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What are the 5 different Antibiotics ?
- Major types:
- 1. anthracyclines
- - doxorubin
- - daunorubicin
- - idarubicin
- - epirubicin
- 2. anthracenedione
- - mitoxantrone
- 3. dactinomycin
- 4. mitomycin
- 5. bleomycin
What is the Mech of action of the Anthracyclines?
- 1. Inserts between the base pairs--> Blocks DNA and RNA synthesis
- 2. Inhibits Topo-2
- 3. Generates Oxygen/ Hydroxyl radicals
How is resistance generated to Anthracyclins?
The cancer cell developes MDR due to increase in Efflux.
What is the Toxicity of Anthracyclins?
What color is it?
- 1. CARDIAC - free radical generated has affinity for cardiac muscle--> leads to Cardiomyopathy (note prevented with Dexrazoxane (Iron Chelating agent)
- 2. bone marrow suppression
- 3. alopecia
- 4. severe nausea and vomiting
- 5. secondary malignancies
- *** The RED DEVIL !!!
Name one in the group
When is it used?
- Similar Action and toxicity to Anthracyclins
- Used in frail patient
Mech of action?
- Insertion inbetween bases
- Used in pediatric tumors (WILMS TUMOR)
- Myelosupression, Vesican
Mech of action?
Mech of resistance?
- -Acts like an Alkylator (cross linking)
- -Used in Anal cancer. Used with 5-FU and radiation to preserve the anal function
- - Associated with TTP
What is the Mech of action of Bleomycin?
- 1. Inserts into DNA
- 2. Produces single and double strand breaks
- 3. Most activity in G2
- - Several uses, Stops Pleural effusions
- - Its creates Free radicals that are Toxic to the LUNG
- and my cause acute anaphylactic reaction
What are the 4 plant alkaloid groups? Where are they from?
- 1. Vinca Alkaloids (periwinkle plant)
- 2. Alkaloid Esters (Yew tree)
- 3. Podophyllotoxin (Mandrake plant)
- 4. Quinoline alkaloids (Happy tree)
What is the Mech of action of the Vinca Alkaloids?
- - bind to microtubular protein ( tubulin)
- - cause depolymerization of microtubules
- - prevents spindle formation
- (leads to mitotic arrest)
Name the Spindle Inhibitors
- Vinca Alkaloids
- Paclitaxel (Taxol)
- Docetaxel (Taxotere)
What is the Toxicity of Vinca Alkaloids?
- -peripheral neuropathies- Because tubular proteins have
- similarities to neural sheath proteins
(note: sensory neuropathy usually reversible while motor often not).
What are the uses for Vinca Alkaloids?
- - Hodgkin’s disease
- - NHL
- - lung cancer
- - gliomas
- - breast cancer (via analogue)
What is the Mech of action of the Taxanes?
what is it used for?
- - binds to tubulin
- - enhances tubulin polymerization
- - prevents spindle disassociation causing
- mitotic arrest
- Ovarian *, Breast and lung cancer
What are some Toxicities of the Taxanes?
- - bone marrow
- - allergies
- - myalgias and arthralgias
- - neurologic
- - skin (particularly nails)
What is the Mech of action of the podophyllotoxins?
What is it used for?
- inhibits DNA topoisomerase-2
--> inhibition of DNA / RNA synthesis
- - testicular cancer
- - lung cancer (especially small cell)
- - NHL
- - minor activity in a variety of cancers
What is the Mechanism of action of the Camptothecins?
What are the Two Clinically active agents?
- Inhibit topoisomerase 1--> leads to arrest of DNA
- replication --> cell death
- - Irinotecan -- used for Colon cancer. Can cause excessive diarrhea (treat with Atropine)
- -topotecan - small cell lung cancer and
- ovarian cancer. Can cause BM supression
What are the MAJOR toxicities of the Antibiotics (note: all make free radicals)
- - Cardiac
- - Cardiac
- - Myelosuppression
- - TTP (renal, cns and micro angiopathic hemolitic anemia)
- - Pulmonary
What are the Major Toxicities of the Plant alkaloids?
What Antibiotic is the only cell cycle specific one?
Name the Vinca Alkaloids
- - vincristine
- - vinblastine
- - vindesine
- - vinorelbine
Name the Alkaloid Esters (Taxanes)
Name the Podophyllotoxins
Name the Quinoline alkaloids (Camptothecins)
What are the General properties of the Miscellaneous agents?
Name Them and their specific Toxicities.
- 1. Heavy metals
- 2. Act as alkylators
- 3. The major toxicity is neurologic (permanent)
- •Carboplatinum --myelosuppression
- •Oxaliplatinum--cold intolerance
What are the uses for the Miscellaneous agents?
- •Cisplatinum-- Lung, Ovarian cancers (most germ cells).
- •Carboplatinum-- Breast, Ovarian, Lung
- •Oxaliplatinum-- Colon
How do you pervent Nephrotoxicity, Neurotoxicity, and cold induced neuropathy of the Platinum Compounds?
- -parenteral and oral hydration
- -replace both potassium and magnesium
- -use of amifostine (scavanges for cisplatin)
- -calcium and magnesium infusions
- -avoidance of cold air and drink