This document discusses various classes of chemotherapy drugs used to treat cancer. It provides details on mechanisms of action, pharmacokinetics, clinical uses, and adverse effects for several alkylating agents, antimetabolites, plant alkaloids, antibiotics, hormones, targeted therapies, and other miscellaneous agents. The key classes covered are alkylating agents, antimetabolites, plant-derived products, and hormonal agents. Adverse effects including bone marrow suppression and nausea are common across many of the drug classes.
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.
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.
Hello friends. In this PPT I am talking about anti-cancer drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
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.
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.
Hello friends. In this PPT I am talking about anti-cancer drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Anticancer Drug, also called Anti-Neoplastic drug, that is effective in the treatment of malignant, or cancerous, disease. There are several major classes of anticancer drugs; these include Alkylating Agents, Anti-metabolites, Plant Alkaloids and Hormones.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.Dr. Ravi Sankar
what is cancer?, History,Malignent tumor, non-malignent tumor(benign tumor),Largest tumor ever removed, tumour growth kinitics, doubling tume, angiogenesis, causes of cancer, drugs, treatment of cancer, classification of anti-cancer agents, mechanism of actions,alkylating agents,anti metabolites, vinka alkaloids, best ways to reducing cancer.
BY P. RAVISANKAR
VIGNAN PHARMACY COLLEGE
VADLAMUDI
GUNTUR
ANDHRA PRADESH
INDIA.
Anticancer drugs: Classification , general toxicity and Alkylating agents.Ameena Kadar
Neoplasm or cancer is one of the dangerous condition. Here we discuss about cancer and it's drug classification, general toxicity and brief description about Alkylating agents.
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
Anticancer Drug, also called Anti-Neoplastic drug, that is effective in the treatment of malignant, or cancerous, disease. There are several major classes of anticancer drugs; these include Alkylating Agents, Anti-metabolites, Plant Alkaloids and Hormones.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.Dr. Ravi Sankar
what is cancer?, History,Malignent tumor, non-malignent tumor(benign tumor),Largest tumor ever removed, tumour growth kinitics, doubling tume, angiogenesis, causes of cancer, drugs, treatment of cancer, classification of anti-cancer agents, mechanism of actions,alkylating agents,anti metabolites, vinka alkaloids, best ways to reducing cancer.
BY P. RAVISANKAR
VIGNAN PHARMACY COLLEGE
VADLAMUDI
GUNTUR
ANDHRA PRADESH
INDIA.
Anticancer drugs: Classification , general toxicity and Alkylating agents.Ameena Kadar
Neoplasm or cancer is one of the dangerous condition. Here we discuss about cancer and it's drug classification, general toxicity and brief description about Alkylating agents.
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Anti-cancer drugs
Anticancer agents are chemical substances that inhibit or kill proliferating cancer cells, while leaving host cells unharmed, or at least recoverable. Cancer is one of the major causes of death and one of the most feared of diseases.
Cancer chemotherapy may consist of using several drugs in combination for varying lengths of time because cancerous cells which are initially suppressed by a specific drug may develop a resistance to that drug.Unfortunately, most of the chemicals that have been found to be successful anti-cancer agents are extremely toxic and must be administered very carefully.
There are three goals associated with the use of the most commonly-used anticancer agents-
1. Damage the DNA of the affected cancer cells.
2. Inhibit the synthesis of new DNA strands to stop the cell from replicating, because the replication of the cell is what allows the tumor to grow.
3. Stop mitosis or the actual splitting of the original cell into two new cells. Stopping mitosis stops cell division (replication) of the cancer and may ultimately halt the progression of the cancer.
Classification of drugs used in cancer chemotherapy
The main anticancer drugs can be divided into the following general categories.
A).Cytotoxic drugs. they include:
1.alkylating agents and related compounds: which act by forming covalent bonds with DNA and thus impeding replication
cyclophosphamide
Cisplatin
Chlorambucil
Carmustine
Lomustine
2.Antimetabolites: which block or subvert one or more of the metabolic pathways involved in DNA synthesis
a)Folate antagonists: Methotrexate
b) Pyrimidine analogues: Fluorouracil, Cytarabine
c) Purine analogues: Mercaptopurine, Pentostatin
3.Natural Products:
a).Cytotoxic antibiotics: substances of microbial origin that prevent mammalian cell division(by causing intercalation)
Doxorubicin
Bleomycin
Dactinomycin
Mitomycin
b)Vinca alkaloids: Vinblastin, Vincristine
c) Epipodophylotoxin: Etoposide,Teniposide
d) Enzymes: L-Asparaginase
B).Hormones
1.Adrenocorticoids: Prednisone for leukaemias and lymphomas
2.Antiestrogen:Tamoxifen for breast tumours
3.Gonadotrophin-releasing hormone analogues: Leuprolide for prostate and breast tumours
4.Antiandrogens: Flutamide for prostate cancer
5.Estrogens:Diethylstilbestrol, Etinyl estradiol
C).Miscellaneous agents that do not fit into the above categories. This group includes a number of recently developed drugs designed to affect specific tumour-related targets.
Procarbazine: inhibits DNA and RNA synthesis and interferes with mitosis.
Hydroxycarbamide (hydroxyurea ): inhibits ribonucleotide reductase.
Mitoxantrone (mitozantrone): causes DNA chain breakage.
Trilostane: inhibits adrenocortical steroid synthesis.
Monoclonal antibodies: rituximab, alemtuzumab, Trastuzumab
Imatinib: inhibits tyrosine kinase signalling pathways
Synthesis of Cyclophosphamide
Structure-Activity Relationship of alkylating agent(Nitrogen mustards):
1.The b
Introduction, Types, Causes,
Symptoms of cancer
Anti-cancer drug &
Recent advances in cancer treatment included Newer drug carrier systems, Nanotechnology, Carbon nanotubes, Cancer Vaccine, Antigen Vaccines, Dendritic Cell Vaccines, DNA Vaccines.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
For Better Surat #ℂall #Girl Service ❤85270-49040❤ Surat #ℂall #Girls
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
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,
33.
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.
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)