Anticancer ppt of pharmacology b pharmacy

Pharmacology anticancer ppt

1. Chemotherapy of
Cancer
Dr. P. SwathiPutta
M.Pharm., Ph.D., PDF

2. Uncontrolled multiplication and spread within the
body of abnormal forms of body's own cells
A mass of tissue formed as a result of
•Abnormal
•Excessive
•Uncoordinated
•Autonomous and
•purposeless
Proliferation of cells
Cancer

3. Synth DNA
precursors,
proteins, etc.
Premitotic
synth of
structures,
mol’s
Cell Cycle

4. Classification
Alkylating Agents:
Nitrogen Mustards
Meclorethamine, Melphalan, Chlorambucil,
cyclophosphamide, ifosfamide
Ethyleneimine : Thiotepa
Alkyl Sulfonate: Busulfan
Nitrosureas
Carmustine,lomustine, streptozocin
Triazines
Dacarbazine, temozolamide

5. Antimetabolites:
Folate Antagonists
Methotrexate
Purine Antagonists
6 Mercaptopurine, 6 Thioguanine, Azathioprine
Pyrimidine antagonists
5 Fluorouracil, cytarabine, gemcitabine
Classification

6. Antibiotics
Actinomycin D, Doxorubicin, Daunorubicin,
Bleomycin, Mitomycin C
Vinca alkaloids
Vincristine, Vinblastine, Vinorelbine
Taxanes
Paclitaxel, docetaxel
Enzymes
L-Asparginase
Classification

7. •Epipodophyllotoxins
–Etoposide, Tenoposide
•Camptothecin analogs
–Topotecan, Irinotecan
•Biological response modifiers
–Interferons,
–Interleukins
•Miscellaneous
Cisplatin , Carboplatin ,Hydroxurea, Procarbazine,
Mitotane, Imatinib
Classification

8. Corticosteroids
Prednisolone
Estrogens
Ethinyl Estradiol
SERM
Tamoxifene, Toremifene
SERD
Fulvestrant
Aromatase Inhibitors
Letrozole, Anastrazole,
Exemestane
•Progestins
–Hydroxyprogesterone
•Anti-androgens
–Flutamide,
Bicalutamide
•5-reductase Inhibitors
–finasteride, dutasteride
•GnRH analogs
–Naferelin, goserelin,
leuoprolide
Classification

9. Mechanism of actions of anticancer drugs

11. Toxic effects
of anticancer chemotherapeutics
Myelotoxicity
Alopecia
Loss of appetite &
weight
Nausea &vomitus
Taste change
Stomatitis,
esophagitis,
constipation, diarrhea
Fatigue
Cardiotoxicity
Neurotoxicity
Lung damage
Sterility &
teratogenicity
Hepatotoxicity &
nefrotoxicity
↓ Wound healing
↓growth (children)
Carcinogenicity

12. Alkylating agents

13. Meclorethamine
Very irritant drug
Dose = 0.4 mg/kg single or divided
Uses
Hematological cancers , lymphomas , solid tumors
Hodkins as part of MOPP, CML, CLL
Adverse effects
Anorexia, nausea, vomiting
Bone marrow depression, aplasia
Menstrual irregularities
Advantage: both cytostatic and hormonal effect

14. Melphalan
Very effective in MULTIPLE MYELOMA
Less irritant locally , less alopecia
Dose:
0.25 mg/kg daily for 4 days every 4-6
weeks
Adverse Effects :
Bone marrow Depression
Infections, diarrhoea and pancreatitis

15. Cyclophosphamide
Neoplasticconditions
Hodgkins
Non hodgkinslymphoma
ALL, CLL, Multiple myeloma
Adverse effects:
Hemorrhagic cystitis,
alopecia,
nausea & vomiting,
SIADH
hepatic damage
Dose: 2-3 mg/kg/day oral
10-15 mg/kg IV every 7-10 days
It can be administered IV, IM, IP.

16. Methotrexate

17. Methotrexate
(folate antagonist)
Kinetics:
Absorbed orally, 50 % protein bound
Disappears rapidly from blood , remains in tissue longer than folate thus causes
prolonged inhibitory effect
C/I in renal impairment
Uses:
Choriocarcinoma, acute lymphoblastic leukemia (children), osteogenic sarcoma,
Burkitt's and other non-Hodgkin‘s lymphomas, cancer of breast, ovary, bladder,
head & neck
Side effects:
Megaloblastic anemia , Thrombocytopenia, leukopenia, aplasia Oral, intestinal
ulcer , diarrhoea, Alopecia , liver damage, nephrpathy
Drug Interactions:
aspirin and sulfonamides displace methotrexate
from plasma proteins.

18. 6-Mercaptopurine
(purine antagonist)
Kinetics:
orally administered, poor penetration
through the BBB, metabolised by
xanthine oxidase, excreted in urine
Use:
Acute leukemia (ALL)
Choriocarcinoma
Adverse Effects:
Bone marrow & GIT mainly
Hepatic necrosis rarely
Hyperuricaemia

19. Fluorouracil
(pyrimidne antagonists)
Orally effective
Uses:
Breast Cancer
Ovarian cancer
Skin cancer
Side effects:
bone marrow depression,

20. Vincristin
(Vinca Alkaloids)
Mechanism:
Cytotoxic:Inhibitionofmitotic
spindleformationbybindingto
tubulin.
M-phaseofthecellcycle
Sideeffects:
Bonemarrowdepression,
epithelialulceration,GI
disturbances,neurotoxicity
Uses:
Metastatictesticularcancer,
Hodgkinsandnon-Hodgkins
lymphoma,Kaposi’ssarcoma,
breast carcinoma,
chriocarcinoma,neuroblastoma

21. Paclitaxel
(Taxanes )
Mechanism:
Cytotoxic: binds to tubulin,
promotes microtubule formation
and retards disassembly; mitotic
arrest results
Uses:
Melanoma and carcinoma of
ovary and breast
Side effects:
Bone marrow supression,
peripheral neuritis, arthralgia,
myalgia and hypersensitive
reactions

22. Cisplatin
(Platinum compounds)
Kinetics:
Non cell cycle specific killing
Administered IV
Highly bound to plasma proteins
Gets concin kidney, intestine, testes
Poorly penetrates BBB
Slowly excreted in urine
Uses:
Testicular cancer (85% -95 % curative
Ovarian cancer
Other solid tumors: lung, esophagus, gastric
Adverse effects:
Emesis, Nephrotoxicity, Peripheral neuropathy ,
Ototoxicity

23. Doxorubicin
(Antibiotic)
Uses:
Acute leukemia, Hodgkin's
disease,
nonHodgkin'slymphomas
breast & ovary,
lung sarcomas,
Side effects:
Cardiac toxicity, affects the heart
muscles, leading to tiredness or
breathing trouble when climbing
stairs or walking, swelling of the
feet .

24. Hydroxyl Urea
(Miscellaneous)
Uses:
CML, Polycythemia,
psoriasis
Dose:
20-30 mg/kg /day orally
Adverse effects:
Myelosuppression (Minimal)
Hypersensitivity
Hyperglycemia
Hypoalbuminemia

25. L-asparaginase
(enzymes)
I.V. or I.M.
Uses:
Acute lymphocytic leukemia,
induction of remission in acute
lymphoblastic leukemia when
combined with vincristine,
prednisone, and anthracyclines
Side effects:
Nausea and vomiting, Poor
appetite, Stomach cramping,
Mouth sores, Pancreatitis.
Less common: blood clotting

26. Glucocorticoids
Marked lympholytic effect so used in acute leukaemias &
lymphomas,
They also
Have Anti-inflammatory effect
Increase appetite, prevent anemia
Produce sense of well being
Increase body weight
Supress hypersensitivity reaction
Control hypercalcemia & bleeding
Non specific antipyretic effect
Increase antiemetic effect of ondansetron

27. Hormones & antagonists
Anti androgens:
FLUTAMIDE & BICALUTAMIDE :
•Androgen Receptor antagonists
•Dose : 250 mg tds, 50mg od resp.
•Palliative effect in metastatic Prostatic Cancer
GnRH agonists:
NAFERELIN :nasal spray / SC inj
↓FSH & LH release from pituitary-↓the release of estrogen & testosterone
USE : Breast Ca, Prostatic Ca
PROGESTINS:
Hydroxyprogesterone –used in metastatic endometrial Ca.
A/E: bleeding
Estrogens:
FOFESTEROL :
Prodrug , phosphate derivative of stilbesterol
600-1200mg IV initially later 120-240 mg orally

28. Newer anticancer drugs
Inhibitors of growth factors receptors
Imatinib: CML (BCR-ABL gene)
Gefitinib: Non small cell cancer of lungs (EGFR)
Dasatinib : CML (Tyrosine kinase inhibitor)
Lapatinib : metastatic breast cancer (HER2/neu)
Sorafinib : renal cell carcinoma (VEGF)
Monoclonal antibodies
Trastuzumab : breast cancer (HER2/neu)
Bevacizumab: metastatic colon cancer (VEGF)
Panitumumab : metastatic colon cancer (EGFR)
Iodine tositumonab : Non hodgkins (CD-20)