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Anticancer drugs Flashcards

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1
Q

Non cell cycle specific

A

Alk agents
Platinum compounds
Antitumor antibiotics

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2
Q

Cell cycle specific

S phase inhibitors

A

Antimetabolites
Hydroxyurea
Topoisomerase inhibitors
Histone deacetylase inhibitors

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3
Q

M cycle specific

A 
Vinca alkaloids
Taxanes
Epothilones
Estramustine
Eribulin
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4
Q

Mucositis

A

Alk agents
5fu
cytarabine
Mtx

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5
Q

Maximum Alopecia

A

Alk agents
Anthracyclines
Topoisomerase inhibitors

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6
Q

Dose limiting toxicity

A

Bone marrow suppresion

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7
Q

Maximum emesis

A

Cysplatin>carmustine>anthracyclines>high dose cyclophosphamide>dacarbazine>mechlorethamine

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8
Q

Minimum emesis

A

Chlorambucil
busulfan
bleomycin

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9
Q

Early onset nausea

late onste nausea

A

Ondansetrron

late onset-palonosetron
aprepitant fosaprepitant-nk1 antagonists

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10
Q

Alkylating agents

Moa

A

Alkyl group of AA-Binds to H atom of dna at N 7 position-mispairing of guanine-thymine->cytotoxicity

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11
Q

Alkylating agents most specific for which phase

A

G1-S phase

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12
Q

Mc leukemia seen in Alk agents
Mechanism of action
Duration

A

AML due to chromosomal deletien at 5 7

4years

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13
Q

Mc leukemia seen with Cisplatin
Moa
duration

A

AML

Duration 2-3 yrs

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14
Q

Topoisomerase inhibitors

Mc leukemia MOA duration

A

AML

translocation of mixed lineage leukemia gene 11q23

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15
Q

Alkylating agents Classification

A

Nitrogen mustards
Nitrosoureas
Methylation
Misc

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16
Q

Meaning of bifunctional alk agents

A

Two reactive groups-cause Dna cross linking-high cytotoxicity

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17
Q

Alk agents with one reactive group

A

Drugs acting via meth

  1. procarbazine
  2. dacarbazine
  3. temozolomide
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18
Q

Drugs causing crosslinking dna

A

Cisplatin

mitomycin c

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19
Q

Nitrogen mustards classification

A 
Cyclophosphamide
Ifosfamide
mechlorethamine
melphalan
chlorambucil
bendamustine
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20
Q

Cyclophosphamide Metaboism and MOA

A

Metabolised by CYP2B6- 4hydroxycyclophosphamide-aldophosphamide and chloracetaldehyde
aldophosphamide-phospharamide mustard-anticancer effect
chloroacetaldehyde-neurotoxicity

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21
Q

hemmorhagic cystitis

A

acrolein

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22
Q

Neoplastic uses of cyclo

A

Breast and ovarian cancer
solid tumors in children
non hodgkins lymphoma

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23
Q

non neoplastic effect of cyclo

A

wegwners granulomatosis
RA
Steroid dependent NS

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24
Q

Hemmorhagic cystitis

A

Ifosfamide>cyclophosphamide
Treated by
Vigorous hydration
mesna

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25
SE of cyclophosphamide
Hemmorhagic cystitis,neurotoxicity SIADH followed by hyponatremia Bone marrow suppresion with relative sparing of platelets Safe in renal dysfunction
26
Ifosfamide | uses
CYP450 Slowly metabolised therefore toxicity is much higher Testicular cancer-BEP regimen add on osteosarcoma
27
chloroacetaldehyde causes
Neurotox-GTCS,Ataxia,coma
28
Most neurotoxic
Ifosfamide>cyclophosphamude
29
Neurotox treatment
Methylene blue
30
which causes vesication
Mechlorethamine
31
Properies of melphalan
High plasma protein binding to both albumin and alpha 1 acid glycoprotein
32
Multiple myeloma treatment
Induction-Lenalidomide Bortezomib dexamethasone ->STem cell transplantation if age <70yrs(Melphalan is contraindicated due to cytotoxicity)
33
MAintenance of multiple myeloma
High risk-lenalidomide+bortezomib | low risk-lenalidmide
34
Uses of Chlorambucil and bendamustine
CLL and hodgkins lymphoma
35
Classification Nitrosoureas
Carmustine Lomustine Somustine Stretpozocin
36
Uses of caarmustine and lomustine
HIghly lipid soluble-tt of brain cancers
37
SE of Nitosoureas
SustINED NEUTROPENIA
38
Streptozocin uses and properties
Precipitated in pancreatic b islet cells | used in pancreatic ca and carcinoid tumor
39
AA by methylation drugs
Procarbaxine dacarbazine temozolomide
40
Uses of dacarbazine
ABVD regmen of HL malihnant melanoma Sarcoma
41
Procarbazine SE
Disulfiram like reacton | Cheese reaction
42
uses of TEmozolomide
DOC-malignant brain tumors | Glioma,Astrocytoma
43
Anticancer drug causing cataract
Busulfan also causes pulmonary fibrosis
44
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
45
Bivalent and Quadrivalent compounds
Cisplatina and carboplatin | oxiplatin
46
Cisplatin mechanism of action
IV-combines with chloride ions becomes inactive-enters cells by copper transporter-chloride replaced by water group-becomes active
47
inactivation of cisplatin
aluminium
48
Dose of cisplatin
20mg/sq m/day
49
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
50
Rx of small cell lung ca
Cisplatin,etoposide
51
Rx of small cell lung cap
Cis,eto,vinorelbine->squamous variety-add gemcitabine | non squamous-premetrexed
52
SE of Cisplatin
Nephrotoxicity,Ototoxicity-Bilateral high frequency irreversible hearing loss,Neurtotoxicity-Stock and glove peripheral sensorimotor neuropathy,Ememsis,Raynauds phenomenon
53
NEphrotoxicity of cisplatin prevention
Forced diuresis by mannitol | Administration of 1-2L of Nacl-Inactivation of cisplatin by chloride compunds
54
Protective uses of Nacl
with cisplatin and amphotericin b
55
Uses of oxaliplatin
Colorectal ca, | Inhibits thymidilate synthetase therefore causes synergism with 5FU
56
Carboplatin dose limiting toxicity
Thrombocytopenia
57
Oxaliplatin dose limiting tox
peripheral neuropathy
58
types of antitumor antibiotics
Anthracyclines and others
59
Classification of anthracyclines
Derived from a fungus streptomyces peucetius | DOxorubicin,Danurubicin,Epirubicin,Valrubicin,Mitoxantrone
60
other drugs under antitumor antibiotics
Actinomycin d mitomycin c Bleomycin
61
Anthracycline toxicity
Requires Fe for free radical production therefore iron chelating agent dexrazoxane is used to prevent toxicity
62
Topoisomerase inhibition
S phase inhibition
63
free radical formation
G2 phase inhibition
64
Doxorubicin uses
ovarian ca,osteosarcoma,lymphoma and multiple myeloma
65
Danurubicin uses
used with doxo for tt of kaposi sarcoma | used alonwith cytrabine for tt of AML
66
Epirubicin and valrubicin uses
breast and bladder ca
67
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
68
lymphoma tt regimen
``` NHL low risk-FCR 1.Fludarabine 2.Cyclophosphamide 3.Rituximab ``` Intermediate risk/High risk CHOP-R 1. Cyclophosphamide 2. Hydroxydanorubicin 3. Oncovin 4. Prednisolone 5. Rituximab ``` Hodgkins lymphoma ABVD regimen 1.Adriamycin aka doxo 2Bleomycin 3.vincristine 4.Dacabazine ```
69
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
70
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
71
Dactinomycin MOA uses SE
Actinomycin d Inhibits RNA polymerase uses 1. Choriocarcinoma 2. wilms tumor 3. Sarcoma SE radiation recall syndrome
72
Antimetabolites SE
Antifolate purine analog pyrimidine analog Mucositis,diarrhoea,secondary leukemia not seen
73
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
74
Methotrexate MOA
Inhibits DHFR and TS | MTX inhibits de novo purine synthesis which affects lymphocytes whivh have no salvage pathway
75
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 ```
76
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
77
RESISTANCE TO MTX
1.Dhfr enzyme induction(Acute resistance)<24hrs 2.chronic resistance GENE MUTATION OR AMPLIFICATION >24HRS 3.Pgp pumps
78
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
79
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
80
Hand foot mouth syndrome causes
Palmar and plantar desquamation and erythema caused by 5FU,capecitabine,gemcitabine,doxorubicin and VEGFR and TK inhibitors
81
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 1. Hand foot mouth syndrome 2. pulmonary toxicity 3. Acute coronary vasospasm 4. In patients with deficient dihydropyrimidinedehydrogenase toxicity can develop
82
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
83
Gemcitabine uses and SE
Pancreatic ca non small cell lung ca HUS,interstital pneumonitis,posterior leukoencephalopathy
84
Azacytadine and decitabine MOA uses
Cause demethylation of DNA | used in myelodysplasia
85
Myelodysplasia with 5q syndrome tt
lenalidomide
86
Treatment of Aml
V VINCRISTINE P PREDNISOLONE A ASPARAGINASE D DAUNORUBICIN
87
ALL TT
Cytarabine+Daunorubicin or idarubicin
88
CLL TT
F Fludarabine C Cyclophosphamide R Rituximab
89
CML TT
Imatinib

Pharmacology (2 decks)

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