SlideShare ist ein Scribd-Unternehmen logo
1 von 41
Downloaden Sie, um offline zu lesen
Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1
Cancer (Malignant neoplasm) is a class of diseases in
which a group of cells display uncontrolled growth,
invasion, and sometimes metastasis. Cancer affects people
at all ages with the risk for most types increasing with age.
Carcinoma: Epithelial cells; breast, prostate, colon and
Lung cancers.
Sarcoma: muscle tissue, Connective tissue
Lymphoma and Leukemia: Hemopoietic cells
Germ cell cancer: germ cells- testicle & ovarian cancers
Blastoma: resembles embryonic tissue
Alkylating agents
Nitrogen mustards -Cyclophosphamide Chlorambucil
Alkyl sulfonates - Busulfan
Nitrosoureas- Carmustine, Lomustine
Ethylenimines- Thiotepa
Triazenes- Dacarbazine
Antimetabolites
Folate antagonist - Methotrexate
Purine analogues -Thioguanine Mercaptopurine
Fludarabine
Pyrimidine analogues -Cytarabine Fluorouracil
Antibiotics
Anthracyclines Doxorubicin hydrochloride
Daunorubicin Bleomycin sulfate C . Mitomycin
Dactinomycin ( Actinomycin D) Plicamycin
Plant derived products
Vinca alkaloids Vincristine Vinblastine
Epipodophyllotoxins Etoposide Teniposide
Taxanes paclitaxel, docetaxel
Hormonal agents
Glucocorticoids- Prednisolone
Estrogens, anti-estrogens- Tamoxifen, Estramustine
Androgens, anti-androgens Flutamide
Progestins – hydroxy progeseterone acetate
Luteinizing hormone–releasing hormone (LH-RH)
antagonists - Buserelin Leuprolide
Immuno modulators Levamisole
Interferons Interferon alfa-2a and 2 b
Interleukins - Aldesleukin
Monoclonal antibodies Rituximab, Alemtuzumab
Ibritumomab, Gemtuzumab
Miscellaneous agents
Hydroxyurea
Procarbazine
Mitotane
Cisplatin Carboplatin
Mitoxantrone
Cellular growth factors -Filgrastim, Sargramostim
Enzymes- L- Asparaginase
Class anticancer drugs
Nitrogen mustards -Cyclophosphamide Chlorambucil,
Mechlorethamine , Alkyl sulfonates -Busulfan,
Nitrosoureas -Carmustine, Lomustine
Ethylenimines -Thiotepa Triazenes Dacarbazine
MOA: Cross-linkage Miss- pairing of bases
Depurination
Cytotoxic agents- alkylation of DNA
Use: Hematologic and solid cancers and used in
combination therapy.
A/E: direct vesicant effects, nausea and vomiting after
30-40 min. of injection, Mutagenic.
Mechanism of action:
Hepatic cytochrome P-450 system, enzymes phosphatase
and phosphamidase (activators) aldophosphamide,
which nonenzymatically breaks down to
Phosphoramide mustard (bifunctional) &
Acrolein(cytotoxic)
Pharmacokinetics:
Oral bioavailability- 90-100%,
IV injection no local irritation
Half-life -- cyclophosphamide -- 3-10 h; aldophosphamide
-- 1.6 h; phosphoramide mustard -- 8.7 h.
Most metabolized-- < 14% unchanged in urine.
Active on lymphoproliferative diseases, e.g., Hodgkin's
disease and Chronic lymphocytic leukemia
Significant activity against multiple myeloma & ovarian,
breast, small cell lung carcinoma
Combinations- CVP, COP regimen, MOPP regimen
Adverse effects:
Cystitis, dysuria, fibrosis, hyponatremia
Bone marrow suppression, most important leukopenia
and thrombocytopenia
Nausea and vomiting said to be rare
Sterile necrotizing hemorrhagic cystitis(Acrolein)
Sulfur mustard, forms toxic cyclic rthylenimmonium ion
Mechlorethamine 0.4 mg/kg IV, in single or divided
doses. PK: Unstable, solutions- just prior to
administration T 1/2 is 10 min. after IV. Little or no intact
drug excreted in urine.
MOPP, Hodgkin’s, leukemia, lymphosarcoma
A/E: Myelosuppression Leukopenia &
Thrombocytopenia Nausea and vomiting Extravasation
Nitrosoureas: Carmustine , Lomustine, Semustine
MOA: Chloro ethyl moiety- capable of alkylating nucleic
acids and proteins Alkylation and Carbamoylation of DNA.
These agents can kill cells in all phases of the cell cycle
P/K: High lipophilicity Unstable, forming highly reactive
decomposition products;
T 1/2 is few min. Renal excretion
Uses -treatment of Hodgkin’s disease, lung cancer
A/E: Bone marrow suppression Leukopenia &
Thrombocytopenia Nausea and vomiting Alopecia ,
Stomatitis , interstitial fibrosis (pulmonary toxicity)
MOA: It is a bifunctional methane sulfonic ester that
forms Intrastrand cross-linkages with DNA.
Palliative treatment of chronic granulocytic leukemia
Busulfan 2–8 mg/d orally; 150– 250 mg/course
P/K: Orally; T 1/2 is <5 min. Excretion in the urine.
Busulfan+ allopurinol prevents excessive uric acid
production from rapid tumor lysis
A/E: Selectively toxic to granulocyte precursors rather
than lymphocytes, interstitial pulmonary fibrosis,
Thrombocytopenia and anemia, gynacomastia
Adverse effects of alkylating agents:
More toxic to bone marrow and gut than to liver and
kidney,
Infertility to both males and females. (3) Mutagenic. (4)
Carcinogenic.
Tumor resistance:
Develops slowly & may require several genetic/
biochemical changes
Folate antagonist Methotrexate
Purine analogues Thioguanine Mercaptopurine
Fludarabine
Pyrimidine analogues Cytarabine Fluorouracil
These are structurally related to naturally occurring
compounds , such as vitamins, amino acids, and
nucleotides. These drugs can compete for binding sites
on enzymes or can themselves become incorporated
into DNA or RNA and thus interfere with cell growth
and proliferation .
Folic Acid Analogue, Carrier transport into cell. (2) Binds
strongly to DHFR to deplete THF, Decreases 1-carbon
transfers in Purine synthesis, Decreases [1-C-THF]
intracellular which decreases dUMP dTMP, Therefore,
decreases NUCLEIC ACID synthesis.
Clinical Uses:
Broad range. Well established: (1) Acute Lymphoblastic
Leukemia of childhood. (2) Choriocarcinoma. (3) Cancers
of breast, bladder, and head & neck. (4) Useful in non-
Hodgkin's lymphomas
Adverse effects:
Dose limiting: a) Myelosuppression
(Thrombocytopenia and Leukopenia 7-10 days after Rx,
Recovery 14-21 days). b) GI toxicity (Oral mucositis is
early sign of GI toxicity, Severe mucositis, Small bowel
ulceration & bleeding, Diarrhea -- requires cessation to
prevent perforation of gut )
(2) Nephrotoxicity: Conventional doses, infrequent
toxicity; High doses, toxicity can be severe
(3) Immunosuppression.
(4) Hepatotoxicity.
Mechanism of action:
(1) Activated by conversion to nucleotide
(2) Inhibits DNA synthesis: Inhibition of Thymidylate
synthase—the most important mechanism of action (MOA)
in rapidly growing tumors (?)
(3) 5-FU Incorporated into RNA: Interfere with RNA
processing - All types, most important MOA in slowly
growing tumors.
Clinical Use of 5-FU:
(1) Single agent: Palliative in advanced colorectal carcinoma
(2) Combination: Breast cancer; Carcinomas of ovary,
stomach, pancreas
(3) Sequential MTX + 5-FU: Head and neck cancer
Adverse effects:
Bone marrow -- esp. with bolus administration.
Leukopenia & Thrombocytopenia ( 9-14 days after start
of Rx, recovery by day 21).
b) GI Toxicity -- esp. with infusion administration. usually
Stomatitis & Diarrhea 4-7 days after treatment
IV bolus: myelosuppression is dominant; Prolonged Rx,
may cause megaloblastic anemia
Hepatotoxicity (elevated transaminases);
myelosuppression less common
Thioguanine
MOA: Incorporation of thionucleotide analogue into DNA or
RNA. Feedback inhibition of purine nucleotide synthesis.
PK: slow- oral; T 1/2 is 24 hr ; C max is 6- 8 hr ; M-Liver, E-
renal.
Uses: Curative combination chemotherapy for acute
myelogenous leukemia.
AE: Myelosuppression, leukopenia and thrombocytopenia,
Liver toxicity 2 mg/kg/d orally
MOA: binds actively to tubulin, a class of proteins that
form the mitotic spindle during cell division. Causes
cellular arrest in metaphase.
PLANT DERIVED PRODUCTS: Vincristine and Vinblastine
PK: highly bound to tissues, M-liver and E- bile.
VC: MOPP for Hodgkin’s/non (1.5 mg/m 2 IV / wk. )
VB: testicular, breast & renal(0.1-0.2mg/kg IV/ wk. )
A/E:VC- Alopecia, neurotoxic , no myelosuppression .
VB- bone marrow toxicity, leukopenia, SIADH
All interact with DNA and/or RNA, but may also interact
with other cellular substituents.
Schedule dependence: LESS "phase-specific" than
antimetabolites.
Tissue necrosis is only generalizable toxicity.
All IV except bleomycin
Mechanism of action:
(1) DNA topoisomerase II inhibitor: Crucial to DNA
replication and transcription.
(2) Traditional explanations of MOA: a) intercalates
between base pairs of DNA and inhibits DNA-dependent
RNA synthesis. b) Generates free radicals that cause
membrane damage and DNA strand breaks.
Doxorubicin(Adriamycin)
Clinical Indications:
Broad spectrum anti-cancer activity.
Hodgkin's disease, non-Hodgkin's lymphomas,
sarcomas, acute leukemia, and breast, lung, and
ovarian carcinomas all responsive
Activity observed in bladder tumors, and carcinomas of
prostate, thyroid, endometrium, head and neck, and
other solid tumors
Adverse effects:
Local Toxicity -- Radiation Recall
Interaction of doxorubicin and radiation in some
tissues to produce enhanced reactions.
Reactions include: a) Skin: ulceration and necrosis. b)
Pulmonary fibrosis and sloughing of esophageal
mucosa. c) Heart, and intestinal mucosa may also be
affected
Three categories of toxicity: a) Local toxicities. b) Acute
toxicities. c) Chronic toxicity
(1) Local Toxicity – Extravasation (Severe local tissue
necrosis)
Adverse effects:
Acute Toxicities
a) Hematologic: Leukopenia with 7-10 days;
recovery typically by 21 days; Thrombocytopenia
and anemia less common
b) If given too fast: "Histamine-release" syndrome;
Cardiac arrest preceded by ECG changes
Chronic Toxicities
a) Cardiomyopathy and congestive heart failure:
require cessation of treatment
PROGESTINS
Progestational agents have been used as second-line
hormonal therapy for metastatic hormone-dependent
breast cancer and endometrial carcinoma previously
treated by surgery and radiotherapy.
Progestins stimulate appetite and restore a sense of
well-being in cachectic patients with advanced stages
of cancer and acquired immunodeficiency syndrome
(AIDS)
Medroxyprogesterone intramuscularly in doses of 400-
1000 mg weekly
Selective Estrogen-Receptor Modulators(SERMs)
High doses of estrogen have long been recognized as
effective treatment of breast cancer. for 8-12 weeks
Tamoxifen citrate is the most widely
studied anti-estrogenic treatment in breast cancer
prevents the development of breast cancer in women at
high risk prior nonmalignant breast
pathology, or inheritance of the BRCA1 or BRCA2 genes.
ADR-Vasomotor symptoms (hot flashes), atrophy of the
lining of the vagina, hair loss, nausea, and
vomiting.
MOA: it binds actively to Estrogen receptors and
competes with endogenous estrogens for the clinical
sites. Inhibits the growth of ovarian, uterus and breast
cancer cells.
PK: orally, T max is 4-7 hr , M- hydroxylation and
glucuronidation, E- in feces.
Synthetic anti-estrogen used in the treatment of breast
cancer.
A/E: Hot flushes, mild nausea, exacerbation, bone
pain, Hypercalcaemia
Selective Estrogen Receptor Downregulators(SERDs)
pure anti-estrogens- fulvestrant
Fulvestrant is used for postmenopausal women with
hormone receptor positive metastatic breast cancer
AROMATASE INHIBITORS
Anastrozole and letrozole nonsteroidal imidazoles
are used as part of the standard of care for treatment
of early-stage and advanced breast
cancer in postmenopausal women
Gonadotropin-Releasing Hormone Agonists and
Antagonists
GnRH agonists -leuprolide, goserelin, triptorelin,
histrelin and buserelin GnRH agonist will
deplete testicular androgens, while the anti-androgen
component competes at the receptor with residual
androgens made by the adrenal glands.
GnRH antagonist- Abarelix
rapidly achieves medical castration
ADR-local reactions and anaphylaxis
Anti-androgens-Cyproterone and Megestrol
Anti-androgens bind to ARs and competitively inhibit the
binding of testosterone and dihydrotestosterone
Advanced prostate cancer
NONSTEROIDAL ANTI-ANDROGENS
Flutamide and Bicalutamide-
Advanced prostate cancer
MOA: Inhibits Asparginase synthase enzyme. L-
Asparginase catalyzes the hydrolysis of L- Aspargine to
Aspartic acid and ammonia. Inhibits protein synthesis –
cell death.
PK: Derived from E.coli , T 1/2 is 6-30 hr , M-by serum
proteases and RES,
Uses Acute lymphoblastic Leukemia, Combination
therapy, non-lymphocytic cancers.
A/E: Hyper sensitivity, Nausea, anorexia, wt loss,
hepatotoxic, hyperglycemia Pancreatitis,
Class anticancer drugs
MOA: binds to DNA at N7, O6 of Guanine, and causes
cross linkage producing alterations in DNA structure and
inhibition of DNA synthesis. Cytotoxic effect similar to
alkylating agents
P/K: orally, extensively binds to proteins, T-max is 4-7 hr,
T 1/2 is 2-4 days. M- hydroxylation and glucuronidation,
E-renal. Testicular and Ovarian cancer.
A/E: Renal toxicity, severe nausea and vomiting, hearing
loss in high frequencies (4000Hz), mild bone marrow
toxicity.
IMATINIB -Acts by inhibiting the Philadelphia
chromosome(bcr-abl kinase) and is very useful in the
treatment of chronic myelogenous leukemia (CML).
Remissions in CML patients are achieved with high
frequency and very low toxicity.
GIST-Gastro-Intestinal Stromal tumors
Neurofibramatosis
RITUXIMAB: acts against CD20 on cell surfaces (normal
and malignant)
Non Hodgkin's lymphoma 375mg/m2, IV. AE:
Hypotension, Dizziness, Anxiety, Nausea, Diarrhea,
Bone marrow depression.
GEMTUZUMAB: acts against CD33 with drawn from
market
Acute Myeloid Leukemia 9 mg/m2, IV AE: chills, fever,
nausea, vomiting, hypoxia, dyspnea, bone marrow
depression.
FILGRASTIM: rG -CSF Acts on precursor hematopoietic
cells in the bone marrow by binding to specific
receptors that stimulate cellular proliferation and
differentiation into neutrophils .
Filgrastim accelerates recovery of neutrophils after
chemotherapy.
Drug is well tolerated mild to moderate bone pain.
MOPP-Mechlorethamine+ Vincristine (Oncovin),
Procarbazine+ Prednisolone
-for hodgkins lymphoma
COAP- Cyclophosphamide + Oncovin(Vincristine)
Ara-C(cytarabine)+ Prednisolone
-for acute lymphoblastic lymphoma
ABVD- Adriamycin(Doxorubicin) + Bleomycin+
Vinblastine+ Dacarbazine
for hodgkins lymphoma
POMP- Prednisolone+Oncovin+Methotrexate+
Purinethol(6-MP) for ALL
Defective activation: Cyclophosphamide requires
metabolic activation, Methotrexate conversion to more
active MTX-polyglutamate in cells
Increased inactivation: e.g., aldehyde dehydrogenase
converse cyclophosphamide to inactive metabolite.
Altered nucleotide pools: Can occur with
antimetabolites.
Altered DNA repair: Repair mechanisms increased, i.e.,
ability to remove cross-links, Affect the action of
bleomycin and other DNA-directed drugs
Altered target: Less affinity for drug, Methotrexate
(Dihydrofolate reductase changes ).
Decreased target: decreased topoisomerase II, e.g.,
etoposide
Gene amplification: Methotrexate (MTX) increase
dihydrofolate reductase, hence Requires more MTX to
block
Decreased accumulation: Decreased uptake
(Methotrexate -- carrier protein decreases). Increased
Efflux (Multidrug Resistance, P-Glycoprotein (gP-170)
in membrane, pumps drug out)
Download slides from
Authorstream-raghuprasada
Slideshare-raghuprasada
Youtube-raghuprasada

Weitere ähnliche Inhalte

Was ist angesagt?

Anticancer drugs 1 introduction and classification
Anticancer drugs 1 introduction and classificationAnticancer drugs 1 introduction and classification
Anticancer drugs 1 introduction and classificationSubramani Parasuraman
 
Anti-cancers and their mechanism of action
Anti-cancers and their mechanism of actionAnti-cancers and their mechanism of action
Anti-cancers and their mechanism of actionJoyce Mwatonoka
 
Antineoplastic agents(ravisankar)
Antineoplastic agents(ravisankar)Antineoplastic agents(ravisankar)
Antineoplastic agents(ravisankar)Dr. Ravi Sankar
 
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.Dr. Ravi Sankar
 
Antineoplastic agents-Anticancer drugs
Antineoplastic agents-Anticancer drugsAntineoplastic agents-Anticancer drugs
Antineoplastic agents-Anticancer drugskencha swathi
 
cancer chemotherapy
cancer chemotherapycancer chemotherapy
cancer chemotherapyNaser Tadvi
 
Medicinal chemistry-Anticancer agents
Medicinal chemistry-Anticancer agentsMedicinal chemistry-Anticancer agents
Medicinal chemistry-Anticancer agentsDHARMENDRA BARIA
 
Medicinal chemistry- antimalerial agents
Medicinal chemistry- antimalerial agentsMedicinal chemistry- antimalerial agents
Medicinal chemistry- antimalerial agentsDHARMENDRA BARIA
 
Anti ulcer drugs classification
Anti ulcer drugs classificationAnti ulcer drugs classification
Anti ulcer drugs classificationZulcaif Ahmad
 
Tetracycline sar
Tetracycline sarTetracycline sar
Tetracycline sarnaseefa
 
Anticancer drugs 4 cytotoxic drugs and antibiotics
Anticancer drugs 4 cytotoxic drugs and antibioticsAnticancer drugs 4 cytotoxic drugs and antibiotics
Anticancer drugs 4 cytotoxic drugs and antibioticsSubramani Parasuraman
 
Drugs Used in Urinary Tract Infection
Drugs Used in Urinary Tract InfectionDrugs Used in Urinary Tract Infection
Drugs Used in Urinary Tract InfectionPravin Prasad
 
immunostimulants
immunostimulantsimmunostimulants
immunostimulantsacademic
 
Antiviral agents
Antiviral agentsAntiviral agents
Antiviral agentsGanesh Mote
 
Management of chemotherapy induced nausea and vomiting
Management of chemotherapy induced nausea and vomitingManagement of chemotherapy induced nausea and vomiting
Management of chemotherapy induced nausea and vomitingAPOLLO JAMES
 

Was ist angesagt? (20)

Anticancer drugs 1 introduction and classification
Anticancer drugs 1 introduction and classificationAnticancer drugs 1 introduction and classification
Anticancer drugs 1 introduction and classification
 
Anticancer drugs 3 antimetabolites
Anticancer drugs 3 antimetabolitesAnticancer drugs 3 antimetabolites
Anticancer drugs 3 antimetabolites
 
Anti-cancers and their mechanism of action
Anti-cancers and their mechanism of actionAnti-cancers and their mechanism of action
Anti-cancers and their mechanism of action
 
Anti cancer drugs
Anti cancer drugsAnti cancer drugs
Anti cancer drugs
 
Antineoplastic agents(ravisankar)
Antineoplastic agents(ravisankar)Antineoplastic agents(ravisankar)
Antineoplastic agents(ravisankar)
 
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
 
Antineoplastic agents-Anticancer drugs
Antineoplastic agents-Anticancer drugsAntineoplastic agents-Anticancer drugs
Antineoplastic agents-Anticancer drugs
 
cancer chemotherapy
cancer chemotherapycancer chemotherapy
cancer chemotherapy
 
Medicinal chemistry-Anticancer agents
Medicinal chemistry-Anticancer agentsMedicinal chemistry-Anticancer agents
Medicinal chemistry-Anticancer agents
 
Medicinal chemistry- antimalerial agents
Medicinal chemistry- antimalerial agentsMedicinal chemistry- antimalerial agents
Medicinal chemistry- antimalerial agents
 
Anti ulcer drugs classification
Anti ulcer drugs classificationAnti ulcer drugs classification
Anti ulcer drugs classification
 
Tetracycline sar
Tetracycline sarTetracycline sar
Tetracycline sar
 
Basic principles of chemotherapy
Basic principles of chemotherapyBasic principles of chemotherapy
Basic principles of chemotherapy
 
Anticancer drugs 4 cytotoxic drugs and antibiotics
Anticancer drugs 4 cytotoxic drugs and antibioticsAnticancer drugs 4 cytotoxic drugs and antibiotics
Anticancer drugs 4 cytotoxic drugs and antibiotics
 
Drugs Used in Urinary Tract Infection
Drugs Used in Urinary Tract InfectionDrugs Used in Urinary Tract Infection
Drugs Used in Urinary Tract Infection
 
immunostimulants
immunostimulantsimmunostimulants
immunostimulants
 
Anti tb drugs
Anti tb drugsAnti tb drugs
Anti tb drugs
 
Antiviral agents
Antiviral agentsAntiviral agents
Antiviral agents
 
Immunostimulants
ImmunostimulantsImmunostimulants
Immunostimulants
 
Management of chemotherapy induced nausea and vomiting
Management of chemotherapy induced nausea and vomitingManagement of chemotherapy induced nausea and vomiting
Management of chemotherapy induced nausea and vomiting
 

Ähnlich wie Class anticancer drugs

Anti Cancer drugs I.ppt
Anti Cancer drugs I.pptAnti Cancer drugs I.ppt
Anti Cancer drugs I.pptnetraangadi2
 
Brief review of renal failure with chemotherapeutic agents
Brief review of renal failure with chemotherapeutic agentsBrief review of renal failure with chemotherapeutic agents
Brief review of renal failure with chemotherapeutic agentsKasarla Ramesh
 
Anticancer drugs: Classification , general toxicity and Alkylating agents.
Anticancer drugs: Classification , general toxicity and Alkylating agents.Anticancer drugs: Classification , general toxicity and Alkylating agents.
Anticancer drugs: Classification , general toxicity and Alkylating agents.Ameena Kadar
 
Cancer Chemotherapy
Cancer ChemotherapyCancer Chemotherapy
Cancer Chemotherapyazsyed
 
Alkylating agents and antimetabolites
Alkylating agents and antimetabolitesAlkylating agents and antimetabolites
Alkylating agents and antimetabolitesGedion Yilma
 
Overview of cancers plants
Overview of cancers plants Overview of cancers plants
Overview of cancers plants Yogesh Dutonde
 
Chemotherapy in hematological diseases
Chemotherapy in hematological diseasesChemotherapy in hematological diseases
Chemotherapy in hematological diseasesShimaa Abdallah
 
Chemotherapy of cancer
Chemotherapy of cancer Chemotherapy of cancer
Chemotherapy of cancer DollyChauhan10
 
Chemotherapy 101
Chemotherapy 101Chemotherapy 101
Chemotherapy 101derosaMSKCC
 
PIK3C Case Study
PIK3C Case StudyPIK3C Case Study
PIK3C Case StudyErin Rivera
 
Chapter 23 topoisomerase inhibitors
Chapter 23 topoisomerase inhibitorsChapter 23 topoisomerase inhibitors
Chapter 23 topoisomerase inhibitorsNilesh Kucha
 
Anticancer agents_Undergraduate class KIU.pptx
Anticancer agents_Undergraduate class KIU.pptxAnticancer agents_Undergraduate class KIU.pptx
Anticancer agents_Undergraduate class KIU.pptxAhemigisha
 

Ähnlich wie Class anticancer drugs (20)

Anti Cancer drugs I.ppt
Anti Cancer drugs I.pptAnti Cancer drugs I.ppt
Anti Cancer drugs I.ppt
 
Canc2
Canc2Canc2
Canc2
 
Anticancer drugs
Anticancer drugsAnticancer drugs
Anticancer drugs
 
Brief review of renal failure with chemotherapeutic agents
Brief review of renal failure with chemotherapeutic agentsBrief review of renal failure with chemotherapeutic agents
Brief review of renal failure with chemotherapeutic agents
 
Anticancer drugs: Classification , general toxicity and Alkylating agents.
Anticancer drugs: Classification , general toxicity and Alkylating agents.Anticancer drugs: Classification , general toxicity and Alkylating agents.
Anticancer drugs: Classification , general toxicity and Alkylating agents.
 
Cancer Chemotherapy
Cancer ChemotherapyCancer Chemotherapy
Cancer Chemotherapy
 
Anticancer drugs - drdhriti
Anticancer drugs - drdhritiAnticancer drugs - drdhriti
Anticancer drugs - drdhriti
 
Alkylating agents and antimetabolites
Alkylating agents and antimetabolitesAlkylating agents and antimetabolites
Alkylating agents and antimetabolites
 
Anti cancer drugs
Anti cancer drugsAnti cancer drugs
Anti cancer drugs
 
Overview of cancers plants
Overview of cancers plants Overview of cancers plants
Overview of cancers plants
 
Cancer
CancerCancer
Cancer
 
Chemotherapy in hematological diseases
Chemotherapy in hematological diseasesChemotherapy in hematological diseases
Chemotherapy in hematological diseases
 
Chemotherapy of cancer
Chemotherapy of cancer Chemotherapy of cancer
Chemotherapy of cancer
 
Chemotherapy 101
Chemotherapy 101Chemotherapy 101
Chemotherapy 101
 
PIK3C Case Study
PIK3C Case StudyPIK3C Case Study
PIK3C Case Study
 
Anti-Cancer-Agents.docx
Anti-Cancer-Agents.docxAnti-Cancer-Agents.docx
Anti-Cancer-Agents.docx
 
Anti cancer drugs
Anti cancer drugsAnti cancer drugs
Anti cancer drugs
 
Chapter 23 topoisomerase inhibitors
Chapter 23 topoisomerase inhibitorsChapter 23 topoisomerase inhibitors
Chapter 23 topoisomerase inhibitors
 
Anticancer agents_Undergraduate class KIU.pptx
Anticancer agents_Undergraduate class KIU.pptxAnticancer agents_Undergraduate class KIU.pptx
Anticancer agents_Undergraduate class KIU.pptx
 
Cancer nanotechnology
Cancer nanotechnologyCancer nanotechnology
Cancer nanotechnology
 

Mehr von Raghu Prasada

Class skeletal muscle relaxants
Class skeletal muscle relaxantsClass skeletal muscle relaxants
Class skeletal muscle relaxantsRaghu Prasada
 
Classs drug metabolism
Classs drug metabolismClasss drug metabolism
Classs drug metabolismRaghu Prasada
 
Class antiadrenergic drugs
Class antiadrenergic drugsClass antiadrenergic drugs
Class antiadrenergic drugsRaghu Prasada
 
Class miscellaneous antibiotics
Class miscellaneous antibioticsClass miscellaneous antibiotics
Class miscellaneous antibioticsRaghu Prasada
 
Class drug absorption
Class drug absorptionClass drug absorption
Class drug absorptionRaghu Prasada
 
Dental pharmacology iii
Dental pharmacology iiiDental pharmacology iii
Dental pharmacology iiiRaghu Prasada
 
Class dental pharmacology 2
Class dental pharmacology 2Class dental pharmacology 2
Class dental pharmacology 2Raghu Prasada
 
Antibiotic resistance 1
Antibiotic resistance 1Antibiotic resistance 1
Antibiotic resistance 1Raghu Prasada
 
Class thyroid and antithyroid drugs
Class thyroid and antithyroid drugsClass thyroid and antithyroid drugs
Class thyroid and antithyroid drugsRaghu Prasada
 
Class introduction to chemoTHERAPY
Class introduction to chemoTHERAPYClass introduction to chemoTHERAPY
Class introduction to chemoTHERAPYRaghu Prasada
 
Class adverse drug reaction
Class adverse drug reactionClass adverse drug reaction
Class adverse drug reactionRaghu Prasada
 
Drm science lecture MENOPAUSE AND CRYOPRESERVATION
Drm science lecture MENOPAUSE AND CRYOPRESERVATIONDrm science lecture MENOPAUSE AND CRYOPRESERVATION
Drm science lecture MENOPAUSE AND CRYOPRESERVATIONRaghu Prasada
 
Drm science lecture 2 CONTRACEPTIVES AND IUDs
Drm science lecture 2 CONTRACEPTIVES AND IUDsDrm science lecture 2 CONTRACEPTIVES AND IUDs
Drm science lecture 2 CONTRACEPTIVES AND IUDsRaghu Prasada
 
Class antileprotic drugs
Class antileprotic drugsClass antileprotic drugs
Class antileprotic drugsRaghu Prasada
 
Class oral contraceptives
Class oral contraceptivesClass oral contraceptives
Class oral contraceptivesRaghu Prasada
 
Class excretion of drugs
Class excretion of drugsClass excretion of drugs
Class excretion of drugsRaghu Prasada
 
Class sources of drugs
Class sources of drugsClass sources of drugs
Class sources of drugsRaghu Prasada
 
Class 1 antidepressants
Class 1 antidepressantsClass 1 antidepressants
Class 1 antidepressantsRaghu Prasada
 

Mehr von Raghu Prasada (20)

Class skeletal muscle relaxants
Class skeletal muscle relaxantsClass skeletal muscle relaxants
Class skeletal muscle relaxants
 
Classs drug metabolism
Classs drug metabolismClasss drug metabolism
Classs drug metabolism
 
Class antiadrenergic drugs
Class antiadrenergic drugsClass antiadrenergic drugs
Class antiadrenergic drugs
 
Class miscellaneous antibiotics
Class miscellaneous antibioticsClass miscellaneous antibiotics
Class miscellaneous antibiotics
 
Class drug absorption
Class drug absorptionClass drug absorption
Class drug absorption
 
Dental pharmacology iii
Dental pharmacology iiiDental pharmacology iii
Dental pharmacology iii
 
Class dental pharmacology 2
Class dental pharmacology 2Class dental pharmacology 2
Class dental pharmacology 2
 
Antibiotic resistance 1
Antibiotic resistance 1Antibiotic resistance 1
Antibiotic resistance 1
 
Class thyroid and antithyroid drugs
Class thyroid and antithyroid drugsClass thyroid and antithyroid drugs
Class thyroid and antithyroid drugs
 
Class introduction to chemoTHERAPY
Class introduction to chemoTHERAPYClass introduction to chemoTHERAPY
Class introduction to chemoTHERAPY
 
Class adverse drug reaction
Class adverse drug reactionClass adverse drug reaction
Class adverse drug reaction
 
Class intro to cns
Class intro to cnsClass intro to cns
Class intro to cns
 
Drm science lecture MENOPAUSE AND CRYOPRESERVATION
Drm science lecture MENOPAUSE AND CRYOPRESERVATIONDrm science lecture MENOPAUSE AND CRYOPRESERVATION
Drm science lecture MENOPAUSE AND CRYOPRESERVATION
 
Drm science lecture 2 CONTRACEPTIVES AND IUDs
Drm science lecture 2 CONTRACEPTIVES AND IUDsDrm science lecture 2 CONTRACEPTIVES AND IUDs
Drm science lecture 2 CONTRACEPTIVES AND IUDs
 
Class ccf
Class ccfClass ccf
Class ccf
 
Class antileprotic drugs
Class antileprotic drugsClass antileprotic drugs
Class antileprotic drugs
 
Class oral contraceptives
Class oral contraceptivesClass oral contraceptives
Class oral contraceptives
 
Class excretion of drugs
Class excretion of drugsClass excretion of drugs
Class excretion of drugs
 
Class sources of drugs
Class sources of drugsClass sources of drugs
Class sources of drugs
 
Class 1 antidepressants
Class 1 antidepressantsClass 1 antidepressants
Class 1 antidepressants
 

Kürzlich hochgeladen

Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communicationskatiequigley33
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfHongBiThi1
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfMedicoseAcademics
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.pptRamDBawankar1
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfHongBiThi1
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismusChandrasekar Reddy
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.kishan singh tomar
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyZurück zum Ursprung
 

Kürzlich hochgeladen (20)

Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communications
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdf
 
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
 
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdfSGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
SGK LEUKEMIA KINH DÒNG BẠCH CÂU HẠT HAY.pdf
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismus
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturally
 

Class anticancer drugs

  • 1. Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC. 1
  • 2. Cancer (Malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth, invasion, and sometimes metastasis. Cancer affects people at all ages with the risk for most types increasing with age. Carcinoma: Epithelial cells; breast, prostate, colon and Lung cancers. Sarcoma: muscle tissue, Connective tissue Lymphoma and Leukemia: Hemopoietic cells Germ cell cancer: germ cells- testicle & ovarian cancers Blastoma: resembles embryonic tissue
  • 3. Alkylating agents Nitrogen mustards -Cyclophosphamide Chlorambucil Alkyl sulfonates - Busulfan Nitrosoureas- Carmustine, Lomustine Ethylenimines- Thiotepa Triazenes- Dacarbazine Antimetabolites Folate antagonist - Methotrexate Purine analogues -Thioguanine Mercaptopurine Fludarabine Pyrimidine analogues -Cytarabine Fluorouracil
  • 4. Antibiotics Anthracyclines Doxorubicin hydrochloride Daunorubicin Bleomycin sulfate C . Mitomycin Dactinomycin ( Actinomycin D) Plicamycin Plant derived products Vinca alkaloids Vincristine Vinblastine Epipodophyllotoxins Etoposide Teniposide Taxanes paclitaxel, docetaxel
  • 5. Hormonal agents Glucocorticoids- Prednisolone Estrogens, anti-estrogens- Tamoxifen, Estramustine Androgens, anti-androgens Flutamide Progestins – hydroxy progeseterone acetate Luteinizing hormone–releasing hormone (LH-RH) antagonists - Buserelin Leuprolide Immuno modulators Levamisole Interferons Interferon alfa-2a and 2 b Interleukins - Aldesleukin Monoclonal antibodies Rituximab, Alemtuzumab Ibritumomab, Gemtuzumab
  • 6. Miscellaneous agents Hydroxyurea Procarbazine Mitotane Cisplatin Carboplatin Mitoxantrone Cellular growth factors -Filgrastim, Sargramostim Enzymes- L- Asparaginase
  • 8. Nitrogen mustards -Cyclophosphamide Chlorambucil, Mechlorethamine , Alkyl sulfonates -Busulfan, Nitrosoureas -Carmustine, Lomustine Ethylenimines -Thiotepa Triazenes Dacarbazine MOA: Cross-linkage Miss- pairing of bases Depurination Cytotoxic agents- alkylation of DNA Use: Hematologic and solid cancers and used in combination therapy. A/E: direct vesicant effects, nausea and vomiting after 30-40 min. of injection, Mutagenic.
  • 9. Mechanism of action: Hepatic cytochrome P-450 system, enzymes phosphatase and phosphamidase (activators) aldophosphamide, which nonenzymatically breaks down to Phosphoramide mustard (bifunctional) & Acrolein(cytotoxic) Pharmacokinetics: Oral bioavailability- 90-100%, IV injection no local irritation Half-life -- cyclophosphamide -- 3-10 h; aldophosphamide -- 1.6 h; phosphoramide mustard -- 8.7 h. Most metabolized-- < 14% unchanged in urine.
  • 10. Active on lymphoproliferative diseases, e.g., Hodgkin's disease and Chronic lymphocytic leukemia Significant activity against multiple myeloma & ovarian, breast, small cell lung carcinoma Combinations- CVP, COP regimen, MOPP regimen Adverse effects: Cystitis, dysuria, fibrosis, hyponatremia Bone marrow suppression, most important leukopenia and thrombocytopenia Nausea and vomiting said to be rare Sterile necrotizing hemorrhagic cystitis(Acrolein)
  • 11. Sulfur mustard, forms toxic cyclic rthylenimmonium ion Mechlorethamine 0.4 mg/kg IV, in single or divided doses. PK: Unstable, solutions- just prior to administration T 1/2 is 10 min. after IV. Little or no intact drug excreted in urine. MOPP, Hodgkin’s, leukemia, lymphosarcoma A/E: Myelosuppression Leukopenia & Thrombocytopenia Nausea and vomiting Extravasation
  • 12. Nitrosoureas: Carmustine , Lomustine, Semustine MOA: Chloro ethyl moiety- capable of alkylating nucleic acids and proteins Alkylation and Carbamoylation of DNA. These agents can kill cells in all phases of the cell cycle P/K: High lipophilicity Unstable, forming highly reactive decomposition products; T 1/2 is few min. Renal excretion Uses -treatment of Hodgkin’s disease, lung cancer A/E: Bone marrow suppression Leukopenia & Thrombocytopenia Nausea and vomiting Alopecia , Stomatitis , interstitial fibrosis (pulmonary toxicity)
  • 13. MOA: It is a bifunctional methane sulfonic ester that forms Intrastrand cross-linkages with DNA. Palliative treatment of chronic granulocytic leukemia Busulfan 2–8 mg/d orally; 150– 250 mg/course P/K: Orally; T 1/2 is <5 min. Excretion in the urine. Busulfan+ allopurinol prevents excessive uric acid production from rapid tumor lysis A/E: Selectively toxic to granulocyte precursors rather than lymphocytes, interstitial pulmonary fibrosis, Thrombocytopenia and anemia, gynacomastia
  • 14. Adverse effects of alkylating agents: More toxic to bone marrow and gut than to liver and kidney, Infertility to both males and females. (3) Mutagenic. (4) Carcinogenic. Tumor resistance: Develops slowly & may require several genetic/ biochemical changes
  • 15. Folate antagonist Methotrexate Purine analogues Thioguanine Mercaptopurine Fludarabine Pyrimidine analogues Cytarabine Fluorouracil These are structurally related to naturally occurring compounds , such as vitamins, amino acids, and nucleotides. These drugs can compete for binding sites on enzymes or can themselves become incorporated into DNA or RNA and thus interfere with cell growth and proliferation .
  • 16. Folic Acid Analogue, Carrier transport into cell. (2) Binds strongly to DHFR to deplete THF, Decreases 1-carbon transfers in Purine synthesis, Decreases [1-C-THF] intracellular which decreases dUMP dTMP, Therefore, decreases NUCLEIC ACID synthesis. Clinical Uses: Broad range. Well established: (1) Acute Lymphoblastic Leukemia of childhood. (2) Choriocarcinoma. (3) Cancers of breast, bladder, and head & neck. (4) Useful in non- Hodgkin's lymphomas
  • 17. Adverse effects: Dose limiting: a) Myelosuppression (Thrombocytopenia and Leukopenia 7-10 days after Rx, Recovery 14-21 days). b) GI toxicity (Oral mucositis is early sign of GI toxicity, Severe mucositis, Small bowel ulceration & bleeding, Diarrhea -- requires cessation to prevent perforation of gut ) (2) Nephrotoxicity: Conventional doses, infrequent toxicity; High doses, toxicity can be severe (3) Immunosuppression. (4) Hepatotoxicity.
  • 18. Mechanism of action: (1) Activated by conversion to nucleotide (2) Inhibits DNA synthesis: Inhibition of Thymidylate synthase—the most important mechanism of action (MOA) in rapidly growing tumors (?) (3) 5-FU Incorporated into RNA: Interfere with RNA processing - All types, most important MOA in slowly growing tumors. Clinical Use of 5-FU: (1) Single agent: Palliative in advanced colorectal carcinoma (2) Combination: Breast cancer; Carcinomas of ovary, stomach, pancreas (3) Sequential MTX + 5-FU: Head and neck cancer
  • 19. Adverse effects: Bone marrow -- esp. with bolus administration. Leukopenia & Thrombocytopenia ( 9-14 days after start of Rx, recovery by day 21). b) GI Toxicity -- esp. with infusion administration. usually Stomatitis & Diarrhea 4-7 days after treatment IV bolus: myelosuppression is dominant; Prolonged Rx, may cause megaloblastic anemia Hepatotoxicity (elevated transaminases); myelosuppression less common
  • 20. Thioguanine MOA: Incorporation of thionucleotide analogue into DNA or RNA. Feedback inhibition of purine nucleotide synthesis. PK: slow- oral; T 1/2 is 24 hr ; C max is 6- 8 hr ; M-Liver, E- renal. Uses: Curative combination chemotherapy for acute myelogenous leukemia. AE: Myelosuppression, leukopenia and thrombocytopenia, Liver toxicity 2 mg/kg/d orally
  • 21. MOA: binds actively to tubulin, a class of proteins that form the mitotic spindle during cell division. Causes cellular arrest in metaphase. PLANT DERIVED PRODUCTS: Vincristine and Vinblastine PK: highly bound to tissues, M-liver and E- bile. VC: MOPP for Hodgkin’s/non (1.5 mg/m 2 IV / wk. ) VB: testicular, breast & renal(0.1-0.2mg/kg IV/ wk. ) A/E:VC- Alopecia, neurotoxic , no myelosuppression . VB- bone marrow toxicity, leukopenia, SIADH
  • 22. All interact with DNA and/or RNA, but may also interact with other cellular substituents. Schedule dependence: LESS "phase-specific" than antimetabolites. Tissue necrosis is only generalizable toxicity. All IV except bleomycin Mechanism of action: (1) DNA topoisomerase II inhibitor: Crucial to DNA replication and transcription. (2) Traditional explanations of MOA: a) intercalates between base pairs of DNA and inhibits DNA-dependent RNA synthesis. b) Generates free radicals that cause membrane damage and DNA strand breaks.
  • 23. Doxorubicin(Adriamycin) Clinical Indications: Broad spectrum anti-cancer activity. Hodgkin's disease, non-Hodgkin's lymphomas, sarcomas, acute leukemia, and breast, lung, and ovarian carcinomas all responsive Activity observed in bladder tumors, and carcinomas of prostate, thyroid, endometrium, head and neck, and other solid tumors
  • 24. Adverse effects: Local Toxicity -- Radiation Recall Interaction of doxorubicin and radiation in some tissues to produce enhanced reactions. Reactions include: a) Skin: ulceration and necrosis. b) Pulmonary fibrosis and sloughing of esophageal mucosa. c) Heart, and intestinal mucosa may also be affected Three categories of toxicity: a) Local toxicities. b) Acute toxicities. c) Chronic toxicity (1) Local Toxicity – Extravasation (Severe local tissue necrosis)
  • 25. Adverse effects: Acute Toxicities a) Hematologic: Leukopenia with 7-10 days; recovery typically by 21 days; Thrombocytopenia and anemia less common b) If given too fast: "Histamine-release" syndrome; Cardiac arrest preceded by ECG changes Chronic Toxicities a) Cardiomyopathy and congestive heart failure: require cessation of treatment
  • 26. PROGESTINS Progestational agents have been used as second-line hormonal therapy for metastatic hormone-dependent breast cancer and endometrial carcinoma previously treated by surgery and radiotherapy. Progestins stimulate appetite and restore a sense of well-being in cachectic patients with advanced stages of cancer and acquired immunodeficiency syndrome (AIDS) Medroxyprogesterone intramuscularly in doses of 400- 1000 mg weekly
  • 27. Selective Estrogen-Receptor Modulators(SERMs) High doses of estrogen have long been recognized as effective treatment of breast cancer. for 8-12 weeks Tamoxifen citrate is the most widely studied anti-estrogenic treatment in breast cancer prevents the development of breast cancer in women at high risk prior nonmalignant breast pathology, or inheritance of the BRCA1 or BRCA2 genes. ADR-Vasomotor symptoms (hot flashes), atrophy of the lining of the vagina, hair loss, nausea, and vomiting.
  • 28. MOA: it binds actively to Estrogen receptors and competes with endogenous estrogens for the clinical sites. Inhibits the growth of ovarian, uterus and breast cancer cells. PK: orally, T max is 4-7 hr , M- hydroxylation and glucuronidation, E- in feces. Synthetic anti-estrogen used in the treatment of breast cancer. A/E: Hot flushes, mild nausea, exacerbation, bone pain, Hypercalcaemia
  • 29. Selective Estrogen Receptor Downregulators(SERDs) pure anti-estrogens- fulvestrant Fulvestrant is used for postmenopausal women with hormone receptor positive metastatic breast cancer AROMATASE INHIBITORS Anastrozole and letrozole nonsteroidal imidazoles are used as part of the standard of care for treatment of early-stage and advanced breast cancer in postmenopausal women
  • 30. Gonadotropin-Releasing Hormone Agonists and Antagonists GnRH agonists -leuprolide, goserelin, triptorelin, histrelin and buserelin GnRH agonist will deplete testicular androgens, while the anti-androgen component competes at the receptor with residual androgens made by the adrenal glands. GnRH antagonist- Abarelix rapidly achieves medical castration ADR-local reactions and anaphylaxis
  • 31. Anti-androgens-Cyproterone and Megestrol Anti-androgens bind to ARs and competitively inhibit the binding of testosterone and dihydrotestosterone Advanced prostate cancer NONSTEROIDAL ANTI-ANDROGENS Flutamide and Bicalutamide- Advanced prostate cancer
  • 32. MOA: Inhibits Asparginase synthase enzyme. L- Asparginase catalyzes the hydrolysis of L- Aspargine to Aspartic acid and ammonia. Inhibits protein synthesis – cell death. PK: Derived from E.coli , T 1/2 is 6-30 hr , M-by serum proteases and RES, Uses Acute lymphoblastic Leukemia, Combination therapy, non-lymphocytic cancers. A/E: Hyper sensitivity, Nausea, anorexia, wt loss, hepatotoxic, hyperglycemia Pancreatitis,
  • 34. MOA: binds to DNA at N7, O6 of Guanine, and causes cross linkage producing alterations in DNA structure and inhibition of DNA synthesis. Cytotoxic effect similar to alkylating agents P/K: orally, extensively binds to proteins, T-max is 4-7 hr, T 1/2 is 2-4 days. M- hydroxylation and glucuronidation, E-renal. Testicular and Ovarian cancer. A/E: Renal toxicity, severe nausea and vomiting, hearing loss in high frequencies (4000Hz), mild bone marrow toxicity.
  • 35. IMATINIB -Acts by inhibiting the Philadelphia chromosome(bcr-abl kinase) and is very useful in the treatment of chronic myelogenous leukemia (CML). Remissions in CML patients are achieved with high frequency and very low toxicity. GIST-Gastro-Intestinal Stromal tumors Neurofibramatosis
  • 36. RITUXIMAB: acts against CD20 on cell surfaces (normal and malignant) Non Hodgkin's lymphoma 375mg/m2, IV. AE: Hypotension, Dizziness, Anxiety, Nausea, Diarrhea, Bone marrow depression. GEMTUZUMAB: acts against CD33 with drawn from market Acute Myeloid Leukemia 9 mg/m2, IV AE: chills, fever, nausea, vomiting, hypoxia, dyspnea, bone marrow depression.
  • 37. FILGRASTIM: rG -CSF Acts on precursor hematopoietic cells in the bone marrow by binding to specific receptors that stimulate cellular proliferation and differentiation into neutrophils . Filgrastim accelerates recovery of neutrophils after chemotherapy. Drug is well tolerated mild to moderate bone pain.
  • 38. MOPP-Mechlorethamine+ Vincristine (Oncovin), Procarbazine+ Prednisolone -for hodgkins lymphoma COAP- Cyclophosphamide + Oncovin(Vincristine) Ara-C(cytarabine)+ Prednisolone -for acute lymphoblastic lymphoma ABVD- Adriamycin(Doxorubicin) + Bleomycin+ Vinblastine+ Dacarbazine for hodgkins lymphoma POMP- Prednisolone+Oncovin+Methotrexate+ Purinethol(6-MP) for ALL
  • 39. Defective activation: Cyclophosphamide requires metabolic activation, Methotrexate conversion to more active MTX-polyglutamate in cells Increased inactivation: e.g., aldehyde dehydrogenase converse cyclophosphamide to inactive metabolite. Altered nucleotide pools: Can occur with antimetabolites. Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links, Affect the action of bleomycin and other DNA-directed drugs
  • 40. Altered target: Less affinity for drug, Methotrexate (Dihydrofolate reductase changes ). Decreased target: decreased topoisomerase II, e.g., etoposide Gene amplification: Methotrexate (MTX) increase dihydrofolate reductase, hence Requires more MTX to block Decreased accumulation: Decreased uptake (Methotrexate -- carrier protein decreases). Increased Efflux (Multidrug Resistance, P-Glycoprotein (gP-170) in membrane, pumps drug out)