Cancer part 2 - Cytotoxic CT Flashcards
Describe the Log Kill hypothesis
It is when the chemotherapy kills off 99% of the cancer cell every round
What are the physical barriers of cytotoxic chemotherapy
No blood supply to supply drug to the middle of a solid mass tumour due to necrosis
Pressure impacts the movement of drugs into tumour (High tumour interstitial pressure )
Adverse effects of Cytotoxic chemotherapy
Nausea
Damage to the GIT
>Causes mouth ulcers
Damage to the the Haemopoietic system
>Myelosuppression (Bone marrow damage)
How can the Mucositis be treated
Local anaesthetics in the from of sweets
What can myelosuppression cause
Increased viral and fungal infections
How can myelosuppression be avoided
Chaning the treatment
How can myelosuppression be avoided
Treatment
>Change the timing of the dose
>Through Transfusion of Platelets,
>CSF
Prevention
>Avoid exposure to infection
>Patients do better at home
>Avoid infected people/crowds
>Watch kitchen hygiene
How long does it take for hair loss to occur
within 1-2 weeks
What side effect of CT agents normally affect men
Gonadal damage: Pt’s become sterile
List some drug specific side effect and the drugs that cause the S/E
Cisplatin: Renal toxicity
Ifosfamide and cyclophosphate: Haemorrhagic cystitis
Doxorubicin: Cardiotoxicity
How does drug resistance occur with Anti-cancer drugs
> Improved proficiency in DNA repair
> Decreased drug activity
> Increased drug inactivity
> Increased efflux of drug
> Alternative biochemical pathway
> Alteration in target enzymes
What factors need to be considered before starting chemotherapy
Patient age- older
Health status
Geographical variation
If it is write for the patient
What percentage of people die within a month of starting chemo and what does that indicate`
8.4% lung cancer, 2.4% breast cancer
Indicates that Chemo was the likely cause of their death
What scales are used to assess pt’s performace status
Zubrod scale (0-4)
Karnofsky scale (100-10)
Who score (0-1)
What are the two types of cell cycle drugs
Cell cycle specific
Cell cycle non-specific
Properties of cell cycle specific drugs
Kills cells most effective at a stage in the cycle
Properties of cell cycle non-specific drugs
Can kill cell at any stage
It is dose dependant
Which class of drugs affect the specific cell cyle stages (Cell specific drugs)
G1:
>Hormonal drugs
>Antineoplastic enzymes
S:
>Topoisomerase-1 inhibitors
>Antimetabolites
G2:
>Epipodophyllotoxin derivatives
>Bleomycin
M:
>Taxanes
>Vinca Alkaloids
List some Antineoplastic enzymes (G1)
Asparaginase
Pegaspargase
List some Topisomerase-1 inhibitors (S)
Topotecan
Irinotecan
List some Subclasses of Antimetabolites (s)
Folate analogues
Purine Analogues
Pyrimidine Analogues
Miscellaneous class: Hydroxyurea
Name some folate analogues
Methotrexate
Name some purine analogues
Cladribine
Fludarabine
Gemcitabine
Mercaptopurine
Pentostatin
Thioguanine
Name some Pyrimidine Analogues
Capecitabine
Cytarabine
Gemcitabine
Floxuridine
Fluorouracil
Name some Epipodophyllotoxin derivatives (S)
Etoposide
Teniposide
Name some Taxanes (M/G2)
Docetaxel
Paclitaxel
Name some Vinca Alkaloids (M)
Vinblastine
Vincristine
Vinorelbine
Name some Cell cycle Non-specific classes
Alkylating agents
Antitumour antibiotics
Miscellaneous
List some Alkylating agents
Busulfan
Chlorambucil
Cyclophosphamide
Ifosfamide
Mechlorethamine
Melphalan
Name some Anti-tumour Antibiotics
Dactinomycin
Daunorubicin
Doxorubicin
Idarubicin
Mitomycin
Mitoxantrone
Name some Miscellaneous non-cell cycle specific drugs
Carboplatin
Carmustine
Cisplatin
Dacarbazine
Hexamethyl-melamine
Hydroxyurea
Lomustine
procarbazine
How are chemotherapy usually administered
They are given as a combination that do not have over lapping mechanisms or toxicities.
Properties of Alkylating agent
> Most effective during the proliferating stages (G1 and S)
Toxic to any rapidly diving cells
Used in combo
Used for solid and lymphatic tumour
They are Mutagenic and carcinogenic leading to secondary malignancy
what is the general mechanism of Alkylating agents
Binds covalently to nucleophilic groups on the nucleotides and prevents DNA replication
Which specific locations do alkylating groups bind
N7 and O6 of guanine
N1 and N3 of adenine
N3 of cytosine
Which binding location is most critical for cytotxic action
Guanine N7
What are some ways that Alkylating agents can cause DNA damage?
> Inter-strand cross-linking of DNA strands - stops strand separation
Intra-strand cross-linking
Base ring cleavage - strand cleavage
De-purination - strand cleavage
Tautomeric mutation - G pairs with T, GC to AT in daughter cells
Ineffective repair - frameshift mutation
What is nitrogen Mustard and how does it cause cancers
Bischloroethylamines (SCH2CH2Cl) developed from nitrogen or sulphurs used in chemical warfare
Lead to tumours (due to damaged DNA from remaining SCH2CH2- group)
What are the mechanism of Alkylating agents (Nitrogen mustards)
Chlorine disaggregates
Undergo intramolecular cyclisation forming an unstable ethylene immonium cation
Tertiary amine is transformed into quaternary ammonium cmpd
Ring opens out to form reactive carbonium ion which performs the alkylation
Carbonium ion is unstable reacts with an electron donor (The DNA)
What does changing the R group on the nitrogen mustards do
Changes the activity and specificity
What are some general side effects of Alkylating agents
> Extravasation damage
N&V
Mucositis
Myelosuppression
Alopecia
Depressed Gametogenic
Increased risk of non-lymphocytic leukaemia
Drug handling/Waste handling
What is the name of the most potent Nitrogen mustard
Mechlorethamine
Why is mechlorethamine not used as often anymore
Very instable
Little drug excreted
lots of Extravasation accident at the injection site
What are the most commonly used Alkylating Drugs
Cyclophosphamide
ifosfamide
How is Cyclophosphamide aministered
Orally
How is ifosfamide Administered
How are both Cyclophosphamide and ifosfamide activated
By the enzyme in the liver- hepatic p450
What causes the resistance of Cyclophosphamide and ifosfamide
Increased DNA repair
Increased production of thiols
What conditions are Cyclophosphamide and ifosfamide used for
Burkitt’s lymphoma and other lymphomas
ALL (acute lymphoblastic leukaemia)
Breast cancer
what are the standard side effects for cytotoxic chemotherapy
> N/V/D
Alopecia
Myelosuppression
Haemorrhagic cystitis - fibrosis of bladder - due to acrolein
Amenoohoea/sterility
Secondary malignancies
Name some other Alkylating drugs
Chlorambucil
Melphalan
What are the properties of Chlorambucil
Carrier molecule delays activation of the drugs for better distribution
Oral admin for lymphocytic leukemias
Properties of mephalan
Has Phenlyalanine as a carrier
>Targets melanomas
Administered orally for myelomas and ovarian cancer
Name tow other nitrogen mustards
Uramutine
Oestramustine
What is a pharmacological sanctuary
When metastasis occurs where a drug can not get to.
>The Brain due to BBB
What is a nitrosourea
A drug made from the slight alteration of nitrogen mustards
what is the function of nitrosourea
To have more access to the pharmacological sanctuary
