antineoplastics Flashcards
Drugs in Nitrogen-mustards
cyclophosphamide, Ifosfamide and chlorambucil
MOA of Nitrogen-mustards
Binds to Guanines and will either cross-link or bind to single strain. Alkylates the DNA and causes strand breakage. cellular replication is affected causing cells apoptosis
non-specific
S/E of nitrogen mustards (cyclophosphamide and ifosfamide)
myelosuppression, alopecia, Haemorrhagic cystitis due to metabolic byproduct of acrolein - give MESNA and fluid
s/e of chlorambucil (alkylating agent)
the usual but may cause seizures
MOA of Dacarbazine
alkylating agent - not specific
analogue of step 8 in purine de-novo
also alkylating agent that affects guanine. pro-drug forms methyltriazenoimidazole
A/E of Dacarbazine (Alkylating agent)
Neutropenia, thrombocytopenia, pain from injected vein, flu syndrome, facial flushing
MOA of Busulfan
Not specific
Alkylating agent. forms cross-links between DNA causes a disruption in cellular replication
A/E of Busulfan (Alkylating agent)
Myelosupression, hyperpigmentation, seizures, tachycardia and pulmonary fibrosis
MOA of Platinum Complexes
Not specific
Cisplatin, Carboplatin and Oxaliplatin
Are activated within the cell by displacement of chloride ions, instead leaving positively charged molecules that are able to react with DNA. Inhibition of DNA replication, transcription, and cell division results in apoptosis. Able to bind to DNA via intra and inter strand cross-links.
A/E of Platinum complexes
Emetic - Cisplatin>Oxaliplatin>Carboplatin
Myelosuppression (especially carboplatin), hypersensitivity, N&V, elevation in liver enzymes, electrolyte imbalance, Myalgia
Name of PARP inhibitors
poly ADP-ribose polymerase enzyme
Olaparib/Veliparib/Niraparib
MOA of PARP inhibitors
Not specific
the enzyme is able to repair single strand damage. Inhibiting PARP will cause double-strand breaks. Tumour cells with mutated non-functional BRCA1 and 2 genes are unable to repair these DNA breaks, resulting in cell death
A/E of PARP Inh
Taste disturbances, reduced appetite, NVD, oral mucositis, anaemia, Neutropenia
MOA of 5-Fluorourical (5-FU)
non-specific, Pyrimidine analogue, antimetabolite
inhibits synthesis of pyrimidine nucleotides by 3 MOA
1. locks thymidylate synthase in inhibited state.
2. RNA incorporation of 5-F-UTP
3. DNA-base pair mismatching (faulty mismatching)
MOA of 5-Fluorourical (5-FU)
non-specific, Pyrimidine analogue, antimetabolite
inhibits synthesis of pyrimidine nucleotides by 3 MOA
1. locks thymidylate synthase in inhibited state.
2. RNA incorporation of 5-F-UTP
3. DNA-base pair mismatching (faulty mismatching)
A/E of 5-FU
Myelosuppression (especially IV bolus)
hand-foot syndrome
angina-like chest pain
NVD
drug interactions of 5-FU
- cisplatin - increases DNA strand breaks
- methotrexate - increases effect
- metronidazole - decreases clearance
- leucovorin - increases cytotoxic effect
MOA of Capecitabine
pro-drug of 5-FU
Converted to fluorouracil by a 3‑step process in which the final step is more active in malignant than normal cells
other pyrimidine analogues
Cytarabine - blocks elongation and temple function by competing for space in DNA
Gemcitabine - analogue of deoxy-cytidine
Azacitidine - hypomethylation of cytosine in DNA (mis-match error)
MOA of Vinca Alkaloids
non-specific
Vinblastine, Vincristine, Vinorelbine
binds to tubulin and blocks the assembly of tubulin. Cells kept in metaphase - apoptosis
A/E of Vinca Alkaloids
Haematological neoplasms myelosuppresion P-gp substrate Peripheral neuropathy urinary retentions - hypertension hyperuricaemia. oral mucositis
MOA of taxanes
non-specific
promotes microtubule formation and inhibits disassembly leading to cell cycle arrest in late G2 and M phase.
A/E of Taxanes
hypersensitivity, peripheral neuropathy, neutropenia, increase liver enzymes, bradycardia, fluid retention, increased tears, changes to nails
MOA of Etoposide
non-specific - Epipodophyllotoxin
Inhibits topoisomerase II resulting in DNA strand breaks and inhibition of cell division in the late S and G2 phases of the cell cycle
A/e of Etoposide
hypersensitivty, hypotension, NVD, taste disturbances, myelosuppression, alopecia
MOA of Topoisomerase Inhibitors
Irinotecan/topotecan
only causes single stranded breaks unlike Topo II. Interfering with coiling and uncoiling of DNA during replication, which inhibits nucleic acid synthesis. Actions are specific for S‑phase
A/E of Topo II inhibitors - irinotecan and topotecan
less damaging to cells
myelosuppression, NVD, oral mucositis
Irinotecan - cholinergic effects exacerbating ASTHMA, CVD and IBD, do not use with these.
MOA of Dactinomycin (Antibiotic)
non-sepcific
1. binds double strand dna (intercalates) and inhibits RNA polymerase
2. topoisomerase 11 induced DNA strand breakage
Pg-substrate - no CNS entry
A/E of Dactinomycin
myelosuppression, NVD, stomatitis, alopecia, extravasation
MOA Anthracyclines (-rubicin)
non-specific
1. intercalates DNA base pairs
2. inhibits topoisomerase II preventing DNA repair
3.Free radical production may also contribute to cytotoxicity
4.. cell membrane binding
P-gp substrates
A/E of anthracyclines
cardiomyopathy, myelosuppression, extravasation (posssible necrosis)
MOA Bleomycin (antibiotic)
non-specific
Inhibits DNA and to a lesser extent RNA synthesis, produces single and double strand breaks in DNA possibly by free radical formation
A/E of bleomycin
pulmonary toxicity, NVD, skin reactions, hypersensitivity.
MOA of Selective Oestrogen Receptor Modulators (SERMs)
Specific - Tamoxifen and toremifene
competes with oestrogen for receptor (ER). Induces tertiary structure change and ER stops binding to ER element on DNA. Stops TGF-b production. Inhibiting tumour growth.
A/E of SERMs
hot flushes, NV, fluid retention, vaginal discharge, irregular menstrual cycle
Tamoxifen - Hypercalcaemia - avoid thiazides
Drug interactions of SERM
Increase metabolism - carbamazepine, phenytoin, phenobarb
Decrease metabolism - erythromycin and ketoconazole
MOA of Aromatase Inhibitors
Anastrozole and letrozole - specific
Exemestase - irreversable inh
inhibiting this enzyme stops the production of Oestrogen as Aromatase generates oestriol and oestradiol.
A/R of Aromatase Inhibitors
similar to Tamoxifen
more bone issues, add vit D to diet and calcium due to bone mineral density loss.
MOA of GnRH - Goserelin/Leuprorelin/triptorelin
Specific
suppresses ovarian and testsicular steroidogensis. GnRH initially stimulates synthesis of FSH, LH, increasing serum testosterone, serum estrogen. Continuous administration of GnRH agonists inhibits gonadotrophin production, and inhibiting the growth of certain hormone-dependent tumours
MOA of Colaspase
specific
Asparaginase breaks down L‑asparagine; certain types of leukaemic cells cannot synthesise this essential amino acid and are therefore unable to grow and survive
A/E of GnRH inhibitors
altered glucose tolerance, anaemia, weight gain, muscle atrophy, loss of body hair.
A/E of colaspase
hypersensitivity, liver damage, prolonged clotting time, increase hypergylcaemia
