Antineoplastic agents can be classified as cytotoxic drugs, hormones, or miscellaneous agents. Cytotoxic drugs include alkylating agents, antimetabolites, plant derivatives, and antibiotics. They work by directly damaging DNA or interfering with cell division and metabolism. Combination therapy is more effective than single agents to increase response rates and decrease resistance development.
Anti-Neoplastic agents(Anti-cancer drugs)-History-Mechanism of actions-Classifications,SAR,Synthesis and Uses.(Medicinal chemistry)
P.Ravisankar
Vignan Pharmacy College
Vadlamudi. Guntur-A.P. India.
Anti-Neoplastic agents(Anti-cancer drugs)-History-Mechanism of actions-Classifications,SAR,Synthesis and Uses.(Medicinal chemistry)
P.Ravisankar
Vignan Pharmacy College
Vadlamudi. Guntur-A.P. India.
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 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.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
This ppt deals with the sulfonamide group of drugs with classification, mechanism, spectrum, resistance, uses and adverse effects discussed in detail. It also discusses in detail about Cotrimoxazole
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,...Dr. Ravi Sankar
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
BY P. RAVISANKAR, VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR,A.P, INDIA.
Calcium channel blockers - Medicinal chemistry for B.Pharm.Purna Nagasree K
This ppt describes about the drugs used as calcium channel blockers, their mechanism of action, metabolism and Structure activity relationship of dihydropyridines
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 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.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
This ppt deals with the sulfonamide group of drugs with classification, mechanism, spectrum, resistance, uses and adverse effects discussed in detail. It also discusses in detail about Cotrimoxazole
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,...Dr. Ravi Sankar
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
BY P. RAVISANKAR, VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR,A.P, INDIA.
Calcium channel blockers - Medicinal chemistry for B.Pharm.Purna Nagasree K
This ppt describes about the drugs used as calcium channel blockers, their mechanism of action, metabolism and Structure activity relationship of dihydropyridines
Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
- 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
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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.
2. Contents
• Classification of antineoplastic agents
• Mechanism of action
• Resistance to antineoplastic agents
• Some treatment protocols
3. Classification of Antineoplastic agents
I. Cytotoxic drugs (directly act on cells)
a) Alkylating agents
i. Nitrogen mustards
ii. Ethyleneimine
iii. Alkyl sulfonate
iv. Nitrosoureas
v. Triazine
4. b) Antimetabolites (act on metabolic pathway
involved in DNA synthesis)
i. Folate antagonist
ii. Purine antagonist
iii. Pyrimidine antagonist
c) Plant derivatives
i. Vinca alkaloids
ii. Taxanes
iii. Epipodophyllotoxin
5. d) Antibiotics
II. Hormones (mainly steroids which suppress
hormone secretion or antagonize hormone
action)
a) Glucocorticoids
b) Estrogen
c) Progestins
d) Antiandrogens
III. Miscellaneous (include
Hydroxyurea, Cisplatin, Monoclonal antibodies
and L.Asparginase)
6. I. CYTOTOXIC DRUGS
a) Alkylating Agents
• Contain chemical groups that can form covalent
bonds with particular nucleophilic substances in
the cell.
• Produce highly reactive carbonium ion
intermediates.
• Forms covalent bond with electron donors like
amine, hydroxyl and sulfhydryl groups.
• Alkylating agents are bifunctional, i.e. they have
two alkylating groups .
7. • The nitrogen at position 7 (N7) of guanine, being
strongly nucleophilic, is probably the main
molecular target for alkylation in DNA.
• N1 and N3 of adenine and N3 of cytosine may
also be affected.
• Being bifunctional they can cause intra- or
interchain cross-linking, abnormal base pairing
or chain scission.
• Interferes not only with transcription but also with
replication.
8. • Main impact is seen during replication (S phase)
when some zones of the DNA are unpaired and
more susceptible to alkylation.
• Results in a block at G2 and subsequent
apoptotic cell death.
11. Mechanism of activation: Cyclophosphamide
Metabolised in the 4-
Inactive
liver by P450 mixed hydroxycyclophos-
Cyclophosphamide
function oxidases phamide
Converted to
Aldophosphamide
phosphoramide (Reversibly) forms
is conveyed to
mustard, the actual aldophosphamide.
other tissues
cytotoxic molecule
12. b. ANTIMETABOLITES
i. Folate Antagonist: Methotrexate
• Folates are essential for the synthesis of purine
nucleotides and thymidylate which in turn are
essential for DNA synthesis and cell division.
• The main action of the folate antagonists is to
interfere with thymidylate synthesis.
14. • FH4 functions as an essential cofactor carrying
the methyl groups necessary for the
transformation of 2´-deoxyuridylate (DUMP) to
the 2´-deoxythymidylate (DTMP) required for the
synthesis of DNA and purines.
• During the formation of DTMP from DUMP, FH4
is converted back to FH2, enabling the cycle to
repeat.
• Methotrexate has a higher affinity than FH2 for
dihydrofolate reductase.Thus inhibits the
enzyme, depleting intracellular FH4.
15. ii. Purine antagonist: 6-mercaptopurine
Converted in the
cells to
6-mercaptopurine
ribonucleotide of
6-mercaptopurine
Suppresses
denovo
No DNA synthesis
biosynthesis of
purines
16. iii. Pyrimidine Antagonist: 5-Fluorouracil
(Analogue of uracil)
5-fluorouracil
Converted to 5-fluoro-2-deoxy uridine
monophosphate
Inhibits thymidilate synthesis
Blocks conversion of deoxyuridilic
acid to deoxythymidilic acid
Inhibition of DNA synthesis
17.
18. c) PLANT DERIVATIVES
i. Vinca Alkaloids
• Vincristine, vinblastine and vindesine: Main
vinca alkaloids used in cancer chemotherapy.
• Obtained from the plant Vinca rosea.
• Inhibit mitosis.
• Bind to tubulin and inhibit its polymerisation into
microtubules, preventing spindle formation in
dividing cells and causing arrest at metaphase.
• Cell cycle specific and phase specific.
19. ii. Taxanes: Paclitaxel
• Obtained from western yew tree.
• Reversibly binds to tubulin and results in the
formation of stable non-functioning microtubule
by promoting polymerization and stabilization of
the microtubules.
• Thus, interferes with mitosis causing cell death.
20. iii. Epipodophyllotoxins: Etoposide
• Semi-synthetic derivative of podophyllotoxin
obtained from Podophyllum peltatum.
• Inhibits enzyme topoisomerase II, leading to
DNA damage.
• Blocks the cell in S-G2 phase of cell cycle.
21. d) ANTIBIOTICS
i. MOA: Dactinomycin
• Intercalates into the minor grooves of double
helix between G-C base pairs of DNA ad
interferes with the movement of RNA
polymerase along the gene preventing
transcription.
• May also cause strand breaks and stabilise DNA
topoisomerase II complex.
22. ii. MOA: Doxorubicin
• Bind to DNA and inhibit both DNA and RNA
synthesis.
• Produces breaks in DNA strands by activating
topoisomerase II and produces semiquinone
free radicals.
• Semiquinone radicals reduce molecular oxygen
to superoxide ions and H2O2 that mediates
single strand scission of DNA.
23. iii. MOA: Bleomycins
• Group of metal-chelating glycopeptide antibiotics
obtained from Streptomyces verticullus.
• Produces chelation of copper or iron ions which
produces superoxide ions that interacts with
DNA.
• Degrade preformed DNA, causing chain
fragmentation and release of free bases.
24.
25. II. HORMONES
a) Glucocorticoids
• Glucocorticoids such as prednisolone and
dexamethasone have marked inhibitory effects
on lymphocyte proliferation
• Used in the treatment of leukaemias and
lymphomas.
• Their ability to lower raised intracranial
pressure, and to mitigate some of the side
effects of anticancer drugs, makes them useful
as supportive therapy .
26. b) Oestrogens
• Diethylstilbestrol and ethinyloestradiol are two
oestrogens used clinically in the palliative
treatment of androgen-dependent prostatic
tumours.
• The latter compound has fewer side effects.
These tumours are also treated with
gonadotrophin-releasing hormone analogues
• Oestrogens can be used to recruit resting
mammary cancer cells into the proliferating pool
of cells, thus facilitating killing by other cytotoxic
drugs.
27. b) Progestins
– Progestins such as megestrol and
medroxyprogesterone have been useful in
endometrial neoplasms and in renal tumours to
bring temporary remission.
c) Anti-Androgen
– Flutamide: androgen antagonist used in prostate
tumors since they increase androgen levels.
28. III. MISCELLANEOUS DRUGS
a) Hydroxyureas
– Acts by blocking the conversion of
ribonucleotide to deoxyribonucleotide by inhibing
the enzyme ribonucleoside diphoshate
reductase.
29. b) Cisplatin
Cisplatin enters the cell
Cl- dissociates leaving a reactive complex
that reacts with water
Interacts with DNA
Causes intrastrand cross-linking probably
between N7 and O6 of adjacent guanine
molecules
Results in local denaturation of DNA
30. c) L-Asparaginase
– Enzyme prepared from E.coli.
– Deaminates asparagine to aspartic acid and
ammonia, and is active against tumour cells, such
as those of acute lymphoblastic leukaemia.
d) Monoclonal Antibodies
– Ex: Rituximab
– Activate the host immune mechanism and kills
the cancer cells.
– Used for β-cell lymphoma.
31. RESISTANCE TO ANTICANCER DRUGS
• Decreased accumulation of cytotoxic
drugs in cells as a result of the increased
expression of cell surface, energy-
dependent drug transport proteins.
• A decrease in the amount of drug taken up
by the cell (e.g. in the case of
methotrexate).
• Insufficient activation of the drug (e.g.
Mercaptopurine, fluorouracil and
cytarabine).
32. • Increase in inactivation (e.g. mercaptopurine).
• Increased concentration of target enzyme
(methotrexate).
• Decreased requirement for substrate (L-
Asparaginase).
• Increased utilisation of alternative metabolic
pathways (antimetabolites).
• Rapid repair of drug-induced lesions (alkylating
agents).
33. • Altered activity of target, for example modified
topoisomerase II (doxorubicin).
• Mutations in various genes, giving rise to
resistant target molecules. (several cytotoxic
drugs).
34. Treatment Protocols
• Combination is more effective than monotherapy
without increasing toxicity.
• Also decreases possibility of development of
resistance.
• Higher responsive rates due to both additive
cytotoxic effects and non-overlapping host
toxicities.