Anticancer Drugs

1. VANDANA SHARMA
M.PHARM
INDIPENDENT PHARMA TUTOR
(9 YEARS)
OM SAM SHAINASCHRAYAI NAMAH SHREE KRISHAN SHARMAM MAMAH
STUDY MATARIAL FOR PHARMACY STUDENTS

2. About cancer we
have discussed in
previous slides

4. Anti- cancer drugs
 Definition
Anticancer, or antineoplastic, drugs are used to treat
malignancies, or cancerous growths. Drug therapy may be used
alone, or in combination with other treatments such as surgery
or radiation therapy.
 Anti cancer drugs kill the cancer cell by first order kinetic means
concentration dependent killing is done by Anti cancer drugs.
 For complete cure of cancer all cancerous cells must be killed as
single cell capable of producing cancer.

5. Purpose
Anticancer drugs are used to control the growth of cancerous cells.
Cancer is commonly defined as the uncontrolled growth of cells, with
loss of differentiation and commonly, with metastasis, spread of the
cancer to other tissues and organs. Cancers are malignant growths.
In contrast, benign growths remain encapsulated and grow within a well
defined area.
Although benign tumors may be fatal if untreated, due to pressure on
essential organs, as in the case of a benign brain tumor, surgery or
radiation are the preferred methods of treating growths which have a
well defined location.
Drug therapy is used when the tumor has spread, or may spread, to all
areas of the body.

6. Anti- Cancer drugs
 Alkylating Agents
(a) Nitrogen mustard- Mechlorethamine,
Cyclophosphamide, Chlorambucil, Melphala
(b) Alkyl sulphonate/ Di butyl sulphonate group-
Busulfan
(c) Nitrosourea derivatives- Carmustine, Semustine,
Lomstine
(d) Ethylene amine dvt- Thiotepa
(e) Triazine- Dacarbazine

7. Anti- Cancer drugs
 Antimetabolite
(a) Folate antagonist- Methotrexate (Amithotrine)
(b) Purine Antagonist- Azathioprine, 6-mercaptopurine
(c) Pyrimidine Antagonist- 5-Florouracil, Cytarabine
 Anticancer Antibiotic- Doxorubicine and Donorubicine,
Actinomycine/Dactinomycine, Bleomycine
 M-Phase/ Mitotic Inhibitors
(a) Vinca Alkaloids- Vincristine, Vinblastine
(b) Taxanes- Azathioprine, 6-mercaptopurine

8. Anti- Cancer drugs
 Enzymes- L-asperginase
 Hormones- Tamoxifen, Finastatine
 Steroids/Immunomodulating Drugs- Pridnisolone,
Methyl-pridanisolone
 Camptothesine analogues- Topothecan,
Irinothecane
 Phodophylotoxine- Etoposide, Teniposide
 Platinum compounds- cisplatine, carboplatine,
oxaliplatine

9. Common adverse effects of Anticancer drugs
1. Suppress bone marrow- Penocytopenia (Decrease all count) means
decrease WBC counts, RBC counts, Platelet counts
2. Anemia
3. Adversely affect multiplying cells- eg loss of hair (Baldness),
wrinkling of hair
4. Decrease sperm count- cause male sterility (oligozoospermia)
5. Decrease ovum count- cause female sterility
6. Nausea and vomiting
5HT3 receptor (intrinsic
ion channel receptor)
present in intestinal
(GIT) mucosa
Serotonin
Cancer
Chemotherapy
and Radiotherapy
Release
Nausea and Vomiting
Ondansetrone and
Grainisitrone (Both are
5HT3 antagonist) S/e of
both Drugs are headache
Induce
Control by
Through

10. 7. Secondary gout
Anti cancer drugs are cytolytic in
action (Destroy cancerous cellv
Decease uric acid synthesisPurine base
hyperuricamia (Secondary gout) in
this condition uric acid crystal
deposit in joint fluid
Increase uric acid level in blood by
destruction nucleic acid eg. purine
base (Adenine and guanine)
present in cell
Cause
Allopurinol (A suicidal inhibitor)
Xanthine oxidase (an enzyme
which help in degradation of
purine base)
Inhibit Xanthine oxidase
Note- So Allopurinol is co- administered with anti cancer drug to decrease
the chances of Secondary gout by inhibition of X.O. enzyme.

11. Alkylating agent
MOA-
Alkylating agent convert into
reactive carbonium ion ( C +) and
transfer alkyl group
to Cellular N7 guanine of
DNA by forming
covalent bonds
Nitrogen Mustered
Mechlorethamine-
It is a first alkalyting agent which
is discovered
Always used as IV

12. Cyclophosphamide
It is a pro drug
Cyclophosphamide
Phosphamide mustard (Active
metabolite)
Aldophosphamide (Active metabolite
Which is form for short time)
Damage blood vessels (vasiculo
toxic) specially kidneys blood
vessels
Acroline (toxic metabolite)
Metabolism
Metabolism
Hemorrhagic cystis (Blood in urine)
Side effect
Side effect
Metabolism
To decrease vesicular toxicity
cyclophosphamide is given with
MESANA

13. Note-
Mesana is SH group donating chemical
Mesana form complex with Acroline (toxic metabolite)
Decrease chances of vesicular toxicity caused by toxic
metabolite Acroline
Ifosfamide
Longer acting congener of cyclophosphamide
Side effect –
same as Cyclophosphamide -Hemorrhagic cystis (Blood in urine)

14.  It is a PHENYL BUTYRIC ACID DERIVATIVE.
 It is a slowly acting drug.
 DOC- chronic lymphatic leukemia (cancer of
lymphatic gland)
Chlorambucil
 Chlorambucil produces its anti-cancer effects by interfering with DNA
replication and damaging the DNA in a cell. The DNA damage induces
cell cycle arrest and cellular apoptosis via the accumulation of cytosolic
p53 and subsequent activation of Bax, an apoptosis promoter.
 Chlorambucil alkylates and cross-links DNA during all phases of the
cell cycle, inducing DNA damage via three different methods of
covalent adduct generation with double-helical DNA:
MOA

15. 1. Attachment of alkyl groups to DNA bases, resulting in the DNA being
fragmented by repair enzymes in their attempts to replace the
alkylated bases, preventing DNA synthesis and RNA transcription
from the affected DNA.
2. DNA damage via the formation of cross-links which prevents DNA
from being separated for synthesis or transcription.
3. Induction of mispairing of the nucleotides leading to mutations.
Melphalan
 An alkylating agent adds an alkyl group (CnH2n+1) to
DNA. It attaches the alkyl group to the guanine base
of DNA, at the number 7 nitrogen atom of the
imidazole ring.
 It is a PHENYL ALANINE DERIVATIVE.

16. MOA-
 Melphalan chemically alters through alkylation of the DNA
nucleotide guanine, and causes linkages between strands of DNA. This
chemical alteration inhibits DNA synthesis and RNA synthesis,
functions necessary for cells to survive. These changes
causecytotoxicity in both dividing and non-dividing tumor cells.
 DOC- Ovarian cancer
 Most common adverse effect- Bone marrow depression

17. Dibutyl sulfonate gp/ Alkyl Sulfonate
Busulfan
Busulfan is a cell cycle non-
specific alkylating antineoplastic agent, in
the class of alkyl sulfonates. Its chemical
designation is 1,4-butanediol
dimethanesulfonate.
Busulfan is used in pediatrics and adults in combination
with cyclophosphamide or fludarabine/clofarabine as a conditioning
agent prior to bone marrow transplantation, especially in chronic
myelogenous leukemia (CML) and other leukemias, lymphomas, and
myeloproliferative disorders.

18.  Busulfan can control tumor burden but cannot prevent transformation or
correct cytogenic abnormalities.
 The drug was recently used in a study to examine the role of platelet-
transported serotonin in liver regeneration.
Side effect-
Pulmonary fibrosis ("busulfan lung"), hyperpigmentation, seizures, hepatic
(veno-occlusive disease) (VOD), emesis, and wasting syndrome.
thrombocytopenia, a condition of( lowered blood platelet count and activity).
Seizures and VOD are serious concerns with busulfan therapy and prophylaxis
is often utilized to avoid these effects. Hepatic VOD is a dose-limiting toxicity.
Antiemetics are often administered prior to busulfan to prevent emesis.
Phenytoin, Levetiracetam, Benzodiazepines - to prevent the busulfan-induced
seizures.
Ursodiol -for prophylaxis of VOD.
Busulfan is listed by the IARC as a Group 1 carcinogen.

19. Nitrosoureas Dvt
Eg: Carmustine, Semustine, Lomustine
Nitrosourea compounds are DNA alkylating agents and
are often used in chemotherapy.
They are lipophilic and thus can cross the blood–brain
barrier, making them useful in the treatment of brain
tumors such as glioblastoma multiforme.
Side effect- Some nitrosoureas (e.g. lomustine) have been associated with the
development of interstitial lung disease.
Ethyleneamine Dvt
Eg: Thiotepa (Seldom used)
N,N',N''-triethylenethiophosphoramide (ThioTEPA
or thiotepa) is an alkylating agent used to treat cancer.

20. ThioTEPA is an organophosphorus compound with the formula
SP(NC2H4)3. It is an analogue of N,N',N''-triethylenephosphoramide
(TEPA). This molecule features tetrahedral phosphorus and is structurally
akin to phosphate. It is derived from aziridine and thiophosphoryl
chloride.
Triazine
Eg: Dacarbazine
Dacarbazine is an antineoplastic chemotherapy drug used in the
treatment of various cancers, among them malignant
melanoma, Hodgkin's lymphoma, sarcoma, and islet cell carcinoma of
the pancreas.
Dacarbazine is a member of the class of alkylating agents, which
destroy cancer cells by adding an alkyl group (CnH2n+1) to its DNA.
Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then
to diazomethane, which is an alkylating agent.

21.  Dacarbazine works by methylating guanine at the
O-6 and N-7 positions. Guanine is one of the four
nucleotides that makes up DNA. The alkylated
DNA strands stick together such that cell division
becomes impossible. This affects cancer cells
more than healthy cells because cancer cells
divide faster. Unfortunately however, some of the
healthy cells will still be damaged.
MOA
Note- It is the most important medications needed in a basic health
system.

22. Continue…………………