Anti cancer Drugs Review From Lipincott And kadzung For Screening test and interview preparation

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 1g Tumor mass=109 cells smallest tumor burden …clinical symptoms appear at this stage

Palliative Chemotherapy= survival is extended

Curative Chemotherapy(Adjuvant)= Solid tumor (i.e Testicular carcinoma)…Reduced by surgery or Radiation…

Cancer , anti cancer drugs , anti metabolite pharmacology


🌟Treatment of Micrometastasis continue after cancer disappear

Curative chemotherapy(Non-adjuvant)= Dissaminated cancer(i.e Leukemia…Drug-chemotherapy to reduce tumor before surgery… 

Each drug have different Organ toxicity& Site of action 

Log kill=Destruction of cancer cell by Anticancer follow 1ST Order kinetics…5-log kill 105 cells 

POMP=For Acute Lymphocytic leukemia; 

Prednisone, Oncovin, Methotrexate, Purinethol. Used for 21days

ANTI-METABOLITES

“S” phase….Cell-Cycle Specific

Methotrexate=Structure related to Folic Acid….Inhibit DHFR (Dihydrofolate reductase)

MOA= enter into the cell by active-transport system same like N5-methylFH4…ϴ Folate→FH2 by DHFR…ϴFH2→FH4 by DHFR…inhibit formation ofN5,N10-Methylene-FH4 Cofactor required for dTMP formation…..also ↓Aenine,Guanine,Thymidine,Methionine,Serine level

Leucovorin/Folinic acid (N5-Formyl-FH4) used to decrease toxicity

T.E= Acute Lymphocytic Leukemia, Choriocarcinoma, Burkitt lymphoma in Childern,  Breast cancer, Head & Neck cancer….Rheumatoid arthritis,Psoriasis

P.K= Hydroxylation into 7-OH-Methotrexate, cause Crystalluria

S.E=Alopecia, Erythhema, Myelosuppression, Cirrhosis, Pulmonary toxicity, Stiff neck,Parpelgia, Seizure, Abortificiant/Teratogenic

6-Mercaptopurine (Purinethol) =thiol (SH) analogue of Hypoxanthine…

MOA=converted into 6-TIMP (Thioinosinic acid) by HGPRT (Hypoxanthine Guanine Phosphoribosyl Transferase)….6-TIMP→TGMP, incorporate into RNA…nonfunctional DNA

ϴIMP↓AMP & XMP….ϴfeedback inhibition of Phosphoribosylamine synthesis Lecsh-Nyhan syndrome lack HGPRT so resistant

S.E= Jaundice, Bone-marrow suppression…metabolize into 6-methyl Mercaptopurine

or Thiouric acid catalyzed by Xanthine Oxidase, when used with Allopurinol ↓conc.

6-Thioguanine=same like 6-MP…metabolize into 2-amino-6-methylThiopurine by

 TPMT (Thiopurine methyltransferase)…Cause Bone marrow suppression

Fludaribine=useful in Chronic Lymphocytic leukemia, Hairy- cell leukemia, non-Hodgkin leukemia…

cause Blindness, encephalopathy

Cladribine=ϴDNA repair….Teratogenic5-Fluorouracil=Pyrimidine analogue…

resemble to Flucytosine (antifungal) F at 5 position 

MOA= enter by carrier mediated system…5-FU→5-FUMP by Phosphoribosyl transferase…5-FUMP→5-FUDP by Uridine kinase…5-FUDP→5-FdUMP by Ribonucleotide reductase…which inhibit dUMP→dTMP 

P.K= metabolize into Fluoro-β-alanine in urine or CO2 which exhale…↑DPD (Dihydropyrimidine dehydrogenase) 

S.E= Ulceration of GIT & oral…Allopurinol mouthwash used to ↓toxicity….also cause „Hand foot syndrome”

Capecitaabine=used in Colorectal cancer, Metastatic Breast cancer (first-line Paclitaxel, Anthracycline)…

contra in Pregnancy, ↑warfarin level

Floxuridine= used in Palliative management of GI adenocarcinoma 

Cytarabine=Cytosine arabinoside enter into cell…phosphorylated into CTP…

ϴDNA polymerase…cause Paralysis, Leukoencephalopathy

Gemcitabine =First-line treatment Metastatic Adenocarcinoma of pancreas,

 used in non-small lung cancer…S.E; Flu-like syndrome, Proteinuria, Hematuria, ↑LFT


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