SALIU DNA and RNA synthesis Examples:. Dactinomycin

 SALIU FS.NSC/2014/865   PCL assignmentAntineoplastic drugs / Anticancer Drugs arenot only used prominently in different types of cancers but also in conjunctionwith surgery, radiotherapy and immunotherapy in the combined modality approachfor many solid tumors, especially metastatic.

Classification of Antineoplastic Agents.1.Alkylating AgentsNitrogen mustards: Melphalan,Cyclophosphamide, IfosfamideNitrosoureasAlkylsulfonatesEthyleneiminesTriazeneMethyl HydrazinesPlatinum Coordination complexes: Cisplatin,Carboplatin, Oxaliplatin2.

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AntimetabolitesFolate Antagonists: MethotrexatePurine antagonistsPyrimidine antagonists: 5-Fluorouracil,CytarabibeNatural ProductsPlant ProductsVinca Alkaloids: Vincristine, VinblastineTaxanes: Paclitaxel, DocetaxelEpipodophyllotoxins: EtoposideCamptothecins: IrinotecaMicroorganism Products3.Antibiotics: Doxorubicin, BleomycinExamples Cyclophosphamide.Mechanisms of Actioncyclophosphamide is an alkylating agent. Itis a widely used as a DNA crosslinking and cytotoxic chemotherapeutic agent.

It is given orally as well as intravenouslywith efficacy.It is inactive in parent form, and must beactivated to cytotoxic form by liver CYT450 liver microsomaal system to 4-Hydroxycyclophamide and Aldophosphamide.4-Hydroxycyclophamide and Aldophosphamideare delivered to the dividing normal and tumor cells. Aldophosphamide is converted into acroleinand phosphoramide mustard.They crosslink DNAs resulting in inhibitionof DNA synthesis Clinical Applications:Breast Cancer,OvarianCancer ,Non-Hodgkin’s Lymphoma Chronic Lymphocytic Leukemia (CLL) ,Softtissue sarcoma ,Neuroblastoma Wilms’ tumor ,Rhabdomyosarcoma .Antimetabolites:Methotresate.Mechanism of Action: Inhibitsformation of FH4 (tetrahydrofolate) from folic acid by inhibiting the enzymedihydrofolate reductase (DHFR); since FH4 transfers methyl groups essential toDNA  synthesis and hence DNA synthesis blocked.

Examples;MethotrexateClinical application: Choriocarcinoma,acute lymphoblastic leukemia (children), osteogenic,sarcoma, Burkitt’s andother non-Hodgkin’s lymphomas, cancer of breast, ovary, bladder, head &neck.Antibiotics :Doxorubicin.Mechanism of Action:It binds to DNA andinhibits RNA synthesis, impaired mRNA production, and protein synthesis andinhibit DNA and RNA synthesis Examples:. Dactinomycin .Daunorubicin, Doxorubicin,Bleomycin.Clinical application:Rhabdomyosarcoma andWilm’s tumor in children;choriocarcinoma (used with methotrexate.Acute lymphocytic/granulocytic leukemias;treatment of choice in nonlymphoblastic leukemia in adults when given withcytarabineAcute leukemia, Hodgkin’s disease, nonHodgkin’s,lymphomas (BACOP regimen), CA of breast & ovary,small cell CA oflung, sarcomas, best available agent for metastatic thyroid CA.

Germ cell tumors of testes and ovary, e.g.,testicular carcinoma (can be curative when used with vinblastine ), squamous cell carcinoma.Question 2:Food as an essentials  component of infection control discuss.Starve a cold, feed a fever.

” Theseoft-heard words of wisdom may not be so wise. Scientific research shows thatsome foods contain compounds that enhance immune system function and makehumans better able to fight infection. These compounds may not preventinfections from developing, but they help activate infection-fighting whiteblood cells and trigger increased production of cells that kill foreigninvaders.-Citrus FruitsVitamin C helps fight infection byincreasing the production of white blood cells, which defend the body againstbacteria and viruses. Vitamin C also increases the production of interferon, asubstance that coats the surfaces of cells to prevent viruses from entering.The Food and Nutrition Board of the Institute of Medicine recommends a dailyintake of 75 mg for men and 60 mg for women.

Just one navel orange contains82.7 mg of vitamin C, more than 100 percent of the DRI.-GarlicGarlic has antimicrobial propertiesconfirmed by scientific research. In a study led by Edward C.

Delaha ofGeorgetown University Hospital, investigators extracted allicin from 10 bulbsof garlic and created a thick paste by mixing the extract with steriledistilled water. They prepared 30 different strains of Mycobacterium and addedthem to petri dishes containing the garlic extract. The researchers examinedeach petri dish daily for 28 days and recorded the growth of the bacteria. Atthe conclusion of the study, they determined that the garlic extract pasteinhibited the growth of all 30 strains.

The results of this study appeared inthe April 1985 issue of “Antimicrobial Agents and Chemotherapy.”-Meat and ShellfishMeat and shellfish contain zinc, a mineralthat affects immune system function. Zinc deficiency impairs the function ofinfection-fighting monocytes, reduces the toxicity of natural “killer cells”and inhibits the immune response designed to engulf foreign particles.

Eatingmeat and shellfish may help replenish zinc stores and ward off infection. Thedietary reference intake for zinc is 9.4 mg per day for adult men and 6.8 mg perday for adult women. One serving of battered oysters — six pieces — has 15.64mg of zinc.

-Fish, Seeds and NutsSome fish, seeds and nuts contain selenium,a mineral that enhances the function of killer cells in the immune system.Tuna, sunflower seeds, red snapper and Brazil nuts contain high amounts of thismineral. One 3-oz. serving of bluefin tuna, for example, contains 39.8 mcg ofselenium.

Adult men and women need 45 mcg of selenium per day, as recommendedby the Food and Nutrition Board of the Institute of Medicine.-Colorful VegetablesColorful vegetables, such as red peppers,carrots, squash, spinach and sweet potatoes, contain carotenoids. Thesecompounds enhance immune system function, making you better able to fightinfection. Carotenoids, particularly beta-carotene, may also increase thenumber of T-helper lymphocytes in the body. These cells activate and coordinatethe response of macrophages and cytotoxic T-cells, which fight infectiousorganisms.ounds derived from ammonia. Question 3:list the principle of chemotherapeutic  resistance.

1:Pre-chemotherapy  assessment.2:Counselling.3:Optimization 4:Modalities 5:Administration.6:Management  of side effect and follow up.Most consider important  is pre -chemotherapeutic  assessment.

Aim:Establishes  diagnosis fitness of patient.Method:clinical evaluation and laboratory  test.Clinical evaluation.

History:detail history            Systemic  involvement.            Co-morbidities.            Performance status.Performance status  : ls an attempt  to qualify the general wellbeing  and daily activitiesof the patient.-Whether they can receive chemotherapy -When dose adjustment  is necessary -As a measure for the require d intensity ofa palliative  care.-Measure of quality of life.Laboratory test includes Diagnostic :histology Extent:imaging,chest xray,CT,MRI,PET,USS,LFT.Baseline:FBC,PCV,WBC,Stool microscopy.Others depending  on the type of cancer eg tumor marker.


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