Anticancer Drugs Flashcards
Adjuvant chemo is used for what stage of cancer
Cancer where neoadjuvant is not given
Stage 1 and above
Thyroid cancer
Neoadjuvants are done for : (6)
- Breast cancer
- Bladder cancer
- CRC
- Esophageal cancer
- NSCLC
- Gastric Adenocarcinoma
Define langerhans histiocytosis
Rx.
Infiltration and accumulation of monocytes,macrophages, dendritic cells in affected tissues.
Can spontaneously regress.
Rx: corticosteroid + arabinoside-cytarabine + vincristine
Rx for osteosarcoma (5)
Rx of choice : surgery
Drugs :
1. High dose MTX
2. Cyclophosphamide
3. Cisplatin
4. Etoposide
5. Doxorubicin
Bone marrow sparing anticancer drugs (3)
- Vincristine
- Bleomycin
- Fludarabine
Rx for prostate cancer (3)
Leuprolide
Goserelin
GNRH antagonist : Degarelix
S/e of mechlorethane. S/e can be reversed by …….
BMS
GM-CSF
Classification of alkylating agents (5)
- Classic nitrogen mustards
- Nitrosureas
- Platinum compounds
- Triazines
- Others
Egs of nitrogen mustards (3)
Mechlorethamine- mustard HCL
Cyclophosphamide
Ifosamide (analogue of cyclophosphamide)
PK of nitrosureas (2)
Eg of nitroureas.
Excellent CNS penetrators. Used for Rx Glioblastoma multiformae
-mustine.
Nitrosurea causing renal damage
S/e of estramustine (2)
Semustine.
Gynecomastia, Thromboembolism
Egs of platinum drugs
Eg of triazines (3)
-platins
-Dacarbazine
-procarbazine
-temozolomide
Busulfan, chlorambucil are ……drugs
MOA of alkylating agents (3)
Alkylating drugs
Produce carbonium ions.
Results in DNA cross linking
abnormal base pairing
breakage of DNA strand.
First nitrogen mustard
Can be given as only ….
What happens if given topical
Mechlorethamine
Iv-local severe vesicant
If topical-cutaneous T cell lymphoma
Prodrug in nitrogen mustard
S/e of cyclophosphamide is due to ….
Cyclophosphamide —> phosphor amide mustard+ acrolein.
Haemorrhagic cystitis is due to Acrolein; protected by mesna.
Very high doses of cyclophosphamide causes ……(3)
Acute myocardial necrosis
Alopecia
SIADH
Ifosfamide S/e
Also a prodrug.
Ifosfamide—>
chloracetaldehyde + acrolein.
Chloracetaldehyde causes Nephro toxicity
Acrolein—> hge cystitis
More harmful than cyclophosphamide.
Increased neurotoxicity,nephrotoxicity,hge cystitis, platelet suppression.
Nitrogen mustards are called ….
Nephrotoxicity of cisplatin seen with in …..part of kidney.
S/e of cisplatin (3)
Radiomimetics - action ~ ionising radiation
PCT,DCT
Nephro toxicity
Ototoxicity- high frequency hearing loss
Neurotoxicity- sensory neuropathy
S/e of carboplatin-
S/e of oxaliplatin (2)
similar to cisplatin but milder, more myelosuppression.
Acute and chronic neurotoxicity
Reversible laryngopharyngeal spasm
Primary action of dacarbazine is on …..
Procarbazine acts mainly on…. S/e
RNA and protein synthesis
MAOI
Disulfiram like reaction with alcohol.
Action of temozolomide.
S/e (2)
Cross BBB - useful for GBM
They have increased bioavailability
Headache, constipation
Busulfan is specific for ….
Adrenal insufficiency can be seen with …..
Other s/e (4)
Myeloid tissue- granulocyte precursors
Busulfan
Hyperpigmentation
Hyperuricemia
Sterility
Pulmonary fibrosis
Busulfan active on ……. Tissue
Chlorambucil active on …….tissue
Myeloid
Lymphoid
Radiosensitizer for head and neck cancer is ….
Role of amifostine
Cisplatin
To decrease cisplatin induced nephrotoxicity
S/e of cytarabine
How does amifostine protect in head and neck cancer
Cerebellar ataxia
Protects against parotid gland atrophy due to radiation of H&N
Amifostine protects against
Gemcitabine is effective against …
Salivary glands
Skin
GIT
not CNS
Pancreatic cancer
Cisplatin induced N&V drug….
Palosetron
How is MTX DOC for choriocarcinoma?
Another drug added for rx of chorizo carcinoma is …..
Reduced folate carrier - transport MTX into cells. In choriocarcinoma; there is increased expression of RFC.
Actinomycin D
Uses of methotrexate
- Increased dose
a. Osteosarcoma
b. ALL
c. Burkitts lymphoma
d. CNS lymphoma ,choriocarcinoma. - Low- moderate dose:
Rheumatoid arthritis
Psoriasis
Ankylosing spondylitis
Low to moderate dose of MTX is …
MTX inhibits …..enzymes and thus decrease …..
Folinic acid is aka……
7.5-25 mg/week
DHFR
DNA & protein synthesis
Leucovorin
Citrovorum factor
When to give folinic acid ? (7)
Doses >100mg/m2
BMS
Mucositis
Acute renal failure
Idiosyncratic pneumonitis
Hepatotoxic
Rash
Hepatotoxic histopathology seen with MTX
MTX toxicity increase when….present
Macrovesicular fatty change
Effusion- pleural effusion, ascites present.
………is seen in extreme MTX toxicity
MTX use in Rheumatoid arthritis. How?
Reversible transient Oligospermia
Increase in extra cellular adenosine by MTX
MTX cleaving enzyme
Resistance to MTX is by ….(2)
Glucarpidase.
Increase in DHFR - gene amplification
Increase in P-gp - throws away any drug that comes into the cell. Responsible for MDR.
Verapamil can be used in anti cancer rx for property of …..
MTX toxicities include: (5)
Inhibit Pgp and increase anti cancer drug action.
- Myelosuppression
- Nephro, hepatotoxic
- Neuro- intrathecal and high dose
- Phototoxicity
- Pulmonary toxicity.
Drugs which increase toxicity of MTX (5)
Aspirin
Penicillin
NSAID
Omeprazole
TMP-SMZ
Methotrexate toxicity Rx. (3)
- Urine alkalisation -increase elimination of acidic drugs
- When MTX- with renal failure: glucarpidase
- Leucovirin may be used.
Drugs that are poor substrates of Pgp. (3)
Cabazitaxel
Eribulin
Ixabepilone
Good substrate for pgp.
Paclitaxel
MOA of pemetrexed.
S/e
…….is used
Thymidylate synthase
Hand foot syndrome
Folic acid/vit b12.
Eggs of folate antagonists
- Methotrexate
- Pemetrexed
Egs of purine antagonists (6)
- 6 MP
- Thioguanine- 6TG
- Azathioprine
- Fludarabine
- Cladribine
- Pentostatin
MOA of pentostatin.
Rx.
Irreversible inhibitor of ADA.
Hairy cell leukaemia
MOA of cladribine
Use: ….
Inhibits DNA polymerase and DNA replication
DOC for hairy cell leukaemia
Fludarabine is ……
MOA
Antiviral-vidarabine
Incorporated into DNA—> inhibit DNA synthesis
Precursor of 6MP
Toxic to ….
Toxic effects increase by ….
Azathioprine
Proliferating lymphocytes
Allopurinol
Drugs that block de novo purine synthesis (2)
Require activation by ……
Mercaptopurine
Thioguanine
HGPRT
S/e of 6MP
Toxicity of 6MP happens when given with ….
Reversible cholestatic jaundice
Allopurinol.
S/e of azathioprine
MOA & S/e of MMF
BMS
Inhibit IMPDH—> decrease purine syn.
S/e: N,V,D
Use of MMF
For prevention of graft rejection.
Triple therapy :
Calcineurin inhibitor + MMF+ steroid
S/e of vincristine (4)
S/e of bleomycin (2)
Peripheral neuropathy
SIADH
Alopecia
Areflexia
Pulmonary fibrosis
Flagellate pigmentation
Difference between vinca alkaloids and taxanes
Vinca: inhibit polymerisation
Taxanes: enhance polymerisation
Vincristine blocks polymerisation in ……phase. It’s called….
Metaphase
Spindle poisons
Taxanes are aka….
Block microtubules in ……phase
Taxols
Anaphase
Prevent disassembly
Glove and stocking pattern peripheral neuropathy seen with …..
What are the epothilones? Use: s/e
Taxanes
Ixabepilone
Use: breast cancer resistance to tax Ames and anthrocyclines
BMS, peripheral neuropathy
Pk of thalidomide
Thalidomide acts via inhibiting …..
S/e of thalidomide (3)
Spontaneous dissociation in blood. No renal or liver metabolism.
Angiogenesis
Sedation
Constipation
P. Neuropathy
S enantiomer of thalidomide is …. It is ….
Lenalidomide. It is more potent, non teratogenic
Uses of thalidomide (6)
- Multiple myeloma
- Kaposi sarcoma
- HIV ass ulcer
- Behcet syndrome
- ENL
- GVHD
Vinca alkaloid derived from ….plant
Topotecan,iridothecan derieved from….
S/e
Periwinkle plant-catharantha alkaloids
Camptotheca acuminata
Cholinergic s/e
Paclitaxel obtained from ….
Indication of paclitaxel (6)
Bark of western yew tree
- Ovarian cancer
- Breast cancer
- H&N cancer
- Small cell lung cancer
- Esophageal cancer
- Prostrate cancer
Histopathology of DCMP in doxorubicin
MOA of anthracyclines
Vacuolated degeneration of myofibrils
Free radicals -interfere with dna intercalation( breaks in DNA to decrease replication)
S/e…..prevented by ……
Anthracyclines are not preferred in radiotherapy. Why?
Cardio toxicity
Dexrazoxane
Radiation recall.-dose reduction to prevent radiation toxicity.
Actinomycin D is aka…..
Bleomycin is a …..drug
Mitoxantrone is ……
Dactinomycin
Antitumor antibiotic drug.
Analogue of doxorubicin
Antitumor antibiotic that causes DNA unwinding
Bleomycin. Moa (5)
Dactinomycin
Chelates copper and iron
Produce superoxide ion, free radical.
Intercalates between DNA strands
Causes chain scissors
Inhibit DNA repair
Bleomycin damages ……pneumocytes
Test for bleomycin toxicity.
Bleonycin toxicity is enhanced by ……
Type 1.
Causes hyperplasia of type 2 pneumocytes.
Decreased DLCO.
Oxygen.
Flagellate hyperpigmentation is also known as …..
Uses of daunorubicin and doxorubicin
Topical rx for psoriasis
Scratch dermatitis
Daunorubicin: haematological malignancy
Acute leukemia
Doxorubicin: solid tumor,
soft tissue sarcoma
Tazarotene.
What is levamisole?
MOA.
Immumodulator antihelminthic
Low dose: immunostimulant
High dose: immunosuppressant
Depolarization by stimulating nicotine receptors
Use of levamisole
Mitomycin C is active at sites of …..
MOA
S/e of mitomycinC
CRC with 5FU
Low oxygen tension
DNA cross links
HUS
Uses of mitomycin C (3)
- SCC of anal canal
- Topical uses: laryngeal stenosis
- Intravitreal bladder cancer
MOA of procarbazine
Drug acts via hypomethylation of DNA
Class of trizene
Acts via methylation of DNA—> dna damage
Decitabine
Drugs that inhibit dna methyl transferase (2)
Use.
Decitabine
Azacytidine
Use: myelodysplastic syndrome
L-asparaginase is obtained from ……
Use.
Moa of hydroxyurea
E coli
ALL
Inhibit ribonucleotide reductase
Decrease dna synthesis
When to stop tamoxifen when conceiving?
SERMS do not inhibit….
3 months before
Vasomotor symptoms of menopause : hot flashes.
Imatinib is ……
DOC for ….
S/e of imatinib (3)
Tk inhibitor . Given oral
CML( BCR-ABL) , GIST (c-kit)
S/e:
1. N/v/d
2 Edema- periorbital, pleural effusion
3. Myalgia
How does resistance to imatinib occur?
Drugs to be given at that time?
Mutation to bcr-abl kinase
Dasatinib> bosutinib>nilotinib
Main c-kit inhibitor
Others (2)
Imatinib
Sunitinib
Regorafenib
EGFR TK inhibitors
ALK Inhibitors (2) use.
BRAF kinase inhibitor
Erlotinib, gefetinib
Crizotinib
Ceritinib.
NSCLC
Vemurafenib
Diseases with EGFR mutation? (4)
- CRC
- NSCLC
- Pancreatic cancer
- H&N cancer
Drugs against EGFR (2)
Cetuximab
Panitumumab
Difference between sunitinib and sorafenib
Sunitinib:
MultiTK inhibitor.
Against : VEGF-RCC
C-kit and PDGFR- GIST
Sorafenib:
VEGFR kit
RAF kinase
Use: RCC.
Other uses of sunitinib:
GIST, pancreatic cancer (SuGiPa)
Other uses of sorafenib:
HCC
Thyroid cancer
Tk given for medullary thyroid cancer (2)
Cabzantinib
Vandetanib
Drug given for myelofibrosis
TK Drugs given for NSCLC (4)
Ruxolitinib
Erlotinib
Gefetinib
Crizotinib
Afatinib
Drugs blocking Her2neu (3)
Ab against her2neu: trastuzumab
Prevent dimerization: pertuzumab
Inhibit intracellular TK: lapatinib, neratinib
Use of bevacizumab(3)
DR
CRC
NSCLC
MAB for CRC
Anti-VEGF (1)
Anti-EGFR (2)
Anti-VEGF: bevacizumab
Anti-EGFR: cetuximab, panituzumab
What are the anti-VEGF drugs ?
Ramu ki Bibi Rani
Ramucirumab: stomach, AdenoCA, NSCLC
Bevazicumab: CRC,NSCLC.
Ranibizumab: decrease bv proliferation in retina
Age related macular edema-wet AMD
Dm macular edema.
Drugs for CA breast (3)
Doxorubicin —s/e CMP
Trastuzumab —s/e CMP
Pertuzumab
Paclitaxel —s/e peripheral neuropathy
Drug for her2neu positive breast cancer refractory to trastuzumab
Lapatinib + capecitabine
Anti CD antagonists (6)
Ritu Is T O O Much
Rituximab
Ibrintumumab
Tositumumab
Ofatimumab
Obintuzumab
MS- Ocrelizumab
Uses of rituximab (6)
NHL
CLL
RA
MS
SLE
TTP
Drug for PNH
Mab for refractory AML in patients >60years
Eculizumab : C5 convertase
Gemtuzumab +ozagamicin - CD33 ab
Differentiation syndrome
Rx
Those Rx for. aml m3 with retinoic acid- fever, pleural and pericardial effusion, chest pain.
Dexamethasone ASAP.
Retinoid to rx mycosis fungoides
Another drug causing differentiation syndrome
Bexarotene- activating RXR.
Isocitrate DH
AML Rx for different subtype
Cytarabine not given in M3. Why?
M0-M7: cytarabine +daunorubicin
M3: ATRA+ arsenic trioxide
Can cause DIC
HDAC inhibitor for mycosis fungoides
(Histone deacetylase inhibitor)
Vorinostat
Romidepsin
Mtor inhibitor for Rx advanced Tcell cancer
Use of everolimus
Temsirolimus
RCC
Breast cancer
what is denileukin difitox?
Use:
Aa+ diphtheria toxin
Mycosis fungoides
S/e of denileukin difitox
Immediate : hypersensitivity
Delayed:
vascular leak syndrome -pulmonary and peripheral edema
MOA and use of aldesleukin
Toxicity of aldesleukin
MOA: IL-2 recombinant
Use: malignant melanoma
Metastatic renal cell cancer
Capillary leak syndrome
Egs of serine threonine kinase inhibitor. Use.
Vemurafenib, dabrafenib- BRAF
Trametinib- MET
Use: malignant melanoma
MOA of bortezomib
Use.
S/e
Proteosome inhibitor -prevent NF kB from preventing apoptosis
Multiple myeloma
Neuropathy
Purified antigen presenting cells used in hormone dependent prostate cancer
Drug inhibiting hedgehog pathway
Use.
Sipuleucel-T
Vismodegib
Metastatic Basal cell cancer
S/e of bevacizumab (4)
Thromboembolism
Gi perforation
Wound dehiscence
Tracheoesophageal fistula
Drugs against M phase
Drugs against G2 phase
METV
Estramustine
Taxanes
Vinca
BED
Bleomycin
Etoposide
Daunorubicin
Drug inhibiting G1 phase
Vinblastine
Action of mesna is …..
Amifostine
Preventing ifosamide bladder toxicity
Against radiation toxicity
MOA of palifermin
Drug given to decrease dry mouth from radiation.
Keratinocyte growth factor inhibitor
Pilocarpine
Use of strontium
L-asparaginase is bone marrow …..
Reduce bone pain from bone mets
Sparing
Drugs for neutropenia
Drug for TCP
Filgistim- G-CSF
Sargramostim- GMCSF
IL-11: Oprelvekin
Drug for ifosamide induced neurotoxicity
Drug for paclitaxel induced hyperuricemia.
Methylene blue
Replace with protein bound paclitaxel
Mc drugs causing mucositis (3)
Cytarabine
5FU
Methotrexate
Prevention of oral mucositis
Diarrhoea is associated with …..
Palifermin
5FU
Capecitabine
Irinotecan
Tk inhibitors :
saorafenib, Sunitinib, imatinib, dasatinib.
EGFR:
Cetuximab, panitumumab, erlotinib.
Drugs causing hyperpigmentation (3)
Busulfan
Hydroxyurea
Liposomal doxorubicin
Hand foot syndrome mx ass with ….(5)
5FU
Capecitabine
Liposomal doxorubicin
Sunitinib, sorafenib
Pemetrexed
Define hand foot syndrome
Tingling , burning of palms and soles
Progress to
severe pain, tenderness,edema and plaque formation
Spread to dorsum of hands and feet
Rx had and foot syndrome by
Cessation of offending agent- pyridoxine
Uses of TNF alpha inhibitors (3)
RA
IBD
Psoriatic arthritis
DOC for SLE
Belimumab-B-lymphocyte stimulator
C/F of TNF alpha inhibitor (3)
- TB: active,
latent: INH for 1mo. - HBV+
- Grade 3,4 CHF
Use of IL-2 receptor blockers
Basiliximab: prevent graft rejection
Docolizumab: M.S
S/e of calcineurin inhibitors (4)
Nephrotoxicity +
1. Hirsuitism
2. Hyperplasia of gums
3. HTN
4. Hyperuricemia
S/e of tacrolimus
Nephrotoxic
D- DM
N- Neurotoxic
D: diarrhea
A: alopecia
Drug which inhibit both EGFR and her2neu
Brentuzumab used for …..
works on …..
Lapatinib
CD30
Hogkins ,anaplastic large cell lymphoma
Daratumumab is against …..
Use:
Alemtuzumab against
Use
CD38
MM
CD 52
CLL
Iblizumab is against …… use
CD6
Psoriasis
MAB against asthma (3)
- Omalizumab -against IgE
- IL-5: mepolizumab, benralizumab
reslizumab-iv - Dupilumab- IL-4,IL-13
Mab used in IBD (3)
Moderate to severe UC &CD
1. Ustekinumab- only CD
2. TNF alpha inhibitors -UC&CD
3. Anti-integrins :
Natalizumab- alpha 4 integrin
Vedolizumab- a4B7
Block B cell migration
Biologicals for psoriasis (3)
- Ustekinumab: IL-12/23
- Guselkinumab: IL-23
- IL-17 inhibitors : SBI
Secukinumab
Brodalumab
Ixekizumab
Biologicals in MS (5)
- Natalizumab
- Alemtuzumab
- Daclizumab
- Basiliximab
- Ocrelizumab- CD20.
What are integrins?
Ab against integrins (2)
Proteins present on T lymphocytes, on adhesion with VCAM, lymphocytes come out I.e, egress lymphocytes from bv.
Natalizumab: a4B1
Vedolizumab: a4B7
Anti IL-1 antibodies
CAR
Canikinumab: CAPS
Anakinra: RA,CAPS
Rilonacept : fusion protein against IL-1
Acute gout: NSAID, colchicine,steroid resistant
IL-6 antibodies
Siltuximab use.
Tocilizumab
Sarilumab
Castle man’s disease
Drugs acting on IL-2 (4)
- Aldesleukin
- Denileukin difitox
- Basilizimab
- Daclizumab
World’s costliest medicine use
Onasemnogene abeparvovec
Spinal muscular dystrophy <2yrs age with SMN1 mutation
What is epigenomics?
Alteration in histone, chromatin, and methylation of DNA sequences
Proteomics
Microbiomics
Study of proteins
Study of bacterial flora of a person
Metagenomics
Study of environmental species which can influence human biology directly or indirectly.
Metabolomics
Study of range of metabolites in cells or organs and ways they are altered in disease states.
