Lecture 1 and 2 (Chemotherapy) Flashcards
(38 cards)
How does the patient develop resistance to chemotherapy drugs?
1- Inc DNA repair ( seen in breast cancer)
2- Formation of trapping agents like ( thiol trapping agents trapping glutathione)
3- Change in target Enzymes ( dihydrofolate reductase changes drug sensitivity) –> tumor resistant to methotrexate
4- Dec activation of prodrugs ( resistance to purine antimetabolites and pyrimidine metabolites)
5- Inactivation of anticancer drug
6- Decreased drug accumulation ( Inc expression of MDR1 causing increased efflux of anticancer drugs
What are the strategies of chemotherapy?
1- primary induction of chemotherapy ( relief symptoms and increase quality of life)
2- Non-adjuvant chemotherapy for localized tumor ( decrease size of tumor )
3- Adjuvant Chemotherapy for solid tumors, surgery, radiation) ( used to Dec metastasis )
What is combination therapy?
it is used when cancer is very aggressive and it means using mutliple drugs at the same time not allowing the cancer to develop resistance ( but have very bad side effects like internal haemorrhage
What is rescue therapy ?
used to control side effects of anticancer drugs
used in case of cyclophosphamide because it causes hemorrhagic cystitis
Drugs used are Mesna, Dexra and leucoverin
what are the usage of Mesna, Dexra and leucoverin respectively
1- Mesna: Neutrlize acruline from cyclophosphamide and stops hemorrhagic cystits and prevent formation of blood cancer and bladder cancer
2- Dexra: is chillating agents chilates free radicles like iron from Doxorubcin protecting from irreversible cardiomyopathy
3- Leucoverin: Prevent methotrexate induced megaloblastic anemia by blocking dihydrofolate reductase
Patient comes with jugular vein distension, peripheral edema and Dyspnea what is the diagnosis
Doxorubcin induced acute congestive heart failure
what is busulfan, mechansim of action and side effects
Busulfan is alkylating agents all of them CCNS
- Busulfan Ablates BM before transplantion to prevent by cross-linking DNA
- Side effects include : Severe myelosuppression ( inc susceptibility to Fungal infection, treated by epotoien, filagrastim and romiblastin), pulmonary fibrosis, hyperpigmentation ( Suprarenal G damage –> Low cortisol –> Inc ACTH –> Inc MSH
What are nitrogen mustards ( cyclophosphamide and Ifosfamide)
Alkylating agents, requires activation by liver and cyclophosphamide needs P-450 to be activated
Side effects include: Myelosuppression, SIADH, Fanconi syndrome ( Ifasfamide) , hemorrhagic cystits and bladder cancer ( prevented by Mesna)
- not given to patient with liver cirrhosis or failure ( AST>ALT and both are high)
Patient 1 has Sweet urine, hypovolemia, High K and acidosis and he is taking an alkylating agent
Patient 2 suffers from water retention, has hyponatremia and Inc urine osmolarity
Patient one has Ifosfamide induced Fanconi syndrome which Proximal renal function dysfunction
Patient 2 has syndrome of inappropriate ADH secertion induced by Cyclophosphamide and ifosfamide
What are Nitrosoureas ( Carmustine and Lomustine)
Alkylating agents that cross BBB so are used for glioblastoma and side effects are CNS toxcity
What is procarbazine
Alkylating agent and weak MAO inhibitor
side effects: Disulfiram like reaction due to inhibiton of aldhyde DH leaeding to acetylaldhyde accumlation after consuming alcholol
What is Methachlorthamine
what is dacarbazine?
Alkylating agents and converts reactive cytotoxic products
Side effects: alopecia, INFERTILITY (V,IMP) and blister formation
Dacarbazine is alkylating agent
what are Platinum compounds what is their usages?
what are the side effects?
Cisplain, carboplatin and oxaliplatin
all of them are CCNS used for solid tumors and lymphomas
Side effects include:
1- GI distress: Green vomit ( Bile) which causes rapid aggressive diarrhea
2- Hematoxic and neurotoxic
3- Peripheral Neuropathy ( first symp is burning sensation, damage to vestibulocochlear system causing ataxia and vertigo and Ototoxcity)
4- Fanconi syndrome Prevented by Amifostine
why is it important to force hydrate the patient during platinum compounds therapy?
We need to make the pateint urinate in 24 hours to prevent renal failure due to obstruction of the proximal convulate tubules
so we use Mannitol and alot of water
What are micortubule INH
they are M phase specfic and stop mitosis include Taxanes and Vinca alkaloids
what are Taxanes
Docetaxel and paclitaxel and they hyperstablize polymerized microtubules preventing detachment and mitosis
what are vinca alkaloids and their side effects and how do we treat constipation caused by them
Vincristine and Vinblastin and they bind to beta tublin inhibiting polymerization of microtubule and prevent mitotic spindle formation
They are used in blood cancers
Vincristine: Crisps nerves and Vinblastins: Blasts BM
and they cause CONSTIPATION due to peripheral neuropathy at mesenteric nerve fibers so no tone and peristalsis giving colic pain to the patient and treated by neostigmine and pyridostigmine
what are topiosemrase INH
1-Irinotecan and Tapotecan inhibit topiosemerase 1
2- Etopside, temiposide inhibit topiosemrase 2
what is Tamoxifen and what is the contraindication for it
Selective Estrogen R modulator it is antagonist in the breast and partial agonist in the endometrium and bone
Side effects: increase thromboembolic embolism, endometrial cancer, breast cancer in males taking prostate cancer therapy
Contraindication: 1- Not given to women with intact endometrial cancer because it will make tumor more aggressive So suggest hysterictomy
2- not given to males taking androgen antagonists because estrogen will become dominant and will cause very aggressive breast cancer
what is methotrexate, side effects and usage and contraindication
Methotrexate is antimetabolites so CCS acting on S phase
- Inhibit hydrofolate reductase inhibting thymidylate
-drugs needs the kidney and needs good hydration to prevent renal failure
- can be give low dose for RA, psoriasis and Ectopic pregnancy and high dose for cancers
- used in ectopic pregnancy because it blocks CNS development by blocking folic A
- side effects include: myelosupression, nephrotoxcity, mucositis ( small ulcers in mouth), pulmonary infiltrates due chornic inflmmation and birth defects
- causes megaloblastic anemia by blocking folic A ( hypersegmented neutrophils) and can be delayed by leucoverin rescure therapy
- never given to pregnant woman
What are Azathioprine, Marcptopurine and thioguanate
- Anti metabolites blocking purine used in blood cancer and sever autoimmune diseases
- both drugs are activated by HGPRTase to toxic metabolites inhibiting enzymes in purine metabolism and increase production of alkaline phosphatase
- cancer can develop resistance and it needs the liver
why we shouldnt give marcptopurines with Xanthine oxidase INH like febuxstate and allopurinol
because the drug wont be actiavted and it will attack BM causing pancytopenia
what is 5-flurouracil
antimetabolite, its converted to 5-FdUMP which inhibit pyrmidine synthesis by inhibiting thymidlate synthase
- it will cause Hand and Foot syndrome: skin repair dec so naive skin is present causing heat intolerance
- converted to FUTP which inhibit purine and pyramidine and inhibit DNA repair
- Cancer can develop resistance by increasing thymdlate synthase and decrease activation of 5-flurouracil
what is Cytabarine
antimetabolite, activated by kinase to AraCTP which inhibit DNA polymerase, tumor can develop resistance
