The document discusses various classes of anticancer drugs including cytotoxic drugs derived from natural sources like plants and microbes. It focuses on the mechanisms of action and classification of antitumor antibiotic drugs derived from Streptomyces bacteria. Specifically, it describes the structures, mechanisms involving DNA intercalation and inhibition of topoisomerases, and clinical uses of important anthracycline antibiotics like doxorubicin, daunorubicin and actinomycin antibiotics like dactinomycin and mitomycin C.
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.
Shortened description of STATURAL ACTIVITY RELATIONSHIP OF ANTIMETABOLITES & its MECHANISM OF ACTION - ANTINEOPLASTIC AGENTS (folate antagonist, purine antagonist & pyridine antagonist)(MEDICINAL CHEMISTRY)
quite useful for B PHARMACY & Pharm D Students.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
Chemotherapy classes
for more lectures please contact
Dr. Salah Mabrouk Khallaf
MD Medical Oncology & BMT
South Egypt Cancer Institute
Email: salahmab76@yahoo.com
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.
Shortened description of STATURAL ACTIVITY RELATIONSHIP OF ANTIMETABOLITES & its MECHANISM OF ACTION - ANTINEOPLASTIC AGENTS (folate antagonist, purine antagonist & pyridine antagonist)(MEDICINAL CHEMISTRY)
quite useful for B PHARMACY & Pharm D Students.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
Chemotherapy classes
for more lectures please contact
Dr. Salah Mabrouk Khallaf
MD Medical Oncology & BMT
South Egypt Cancer Institute
Email: salahmab76@yahoo.com
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.
Antibiotics
Dactinomycin, Daunorubicin, Doxorubicin, Bleomycin
Examples of antineoplastic antibiotics include doxorubicin, daunorubicin, bleomycin, mitomycin, and dactinomycin, all of which are derived from species of Streptomyces bacteria.
While these drugs may have antibacterial activity, they are generally too dangerous and toxic for that use. Antineoplastic antibiotics are associated with blood cell damage, hair loss.
Dactinomycin, also known as actinomycin D
C62H86N12O16
Lactone rings in the dactinomycin stabilizes the peptide chains in such a conformation which enables the formation of four extra Hydrogen bonds between phosphodiester oxygens and peptide-NH groups.
Amino acid composition contributes to the biological activity of dactinomycin.
Replacing the proline by hydroxylproline can change the minimal inhibitory concentration of the drug.
The different conformation in the peptide can result in the different biological activity of the drug.
If pipecolic acid is attached with the drug then it can only inhibit the growth of gram positive bacteria but not gram negative bacteria
Replacement of both the proline residues with the pipecolic acid reduces the biological activity of the drug and the binding capacity of the drug with DNA
Replacement of both the proline residues with the pipecolic acid reduces the biological activity of the drug and the binding capacity of the drug with DNA
Osteosarcoma
Soft tissue sarcoma
Locoregional solid tumours
Gestational trophoblastic neoplasm
Metastatic testicular tumours
Ewing’s sarcoma
Ovarian cancer
Childhood rhabdomyosarcoma
Wilms’ tumour (Kidney cancer in children's
Daunomycin
C27H29NO10
anthracycline-type antitumor drugs
Substitution at 2nd position decreases the biological activity of drug.
Biological activity can be increased by substitution at 3rd
8th position has direct relationship with the biological activity of drug and thus, substitution at 8th position can increase the biological activity of drug.
Substitution at 1st and 7th position will have negative impact on the biological activity of the drug.
Acute Myelogenous leukemia
Acute lymphoblastic leukemia
Acute promyelocytic leukemia
Acute Myelogenous leukemia
Acute lymphoblastic leukemia
Acute promyelocytic leukemia
Anthracyclic antibiotic cytotoxic drug
C27H29NO11
Doxorubicin firms complexes with DNA by intercalation between base pairs.
The drug then stabilizes DNA-topoisomerase II and thus topoisomerase activity is inhibited
Relegation of the DNA is prevented
Cell death
Uterine sarcoma
Transitional cell bladder cancer
Thyroid cancer
Thyomas
Soft tissue sarcoma
Small cell lung cancer
Ovarian cancer
Neuroblastoma]
Bleomycin chelates metal ions and produces pseudoenzymes.
ii. The pseudoenzymes so formed reacts with Oxygen to produce hydroxide and superoxides free radicals.
iii. Cleaving of DNA by the free radicals
For the complexation and oxygen activation, N terminal is responsible.
Hodgkin’s lymphoma
This document was prepared by Afifa Binta Saifuddin and her group members for the assignment purpose for Department of Pharmacy, East West University, Bangladesh. Uploaded by Tousif Azmain.
Cellular defense against fatal associations between proteins
and DNA
Date:
July 3, 2014
DNA 'replication fork' reconstituted for the first time
Date:
July 9, 2014
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.
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.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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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.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
- 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
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
1. 1
A. Cytotoxic drugs
1. Alkylating agents
2. Platinum coordination complexes
3.Antimetabolites
4.Antibiotics
5. Plants
B. Targeted drugs
1. Tyrosine protein kinase inhibitors
2. EGF receptor inhibitors
3. Angiogenesis inhibitors
4. Biological response modifiers
C. Hormonal drugs
CLASSIFICATION OF ANTICANCER DRUGS
2. Drugs from Natural source
A variety of the anticancer agents available
today are derived from natural sources
Microbial sources (antibiotics) and
Plants
Both the antibiotic and natural product from
plants classes have multiple inhibitory effects
on cell growth; however,
They primarily act to disrupt DNA function
and cell division.
3. Mechanisms by which these agents target DNA is
Intercalation,
Alkylation, and
Strand breakage either directly or as a result of enzyme
inhibition.
Steps in Intercalation
Intercalating drugs contain a planar aromatic or
heteroaromatic ring system which can slip into the double helix
of DNA and distort its structure.
Drug should induce a cavity between base pairs so that
insertion may occur b/n drug and DNA.
The interaction of the intercalator (drug) and the adjacent base
pairs of DNA occurs by the overlap of p-orbitals of the
intercalator and the base pairs.
The p-orbitals of the intercalator/intercalation species are
provided by a combination of aromatic and conjugated systems
that impart the planarity required for intercalation.
4. The side chains of intercalator has a cationic
moiety, which may form ionic bonds with the anionic
phosphate backbone in DNA.
The overall result of these interactions is to cause
a local bend or kink or cut in DNA resulting in a local
shape distortion.
Inhibition of topoisomerase /DNA gyrase
(Topoisomerase enzymes are responsible for the
unwinding and relaxation of DNA so that transcription
may occur)
5. Classification of Antitumor Antibiotics drugs
Many of the antineoplastic antibiotics are produced by
the soil fungus Streptomyces.
Anthracyclines: Doxorubicin, Daunorubicin,
Epirubicin, Mitoxantrone, and Idarubicin.
Actinomycins/Chromomycins: Dactinomycin
and Plicamycin.
Miscellaneous: Mitomycin and Bleomycin.
6. Antracyclines
Doxorubicin (previously called adriamycin)
belongs to a group of naturally occurring antibiotics called
the anthracyclines, and was isolated from Streptomyces
peucetius in 1967.
It is very similar in structure to Daunorubicin—differing
only in one hydroxyl group at C9 acetyl group in
daunorubicin & hydroxy acetyl group in doxorubicin.
O
O
OH
OH
OH
C CH2
O
OH
OO
H
H
OH
H
NH2H
H
CH3
OCH3
ABCD
Doxorubicin
1
2
3
4 5 6 7
8
9
1011
12
O
O
OH
OH
OH
C CH3
O
OO
H
H
OH
H
NH2H
H
CH3
OCH3
ABCD
Daunorubicin
1
2
3
4 5 6 7
8
9
1011
12
7. The second generation anthracyclines
Epirubicin and Idarubicin lacks the methoxy
group at C4 , so it is more polar and has an
altered metabolism which prolongs its half-
life.
O
O
OH
OH
OH
C CH2
O
OH
OO
H
OH
H
H
NH2H
H
CH3
OCH3
ABCD
Epirubicin
O
OH
OH
OH
OH
C CH3
O
OO
H
H
OH
H
NH2H
H
CH3
ABCD
Idarubicin
1
2
3
4 5 6 7
8
9
101112
8. SAR
• The anthraquinone chromophore is an important structural feature of the
anthracyclines.
• the anthraquinone chromophore, consisting quinone and a hydroquinone
moiety on adjacent rings.
• The phenolic hydroxy groups present in this core were found to undergo
ready acylation and alkylation under standard reaction conditions.
• It has been shown that, O-methylation of the C-6 or C-11 phenolic groups
results in analogs with markedly reduced activity,
• whereas C-4 modifications such as demethylation and deoxygenation do
not affect bioactivity.
• The transformation of the C-5 carbonyl to the corresponding imino
functionality resulted in an analog that retained activity and was found to
be significantly less cardiotoxic than the parent compound.
• Ring-A, alicyclic moiety bearing the two-carbon side chain group and
the tertiary hydroxyl group at C-9 and also having a chiral hydroxy group
at C-7, which in turn connected to the aminosugar unit;
• the amino sugar residue, attached to the C-7 hydroxy group through an a-
glycosidic linkage;
11. Mitoxantrone
It is a simplified, synthetic analogue of the
anthracyclines where the tetracyclic ring system has
been ‘pruned’ back to the planar tricyclic system
required for intercalation.
• There is no sugar ring which is responsible for cardio
toxic side effects.
• The pharmacophore
groups are highlighted in
box and which are responsible
For binding with DNA base
Pairs.
Anthrace ring interculate b/n DNA
base pairs.
12. Uses of Anthracyclines
Doxorubicin is used to treat a broad spectrum of solid
tumours, as well as acute leukaemias, lymphomas, and
childhood tumours.
Daunorubicin is indicated for acute leukaemias.
Epirubicin is considered effective against breast cancer.
Idarubicin is used in the treatment of haematological
malignancies and can be given orally.
Both epirubicin and idarubicin are second-generation
anthracyclines with less cardiac toxicity than doxorubicin
or daunorubicin.
Mitoxantrone is used for the treatment of certain
leukaemias and lymphomas, and for advanced breast
cancer.
13. Side effects of Anthracyclines
Causes cardiotoxicity
Interference with ryanodine receptors of the
sarcoplasmic reticulum in the heart muscle cells
Sugar residue is one of the cause for cvs toxicity
Free-radical formation in the heart
Leads to forms of congestive heart failure, often years
after treatment
Counteract with dexrazoxane
Liposomes can be useful as carriers to deliver
doxorubicin to target tumours and this approach
is associated with less cardiac toxicity.
Extravasation injury produce extensive local
necrosis.
14. Extravasation Injury by Doxorubicin
Redness , swelling blisters Tissue necrosis
surgery to remove tissue permanent damage
15. Actinomycins
The Actinomycins are a group of compounds
that are isolated from various species of
Streptomyces,
Phenoxazone chromophore
And has di pentapeptide portion
The 1St drug from this group is Actinomycin D
which is known as Dactinomycin
Other Pilcamycin
16. Actinomycin-D/ Dactinomycin
Phenoxazone chromophore
And has di pentapeptide
portion
The pentapeptides namely L-
threonine, D-valine, L-proline,
sarcosine, and L-methylvaline
form a lactone via the side
chain hydroxyl of L-threonine
and the carboxyl group of L-
methylvaline
An amide linkage is present b/n
the amino group of L-threonine
and carbonyls of 1 and 9 of
Phenoxazone chromophore
17. • The structural feature of dactinomycin important for
its mechanism of cytotoxicity is
• the planar phenoxazone ring, which facilitates
intercalation between DNA base pairs.
• The peptide loops are located within the minor groove
and provide for additional interactions.
• Dactinomycin binds noncovalently to double-stranded
DNA by partial intercalation between adjacent guanine
cytosine bases resulting in inhibition of DNA function.
• Additional hydrophobic interactions and hydrogen
bonds are formed between the peptide loops and the
sugars and base pairs within the minor groove.
18. Mechanism of action of Dactinomycin
Minor GrooveD
D
By an effect on topoisomerase II
that unwinds the DNA helix for
replication
It intercalates, in the minor groove
of DNA, between adjacent guanine-
cytosine pairs thus preventing
transcription.
DNA synthesis may also be inhibited,
and the agent is considered as cell
cycle specific for the G1 and S
phases.
Block DNA Gyrase/ topoisomerase
Uses
is given mainly intravenously to treat
paediatric solid tumours, including
Wilm's tumour and Ewing's tumour
23. Uses of Mitomycin C
Adenocarcinoma of the stomach, colon, or pancreas.
Its use and application in ophthalmology has been increasing
in recent years because of its modulatory effects on wound
healing.
Current applications include
Pterygium surgery,
Glaucoma surgery,
Corneal refractive surgery,
Cicatricial eye disease,
Conjunctival neoplasia and allergic eye disease.