Doxorubicin
Doxorubicin
Chemical data
Formula
C27H29NO11
Mol. mass
543.52 g/mol
Pharmacokinetic data
Bioavailability
5% (Oral)
Metabolism
CYP3A4
Half life
12–18.5 hours[1]
Excretion
Biliary and fecal
Therapeutic considerations
Pregnancy cat.
D(AU) D(US)
Legal status
POM(UK) ℞-only(US)
Routes
Intravenous
Doxorubicin , trade name Adriamycin; also known as hydroxydaunorubicin) is a drug used in cancer chemotherapy. It is an anthracycline antibiotic,
Doxorubicin
Chemical data
Formula
C27H29NO11
Mol. mass
543.52 g/mol
Pharmacokinetic data
Bioavailability
5% (Oral)
Metabolism
CYP3A4
Half life
12–18.5 hours[1]
Excretion
Biliary and fecal
Therapeutic considerations
Pregnancy cat.
D(AU) D(US)
Legal status
POM(UK) ℞-only(US)
Routes
Intravenous
Doxorubicin , trade name Adriamycin; also known as hydroxydaunorubicin) is a drug used in cancer chemotherapy. It is an anthracycline antibiotic,
Mechanism of action
The exact mechanism of action of doxorubicin is complex and still somewhat unclear, though it is thought to interact with DNA by intercalation.Doxorubicin is known to interact with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which unwinds DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication.
The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures
The exact mechanism of action of doxorubicin is complex and still somewhat unclear, though it is thought to interact with DNA by intercalation.Doxorubicin is known to interact with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which unwinds DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication.
The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures
Clinical use
Doxorubicin is commonly used to treat some leukemias, Hodgkin's lymphoma, as well as cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and others.Commonly used doxorubicin-containing regimens are CA (cyclophosphamide, Adriamycin), TAC (Taxotere, CA), ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine), BEACOPP, CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisone) and FAC (5-Fluorouracil, Adriamycin, Cyclophosphamide). Doxil is used primarily for the treatment of ovarian cancer where the disease has progressed or recurred after platinum-based chemotherapy, or for the treatment of AIDS-related Kaposi's sarcoma
Side effects
Acute side-effects of doxorubicin can include nausea, vomiting, and heart arrhythmias. It can also cause neutropenia (a decrease in white blood cells), as well as complete alopecia (hair loss). When the cumulative dose of doxorubicin reaches 550 mg/m², the risks of developing cardiac side effects, including congestive heart failure, dilated cardiomyopathy, and death, dramatically increase. Doxorubicin cardiotoxicity is characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation. Reactive oxygen species, generated by the interaction of doxorubicin with iron, can then damage the myocytes (heart cells), causing myofibrillar loss and cytoplasmic vacuolization. Additionally, some patients may develop Palmar plantar erythrodysesthesia, or, "Hand-Foot Syndrome," characterized by skin eruptions on the palms of the hand or soles of the feet, characterized by swelling, pain and erythema.
Due to these side effects and its red color, doxorubicin has earned the nickname "red devil"or "red death."
Doxorubucin can also cause reactivation of Hepatitis B
Doxorubicin is commonly used to treat some leukemias, Hodgkin's lymphoma, as well as cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and others.Commonly used doxorubicin-containing regimens are CA (cyclophosphamide, Adriamycin), TAC (Taxotere, CA), ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine), BEACOPP, CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisone) and FAC (5-Fluorouracil, Adriamycin, Cyclophosphamide). Doxil is used primarily for the treatment of ovarian cancer where the disease has progressed or recurred after platinum-based chemotherapy, or for the treatment of AIDS-related Kaposi's sarcoma
Side effects
Acute side-effects of doxorubicin can include nausea, vomiting, and heart arrhythmias. It can also cause neutropenia (a decrease in white blood cells), as well as complete alopecia (hair loss). When the cumulative dose of doxorubicin reaches 550 mg/m², the risks of developing cardiac side effects, including congestive heart failure, dilated cardiomyopathy, and death, dramatically increase. Doxorubicin cardiotoxicity is characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation. Reactive oxygen species, generated by the interaction of doxorubicin with iron, can then damage the myocytes (heart cells), causing myofibrillar loss and cytoplasmic vacuolization. Additionally, some patients may develop Palmar plantar erythrodysesthesia, or, "Hand-Foot Syndrome," characterized by skin eruptions on the palms of the hand or soles of the feet, characterized by swelling, pain and erythema.
Due to these side effects and its red color, doxorubicin has earned the nickname "red devil"or "red death."
Doxorubucin can also cause reactivation of Hepatitis B
No comments:
Post a Comment