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Antineoplastic
and
Immunosuppressant drugs
Mohamad Ashraf S. Ismail
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Antineoplastic Drugs
Antineoplastic drugs are sometimes called cancerchemotherapeutic agents and are primarily usedto treat cancer.
These drugs are also used to treat inflammatorydisorders such as psoriasis, rheumatoid arthritis,and systemic lupus erythematosus.
More often than not, multiple drug therapy is used
to treat the different types of cancers.
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Antineoplastic Drugs
These drugs exert their pharmacologic effects byinterfering with the metabolism or reproductivecycle of the tumor cells and thereby destroyingthem.
Antineoplastic drugs are classified as either cellcycle specific or cell cycle nonspecific.
Antineoplastic drugs target rapid dividing tumorcells.
However, they also affect rapidly dividing normalcells that leads to their many adverse effects.
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DRUG CLASSIFICATION
Alkylating agents
Antimetabolites
Hormones
Antitumor antibiotics
Immunomodulators
Plant extracts
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Adverse Drug Effects
Bone Marrow Suppression Bone marrow suppression leads to leukopenia,
agranulocytosis, thrombocytopenia, or anemia.
This puts the patient at risk for serious infectionbecause of the lack of white blood cells.
Osteonecrosis Osteonecrosis of the jaw bone is a recently
recognized adverse effect of the bisphosphonates. The majority of cases (94%) have been reported in
patients receiving intravenous bisphosphonates totreat multiple myeloma or metastatic carcinomas.
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Adverse Drug Effects
Osteonecrosis
Most of the cases have been reported aftertooth extractions and other dental procedures
that traumatize the jaw. It is very difficult to treat once it is diagnosed.
Good home oral hygiene can help to minimizethe risk of osteonecrosis.
Maintenance of oral health exams and otherdental procedures should be performed prior tostarting therapy or within 3 months ofbeginning therapy.
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Adverse Drug Effects
Osteonecrosis
If osteonecrosis is present, then dead boneshould be removed as necessary with minimal
trauma to the adjacent tissue. Chlorhexidrine rinses, systemic antibiotics, and
analgesics should be used if clinicallynecessary.
Bisphosphonates are normally stopped untilthe bone heals or the patient requires it to treatthe cancer.
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Adverse Drug Effects
Gastrointestinal
These drugs are known for causing significantnausea, vomiting, diarrhea, stomatitis, and oral
ulcerations. Patients should rinse with a dilution of
lukewarm water and baking soda aftervomiting.
Aspirin and NSAIDs should be avoidedbecause of the increased risk for GI adverseeffects.
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Adverse Drug Effects
Xerostamia and Caries
May occur due to suppression of salivaryfunction,but it is usually not permanent,so the
treatment is usually palliative. Dry mucosa may also be more prone to
bleeding.
Due to xerostomia,there is an increasedincidence of candidiasis and dental/rootcarries.
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Adverse Drug Effects
Mucositis Oral mucositis(OM)
Is an inflammation leading to ulcerations ormouth sores on the buccal,labial,and soft
palate mucosa,along with the ventral surfaceof the tongue and floor of the mouth.
It is difficult to preventas well as treatmucositis;however it is not permanent.
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Adverse Drug Effects
Taste
Alteration in taste are commonly seen incancer patients which may occur due to a
drugs ability to affect sensitive taste buds. Esophagitis
Is caused by damaged to the mucosal lining
and usually presents as dysphagia(difficultyof swallowing).
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Adverse Drug Effects
Immunosuppression Patients are at higher risk for bacterial, viral,
and fungal infections.
Oral Effects Antineoplastic drugs can cause oral
discomfort, sensitivity of the teeth and gums,mucosal pain and ulceration, gingivalhemorrhage, xerostomia, and impaired taste
sensation. Ice chips and nonalcohol mouth rinses can
help with the dry mouth.
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Immunosuppressant drugs
Immunosuppressant drugs, which are alsocalled anti-rejection drugs, are used toprevent the body from rejecting a
transplanted organ.
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Purpose When an organ, such as a liver, heart or kidney, is
transplanted from one person (the donor) into another
(the recipient), the immune system of the recipienttriggers the same response against the new organ that itwould have against any foreign material, setting off achain of events that can damage the transplanted organ.This process is called rejection. It can occur rapidly(acute rejection), or over a long period of time (chronic
rejection). Rejection can occur despite close matching ofthe donated organ and the transplant patient.Immunosuppressant drugs greatly decrease the risks ofrejection, protecting the new organ and preserving itsfunction. These drugs act by blocking the recipient's
immune system so that it is less likely to react against thetransplanted organ. A wide variety of drugs are availableto achieve this aim but work in different ways to reducethe risk of rejection.
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In addition to being used to prevent organrejection, immunosuppressant drugs are alsoused to treat such severe skin disorders aspsoriasis and such other diseases asrheumatoid arthritis, Crohn's disease (chronicinflammation of the digestive tract), andpatchy hair loss (alopecia areata). Some of
these conditions are termed "autoimmune"diseases, indicating that the immune systemis reacting against the body itself.
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DescriptionImmunosuppressant drugs can be classified according to their specific
molecular mode of action. The four main categories of
immunosuppressant drugs currently used in treating patients withtransplanted organs are the following:
Cyclosporins (Neoral, Sandimmune, SangCya). These drugs act byinhibiting T-cell activation, thus preventing T-cells from attackingthe transplanted organ.
Azathioprines (Imuran). These drugs disrupt the synthesis of DNAand RNA as well as the process of cell division.
Monoclonal antibodies, including basiliximab (Simulect),daclizumab (Zenpax), and muromonab (Orthoclone OKT3). Thesedrugs act by inhibiting the binding of interleukin-2, which in turnslows down the production of T-cells in the patient's immunesystem.
Such corticosteroids as prednisolone (Deltasone, Orasone).These drugs suppress the inflammation associated with transplantrejection.
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Most patients are prescribed a combination ofdrugs after their transplant, one from each ofthe above main groups; for example, theymay be given a combination of cyclosporin,
azathioprine, and prednisolone. Over a periodof time, the doses of each drug and thenumber of drugs taken may be reduced asthe risks of rejection decrease. Most
transplant patients, however, will need to takeat least one immunosuppressive medicationfor the rest of their lives.
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Immunosuppressants can also be classified accordingto the specific organ that is transplanted:
Basiliximab (Simulect) is also used in combination
with such other drugs as cyclosporin andcorticosteroids in kidney transplants.
Daclizumab (Zenapax)is also used in combinationwith such other drugs as cyclosporin and
corticosteroids in kidney transplants. Muromonab CD3 (Orthoclone OKT3) is used along
with cyclosporin in kidney, liver and heart transplants.
Tacrolimus (Prograf) is used in liver and kidney
transplants. It is under study for bone marrow, heart,pancreas, pancreatic island cell, and small boweltransplantation
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Some immunosuppressants are also used to treat a variety ofautoimmune diseases:
Azathioprine (Imuran) is used not only to prevent organ rejection inkidney transplants, but also in treatment of rheumatoid arthritis. It has
been used to treat chronic ulcerative colitis, although it has proved tobe of limited value for this use.
Cyclosporin (Sandimmune, Neoral) is used in heart, liver, kidney,pancreas, bone marrow, and heart/lung transplantation. The Neoralform of cyclosporin has been used to treat psoriasis and rheumatoid
arthritis. The drug has also been used to treat many other conditions,including multiple sclerosis, diabetes, and myasthenia gravis.
Glatiramer acetate (Copaxone) is used in the treatment of relapsing-remitting multiple sclerosis. In one study, glatiramer reduced thefrequency of multiple sclerosis attacks by 75% over a two-year period.
Mycopehnolate (CellCept) is used along with cyclosporin in kidney,
liver, and heart transplants. It has also been used to prevent the kidneyproblems associated with lupus erythematosus.
Sirolimus (Rapamune) is used in combination with other drugs,including cyclosporin and corticosteroids, in kidney transplants. Thedrug is also used to treat patients with psoriasis.
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Side effects Increased risk of infection is a common side effect of all
immunosuppressant drugs. The immune system protects the body frominfections; when the immune system is suppressed, infections are morelikely. Taking such antibiotics as co-trimoxazole prevents some ofthese infections. Immunosuppressant drugs are also associated with aslightly increased risk of cancer because the immune system plays arole in protecting the body against some forms of cancer. For example,the long-term use of immunosuppressant drugs carries an increased
risk of developing skin cancer as a result of the combination of thedrugs and exposure to sunlight.
Other side effects of immunosuppressant drugs are minor and usuallygo away as the body adjusts to the medicine. These include loss ofappetite, nausea or vomiting, increased hair growth, and trembling orshaking of the hands. Medical attention is not necessary unless these
side effects continue or cause problems. The treating physician should be notified immediately if any of the
following side effects occur:
unusual tiredness or weakness
fever or chills
frequent need to urinate
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Managing Patients ReceivingAntineoplastic Drugs
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Managing Patients ReceivingAntineoplastic Drugs
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