Cancer! Hearing this word from the doctor
will obviously make one sad. But imagine
if there is a good drug to treat most of
the cancers. Methotrexate is one
such drug it is used as an anti-cancer
drug for so many years to treat so many
types of cancers watch this video till
the end to know all the things you must
know about methotrexate and don't forget
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med vids made simple and this video is
about methotrexate. methotrexate is an
anti metabolite drug which means it
inhibits DNA synthesis in the cancer
cells. So let's talk about methotrexate
in a bit more detail methotrexate is a
folic acid analogue it inhibits an
enzyme known as dihydrofolate reductase
which is very important in DNA synthesis
now take a look at this step there is
dihydrofolic acid which is known as
DHFA and it is converted into
tetrahydrofolate acid which is
abbreviated as THFA now this is a very
important step in DNA synthesis now as
you can see here the dihydrofolate
reductase enzyme is involved in this
conversion but methotrexate being a
folic acid analog will inhibit this step
so there won't be adequately THFA
formation DNA synthesis is affected now
methotrexate has got a cell cycle
specific action I mean to say that it
kills the cancer cells which are
especially in the S phase of the cell
cycle the thfa which is not allowed to be
produced by methotrexate is actually
involved in one carbon transfer reactions
which you'll be already aware of. This
includes purine synthesis and various
amino acid inter-conversions all these
are affected now
methotrexate also inhibits one more
enzyme known as thymidylate synthase
this further worsens DNA synthesis so
that's beneficial to treat cancer of
course so in addition to DNA synthesis
RNA synthesis and protein synthesis are
also inhibited by methotrexate to some
extent let's talk about the significant
pharmacokinetic properties of
methotrexate. Methotrexate is almost
well absorbed orally and it is excreted
unchanged in urine most of the times and
it remains in protein bound state
in the body the important uses of
methotrexate includes it can be used to
treat choriocarcinoma
acute leukemia in children to maintain
remission non-hodgkin lymphoma breast
cancers bladder cancers and in various
head and neck cancers apart from that
methotrexate also has some
immunosuppressant properties that makes
it suitable to be used in conditions
such as rheumatoid arthritis psoriasis
and in various other autoimmune
disorders now let's talk about toxicity
of this drug the main toxicity is bone
marrow suppression
leading to development of megaloblastic
anemia pancytopenia which means all cell
lines are decreased mucositis which
means inflammation of the mucosa all over
the body and diarrhea is very often in
these patients in addition to that the
patients can have gastrointestinal bleeding
these are significant side effects in
addition to that the patient can have
many side effects now there is something
known as folinic acid rescue
therapy this is used in methotrexate
toxicity to help the patients to
overcome the toxicity folinic acid can
successfully and rapidly reverse the
toxic effects produced by methotrexate
now this allows the doctors
to use high doses of methotrexate in
some highly resistant cancers this makes
it suitable for the doctors to use high
doses of methotrexate to treat
difficult to treat cancers now let's
talk about pemetrexed
which is actually a congener of
methotrexate it has got many
similarities with methotrexate now its
main action is by targeting enzyme thymidylate synthase and it also affects
DNA synthesis it has got almost similar
side effects to that of methotrexate
and it causes a very unique adverse
effect known as hand foot syndrome where
there'll be painful rashes all over the body it
can be treated with a steroid known as
dexamethasone now uses of pemetrexed
it has been approved to be used in
conditions such as mesoepithelioma
and some non small cell lung carcinoma
in combination with cisplatin
