone (ADH). SIADH is characterized by impaired water excretion leading to dilutional hyponatremia, which is mainly asymptomatic but may cause neurologic symptoms. S Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Vinorelbina

• Indicações:
  • Cancro do pulmão de não pequenas células
  • Outras indicações “off-label” incluem cancro da mama metastástico e cancro do colo do útero.
• Efeitos adversos:
  • Mielossupressão
  • Toxicidade GI: íleo paralítico, obstipação, oclusão intestinal
  • Hepatotoxicidade: ↑ transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis, bilirrubina
  • Neuropatia periférica
  • Toxicidade pulmonar: broncoespasmo, síndroma de dificuldade respiratória aguda
  • SIADH SIADH Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of impaired water excretion due to the inability to suppress the secretion of antidiuretic hormone (ADH). SIADH is characterized by impaired water excretion leading to dilutional hyponatremia, which is mainly asymptomatic but may cause neurologic symptoms. S Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Contraindicações e interações medicamentosas

• Contraindicações:
  • Mielossupressão grave
  • Infeção bacteriana ativa
  • Vincristina: forma desmielinizante da síndrome de Charcot-Marie-Tooth
• Interações medicamentosas:
  • Inibidores de CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers): ↑ concentração de alcaloides da vinca
  • ↓ Efeitos terapêuticos das vacinas (vivas e inativas)
  • ↑ Efeitos tóxicos das vacinas vivas

Inibidores da Topoisomerase I

Descrição

• Os inibidores da topoisomerase I são derivados da árvore Camptotheca acuminata.
• Farmacodinâmica:
  • Inibiem a enzima topoisomerase I
  • Inibição da topoisomerase I → sem enzima para cortar e voltar a ligar os filamentos de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure individuais → danos no DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
• Farmacocinética:
  • As formulações dependem do fármaco, mas, em geral, há formulações IV e orais.
  • Metabolismo: hepático
  • Excreção: hepatobiliar (irinotecano) ou renal (topotecano)
• Fármacos nesta classe:
  • Irinotecano
  • Topotecano

Irinotecano

• Um pró-fármaco convertido em SN-38 (o metabolito ativo que inibe a topoisomerase I) no fígado pelas enzimas carboxilesterases
• Indicações:
  • Cancro colorretal avançado como parte do regime de quimioterapia FOLFIRI (ácido folínico, fluorouracilo, irinotecano)
  • Também utilizado para indicações “off-label”
• Efeitos adversos:
  • Mielossupressão
  • Diarreia grave:
    • Precoce (< 24 horas): efeito colinérgico que pode ser tratado com atropina
    • Tardio (2-10 dias): mais MAIS Androgen Insensitivity Syndrome grave e pode levar a alterações eletrolíticas
  • Toxicidade pulmonar
  • Nefrotoxicidade
  • Tromboembolismo
  • Extravasamento

Topotecano

• Liga-se ao agregado DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure/topoisomerase I → estabiliza o complexo de clivagem, prevenindo a ligação de volta da cadeia de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure clivada → danos no DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
• Indicações:
  • Cancro do ovário
  • Cancro do pulmão de pequenas células
  • Cancro cervical
• Efeitos adversos:
  • Mielossupressão
  • Diarreia (semelhante ao irinotecano)
  • Toxicidade pulmonar
  • ↑ Transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis, bilirrubina
  • Enterocolite neutropénica
  • Extravasamento

Contraindicações e interações medicamentosas

• Contraindicações:
  • Hipersensibilidade ao fármaco
  • Mielossupressão grave
  • Disfunção renal grave
  • Gravidez
• Interações medicamentosas:
  • Topotecano e fatores de estimulação de colónias de granulócitos:
    • ↑ Toxicidade pulmonar/patologia pulmonar intersticial
    • ↑ Mielossupressão
  • Irinotecano:
    • Inibidores de CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers): ↑ metabolito(s) ativo(s) do irinotecano
    • Azolas: ↑ metabolito(s) ativo(s) do irinotecano
  • ↓ Efeitos terapêuticos das vacinas (vivas e inativas)
  • ↑ Efeitos tóxicos das vacinas vivas

Inibidores da Topoisomerase II

Descrição

• A topoisomerase II Topoisomerase II DNA topoisomerases that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. Fluoroquinolones introduz uma quebra na cadeia dupla do DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure para aliviar o superenrolamento.
• Farmacodinâmica:
  • Inibe a topoisomerase II Topoisomerase II DNA topoisomerases that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. Fluoroquinolones (que corta ambas as cadeias de DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure, alivia o superenrolamento do DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure e volta a ligar as cadeias)
  • Resulta em danos no DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
• Farmacocinética:
  • Disponível em formulações orais e IV
  • Metabolismo: hepático
  • Excreção: renal (etoposído), fezes através de excreção biliar (antraciclinas)
  • Fármacos:
    • Antraciclinas
    • Etoposido
    • Teniposido

Etoposido

• Indicações:
  • Cancro do pulmão de pequenas células
  • Cancro do testículo
• Efeitos adversos:
  • Mielossupressão
  • Alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia
  • Hipotensão (com infusão rápida)
  • Extravasamento
  • Malignidades secundárias
• Contraindicações:
  • Hipersensibilidade ao fármaco
  • Mielossupressão grave
  • Disfunção renal grave
  • Disfunção hepática grave
• Interações medicamentosas:
  • Etoposido: ↑ efeito anticoagulante dos antagonistas da vitamina K (por exemplo, varfarina)
  • ↓ Efeitos terapêuticos das vacinas (vivas e inativas)
  • ↑ Efeitos tóxicos das vacinas vivas

Teniposido

• Indicação: leucemia linfoblástica aguda
• Efeitos adversos:
  • Mielossupressão
  • Alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia
  • Diarreia, náuseas, vómitos
  • Extravasamento
  • Hipotensão (com infusão rápida)
• Contraindicação:
  • Hipersensibilidade ao fármaco
  • Mielossupressão grave
• Interações medicamentosas:
  • Pode aumentar os efeitos neurotóxicos da vincristina
  • ↓ Efeitos terapêuticos das vacinas (vivas e inativas)
  • ↑ Efeitos tóxicos das vacinas vivas

Comparação com Outros Agentes Quimioterápicos