Sketchy Pharm

Anti-Neoplastics
MTX, 5-FU, Hydroxyurea

General
• MTX, 5-FU, and Hydroxyurea block synthesis of thymidine
(hexagonal pyrimidine plate) (thymidylate synthetase-methylates
Dump)
• dUMP is converted to dTMP (plate with dumplings, plate with
"T" shaped chops1cks)
 thymidylate synthase (guy moving carbon sushi off 4-leaf
boat) catalyzes the conversion of methylated THF to DHF
(takes carbon from it to give to dUMP) (sushi boat with
4 leaves and a c-shaped carbon sushi becoming a boat with
2 leaves) and methylates dUMP to dTMP (transferring the
carbon sushi from the boat to the dumpling plate)
 DHF (boat with 2 leaves) is then converted back to THF
(boat with 4 leaves) by dihydrofolate reductase (add 2
hydrogens, so reducing) (sushi guy adding 2 leaves)
 THF is then re-methylated (gets a carbon) (addi1on of
carbon sushi)
• UDP is the precursor to pyrimidine nucleosides (UDP sign)
 DUP is converted to deoxy-UDP by ribonucleo1de reductase
(guest list waitress)
-S phase specific, since target rapidly dividing cells (blocks DNA
Synthesis)
Overview: Thymidylate Synthesis (pyrimidine in DNA):
1) UDP-> dUMP (by ribonucleotide reductase) ]- hydroxyurea
2) dUMP-dTMP (by thymidylate synthase) ]- 5 FU
a. (needs THF -FOLATE)
i. DHF->THF (by DHF reductase) ]- methotrexate
(acts like folate)
Antimetabolites
Methotrexate (meat stick) (DHF Reductase)
• a cytotoxic folate analog
• attacks rapidly dividing cells and inhibits proliferation of
immune cells (torn an1body lantern)
• blocks the conversion of DHF to THF by competitively
inhibitng DHF reductase (meat chef blocking leaf-sushi
guy) ( cant change DHF -> THF)
○ leads to buildup of DHF (buildup of 2-leaf boats)
and decreased dTMP levels, decreased DNA
synthesis cycle (Sushi phase sign) blocking DNA
synthesis (chops1cks blocking ramen-DNA on sign)
blocks the S phase of the cell (works
• treats:
○ many types of malignancies (cracked crab)
[Leukemias, lymphomas, breast, head and neck, lung]
○ used with misoprostol as an abortion method
(blocks trophoblast, hindering implantation)
○ ectopic pregnancy (baby keychain)
○ molar pregnancy, trophoblastic tumors and
choriocarcinoma (mole falling out of backpack), since
rapidly turning over
○ psoriasis (silvery scale kneepads)
(hyperproliferation of epidermis) [immunosuppressive-
also stops proliferation of immune cells]
○ rheumatoid arthritis (bone lantern with flame)-
long term management- disease modifying rheumatic
drugs. Inhibit proliferation of immune cells that
contribute to chronic inflammation and long term joint
destruction. [short term-NSAIDS/Glucocorticoids]
-Immune Suppression- IBD, SLE, Vasculitis,
Dermatomyositis
• side effects
○ folate deficiency (falling leaves) leading to
megaloblastic anemia (fireworks lantern)
myelosuppression with pancytopenia (bone marrow
depletion) and increased risk of infection (depleted
bone serving tray, immunocompromised cane)
○ pulmonary fibrosis- gradual onset dyspnea,
progress to symptoms at rest. PFT- restrictive, dec
diffusion capacity, bilateral diffuse patterns of small
opacity, lower lobes. Honeycomb appearance (fibro1c
lung bonsai tree)
○ hepatotoxicity (liver spot on apron)- direct damage to
hepatocyte (elevated LFTs)
○ alopecia (bald guy)
○ mucositis- soreness of mouth (guy poking meat s1ck
into his mouth)
○ reverse toxic effects with Leucovorin (lucky feline)
a folinic acid
§ does not require DHF reductase
§ displaced MTX from binding sites to restore
normal folate levels
5-Fluorouracil -Blocks thymidylate synthase ( full, 5-finger
waiving guy in yellow)
• a pyrimidine analog (empty hexagonal plate)
-blocks thymidylate synthase (guy moving carbon sushi
off 4-leaf boat) to block thymidine synthesis and DNA
synthesis (5-FU complexes with THF to inhibit TS, stops the
donation of Carbon, so can’t synthesize dTMP from dUMP)
•blocks the S phase of the cell cycle (Sushi phase sign)
blocking DNA synthesis (chops1cks blocking ramen-DNA on
sign)
○ causes buildup of dUMP (buildup of dumpling
plates)
• used in many solid tumors (cracked crab)- colorectal
cancer, breast, head, pancreas, basal cell carcinoma
• side effects
○ loss of epithelium in intestines(rapidly dividing
cells) leading to diarrhea (brown stained pants)
○ photosensi1vity (flashing camera)- cutaneous
complications, hyperpigmentation
○myelosuppression with pancytopenia and
increased risk of infec1on (depleted bone serving tray,
immunocompromised cane)
§ worsened with Leaucovorin (falling lucky
feline)
Hydroxyurea blocks RIBONUCLEOTIDE REDUCTASE (hydro-

rock area in back le^)
-UDP- precursor to all dUMP, dTMP, pyrimidine synthesis
• blocks ribonucleotide reductase (ribonucleotide
reductase waitress list waitress being pushed aside)
blocks the S phase of the cell cycle (Sushi phase sign)
sign)
•blocks the S phase of the cell cycle (Sushi phase sign)
sign)
•increases hemoglobin F (baby with hemoglobin coin)
• treats CML, AML, head/neck cancer, melanoma,
(cracked crab)
• also treats veno-occlusive crises in sickle cell (zen
sickle)
○ increases hemoglobin F (baby with hemoglobin
coin)
• side effects
○ GI upset, diarrhea (since rapidly dividing cells are
targeted)
-myelosuppression with pancytopenia and increased
risk of infec1on (depleted bone serving tray,
immunocompromised cane)

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Anti-Neoplastics

MTX, 5-FU, Hydroxyurea

Hydroxyurea blocks RIBONUCLEOTIDE REDUCTASE (hydro-

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