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CHEMOTHERAPEUTIC DRUGS
(Anticancer Drugs)

Cancer chemotherapy often involves the use of cytotoxic drugs,

which are a specific class of chemotherapeutic agents designed to
target and destroy rapidly dividing cells, including cancer cells.
Chemotherapeutic drugs, also known as anticancer drugs are
medications used to treat various types of cancer. These drugs can
be categorized into several classes, each with its own mechanisms
of action, examples, and pharmacokinetics.

CYTOTOXIC DRUGS

1.ANTIMETABOLITES:
Antimetabolites are structurally related to normal
compounds that exist within the cell. They generally interfere
with the availability of normal purine or pyrimidine nucleotide
precursors, either by inhibiting their synthesis or by competing
with them in DNA or RNA synthesis.
A. Methotrexate (MTX), Pemetrexed, and
Pralatrexate

 Mechanism of Action: MTX is structurally related to

folic acid and acts as an antagonist of the vitamin by inhibiting
 mammalian dihydrofolate reductase (DHFR), the enzyme that
converts folic acid to its active, coenzyme form, tetrahydrofolic
acid (FH4).The inhibition of DHFR can only be reversed by a
1000-fold excess of the natural substrate, dihydrofolate (FH2),
or by administration of leucovorin, which bypasses the blocked
enzyme and replenishes the folate pool. MTX is specific for the
S-phase of the cell cycle. Pemetrexed is an antimetabolite
similar in mechanism to methotrexate. However, in addition to
inhibiting DHFR, it also inhibits thymidylate synthase and
other enzymes involved in folate metabolism and DNA
synthesis. Pralatrexate is a newer antimetabolite that also
inhibits DHFR.
 Adverse Effects: Adverse effects of these drugs include
myelosuppression (anemia, thrombocytopenia, and
leukopenia), gastrointestinal disturbances, fatigue, mucositis,
renal dysfunction, skin sensitivity. Pralatrexate and
Pemetrexed requires supplementation with folic acid and
vitamin B12.
 Pharmacokinetics: Methotrexate has multiple
administration routes but limited oral absorption, widespread
distribution, and limited blood-brain barrier penetration. It
undergoes liver metabolism and renal elimination. Pemetrexed
is administered intravenously, rapidly distributes to tissues,
and necessitates dose adjustments in renal impairment.
Pralatrexate is given intravenously, has extensive tissue
distribution, and undergoes hepatic metabolism and renal
elimination. Dose adjustments are needed for impaired renal
function. Monitoring blood levels and renal function is vital for
optimizing therapy and reducing toxicity.
 Therapeutic uses:
1. MTX, usually in combination with other drugs,is effective
against acute lymphocytic leukemia, breast cancer, bladder
cancer, and head and neck carcinomas.

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 2. It is also used in lower doses to treat autoimmune diseases
like rheumatoid arthritis, psoriasis, and inflammatory bowel
disease.
3. Pemetrexed is primarily used in non–small cell lung cancer.
4. Pralatrexate is used in relapsed or refractory T-cell
lymphoma.

B. 6-Mercaptopurine

 Mechanism of Action: 6-Mercaptopurine interferes with

the synthesis of DNA and RNA by acting as a purine analogue.
It gets incorporated into the nucleic acids, disrupting their
structure and function. Additionally, 6-MP inhibits several
enzymes involved in purine metabolism, leading to a reduction
in the production of purine nucleotides required for DNA and
RNA synthesis. This interference ultimately impairs the growth
and proliferation of rapidly dividing cells, including cancer
cells.
 Pharmacokinetics: Oral absorption is erratic and
incomplete. Once it enters the blood circulation, the drug is
widely distributed throughout the body, except for the
cerebrospinal fluid (CSF). The bioavailability of 6-MP can be
reduced by first-pass metabolism in the liver. 6-MP is
converted in the liver to the methyl mercaptopurine derivative
or to thiouric acid (an inactive metabolite. The parent drug and
its metabolites are excreted by the kidney.
 Adverse Effects: Common adverse effects of 6-
Mercaptopurine include myelosuppression, nausea, vomiting,
and git disturbances. Hypersensitivity reactions and
hepatotoxicity can also occur. Additionally, there is a risk of

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 bone marrow suppression and an increased susceptibility to
infections.
 Therapeutic uses:
1. Primarily in the treatment of hematological malignancies,
including acute lymphoblastic leukemia.
2. IBD treatment, 6-MP helps to reduce inflammation and
modulate the immune response to control disease activity.

C. 5-Fluorouracil

 Mechanism of Action: 5-Fluorouracil is a pyrimidine

analogue that interferes with DNA and RNA synthesis by
inhibiting the enzyme thymidylate synthase. It is incorporated
into DNA and RNA, causing chain termination and inhibiting
further nucleotide addition. This disruption of nucleotide
synthesis inhibits cell division and ultimately leads to cell
death.
 Pharmacokinetics: 5-FU can be administered orally, but
intravenous (IV) administration is more common. It distributes
widely throughout the body, including into tumor tissues. 5-FU
undergoes hepatic metabolism, primarily by the enzyme
dihydropyrimidine dehydrogenase (DPD). It is excreted
through the urine as metabolites.
 Pharmacodynamics: 5-FU is cell-cycle specific, affecting
cells primarily in the S phase of the cell cycle when DNA
synthesis occurs. It induces cytotoxic effects, leading to cell
death or apoptosis.
 Therapeutic uses:

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 1. Treat various cancers, including colorectal cancer, breast
cancer, head and neck cancer, and gastrointestinal tumors.
2. It is also used for actinic keratosis (a skin condition) and as
part of combination chemotherapy regimens for different
cancer types.

D. Fludarabine

 Mechanism of Action: Fludarabine is a prodrug that

gets converted into its active form (2-F-araA) and interferes
with DNA and RNA synthesis, leading to cell death in rapidly
dividing cancer cells.
 Pharmacokinetics: Administered intravenously (IV).
Metabolized in the liver. Partial elimination through urinary
excretion.
 Uses: Effective in treating chronic lymphocytic leukemia
(CLL), hairy cell leukemia, and some forms of indolent non-
Hodgkin lymphoma.
 Adverse Effects:Common side effects include bone
marrow suppression, immune system weakening, nausea,
vomiting, fatigue, and skin rashes. Neurotoxicity, secondary
cancers, and other serious side effects can also occur.
Monitoring by healthcare professionals is crucial.
Similarly other antimetabolites includes Cladribine,
Capecitabine, Azacitidine, Gemcitabine etc

3. ANTIBIOTICS:
The interactions of the antitumor antibiotics, which result in
the breakdown of DNA activity, are principally responsible for
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 their cytotoxic action. Their capacity to prevent topoisomerases
from functioning in addition to intercalation.

A. Anthracyclines: Doxorubicin,
daunorubicin, idarubicin, epirubicin, and
mitoxantrone:
Anthracycline antibiotics include doxorubicin and
daunorubicin. The hydroxylated version of daunorubicin is
called doxorubicin. There is also idarubicin, a 4-demethoxy
analog of daunorubicin, epirubicin, and mitoxantrone.
 Mechanism of action: Doxorubicin and other
anthracyclines induce cytotoxicity through several different
mechanisms. For example, doxorubicin-derived free radicals
can induce membrane lipid peroxidation, DNA strand
scission, and direct oxidation of purine or pyrimidine bases,
thiols, and amines.
 Pharmacokinetics: These drugs are administered via
IV due to gastrointestinal ineffectiveness. IV extravasation
can harm tissues. They widely distribute in the body, binding
to plasma proteins and tissues, but can't access the brain or
testes. Liver metabolism necessitates adjustments for liver
issues. Primary elimination occurs via bile, with minimal
renal excretion. Their red color may make veins near the
infusion site visible, and urine may turn reddish.
 Pharmacodynamics: These antibiotics have potent
cytotoxic effects on rapidly dividing cells, including cancer
cells but can also affect healthy tissues.
 Adverse Effects: Myelosuppression, nausea, vomiting,
diarrhea, mucositis, cardiac toxicity, alopecia, red coloration
of urine. Strong vesicants.
 Therapeutic uses:

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 1. Doxorubicin is one of the most important and widely used
anticancer drugs. It is used in combination with other agents
for treatment of sarcomas and cancers including breast, lung,
and lymphomas.
2. Daunorubicin and idarubicin are used in the treatment of
acute leukemias.
3. Mitoxantrone is used in prostate cancer.

B. Bleomycin
Bleomycin is cell cycle specific and causes cells to accumulate in
the G2 phase. It cause scission of DNA by an oxidative process.

 Mechanism of Action: A DNA–bleomycin–Fe2+

complex appears to undergo oxidation to bleomycin–Fe3+.
The liberated electrons react with oxygen to form superoxide
or hydroxyl radicals, which, in turn, attack the
phosphodiester bonds of DNA, resulting in strand breakage
and chromosomal aberrations.
 Pharmacokinetics: Bleomycin is administered by a
number of routes. The bleomycin-inactivating enzyme (a
hydrolase) is high in a number of tissues (for example, liver
and spleen) but is low in the lung and is absent in skin
(accounting for the drug’s toxicity in those tissues). Most of
the parent drug is excreted unchanged in the urine.
 Pharmacodynamics: It includes cytotoxicity against
rapidly dividing cells, including cancer cells. It triggers
apoptosis. Unlike some other chemotherapy drugs,
bleomycin does not typically cause myelosuppression, which
is a common side effect of many anticancer agents.
 Adverse Effects: Pulmonary fibrosis, alopecia, skin
reactions, hyperpigmentation of hands, fever, chills,

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 anaphylaxis. The pulmonary fibrosis that is caused by
bleomycin is often referred as “bleomycin lung.”

 Therapeutic uses:
It is primarily used in the treatment of testicular cancers and
Hodgkin lymphoma.

3. ALKYLATING AGENTS:
Alkylating agents exert their cytotoxic effects by
covalently binding to nucleophilic groups on various cell
constituents. Alkylation of DNA is probably the crucial cytotoxic
reaction that is lethal to the tumor cells. Alkylating agents do not
discriminate between cycling and resting cells, even though they
are most toxic for rapidly dividing cells.

A. Cyclophosphamide and ifosfamide

These drugs are very closely related mustard agents that share
most of the same primary mechanisms and toxicities. They are
cytotoxic only after generation of their alkylating species, which
are produced through hydroxylation by cytochrome P450
(CYP450).
 Mechanism of action: Cyclophosphamide is the most
commonly used alkylating agent. Both cyclophosphamide
and ifosfamide are first biotransformed to hydroxylated
intermediates primarily in the liver by the CYP450
system.The hydroxylated intermediates then undergo
breakdown to form the active compounds, phosphoramide
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 mustard and acrolein. Reaction of the phosphoramide
mustard with DNA is considered to be the cytotoxic step. The
parent drug and its metabolites are primarily excreted in
urine.
 Pharmacokinetics: Cyclophosphamide is available in
oral or IV preparations, whereas ifosfamide is IV only.
Cyclophosphamide is metabolized in the liver to active and
inactive metabolites, and minimal amounts are excreted in
the urine as unchanged drug. Ifosfamide is metabolized
primarily by CYP450 3A4 and 2B6 isoenzymes. It is mainly
renally excreted.
 Pharmacodynamics: The primary pharmacodynamic
effect of cyclophosphamide and ifosfamide is their
cytotoxicity against cancer cells.They are cell-cycle non-
specific, meaning they can affect cells in various phases of
the cell cycle.
 Adverse Effects: A unique toxicity of both drugs is
hemorrhagic cystitis, which can lead to fibrosis of the
bladder. A fairly high incidence of neurotoxicity has been
reported in patients on high-dose ifosfamide, probably due
to the metabolite, chloroacetaldehyde.
 Therapeutic uses:
1. Cyclophosphamide and ifosfamide are employed in the
treatment of various cancers and in the management of
autoimmune diseases, such as lupus and rheumatoid
arthritis.

B.Nitrosoureas:

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 Carmustine and lomustine are closely related nitrosoureas.
Because of their ability to penetrate the CNS, the nitrosoureas are
primarily employed in the treatment of brain tumors.
 Mechanism of action: The nitrosoureas exert cytotoxic
effects by an alkylation that inhibits replication and,
eventually, RNA and protein synthesis. Although they
alkylate DNA in resting cells, cytotoxicity is expressed
primarily on cells that are actively dividing. Therefore,
nondividing cells can escape death if DNA repair occurs.
Nitrosoureas also inhibit several key enzymatic processes by
carbamoylation of amino acids in proteins in the targeted
cells.
 Pharmacokinetics: Despite their structural similarities,
carmustine is administered intravenously (IV) and as
chemotherapy wafer implants, while lomustine is given
orally. Both drugs have significant lipophilicity, leading to
extensive distribution throughout the body. Their
remarkable feature is their ability to easily enter the central
nervous system (CNS). They undergo extensive metabolism,
with lomustine forming active metabolites. The primary
route of excretion for nitrosoureas is through the kidneys.
 Adverse Effects: Nitrosoureas, like carmustine and
lomustine, can lead to various adverse effects, including
myelosuppression, git disturbances, pulmonary toxicity,
hepatotoxicity, renal dysfunction, neurotoxicity, skin
reactions, and an increased risk of secondary malignancies.
Their ability to penetrate the central nervous system (CNS)
can result in neurological side effects.

 Therapeutic uses:

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 Their ability to penetrate the blood-brain barrier makes
them effective against brain tumors.

C. Dacarbazine:
Dacarbazine is a drug that transforms into an active
form called MTIC, which can damage DNA by attaching
methyl groups. This action, similar to other alkylating
agents, is how it works as a cancer treatment.
Dacarbazine is used to treat melanoma and Hodgkin
lymphoma.

D. Temozolomide:
Temozolomide is a drug used for tough-to-treat brain tumors
like glioblastomas and anaplastic astrocytomas, as well as
metastatic melanoma. It's related to dacarbazine but doesn't need
the CYP450 system for activation; it works under normal pH
conditions. It also inhibits a DNA repair enzyme. Unlike
dacarbazine, it crosses the blood-brain barrier and can be given as
a pill or injection, with good oral absorption. The body excretes it
in urine.

E. Other alkylating agents:

Mechlorethamine, use in lymphatic cancer treatment due to
its ability to reduce lymphocyte counts, Melphalan, derived
from nitrogen mustard, is used to treat multiple myeloma and can
be taken orally, but absorption and plasma concentration vary
among patient. Chlorambucil treats chronic lymphocytic
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leukemia, with moderate blood-related side effects and GI upset.
Busulfan is effective against chronic granulocytic leukemia but
can cause pulmonary fibrosis, especially in older patients. All
these agents are associated with an increased risk of leukemia, a
known side effect of alkylating agents.

4. Natural Product Cytotoxic Drugs:

This category of anticancer agents is derived from natural
sources, such as plants, microbes, or marine organisms. These
drugs are often synthesized or isolated from these natural
sources due to their potential to inhibit the growth of cancer
cells or interfere with their functions. Natural cytotoxic drug
includes;

A. Vinca Alkaloids (Vinblastine and Vincristine):

 Mechanism of Action: Inhibit microtubule
formation, disrupting cell division.
 Pharmacokinetics: Administered intravenously,
undergo metabolism in the liver, and are excreted in
bile and urine.
 Uses: Used in various cancers, including lymphomas,
leukemias, and solid tumors.
 Adverse Effects: Neuropathy, myelosuppression,
constipation, and GI disturbances.

B. Taxanes (Paclitaxel and Docetaxel):

 Mechanism of Action: Stabilize microtubules,
preventing cell division.
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  Pharmacokinetics: Administered intravenously,
extensively metabolized in the liver, and excreted in
bile and feces.
 Uses: Effective against breast, ovarian, and lung
cancers, among others.
 Adverse Effects: Neuropathy, myelosuppression,
hypersensitivity reactions, and fluid retention.

C. Camptothecins (Topotecan and Irinotecan):

 Mechanism of Action: Inhibit topoisomerase I,
an enzyme required for DNA replication.
 Pharmacokinetics: Administered intravenously,
undergo hepatic metabolism, and are excreted in bile
and feces.
 Uses: Used in colorectal, ovarian, and small cell lung
cancers.
 Adverse Effects: Diarrhea (common with
irinotecan), myelosuppression, and fatigue.

D. Etoposide:
 Mechanism of Action: Inhibits topoisomerase
II, disrupting DNA replication.
 Pharmacokinetics: Administered orally or
intravenously, metabolized in the liver, and excreted in
urine and feces.
 Uses: Effective against small cell lung cancer,
testicular cancer, and lymphomas.
 Adverse Effects: Myelosuppression, nausea,
vomiting, and hair loss.

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 E. Podophyllotoxin Derivatives (Etophylline and
Teniposide)

 Mechanism of Action: Inhibit topoisomerase II,

interfering with DNA replication.
 Pharmacokinetics: Administered intravenously,
undergo metabolism, and are excreted in urine.
 Uses: Etophylline is used in testicular cancer, while
teniposide is used in leukemia.
 Adverse Effects: Myelosuppression, nausea, vomiting,
and diarrhea.

IMMUNOGLOBULINS
Monoclonal antibodies are immunoglobulins derived from a
monoclonal cell line and which have a defined specificity.

A. Trastuzumab
Trastuzumab, a humanized monoclonal antibody, is designed to
selectively target the extracellular portion of the HER2 growth
receptor, which possesses inherent tyrosine kinase activity.
 Mechanism of action: Trastuzumab binds to HER2
sites in breast cancer, gastric cancer, and gastroesophageal
tissues and inhibits the proliferation of cells that overexpress

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 the HER2 protein, thereby decreasing the number of cells in
the S-phase. By binding to HER2, it blocks downstream
signaling pathways, induces antibody-dependent
cytotoxicity, and prevents the release of HER2.
 Pharmacokinetics: Trastuzumab is given via IV,
doesn't absorb orally, has a wide distribution, especially in
tumors, and is mainly cleared through proteolytic
degradation, mostly via the RES, with some renal excretion.
 Pharmacodynamics: It targets HER2 in cancer cells,
blocking growth signals, slowing cell division, and promoting
immune-based cell destruction like ADCC.
 Adverse effects: The most serious toxicity associated
with the use of trastuzumab is congestive heart failure. The
toxicity is worsened if given in combination with
anthracyclines. Extreme caution should be exercised when
giving the drug to patients with preexisting cardiac
dysfunction.
 Therapeutic uses:
Primarily in the treatment of cancers that overexpress the
HER2 protein, including breast, gastric and metastatic
cancers.

B.Rituximab
Rituximab was the pioneering monoclonal antibody approved for
cancer treatment. Engineered through genetic modification, it's a
chimeric monoclonal antibody designed to target the CD20
antigen present on both normal and malignant B lymphocytes.

 Mechanism of Action: Rituximab sticks to the CD20

antigen on B lymphocytes using its Fab domain, and its Fc
domain signals the immune system to attack the B cells. This
causes the immune system to destroy the B cells through
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 processes like complement activation and antibody-
dependent cell-mediated cytotoxicity.
 Pharmacokinetics: Administered intravenously and
has a slow elimination rate, leading to a longer duration of
action.
 Pharmacodynamics: It targets CD20 on B cells,
leading to immune system-mediated B cell destruction. It's
used in cancer therapy to reduce B cell activity.
 Adverse Effects: Common adverse effects include
infusion reactions, fever, and chills during treatment. There's
also a risk of severe reactions, including infections and heart
and lung problems.
 Therapeutic uses: Rituximab is effective in the
treatment of lymphomas, chronic lymphocytic leukemia, and
rheumatoid arthritis.

C. Bevacizumab
The immunoglobulin bevacizumab is an IV antiangiogenesis
agent.

 Mechanism of Action: It attaches to and stops

vascular endothelial growth factor from stimulating the
formation of new blood vessels. Without new blood vessels,
tumors do not receive the oxygen and essential nutrients
necessary for growth and proliferation.
 Therapeutic uses: It is approved for use as a first-line
drug against metastatic colorectal cancer and is given with
5-FU–based chemotherapy.

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  Adverse Effects: Hypertension, proteinuria, bleeding,
GIT perforation, impaired wound healing, fatigue, nausea,
diarrhea and headache, etc.

D. Cetuximab and panitumumab

 Mechanism of Action: Cetuximab targets the

epidermal growth factor receptor (EGFR) on the surface of
cancer cells. By doing so, it interferes with the growth-
promoting pathways of these cells, inhibiting their
proliferation and progression.
 Pharmacokinetics: Administered intravenously. It
has a distribution to target tissues, and its elimination
occurs through various pathways.
 Therapeutic Uses: Cetuximab is approved for treating
KRAS wild-type metastatic colorectal cancer and head and
neck cancers. It plays a crucial role in inhibiting cancer
growth by targeting EGFR.
 Adverse Effects: Skin rash, electrolyte wasting,
infusion reaction, Diarrhea.

TYROSINE KINASE INHIBITOR

The tyrosine kinases are a family of enzymes that are involved in
several important processes within a cell, including signal
transduction and cell division. Many tyrosine kinase inhibitors are

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available for the treatment of cancer. Some of the more common
agents are discussed below;

A. Imatinib, dasatinib, and nilotinib

 Mechanism of Action: Imatinib is a signal

transduction inhibitor used to treat chronic myelogenous
leukemia (CML) and GI stromal tumors. It specifically
inhibits tumor tyrosine kinase activity, targeting the
deregulated BCR-ABL kinase in CML and unregulated
tyrosine kinase expression in GI stromal tumors. By
occupying the "kinase pocket," it prevents tyrosine
phosphorylation and inhibits cell proliferation.
 Pharmacokinetics: Imatinib, as well as nilotinib and
dasatinib, is available in oral formulations. They are well-
absorbed and have bioavailability. These drugs undergo
hepatic metabolism and renal excretion.
 Therapeutic Uses:
1. Imatinib is used to treat CML and GI stromal tumors.
2. Nilotinib and dasatinib are also first-line options for
CML.
 Adverse Effects: Notable toxicities associated with these
drugs include fluid retention and QT prolongation.

B. Erlotinib:

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  Mechanism of Action: Erlotinib inhibits the epidermal
growth factor receptor tyrosine kinase. It's an oral agent used
to treat non–small cell lung cancer and pancreatic cancer.
 Pharmacokinetics: Erlotinib is absorbed orally and
extensively metabolized in the liver by the CYP3A4 enzyme.
 Therapeutic Uses: It's approved for non–small cell lung
cancer and pancreatic cancer treatment.
 Adverse Effects: Commonly diarrhea, nausea, acne-like
skin rashes, and ocular disorders. A rare but potentially fatal
side effect is interstitial lung disease, characterized by acute
dyspnea and cough.

C. Sorafenib and Sunitinib:

 Mechanism of Action: Sorafenib and sunitinib are oral

kinase inhibitors used primarily in renal cell carcinoma.
Sorafenib is also used in hepatocellular carcinoma, while
sunitinib is employed in GI stromal tumors and pancreatic
neuroendocrine tumors. They target cell surface kinases
involved in tumor signaling, angiogenesis, and apoptosis,
thereby inhibiting tumor growth.
 Pharmacokinetics: Both drugs are administered orally.
 Therapeutic Uses:
1. Sorafenib and sunitinib are used in renal cell carcinoma.
2. Sorafenib is also used in hepatocellular carcinoma, while
sunitinib is employed in GI stromal tumors and pancreatic
neuroendocrine tumors.
 Adverse Effects: Common adverse effects include
diarrhea, fatigue, hand and foot syndrome, and
hypertension.

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 STEROID HORMONES
Steroid hormone-sensitive tumors can be hormone-responsive,
hormone-dependent, or both. Removing hormonal stimuli can be
done through surgery or medication.

A. Prednisone:
 Mechanism of Action:Prednisone, a potent synthetic
corticosteroid, has anti-inflammatory properties and less
mineralocorticoid activity than cortisol. It induces remission
in acute lymphocytic leukemia and treats Hodgkin and non-
Hodgkin lymphomas. At high doses, cortisol can break down
lymphocytes, leading to hyperuricemia.
 Pharmacokinetics: Prednisone is well-absorbed orally,
binds to plasma albumin and transcortin, and is metabolized
in the liver via 11-β-hydroxylation to its active form,
prednisolone. Prednisolone binds to receptors, triggering
protein production, and is later glucuronidated and excreted
in urine along with the parent compound.
 Therapeutic Uses: Prednisone is primarily used to
induce remission in acute lymphocytic leukemia and treat
Hodgkin and non-Hodgkin lymphomas.
 Adverse Effects: Adverse effects of prednisone include
Hyperglycemia, infection, ulcers, pancreatitis, mood
changes, cataract formation, osteoporosis.

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 B. Tamoxifen

 Mechanism of Action: Tamoxifen is a selective

estrogen receptor modulator (SERM). It binds to estrogen
receptors in breast tissue, preventing them from initiating
transcription and depleting estrogen receptors, thus
suppressing the effects of natural hormones and growth
factors.
 Pharmacokinetics: Tamoxifen is effective orally,
metabolized by the liver, and excreted primarily in feces. It
inhibits CYP3A4 and P-glycoprotein.
 Therapeutic uses:
1. used for first-line therapy in the treatment of estrogen
receptor–positive breast cancer.
 Adverse Effects: Hot flashes, N, V, vaginal bleeding,
hypercalcemia, thromboembolism.

 Leuprolide

 Mechanism of Action: Leuprolide is a gonadotropin-

releasing hormone (GnRH) analog used to lower estrogen
levels. It's often used in combination with drugs like
tamoxifen to treat hormone-sensitive breast cancer in
premenopausal women. By reducing estrogen levels, it helps
manage estrogen receptor–positive breast cancer.
 Pharmacokinetics: Leuprolide is administered
subcutaneously. It suppresses gonadotropin secretion,
ultimately lowering estrogen levels. It has a relatively short
half-life and needs regular administration.

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  Therapeutic uses:
1. Used to treat hormone-sensitive breast cancer in
premenopausal women.
2. It lowers estrogen levels and is often administered in
combination with other medications like tamoxifen to
manage estrogen receptor–positive breast cancer.
 Adverse Effects: Common side effects include
menopausal symptoms like hot flashes, mood changes, and
vaginal dryness. Long-term use may lead to bone density loss
and cardiovascular risks.

C. Estrogen

 Mechanism of Action: They inhibit prostatic tissue

growth by blocking LH production, which reduces androgen
synthesis in the testes. This affects tumors dependent on
androgens.
 Pharmacokinetics: Typically administered orally,
metabolized in the liver, and distributed widely in the body.
However, their use has been largely replaced by GnRH
analogs due to fewer adverse effects.
 Therapeutic uses: used to treat prostatic cancer by
inhibiting prostatic tissue growth by blocking LH
production, reducing androgen synthesis in the testes.
 Adverse Effects: Estrogen treatment can cause serious
complications, such as thromboemboli, myocardial
infarction, strokes, and hypercalcemia. Men who are taking
estrogens may experience gynecomastia and impotence.

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 -The end-

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