Jashore University of Science & Technology

Department of pharmacy
Course tittle :Human Physiology and Anatomy-IV
Course code:PHAR 2209

An Assignment on Fluorouracil (5-FU)

Submitted BY: Submitted To:

Name:Al-Fatiha Nafsi
ID:181039 Md.Nazmul Hasan Zilani
2 year, 2nd semester
nd Lecturer
Session:2018-19 Department of pharmacy
Department of pharmacy Jashore University of Science & Technology
Jashore University of Science & Technology

Date of Submission :17-12-20

 Index
Serial No: Content Name: Page:

01. Introduction of 5-FU 4

02. Does it kill cancer cells? Indication of 5- 5

FU
03. Clinical pharmacology and laboratory 6
test
O4. Medical uses and 5-FU Injection and 7-8
cream.
05. Drug interaction and teratogenic effects 9

06. Chemo work and dosage form 10

07. Molecular mechanism,administration 11-13

route and metabolism pathway .

08. Contraindication and adverse effects 14

09. Warnings and precaution 15
Presentations Topic:5-FU
 Fluorouracil (5-FU)
Introduction

** A drug used to treat cancers of the breast, colon, rectum, stomach, and pancreas.5-fluorouracil
(5-FU) is a chemotherapeutical agent used to treat cancers including breast and colorectal. Working as
an antimetabolite to prevent cell proliferation, it primarily inhibits the enzyme thymidylate synthase
blocking the thymidine formation required for DNA synthesis.
Physical and chemical Data
Formula: C4H3FN2O2Molar
Mass: 130.078 g·mol−13D
Melting point: 282–283 °C (540–541 °F)
 Does it kill cancer cells? Indication of 5-FU
5-fluorouracil is the treatment of other conditions and types of cancer. It stops cells from
making DNA and may kill cancer cells. 5-fluorouracil is a type of antimetabolite.It kills
cancer cells in the topical layers of the skin but it can't reach cancer cells that growth
deeply.

Fluorouracil is indicated alone or in combination for:

➢Carcinoma of the colon or rectum

➢Carcinoma of the stomach and exocrine pancreas
➢Carcinoma of the liver
➢Carcinoma of the breast
➢Carcinoma of the bladder
➢Carcinoma of the lung
➢Epithelial ovarian carcinoma
➢Cervical carcinoma.
 Clinical pharmacology And Laboratory Test
The clinical pharmacology of 5-FU is characterized by marked intra- and interpatient variability, nonlinear
elimination kinetics, and erratic oral bioavailability.Following an intravenous bolus dose of 500-600 mg/m², 5-FU
disappears rapidly from plasma with a half-life of 8-14 minutes.

Laboratory Test

Carcinogenesis Mutagenesis Impairment

of Fertility
 Medical Uses And 5-FU Injection
Medical Uses
systemically :
1. anal. Topically(skin)
2. Breast.
3. Colorectal. 1. Actinic keratoses
4. Oesophageal. 2. Skin cancers and Bowen's
5. Stomach. disease
6. Pancreatic. 3. Eye drops
7. Skin cancers.

Fluorouracil Injection
1. It's USP an antineoplasticantimetabolite,
2. It is a sterile.
3. Nonpyrogenic injectable solution for intravenous administration.
4. Each mL contains 50 mg fluorouracil in water for injection USP.
5. pH is adjusted to approximately 9.2 with sodium hydroxide.
Fluorouracil cream And side Effects
This cream is used for

1. Treat cancers of the breast

2. Colon
3. Rectum
4. Stomach
5. pancreas.

Common side effects of 5-FU cream

1. Application site reactions common cold.

2. Allergy.
3. upper respiratory infection.
4. muscle soreness.
5. sinus infection.
6. sun sensitivity.
 Drug Interaction And Teratogenic effects
Drug Interaction
Teratogenic effect
Interaction for fluorouracil :
1. Aspirin Low Strength (aspirin)
Fluorouracil may cause fetal harm when administered to a 2. Ativan (lorazepam)
pregnant woman. Fluorouracil has been shown to 3. Avastin (bevacizumab)
be teratogenic in laboratory animals. Fluorouracil exhibited 4. Benadryl (diphenhydramine)
maximum teratogenicity when given to mice as 5. Celebrex (celecoxib)
single intraperitoneal injections of 10 to 40 mg/kg on day 6. Decadron (dexamethasone)
10 or 12 of gestation. togenic. 7. Fentanyl Transdermal System (fentanyl)
8. Fish Oil (omega-3 polyunsaturated fatty acids)
9. irinotecan
10. leucovorin
11. levamisole
 Chemo work And Dosage Form
Chemo work

5-fluorouracil (5-FU) is a chemotherapeutical agent used to treat cancers including breast and colorectal
Working as an antimetabolite to prevent cell proliferation, it primarily inhibits the enzyme thymidylate synthase
blockingse blocking the thymidine formation required for DNA synthesis.
Dosage form

For precancerous skin condition caused by the sun:

For skin cancer: Adults—Use the 5% cream on the affected areas of skin two times a day.

FDA-approved dose of 5-fluorouracil for the treatment of pancreatic cancer is 400 mg/m2 IV bolus on day
1, followed by 2,400 mg/m2 continuous IV infusion over 46 hours, every 2 weeks in combination with
leucovorin or as a component of a multidrug chemotherapy regimen.
 Molecular Mechanism of action
What is molecular mechanism of action

The molecular mechanism action of a medicine is the connection of

the molecular interactions between the therapeutic treatment and the biological target (e.g.,
receptor, enzyme, etc.) that yields thphysiological response.

Mechanism of Action

The main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the
drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase
(TS) to form a covalently bound ternary complex. This inhibition of the formation of thymidylate from
uracil, which leads to the inhibition of DNA and RNA synthesis and cell death.It incorporated into
RNA in place of uridine triphosphate (UTP), producing fraudulent RNA and interfering with RNA
processing and protein synthesis.
 5-FU

Catabolism Anabolism
DPD Cytotoxic nucleotides

Dihydrofluorouracil

Alfa fluro –Beta-ureido propionic acid

Fluoro deoxy uridine Fluoro deoxy Uridine tri

mono phosphate phosphate
Alfa-Fluoro-Beta Alanine
Fluorouridine- triphosphate
 Administration route And Metabolism Pathway of 5-FU

Administration route
Pathway of Metabolism
1. Bolus intravenous (IV)
2. Continuous IV infusion
3. Intermittent IV infusion
4. Hybrid schedule of bolus plus intermittent IV infusion
5. Addition of the biochemical modulator leucovorin (LV)

The 5-FU inhibitation

5-FU is an effective chemotherapeutic drug developed as an

inhibitor of TS, which leads to a thymine-less cell death. And it
is also a pyrimidine analogue misincorporated into RNA and
DNA in place of uracil or thymine.
 Contraindication And Adverse Effects of Fluorouracil

Contraindication Adverse Effects

Durning systemic use:

1. Hypersensitivity 1. Nausea
2. Poor nutritional status 2. Vomiting
3. Myelosuppression 3. Diarrhea (see below for details)
4. Headache
4. Serious infection
5. Mucositis
5. Recent serious surgery
6. Dihydropyrimidine Dehydrogenase (DPD)
During Topical use:
deficiency
1. Local pain
2. Itchiness
3. Burning
4. Stinging
5. Crusting
6. Weeping
 Warnings And precautions
Warnings
1. Fluorouracil should be administered under the supervision of an
experienced cancer chemotherapy physician because of the
possibility of severe toxic reactions
2. Patient should be hospitalized for initiation of the therapy.
Precautions
1. Increased sensitivity to sunlight may occur
Avoid prolonged exposure to sunlight.
2. Minimise skin contact with harsh detergents or
chemicals - use protective gloves.
3. Do not receive any kind of immunization or
vaccination without doctor's approval while
taking Fluorouracil.
4. Use contraceptives, and do not conceive a child
(get pregnant) while taking Fluorouracil.
• Fluorouracil – Definition and More from the Free Merriam-
Webster Dictionary“
• Joag, Madhura G.; Sise, Adam; Murillo, Juan Carlos; Sayed-
Ahmed, Ibrahim Osama; Wong, James R.; Mercado, Carolina;
Galor, Anat; Karp, Carol L. (2016-03-27).

• British national formulary : BNF 69 (69 ed.). British Medical

Association. 2015
• .Health Organization model list of essential medicines: 21st list
2019. Geneva: World Health Organization.