Anticancer drugs Flashcards
Non cell cycle specific
Alk agents
Platinum compounds
Antitumor antibiotics
Cell cycle specific
S phase inhibitors
Antimetabolites
Hydroxyurea
Topoisomerase inhibitors
Histone deacetylase inhibitors
M cycle specific
Vinca alkaloids Taxanes Epothilones Estramustine Eribulin
Mucositis
Alk agents
5fu
cytarabine
Mtx
Maximum Alopecia
Alk agents
Anthracyclines
Topoisomerase inhibitors
Dose limiting toxicity
Bone marrow suppresion
Maximum emesis
Cysplatin>carmustine>anthracyclines>high dose cyclophosphamide>dacarbazine>mechlorethamine
Minimum emesis
Chlorambucil
busulfan
bleomycin
Early onset nausea
late onste nausea
Ondansetrron
late onset-palonosetron
aprepitant fosaprepitant-nk1 antagonists
Alkylating agents
Moa
Alkyl group of AA-Binds to H atom of dna at N 7 position-mispairing of guanine-thymine->cytotoxicity
Alkylating agents most specific for which phase
G1-S phase
Mc leukemia seen in Alk agents
Mechanism of action
Duration
AML due to chromosomal deletien at 5 7
4years
Mc leukemia seen with Cisplatin
Moa
duration
AML
Duration 2-3 yrs
Topoisomerase inhibitors
Mc leukemia MOA duration
AML
translocation of mixed lineage leukemia gene 11q23
Alkylating agents Classification
Nitrogen mustards
Nitrosoureas
Methylation
Misc
Meaning of bifunctional alk agents
Two reactive groups-cause Dna cross linking-high cytotoxicity
Alk agents with one reactive group
Drugs acting via meth
- procarbazine
- dacarbazine
- temozolomide
Drugs causing crosslinking dna
Cisplatin
mitomycin c
Nitrogen mustards classification
Cyclophosphamide Ifosfamide mechlorethamine melphalan chlorambucil bendamustine
Cyclophosphamide Metaboism and MOA
Metabolised by CYP2B6- 4hydroxycyclophosphamide-aldophosphamide and chloracetaldehyde
aldophosphamide-phospharamide mustard-anticancer effect
chloroacetaldehyde-neurotoxicity
hemmorhagic cystitis
acrolein
Neoplastic uses of cyclo
Breast and ovarian cancer
solid tumors in children
non hodgkins lymphoma
non neoplastic effect of cyclo
wegwners granulomatosis
RA
Steroid dependent NS
Hemmorhagic cystitis
Ifosfamide>cyclophosphamide
Treated by
Vigorous hydration
mesna
SE of cyclophosphamide
Hemmorhagic cystitis,neurotoxicity SIADH followed by hyponatremia
Bone marrow suppresion with relative sparing of platelets
Safe in renal dysfunction
Ifosfamide
uses
CYP450
Slowly metabolised therefore toxicity is much higher
Testicular cancer-BEP regimen add on
osteosarcoma
chloroacetaldehyde causes
Neurotox-GTCS,Ataxia,coma
Most neurotoxic
Ifosfamide>cyclophosphamude
Neurotox treatment
Methylene blue
which causes vesication
Mechlorethamine
Properies of melphalan
High plasma protein binding to both albumin and alpha 1 acid glycoprotein
Multiple myeloma treatment
Induction-Lenalidomide
Bortezomib
dexamethasone ->STem cell transplantation if age <70yrs(Melphalan is contraindicated due to cytotoxicity)
MAintenance of multiple myeloma
High risk-lenalidomide+bortezomib
low risk-lenalidmide
Uses of Chlorambucil and bendamustine
CLL and hodgkins lymphoma
Classification Nitrosoureas
Carmustine
Lomustine
Somustine
Stretpozocin
Uses of caarmustine and lomustine
HIghly lipid soluble-tt of brain cancers
SE of Nitosoureas
SustINED NEUTROPENIA
Streptozocin uses and properties
Precipitated in pancreatic b islet cells
used in pancreatic ca and carcinoid tumor
AA by methylation drugs
Procarbaxine
dacarbazine
temozolomide
Uses of dacarbazine
ABVD regmen of HL
malihnant melanoma
Sarcoma
Procarbazine SE
Disulfiram like reacton
Cheese reaction
uses of TEmozolomide
DOC-malignant brain tumors
Glioma,Astrocytoma
Anticancer drug causing cataract
Busulfan also causes pulmonary fibrosis
platinum compounds MOA
Free electrons of PC-Bind to N7 position of guanine in dna-formation of platinum based crosslinks-anticacncer effect and secondary leukemia AML
Bivalent and Quadrivalent compounds
Cisplatina and carboplatin
oxiplatin
Cisplatin mechanism of action
IV-combines with chloride ions becomes inactive-enters cells by copper transporter-chloride replaced by water group-becomes active
inactivation of cisplatin
aluminium
Dose of cisplatin
20mg/sq m/day
cisplatin uses
Lung ca-Alongwith etoposide,gemcitabine,premetrexed
double platin therapy with carboplatin
GIT ca-DOC for esophageal and gastric ca alongwith taxanes and 5FU
Urogenital ca Ovarian ca-cisplatin+paclitaxel Bladder ca-Gemcitabine+cisplatin Testicular ca-Bleomycin+etoposide+cisplatn CErvical ca-DOC
HEad and neck ca-cisplatin+5fu
Osteosarcoma
Rx of small cell lung ca
Cisplatin,etoposide
Rx of small cell lung cap
Cis,eto,vinorelbine->squamous variety-add gemcitabine
non squamous-premetrexed
SE of Cisplatin
Nephrotoxicity,Ototoxicity-Bilateral high frequency irreversible hearing loss,Neurtotoxicity-Stock and glove peripheral sensorimotor neuropathy,Ememsis,Raynauds phenomenon
NEphrotoxicity of cisplatin prevention
Forced diuresis by mannitol
Administration of 1-2L of Nacl-Inactivation of cisplatin by chloride compunds
Protective uses of Nacl
with cisplatin and amphotericin b
Uses of oxaliplatin
Colorectal ca,
Inhibits thymidilate synthetase therefore causes synergism with 5FU
Carboplatin dose limiting toxicity
Thrombocytopenia
Oxaliplatin dose limiting tox
peripheral neuropathy
types of antitumor antibiotics
Anthracyclines and others
Classification of anthracyclines
Derived from a fungus streptomyces peucetius
DOxorubicin,Danurubicin,Epirubicin,Valrubicin,Mitoxantrone
other drugs under antitumor antibiotics
Actinomycin d
mitomycin c
Bleomycin
Anthracycline toxicity
Requires Fe for free radical production therefore iron chelating agent dexrazoxane is used to prevent toxicity
Topoisomerase inhibition
S phase inhibition
free radical formation
G2 phase inhibition
Doxorubicin uses
ovarian ca,osteosarcoma,lymphoma and multiple myeloma
Danurubicin uses
used with doxo for tt of kaposi sarcoma
used alonwith cytrabine for tt of AML
Epirubicin and valrubicin uses
breast and bladder ca
SE of anthracyclines
Cardiotoxicity-maximum with doxo/dano
Acute-Pericarditis and myocarditis followed by arrhytmia
Chronic use-COngestive heart failure and dilated cardiomyopathy
Vacuolar myofibril degeneration in heart with chronic use
Vesication-doxo
Red discolouration of urine is seen with doxo/danorubicin
Radiation recall syndrome-Doxo/Dano/Actinomycin d
lymphoma tt regimen
NHL low risk-FCR 1.Fludarabine 2.Cyclophosphamide 3.Rituximab
Intermediate risk/High risk CHOP-R
- Cyclophosphamide
- Hydroxydanorubicin
- Oncovin
- Prednisolone
- Rituximab
Hodgkins lymphoma ABVD regimen 1.Adriamycin aka doxo 2Bleomycin 3.vincristine 4.Dacabazine
bleomycin metabolism and SE
Metabolised by bleomycin hydrolase.
BH deficient in lungs and skin
Lungs-causes type 1 pneumocyte damage and type 2 compensatory hyperplasia-pulmonary fibrosis
Skin-flagellate dermatitis
Raynauds phenomena
acute hypertension
Mitomycin c MOA and uses`andSE
MOA
inhibts topoisomerase2
alkylates DNA
uses-Anal and bladder cancer used topically
in post nasal surgery for synechia prevention and also ito prevent laryngoesophageal stensosi
SE
HUS
TTP
PF
Dactinomycin MOA uses SE
Actinomycin d
Inhibits RNA polymerase
uses
- Choriocarcinoma
- wilms tumor
- Sarcoma
SE radiation recall syndrome
Antimetabolites SE
Antifolate
purine analog
pyrimidine analog
Mucositis,diarrhoea,secondary leukemia not seen
DNA SYNTHESIS
Dump-tmp by enzyme thymidylate synthase
TMP is required for Dna synthesis
Thymidylate synthase requires cofactor methyl group donated by THF (DHF-THF by enzyme DHFR)
Inhibition of DHFR inhibits DNA synthesis
Methotrexate MOA
Inhibits DHFR and TS
MTX inhibits de novo purine synthesis which affects lymphocytes whivh have no salvage pathway
Uses of MTX
Metotrecat Multiple sclerosis Ectopic prego Transplant rejection GVHD Osteosarcoma topically for psoriasis rheumatoid arthritis it is DMARD of choice Wegeners granulomatosis All Trophoblastic disease Chorioca
SE of MTX
Myelosuppresion
To minimise Leucovorin is given
Mucositis
Renal toxicity-To use in patients with Renal failure given alongwith Glucarpidase which metabolises MTX into inactivr metabolites which are excreted in liver
Glucarpidase also breaks down leucovorin,therefore not given 2hr before or after intake of Leycoborin/folinic acid
Hepatotoxicity and Cirrhosis seen in prolonged tt
Crystalliuria-To prevent bicarbonate is given which alkalinzes the urine,MTX becomes more watet soluble as it is acidic drug
Intrathecal administration can cause meningismus,arachnoiditis and seizures
RESISTANCE TO MTX
1.Dhfr enzyme induction(Acute resistance)<24hrs
2.chronic resistance
GENE MUTATION OR AMPLIFICATION >24HRS
3.Pgp pumps
Pemetrexed uses and SE
Non small cell non squamous lung ca with xisplatin and in mesothelioma
SE
Less as compared to MTX,less potent inhibitor of DHFR also blocks TS,also block GART
low dose folinic or folic acid given to ameliorate toxicity
Inj B 12 also required
pyrimidine analogs
5FU
MOA
5fu-metabolised in tumor cells into fluorodeoxyuridylmonophosphate fdump-competively inhibits Thymidylate synthase,
Leucovorin increases sensitivity of TS to fdump by forming ternary complex with fdump and TS
Hand foot mouth syndrome causes
Palmar and plantar desquamation and erythema caused by 5FU,capecitabine,gemcitabine,doxorubicin and VEGFR and TK inhibitors
5FU uses and SE
Uses
1.colorectal ca-FOLINIC ACID+5FU+OXALIPLATIN
FOLFIRI-FOLINIC ACID+5FU+IRINOTECAN
FOLFIRINOX-FOLINIC ACID +5FU+IRINOTECAN+OXALIPLATIN
2.Head and neck ca alongwith cisplatin
3.Anal carcinoma with mitomycin c as topical agent
SE
- Hand foot mouth syndrome
- pulmonary toxicity
- Acute coronary vasospasm
- In patients with deficient dihydropyrimidinedehydrogenase toxicity can develop
Cytarabine MOA and SE
Inhibits DNA polymerase
Uses: alongwith daunorubicin or idarubicin in AML CML High grade lymphoma Lymphomatous meningitis
Myelosuppresion Drug limiting toxicity
high doses-cerbellar symptoms-dysarthhia,ataxia
cerebral tox-seizures and dementia
NON CARDIOGENIC PULMONARY EDEMA
Gemcitabine uses and SE
Pancreatic ca
non small cell lung ca
HUS,interstital pneumonitis,posterior leukoencephalopathy
Azacytadine and decitabine MOA uses
Cause demethylation of DNA
used in myelodysplasia
Myelodysplasia with 5q syndrome tt
lenalidomide
Treatment of Aml
V VINCRISTINE
P PREDNISOLONE
A ASPARAGINASE
D DAUNORUBICIN
ALL TT
Cytarabine+Daunorubicin or idarubicin
CLL TT
F Fludarabine
C Cyclophosphamide
R Rituximab
CML TT
Imatinib