Antineoplastic therapy - Antibiotics Flashcards
How do the antibiotics work?
They directly bind DNA or intercalate between DNA base pairs, preventing DNA replication
They inhibit DNA polymerase
Avoid extravasation because it can cause severe tissue injury.
How does Dactinomycin work?
Intercalates DNA between guanine and cytosine, single strand breaks
NOT cell cycle specific
Note: It’s one of the most potent tumor agents
How is Dactinomycin administered?
IV only
Indications for Dactinomycin?
Rhabdomyosarcoma
Choriocarcinoma
Wilm’s tumor in children
Toxicities with Dactinomycin?
Pancytopenia Anorexia Nausea and vomiting Alopecia GI effects
How do Daunorubicin, Doxorubicin work?
Intercalate into DNA, preventing uncoiling, inhibits Topoisomerase II which repairs strand breaks
Binds to cell membranes, alters IP3 activation, may play a role in cardiotoxicity
Which drug has a lifetime max dose because of cardiotoxicity?
Doxorubicin
Why do Daunorubicin, Doxorubicin cause cardiotoxicity?
Metabolism forms semiquinone intermediates, forming free radicals
Tumors AND cardiac tissue are low in superoxide dismutase, cardiac tissue is also low in catalase (H2O2)
May be important in cardiotoxicity
Indications for Daunorubicin?
AML
Liposomal prep is used for Kaposi sarcoma
Indications for Doxorubicin?
Breast Bladder Lung Ovarian Testicular Thyroid Stomach ALL Hodgkin's and Non-hodgkin's Sarcoma Neuroblastoma
Toxicities of Daunorubicin, Doxorubicin
Moderate nausea, vomiting, stomatitis Dose limiting myelosuppression Cardiac toxicity, related to cumulative dose (Doxy it's 550 mg/m2) Myocardial cell damage, heart failure Discoloration in urine - turns red Mucosal ulcerations GI disturbances Alopecia Severe vesicant properties!!! NO EXTRAVASATION when administering it Secondary leukemia's Teratogenic
How can we prevent free radicals with Daunorubicin, Doxorubicin?
Dexrazoxane - Fe++ chelator prevents free radicals
Lipid complexes also are not taken into heart cells
Which antibiotic is used in the ABVD regimen? What’s that for?
Doxprubicin, in the Adriamycin part of the ABVD regimen for Hodgkin’s disease
Also Bleomycin!
ABVD = Adriamycin, Bleomycin, Vinblastine, Dacarbazine
What is Idarubicin used for?
AML
ALL
CML
How does Idarubicin compare to Doxorubicin, Daunorubicin?
More mucosistitis
Red urine still
Teratogenic
But less cardiotoxic
What is Epirubicin used for?
Bladder, head and neck, breast, lung, ovarian
Toxicities with Epirubicin
Severe N & V, cardiac toxicity, red urine, teratogenic
What is Valrubicin used for?
Introduced in 1998 for bladder tumors, reintroduced in 2009 for resistant bladder tumors
Red urine
Teratogenic
What is Mitoxantrone used for?
AML
Prostate
Also used in progressive, relapsing MS
Toxicities with Mitoxantrone?
Less cardiotoxic Bone marrow suppression Alopecia Hepatic toxicity Sexual dysfunction Blue green urine and nails (bc injection is blue) Not the same vesicant properties. yay
How is Bleomycin administered?
IV
IM
SubQ
Instilled in bladder
How does Bleomycin work?
Flat ring structure can intercalate into DNA
Metal binding core complexes with Fe and Cu
In presence of O2, metal complex produces free radicals to break DNA and cause lipid peroxidation
SPECIFIC FOR G2 PHASE
Indications for Bleomycin?
Cervical Bladder Head & Neck Pancreatic Testicular Ovarian Hodgkin's and Non-hodgkin's lymphoma Sarcoma
Toxicities associated with Bleomycin?
Low myelosuppression, teratogenic Dry cough can lead to pulmonary fibrosis Fever and chills Mild nausea and vomiting Alopecia Mucosal ulcerations Skin reactions, hyperpigmentation, blistering of skin
What is Mitomycin used for?
Anal cancer
Toxicities of Mitomycin?
Cumulative severe bone marrow suppression (8 weeks between treatments) Neurological abnormalities Pulmonary toxicities Alopecia Secondary leukemias
