Anti-tumour antibiotics Flashcards
What are the Anti-tumour antibiotics?
- Belomycin
- Doxorubicin (and pegalated liposomal - Caelyx)
- Epirubicin
- Mitomycin
What is the mechanism of action of anti-tumour antibiotics?
- Intercalating into DNA to disrupt it’s structure
- Metal ion chelation
- Inhbit enzymes e.g. DNA topoisomerase II - prevents DNA unwinding and replication
- Cell cycle arrest in S phase
- Generate free radicals (ROS) that can damage DNA and proteins
What bacteria does bleomycin come from?
Streptomyces verticillus
What is the mechanism of action of Bleomycin?
ssDNA and dsDNA breaks through formation of an intermediate iron complex
DNA synthesis and -> RNA and protein synthesis inhbited
How is bleomycin distributed?
Rapid distribution to tissues with high distribution to skin, lungs, kidneys, peritoneum, and lymphatics
No PPB
How is bleomycin metabolised?
Inactivated by hydrolases in tissues
Active and inactive metabolites
Squamous cells highly sensitive due to high levels of hydrolase in them
How is bleomycin eliminated?
66% Urine
What is the half life of IV bleomycin?
2-5 hours
Half life increases exponentially as CrCl falls
What are the indications for bleomycin?
- Squamous cells e.g. H&N, skin, penis, cervix, vulva
- Testicular
What are the adverse events associated with bleomycin?
- Pulmonary tox
- Hair loss
- Hyperkeratosis
- Hyperpigmentation
- Mucositis
- Wight loss
- Pyrexia
What drugs does bleomycin interact with?
- Cisplatin
- Nephrotoxins
- Other pulmonary tox e.g. methorexate
- Digoxin
What are the anthracycline chemotherapies?
- Doxorubicin
- Epirubicin
How is doxorubicin ditriuted?
Widly into tissues
85% PPB
How is doxorubicin metabolised?
Liver and tissues
Worse clearance in liver dysfunction
Doxorubicinol major metabolite
How is doxorubicin eliminated?
Liver and biliary - 40-50% via faeces within 7 days
Reduced clearance in obese
