Chemotherapeutic agents
Summary
TLDRThis video script offers an insightful overview of chemotherapeutic agents used in cancer treatment. It covers various drug classes, including alkala agents, antimetabolites, microtubular targeting agents, topoisomerase inhibitors, anthracyclines, and monoclonal antibodies. Each class's mechanism of action and side effects are discussed, providing a comprehensive understanding of how these agents target cancer cells while minimizing harm to healthy cells.
Takeaways
- 🔬 Chemotherapeutic agents are drugs used to treat cancer by interfering with the ability of cancer cells to grow and divide.
- 🌿 Vinca alkaloids and taxanes are two classes of chemotherapeutic agents that affect microtubules, leading to cell death by disrupting cell division.
- 🔄 Topoisomerase inhibitors, such as Topo I and Topo II, prevent the relaxation of supercoiled DNA, leading to cell death by inhibiting DNA replication.
- 🧪 Alkylating agents, including both typical and atypical agents like platinum compounds, work by attaching to DNA, causing cross-linking and preventing replication.
- 💊 Antimetabolites mimic normal cell compounds to inhibit DNA replication, with specific action during the S phase of the cell cycle.
- 🌐 Microtubule targeting agents, like vinca alkaloids and taxanes, either destroy or stabilize microtubules, preventing their function and halting cell division.
- 🩺 Monoclonal antibodies are engineered to target specific proteins or receptors on cancer cells, offering a more targeted approach to cancer treatment.
- 💉 Anthracyclines have a complex mechanism of action, including intercalating DNA, inhibiting topoisomerase II, and generating reactive oxygen species.
- 🩹 Side effects of chemotherapeutic agents can be severe, including myelosuppression, neuropathy, and organ toxicity, and vary depending on the class of the drug.
- 🧬 Hormonal therapies, such as anti-estrogens for breast cancer and anti-androgens for prostate cancer, aim to block hormone production or activity to inhibit cancer growth.
Q & A
What are the two classes of chemotherapeutic agents that affect microtubules?
-The two classes of chemotherapeutic agents that affect microtubules are Vinca alkaloids and Taxanes.
How do Alkylating agents damage DNA?
-Alkylating agents damage DNA by attaching alkyl groups to DNA, usually between two base pairs, allowing for cross-linking of base pairs, which damages the DNA and makes it unable to replicate, leading to cell death.
What are the side effects commonly associated with Alkylating agents?
-Common side effects of Alkylating agents include myelosuppression, nausea and vomiting, secondary malignancies, infertility, and hemorrhagic cystitis.
Which chemotherapeutic agent is known to be the strongest inducer of nausea and vomiting?
-Cisplatin is known to be the strongest inducer of nausea and vomiting among the chemotherapeutic agents discussed.
How do antimetabolites inhibit DNA replication?
-Antimetabolites inhibit DNA replication by mimicking normal cell compounds, thereby interfering with the normal process of DNA replication.
What are the three categories of antimetabolites mentioned in the script?
-The three categories of antimetabolites mentioned are folate inhibitors, pyrimidine inhibitors, and purine analogs.
What is the primary side effect of Methotrexate, a folate inhibitor?
-The primary side effect of Methotrexate is mucositis, along with myelosuppression.
How do microtubular targeting agents like Vinca alkaloids and Taxanes affect cancer cells?
-Vinca alkaloids destroy microtubules, preventing their function, while Taxanes stabilize microtubules, both rendering them useless and inhibiting mitosis.
What are the side effects associated with Topoisomerase inhibitors?
-Side effects associated with Topoisomerase inhibitors include myelosuppression, mucositis, and secondary malignancies such as acute myeloid leukemia.
What is the mechanism of action of Anthracyclines?
-Anthracyclines have an ambiguous mechanism of action; they can intercalate DNA, inhibit topoisomerase II, generate reactive oxygen species, and cause alkylation.
What are the side effects of administering Anthracyclines?
-Side effects of administering Anthracyclines include an increased risk of biventricular heart failure based on cumulative dose and tissue necrosis in case of extravasation.
Outlines
🔬 Chemotherapeutic Agents Overview
The script introduces various chemotherapeutic agents used in cancer treatment, focusing on their mechanisms of action and side effects. It discusses three main classes of drugs: alkala agents, antimetabolites, and microtubular targeting agents. Alkala agents, such as cyclophosphamide and cisplatin, work by attaching to DNA and causing cross-linking, which damages the DNA and leads to cell death. Antimetabolites inhibit DNA replication by mimicking normal cell compounds and are specific to cells in the S phase of the cell cycle. Microtubular targeting agents, like vinka alkaloids and taxanes, affect the mitotic spindle, preventing cell division. The script also mentions the importance of these agents being more effective at killing cancer cells than normal cells.
💊 Side Effects and Specific Agents
This section delves into the side effects associated with chemotherapeutic agents, such as myelosuppression, nausea, vomiting, and neuropathy. It also highlights specific agents within each class, including typical and atypical alkala agents, and their unique side effects. For instance, cisplatin is noted for its strong induction of nausea and vomiting, while atypical alkala agents like nitrosoureas can cause pulmonary toxicity and central nervous system problems. The script emphasizes the need for careful administration and the management of these side effects in cancer treatment.
🧬 DNA Interaction and Topoisomerase Inhibitors
The script explains how anthracyclines interact with DNA, potentially intercalating between strands, inhibiting topoisomerase 2, generating reactive oxygen species, and causing cross-linking between DNA base pairs. It also discusses topoisomerase inhibitors, which prevent the relaxation or recoiling of supercoiled DNA, leading to cell death. Specific drugs like topotecan and irinotecan are mentioned, along with their side effects, which include myelosuppression and diarrhea. The section also touches on the use of these drugs in combination regimens, such as the 7+3 chemotherapy plan.
🏥 Monoclonal Antibodies and Other Therapies
The final paragraph discusses monoclonal antibodies, which are synthesized to target specific receptors or factors that inhibit cancer growth. The script explains the origin of these antibodies based on their suffixes, indicating whether they are derived from mice, chimeric, humanized, or fully human. Examples include rituximab, which targets CD20 for lymphoma treatment, and bevacizumab, which targets vascular endothelial growth factor for solid tumors. The script also briefly mentions other chemotherapeutic agents like bleomycin, which causes lung toxicity, and hormonal therapies for breast and prostate cancer. The summary concludes with a note on the importance of understanding the mechanisms of action and side effects of these agents in chemotherapy.
Mindmap
Keywords
💡Chemotherapeutic Agents
💡Alka Agents
💡Antimetabolites
💡Microtubular Targeting Agents
💡Topoisomerase Inhibitors
💡Anthracyclines
💡Monoclonal Antibodies
💡Myelosuppression
💡Peripheral Neuropathy
💡Extravasation
💡Hormonal Therapies
Highlights
Vinka alkaloids and taxanes are chemotherapeutic agents that affect microtubules, playing a crucial role in cancer treatment.
Topoisomerase inhibitors can lead to cell death by preventing the relaxation of supercoiled DNA.
Chemotherapeutic agents aim to kill cancer cells more effectively than normal cells, ensuring minimal harm to healthy tissue.
Alkylating agents attach alkyl groups to DNA, causing cross-linking that damages DNA and leads to cell death.
Cyclophosphamide and ifosfamide are typical alkylating agents with various side effects, including myelosuppression and nausea.
Platinum compounds, such as cisplatin, work by cross-linking purine DNA bases and have side effects like nephrotoxicity.
Nitrosoureas, related to mustard gas, cause pulmonary toxicity and central nervous system problems.
Antimetabolites inhibit DNA replication by mimicking normal cell compounds and are specific to cells in the S phase.
Methotrexate, a folate inhibitor, is commonly used and requires leucovorin to protect healthy cells from its effects.
5-FU, a pyrimidine inhibitor, causes myelosuppression and GI problems depending on its administration method.
Capecitabine is an oral prodrug for 5-FU, and its side effect includes hand-foot syndrome.
Microtubular targeting agents, like vinca alkaloids, inhibit mitosis by destroying microtubules, preventing chromosome separation.
Taxanes stabilize microtubules, preventing their function and leading to cell death by disrupting chromosome separation.
Anthracyclines have a multifaceted mechanism of action, including intercalating DNA and generating reactive oxygen species.
Monoclonal antibodies are synthesized to target specific receptors known to inhibit cancer growth.
Rituximab targets CD20, commonly used to treat lymphomas, and is an example of a monoclonal antibody.
Bevacizumab targets VEGF and is used for solid tumors, with a side effect of GI perforation due to its mechanism of action.
Hormonal therapies, such as tamoxifen for breast cancer and anti-androgens for prostate cancer, target hormone production to inhibit cancer growth.
Transcripts
this is a short video on
chemotherapeutic agents we have a few
scattered pictures and diagrams here to
start on the left we have vinka alids
and taxanes which are two classes that
affect microtubules we'll talk about how
those affect macrotubes and and the
action of killing cancer we have in the
middle the two Topo isomerase Inhibitors
and we're going to talk about how those
can lead to cell death as long as well
as a couple examples of those and on the
right here we have a general graph that
shows how when we use chemotherapeutic
agents we want to ensure that they kill
cancer cells better than they kill
normal cells so we're going to jump
right into talking about the classes of
these chemical agents used in the
treatment of cancer this is
chemotherapeutic
Agents we're going to start with alkala
agents first this is the first class
we're going to be talking about now
alkala agents in general attach alkal
groups to DNA they usually attach groups
between two base pairs allowing for
cross-linking of base pairs this of
course damages the DNA makes you unable
to replicate it and it kills the cell
that way now the good thing about
ulating agents is that they they are not
specific to any part of the cell cycle
so they should be working on all cells
regardless of what part of the cell
cycle they're
in we have some common typical alkala
agents here we have typical and atypical
alkala agents we're going to start
talking about the typical ones the two
that are that are important to know are
cyclophosphamide and if phosphamide now
there's a whole list of side effects
with these and a lot of them are the
ones that you might classically think of
as side effects to chemotherapy we have
Milos supression which means a drop in
white blood cells a drop in hemoglobin
and a drop in the crits we have nausea
and vomiting that's the big one
Everybody's scared of nausea and
vomiting when getting chemo we have
secondary malignancies we have
infertility and hemorrhagic cystitis
which is a problem with the kidneys you
get blood in the urine and you have pain
with urination um it's caused by the
irritation of the bler from the acryline
metabolite now we have atypical alkala
agents as well we're going to start off
by talking about the Platinum compounds
these work by coal binding purine DNA
bases we're going to talk about three of
these first we have cisplatin which has
side effects of nephrotoxicity and
nausea and vomiting this is actually the
strongest inducer of nausea and vomiting
that we're going to be talking about
today it's extremely poent potent and it
it almost certainly causes vomiting in a
patient if you don't give them any
medication for for vomiting when you're
administering cisplatin we have carop
platin which causes platelet problems
and we have oxop platin which causes
cold sensitivity and it's worth
mentioning that all of these Platinum
compounds also cause peripheral
neuropathies or like a like the pins and
needles tingling in your in your fingers
and fingers and toes next group of
atypical alkala agents are the nitroso
uras now these are two acronyms bcnu
ccnu the actual names for these drugs
have mus in them M like car musine it's
because they are related to mustard gas
that was used during one of the world
wars so it's easy to remember that these
which are related to mustard gas if you
look up the full names of them cause
pulmonary toxicity and it's also worth
mentioning that they also cause fitis
and central nervous system problems so
these are the alkala agents next we're
going to talk about antimetabolites we
also have three categories of these but
first antimetabolites inhibit DNA
replication by mimicking normal cell
compounds and because these are
inhibiting DNA replication they are
specific to cells that are in the S
phase because you undergo DNA repli
replication in the S
phase first group we're going to talk
about is folate Inhibitors and the big
one here is methotraxate very commonly
used drug it inhibits dihydrofolate
reductase which is an enzyme that
prevents the Regeneration of
tetrahydrofolate and it inhibits the
conversion of folate which is a dietary
supplement something that we get from
our food into
tetrahydrofolate when when we administer
Methotrexate we always want to do it
with lucor lucor is an adant that
protects the healthy cells it actually
gives the healthy cells another method
of getting folate another method of
using folate and uh Methotrexate and
lucor go together for that reason side
effect of Methotrexate is mucositis and
Milo supression Milo suppression is
going to come up quite a bit next group
of antimetabolites are the peridian
Inhibitors big one here is 5fu five fluo
urasil which inhibits the enzyme
thymidilate
synthetase when you administer 5fu as a
Bolis it's going to cause Milo
suppression if you administer it in a
continual dose it's going to cause GI
problems like diarrhea mucositis so the
side effects of 5fu depend on how you
administer it you also want to use lcav
Orin with 5fu for a different reason
this time this time lcav Orin helps the
mechanism of action of 5fu when you use
methotraxate and lucor lucor protects
the healthy cells when you use 5fu and
Lorin lucor potentiates the mechanism of
action of 5fu it's worth noting the
difference of lucor between its use in
Methotrexate and five floro
uracil Cape cabine is essentially an
oral prodrug for 5fu now 5fu normally is
not administered orally cap cadine is a
pro drug which means that it must be
further processed in the body before it
becomes active and that's cap citadine
one of the side effects of cap citadine
is hand foot syndrome your palms and
your feet become red they can start
blistering and the last of the
perimidine Inhibitors is
cabine which is a rabinos c it's a DNA
chain
Terminator side effect here is
conjunctivitis and cerebral neural
defects so a or cabine causes
conjunctivitis and cerebral defects so
CCC a conjuntivitis cerebral neural
defects it's also worth mentioning that
cabine is the seven and seven plus
chemotherapy if you haven't heard of
that it's like a 10-day regimen of
chemotherapy that's very common for the
first seven days you're going to be
administering cabine and that's before
three days of anthracyclin we'll talk
about anthracyclin in a
second and there's one other class of
antimetabolites called the purine analog
and the one that is important to know is
six mapto purine easy to remember that
as a purine analog six
mercaptopurine so we have three classes
of antimetabolites which is a larger
class of therapeutic drugs we have
folate Inhibitors perimidine Inhibitors
and purine
analoges now another class microtubular
targeting
agents these drugs inhibit mitosis
mitosis of course uh occurs during the
mphase they uh specifically Target the
microtubular activity during mitosis
we're going to talk about how they do
that vinka alids firstly destroy
microtubules easy to remember vinka
alids destroy microtubules and that
obviously prevents their function three
vinka alids are listed here blast is
underlined you'll see why in a second
side effects of vinka alids are
peripheral neuropathy and Milo
suppression blast is the strongest of
the of those three in suppressing the uh
the the immune system so BL Vin VIN
blastin is the strongest Milos
supressive chemotherapeutic drug it has
the strongest side
effect one important thing to remember
about vinka alids is that you cannot
inject them directly into the spine they
are fatal if given intrathecally
next group of microt tual targeting
agents are the tanses these stabilized
microtubules which prevent them from
doing what they actually need to do
which prevent the microtubules from
actually touching the chromosomes and
pulling them apart during metaphase so
vinka alids destroy them tanes stabilize
them both render them
useless two Texans that are important to
know were pexel and dosex side effect of
these are mild suppression we're going
to be seeing that a lot and peripheral
neuropathies there's also hyper
sensitivity associated with these and
it's important to note that the hypers
sensitivity doesn't come from the drugs
doesn't come from pxel and doxal
directly but rather it comes from the
diluents that the drugs are dissolved in
these diluents cremophor and tween80
both cause hypers sensitivity the one
from pcxl cremor is a little more
potent if we don't want to deal with
this hypers sensitivity we could also
administer a braan which is a different
formulation of pxel it's protein bound
pxel and it helps us avoid hypers
sensitivity that's involved with the
cremor diluent in pet
axel one of the trade-offs of using
abraxane versus pet Axel is that you
have more neuropathy so you have less
hypers sensitivity but more
neuropathy next class toois Inhibitors
there's Topo isomerous one Topo isas 2
the ones that inhibit Topo one prevent
the relaxation of super coil DNA two of
these to remember Topo tan and irin
iroan iroan has a fun pneumonic to help
you remember what it does we'll get in
that in a second both of these cause myo
suppression like almost everything else
we're talking about iroan causes
diarrhea e it remember because ireno
Tean sounds like I ran to the can you
ran to the can when you have diarrhea
caused by
aroan Topo 2 inhibitors prevent
recoiling of DNA after transcription
couple of these to remember are toide
and teniposide both ending in ide Topo
isas two Inhibitors both have side
effects of M suppression mucositis and
secondary malignancies such as causing
AML acute acute myoblast leukemia these
are the three fourm that are associated
with topo2 Inhibitors such as etoposide
and teniposide
next class that we want to talk about
are the
anthracyclines anthracyclines kind of
have an ambiguous mechanism of action
they do a bunch of stuff they could do
more than one of these they could just
do a few of these some of them are
listed here they can intercalate DNA
which means that they insert themselves
between the actual the two actual
strands of DNA preventing their
replication and preventing synthesis of
RNA from that DNA so they intercalate
DNA and just inhibit the use of that DNA
they can also inhibit too isomerase 2
one of them do rubinson uh in particular
inhibits do or inhibits topoisomerase 2
they can generate reactive oxygen
species that cause oxidative damage to
the DNA and they also might cause alkal
which like we saw with the alkala agents
can cause cross-linking between DNA
based Pairs and uh and essentially
render the DNA useless kind of like
intercol of DNA anthocyans are easy to
remember because they all end in rubison
these are the rubinson dxor rubinson
Donar rubison you can read the rest
there Ida rubenson and EP rubison side
effects of these are pretty common to
all of them B ventricular heart failure
and this is based on the dose the
cumulative dose of the rubison
administered so there's like a limit for
each of these Rubin so Dr ubon's limit
might be some number you can only give a
person so much doxy rubenson before they
hit that number and be at a
statistically significant increase risk
for biventricular heart failure one
other side effect for the anthocyans is
that they are necrotic with extrav this
means that if you when you're normally
injecting these into the veins if you
miss the veins and accidentally get some
of these anthy into the surrounding
tissue they can cause necrosis of that
tissue leave very nasty looking wounds
they could tear up somebody's whole arm
tear up somebody's wrist if you miss
when inserting a vein so nurses are
trained really well to to be very
careful about administering anthres if
you want to look up some pictures of
this it looks pretty nasty it's kind of
fun to look at uh you can you can look
up anthy extravasion and it should be
pretty easy to
find it's also worth noting that
anthocyans are the three in the
aforementioned 7 plus three chemotherapy
so you have seven days of cabine
followed by three days of one of the
anthocyans such as duct
rubenson next class are the monoclonal
antibodies these are antibodies that are
synthesized to a specific Target that
has been known to inhibit cancer we'll
give you a bit more detail here the
origin of the monocolonal antibodies can
be determined from the suffixes so monal
antibodies ending in omab Come From Mice
or Mouse is easier to remember the O
from omab o from
Mouse the xab ending or imab uh comes
from the
chimeric antibodies these chimeric
antibodies are a cross between human and
mouse so they have some human in them
this list by the way is is in decreasing
order of how much mice is involved in
these antibodies so this umab this next
one is humanized which means it's about
10% Mouse 90% human easy to remember
because umab has a u in it just like
human then finally the fully human
antibodies are called mumab now these
mums are 100% human so I believe the the
chimeric antibodies are about 33% human
the humanized antibodies are about 10%
human and the fully human antibodies
excuse me the umab antibodies are about
10% Mouse and the fully human antibodies
are about 0%
Mouse we have a list of four important
monoclonal antibodies that are that are
probably worth knowing uh start with
rmab very commonly used it targets cd2
which is a receptor very common to B
cells it's used to treat lymphomas or
the abnormal proliferation of B cells
that you often see in lymphomas and
we're not going to we're not going to be
discussing the toxicity for the first
two but Target cd20 used for
lymphomas there's another one used for
breast cancer targets her too also not
as not as significant camab targets the
egfr receptor andth thelial growth
factor receptor this is uh used to treat
solid tumor and it was initially
developed to treat color rectal cancer
one of the side effects of camab is that
you get hypers sensitivity in the form
of an acneform rash so it looks like you
have dots all over your skin you get a
rash if you use camab another one that's
worth knowing is Bez
bevacizumab which targets VF which is a
vascular endothelial growth factor also
used for solid tumors um initially
developed for coloral and lung cancers
this is a problem because it can cause G
ey perforation VF is a factor that
promotes angiogenesis promotes the
growth of of blood vessels into new
parts of the body or into tumors if you
inhibit those you can weaken the GI
tract and cause perforation of the GI
tract and finally we're going to have a
short list of other chemotherapeutic
agents bomy is worth noting because it
causes lung toxicity just like the the
ones related to mustard gas that we
talked about earlier the nitroso uras
bomy also causes long
toxicity side effects of this long
toxicity include pulmonary fibrosis
interstial pneumonitis and hypers
sensitivity pneumonitis which includes
cough for having infiltrates in the
lungs and there are a couple other
hormonal therapies that are worth
knowing some of these are for breast
cancer specifically the
antiestrogens such as tamoxifen and the
aromatase inhibitor
rheumatism I don't think I have any
examples here but they block the
synthesis of estrogen actually there are
a couple examples ending in OZO so the
one that's important to know is the
anti-estrogen
tamoxifen there are also some hormonal
therapies for prostate cancer such as
the anti-androgens and there should be a
small list of these like the LH RH
antagonists or excuse me lhrh agonists
the GnRH antagonists and the cyp17
Inhibitors and if you look up the
production of testosterone you can kind
of see how these three subclasses of
anti-androgens all kind of inhibit
testosterone production in a different
way all with the evental goal of
preventing Androgen stimulation of
prostate cancer so these are other
chemotherapeutic agents that didn't
really fit into the other categories
this has been a brief review of
chemotherapy agents I hope it was
helpful and I hope it was uh good a good
introduction to to commonly use drugs
and their mechanisms of actions and side
effects thanks for listening
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