REPORT

IN
PHCHEM 49
ANTINEOPLASTIC DRUGS
SUBMITTED BY:
Alduheza, Shynne B.
Espaa, Lorebeth L.
Flores, Chiena Mae S.
Lo, Manuel Timothy Jude
C.
Tan, Marie Charmaine B.
SUBMITTED TO:
Mrs. Honeylene B. Paloma

CANCER
-uncontrolled growth of cells or tissues characterized with the
formation of a neoplasm
-classified according to:
cellular origin
benign or malignant state of histogenic differentiation
a.benign: fibroma
b.malignant: melanoma, sarcoma
ANTINEOPLASTIC DRUGS
-chemotherapeutic agents
-mechanism of action is targeted towards arresting aberrant cell
proliferation associated with cancerous cell growth
-carcinogenic, teratogenic, and mutagenic
CELL CYCLE
Phases:
Interphase
G0- resting stage, subphase of G1
G1- period between mitosis and DNA synthesis
last several hours to days
cell organelle synthesis and centriole replication
S- start of DNA synthesis and replication of chromosomes
G2- ends when mitosis start
M- begins with mitosis and ends with cytokinesis
Prophase, Metaphase, Anaphase, Telophase

Cell cycle specific agents

-interfere with at least one specific phase of cellular replication
Cell cycle non-specific agents
-act on both proliferating and resting cells

CLASSIFICATIONS OF ANTINEOPLASTIC DRUGS

A. Antimetabolites
MOA: alter normal cellular functions by substituting for components
with key metabolic processes
Net effect: disruption of nucleic acid synthesis effective on rapidly
proliferating cells mostly during the S phase
Indications:
-induction and maintenance of remission of leukemias,metatstatic
breast cancer, carcinomas
-used in the management of other proliferative disorders like
psoriasis and RA

Classes:
1. Pyrimidine analogs- 5-fluorouracil
2. Purine analogs- 6-mercaptopurine
3. Folate analogs- methotrexate
Acute toxicity
-GI: nausea, vomitting, diarrhea
-dermatologic: alopecia
-CNS: headache, blurred vision
-extravasation
-parenterally administered antimetabolites
-requires optimum administration technique:
a.discontinuation of medication
b.antidote administration
c.surgical debridement with skin grafting
d.antibiotic antineoplastics
Clinical Management of ADRs
-Leucovorin: specific antidote for MTX overdose as a therapeutic

modality
-rescue procedure permits the intracellular accumulation of MTX in
concentrations sufficient to inactive dihydrofolate
reductase
-used along with other chemotherapeutic agents in patients with
nonmetastatic osteosarcoma
B. Alkylating Agents
strong electrophiles: highly reactive carbonium ions
replacement with alkyl radicals: cross linking abnormal base pairing
net effect:
-production of defective DNA
-abortive reproduction of cells
effective on proliferative cells
not phase specific
act on any stage
Indications:
a.pallative treatment of malignancies susceptible to drugs
-malignant lymphoma
-leukemia
-germ cell, and progressive testicular, ovarian, and prostate
cancer
-myeloma
-brain tumor
b.others
-metastatic cancer
-neuroblastoma
-nonmalignant nephritic syndrome
Classes:
1. Nitrogen mustards- cyclophosphamide
2. Ethyleneamine and metyleneamine derivatives- thiotepa
3. Alkyl sulfonates- busulfan
4. Nitrosoureas- carmustine
5. Triazenes- dacarbazine
6. Platinum coordination complexes- cisplatin

Acute Toxicity

Clinical Management of ADRs

-monitor signs and symptoms of toxicity:

clinical measurement of hematologic, renal, and metabolic
functions
general supportive therapy
-recourse actions:
dose adjustment
discontinuation of drug
replacement of other drug
C. Miscellaneous Chemotherapeutic Drugs
Classes:
1. Natural Products
a. Vinca Alkaloids
- Vinblastine (Velba), Vincristine (Vincasar PFS)
- derived from periwinkle plant (Catharanthus roseus)
- cell specific (M phase)
- MOA: binds specifically to tubulin
- apoptotic changes: ecposure of normal and malignant cells to
plant alkaloids
- neurotoxic: disruption of microtubules involved in intracellular
movement, axonal transport, and phagocytosis
- irritation: improper positioning of i.v. needle or catheter
b. Taxoids
- Paclitaxel (Taxol)
- naturally derived from Pacific Yew plant
- M- phase specific
- MOA: promotes assembly of microtubules by stimulating
tubulin polymerization, rendering stable, nonfunctioning
microtubules
- resulting network bundles of microtubules:
-incapable of dynamic reorganization inhibiting cellular
mitosis ans proliferation

c. Epidophyllotoxins
- Etoposide (VePesid)
semisynthetic derivative of podophyllotoxin
G2- phase selective
high concentrations: cytolysis of cells entering mitosis
low concentrations: prevent cells from prophase entry
- Teniposide
causes single and double-stranded breaks by inhibiton of
type II topoisomerase activity
ADRs: severe myelosuppression and hypersensitivity reactions
d. Antibiotics
- MOA: disruption of DNA-dependent RNA synthesis, inhibition of
mitosis
- derived from eubacterial and actinomycetes genuses
- rapidly proliferating normal and neoplastic cells
- phase-specific
hemolytic uremic syndrome:
microangiopathic hemolytic anemia
thrombocytopenia
irrevesible renal failure

hemolytic uremic syndrome:

microangiopathic hemolytic anemia
thrombocytopenia
irrevesible renal failure
drug: mitomycin C
Pentostatin
-antimetabolite
-transition state analog
-interferes adenosine deaminase and its specific inhibition
results to:
-accumulation of ATP and deoxyadenosine nucleotides
-blockage of ribonucleotide reductase
-suspension of DNA synthesis
2. Hormones and Antagonists
-interaction of synthetic nonsteroidal chemicals with nuclear and
cell
membrane growth stimulatory receptor proteins
-greater specificity for tissues responsie to counterbalancing effects
-capable of occupying nuclear or membrane steroid receptors,
redirecting
feedback mechanism, and inhibiting normal or abnormal
function of tissues

- inhibit uncontrolled cell proliferation without direct cytotoxic effect

-used initially or as adjunctive therapy in pallative treatment of
malignancies susceptible to drugs

3. Platinum Coordination Complexes

-include:
Cisplatin(Platinol AQ)
Carboplatin (Paraplatin)
-phase-nonspecific
-MOA: produce interstrand DNA crosslinks rather than DNA-protein
intercalation
-toxicities and net effect are similar to alkylating agents
-inital and secondary treatment of ovarian carcinoma, testicular
tumors, and advanced bladder cancer
4. Substituted Urea
-Hydroxyurea (Hydrea)
-with antimetabolite action

-S-phase specific
-interfere with conversion of ribonucleotides to
deoxyribonucleotides
-inhibits incorporation of thymidine into DNA
-treatment of melanoma and leukemia
-used concomittantly with irradiation therapy: squamous cell
carcinoma of head and neck