Antineplastic+Drugs

=Antineoplastic Drugs: = 

Alklating drugs (Nitrogen mustards):  Pharmacokinetics: As with alkylating drugs, the absorption and distribution of nitrogen mustards vary widely. Notrogen mustards are metabolized in the liver and excreted by the kidney. Mechlorethamine undergoes metabolism so rapidly that, after a few minutes, no active drug remains. Most nitrogen mustards possess more intermediate half-lives than mechlorethamine. Pharmacodynamics: Nitrogen mustards form covalent bonds with DNA molecules in a chemical reaction known as alkylation. Alkylated DNA can’t replicate properly, thereby resulting in cell death. Unfortunately, cells may develop resistance to cyotoxic effects of nitrogen mustard. Pharmacotherapeutics: Because they produce leucopenia; reduced number of white blood cells, nitrogen mustards are effective in treating malignant neoplasm, such as Hodgkin’s disease (cancer that causes painless enlargement of the lymph nodes, spleen, and lymphoid tissues) and leukemia (cancer of the blood forming tissues), that can have an associated elevated WBC count. Drug Interactions: Nitrogen mustards interact with several other drugs: Adverse reaction: Many patient experience fatigue during during nitrogen mustard therapy. Other adverse reactions include : Alkyl sulfonates:  Used to treat chronic myelogenous leukemia, polycythemia vera, and other myeloproliferative disorders. Busulfan is used at high doses to treat leukemia during bone marrow transplantation.
 * Calcium-containing drugs and food, such as antacids and dairy products, reduce absorption of estramustine.
 * Taking cyclophosphamide with cardiotoxic drugs produces additive cardiac effects.
 * Cyclophosphamide can reduce serum digoxin levels
 * An increased risk of ifosfamide toxicity exists when the drug is taken with allopurinol, barbiturates, chloral hydrate, or phenytoin.
 * Corticosteroids reduce the effects of ifosfamide.
 * The lung toxicity threshold of varmustine may be reduced when thaken with melphalan.
 * Onterferon alpha may reduce the serum concentration of melphalan.
 * Bone marrow suppression, leading to severe leucopenia and thrombocytopenia
 * Nausea and vomiting from central nervous system irritation
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Stomatitis
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Reversible hair los s

Pharmacokinetics: Busulfan is absorbed rapid and well from the GI tract. Little is known about its distribution. Busulfan is metabolized extensively in the liver before urinary excretion. It s half-life is 2 to 3 hours.

Pharmacodynamcs: <span style="font-size: 10pt; font-family: 'Arial Narrow'; msofareastfontfamily: 'Times New Roman'; msobidifontfamily: 'Times New Roman'; msoansilanguage: EN-US; msofareastlanguage: EN-US; msobidilanguage: AR-SA;">As an alkyl sulfonate, busulfan forms covalent bonds with the DNA molecules in alkylation. <span style="font-family: 'Comic Sans MS', cursive;"> <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacotherapeutics: Busulfan primarily affects granulocytes and to a lesser degree, platelets. Because of its action on granulocytes, it has been used for treating chronic myelogenous leukemia and in conditioning regins for bone marrow transplantation. Busulfan is also effective in treating polycythemia vera. However, others drugs are usually used to treat polycythemia vera because busulfan can cause severe myelosuppression (halting of bone marrow function).

Drug Interactions: There’s an increased risk of bleeding when busulfan is taken with anticoagulatants or aspirin. Concurrent use of busulfan and thioguanine may cause liver toxicity, esophageal varices (enlarged, swollen veins in the esophagus), or portal hypertension (increased pressure in theportal vein of the liver). <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;"> Adverse reactions: The major adverse reaction to busulfan is bone marrow suppression, producing severe leucopenia, anemia, and thrombocytopenia, which is usually dose related and reversible. <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;"> <span style="font-size: 11pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Nitrosoureas : <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Halt cancer cell reproduction. Pharmacokinetics: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">When IV carmujstine achieves a steady-state volume of distribuation. With oral administration, lomustine is absorbed adequately, although incompletely. Streptozocin is administered IV because it’s poorly absorbed orally. Nitrosoureas are lipophilic drugs and are distributed to fatty tissues and cerebrospinal fluid. They’re metabolized extensively before urine excretion. Pharmacodynamics: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">During a process called bifunctional alkylation, nitrosoureas interfere with amino acids, purines, and DNA needed for cancer cells to divide, thus halting their reproduction. Pharmacotherapeutics: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">The nitrosoureas are highly lipid soluble, which allows them or their metabolites to easily cross the blood brain barrier. Because of this ability, nitrosoureas are used to treat brain tumors and meningeal leukemias. Drug interactions: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Each of the nitrosoureas has its own interactions with other drugs: Adverse reactions: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">All of the nitrosoureas can produce severe nausea and vomiting. <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Carmustine and lomustine produce bone marrow suppression that begins 4-6weeks after treatment and last 1-2weeek. These drugs shouldn’t given more frequently than every 6 wks. Kidney toxicity and kidney failure may also occur with patients taking nitrosourseas. High-dose carmustine may produce reversible liver toxicity. Carmustine may cause delayed lung toxicity characterized by lung infiltrates or fibrousis that can occur years after treatment. In patients who receive prolongedtherapy with total dosages greater than 1400mg/m2, pulmonary toxicity can occur anywhere from 9 days to 15 yrs after treatment.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Cimetidine may increase carmustine’s bone marrow toxicity.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Kinystube ysed with anticoagulants or aspirin increases the risk of bleeding; avoid using these drugs together.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Streptozocin can prolong the elimination half-life of doxorubicin, prolonging leucopenia and thrombocytopenia

<span style="font-size: 11pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Triazenes <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacokinetics: After IV injection, dacarbazine is distributed throughout the body and metabolized in the liver. Within 6 hours, 30% to 46% of a dose is excreted by the kidneys. In a patient with kidney or liver dysfunction, the drug’s half-life may increases to 7hours. Pharmacodynamics: Dacarbazine first must be metabolized in the liver to become an alkylated drug. It seems to inhibit RNA and protein synthesis. Like other alkylating drugs, dacarbazine is cell cycle-nonspecific.

Pharmacotherapeutics: Darcarbazine is used primarily to treat patients with malignant melanoma. It’s also used with other drug to treat patients with Hodgkin’s Disease.

Drug Interactions: No significant drug interactions have been reported with dacrabazine.

Adverse Reactions” Dacarbaine use may cause the following adverse reactions


 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Leukopenia
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Thrombocytopenia
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Nausea and vomiting
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Phototoxicity
 * <span style="font-family: 'Comic Sans MS', cursive;"><span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Flulike syndrom e
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Hair los s

<span style="font-size: 11pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Ethylenimines <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacokinetics: After IV administration, thiotepa is 100% bioavailable. Signficant systemic absorption may occur when it’s administered into pleural or peritoneal spaces to treat malignant effusions or instilled into the bladder. Thiotepa crosses the blood-brain barrier and is metabolized extensively in the liver. Thiotepa and its metabolites are excreted in the urine.

Pharmacodynamics: Thiotepa exerts its cytotoxic activity by interfering with DNA replication and RNA transcription. Ultimately, it disrupts nucleic acid function and causes cell death.

Pharmacotherapeutics: Thiotepa is used to treat bladder cancer. This alkylating drug is also prescribed for palliative treamtnet of lymphomas and ovarian or breast carcinomas. Thiotepa is used to treat intracavitary effusions. It may also prove useful in the treatment of lung cancer.

Drug Interaction: Thiotepa may interact with other drugs: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Adverse reactions: The major adverse reaction to thiotepa are blood related and include leucopenia, anemia, thrombocytopenia, and pancytopenia, which may be fatal. Other adverse reactions include: <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Alkylating-like drugs <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacokinetics: Distribution and metabolism of carboplatin aren’t clearly defined. After IV administration, carboplatin is eliminated primarily by the kidneys. The elimination of carboplatin is biphasic. It has an initial half-life of 1 to 2 hours and a terminal half-life of 21/2 to 6 hours. Oxaliplatin is 70%-90% bound to plasma proteins and is eliminated primarily by the kidneys. When administered intrpleurally or intraperitoneally, cisplatin may exhibit significant systemic absorption. Highly protein bound, cisplatin reaches high concentrations in the kidneys, liver, intestine and testes but has poor CNS penetration. The drug undergoes some liver metabolism, followed by excretion through the kidneys. Plantinum is detectable in tissue for at least 4 months after administration.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Concurrent use of thiotepa, anticoagulants, and aspirin may increase the risk of bleeding.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Taking thiotepa with neuromuscular blocking drugs may prolong muscular paralysis.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Concurrent use of thiotepa and other alkyulating drugs or radiation therapy may intensify toxicity rather than enhance the therapeutic response.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">When used with succinylcholine, thiotepa may cause prolong respirations and apnea. Thioptepa appears to inhibit the activity of cholinesterase, the enzyme that deactivates succinylcholine.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Nausea and vomiting
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Stomatitis and ulceration of the intestinal mucosa
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Hives, rash and pruritu s

Pharmacodynamics: Like alhylating drugs, carboplatin, oxaliplatin, and cisplatin are cell cycle-nonspecific and inhibit DNA synthesis. They act like bifunctional alkylating drugs by crossing-linking strands of DNA and inhibiting DNA synthesis.

Pharmacotherapeutics: These alkylating-like drugs are used to treat several cancers: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Drug interactions: These alkylating-like drugs interact with a few other drugs: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;"> Adverse reactions: Carboplatin and cisplatin produce many of the same adverse reaction as the alkylating drugs: <span style="font-size: 11pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Antimetabolite Drugs <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Folic acid analogues :
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Carboplatin is used primarily to treat ovarian and lung cancer.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Cisplatin is prescribed to treat bladder and metastatic ovarian and testicular cancers.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Cisplatin may also be used to treat head, neck, and lung cancer.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Oxaliplatin is used in combination with other agents in colorectal cancer.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">When carboplatin, cisplatin, or oxaliplatin are administered with an aminoglycoside, the risk of toxicity to the kidney increases.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Taking carboplatin or cisplatin with bumetanide, ethacrynic acid, or furosemide increases the risk of ototoxicity.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Cisplatin may reduce serum phenytoin levels.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Carboplatin can produce bone marrow suppression
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Kidney toxicity can occur with cisplatin, usually after multiple courses of therapy. Carboplatin is less toxic to the kidneys.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">With long-term cisplatin therapy, neurotoxcity can occur. Neurotoxicity is less common with carboplatin.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Tinnitus and hearing loss, which is usually permanent, may occur with cisplatin. It’s much less common with carboplatin.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Cisplatin can also produce marked nausea and vomiting.

<span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacokinetics: Methotrexate is absorbed well and distributed throughout the body. It can accumulate in any fluid collection, such as ascites or pleural or pericardial effusion. This can result in prolonged elimination and higher than expected toxicity, especially myelosuppression. At usual dosages, methotrexate doesn’t enter the CNS readily. Although methotrexate is metabolized partially, it’s excreted primarily unchanged in urine. Methotrexate exhibits a three-part disappearance from plasma; the rapid distributive phase is followed by a second phase, which reflects kidney clearance. The last phase, the terminal half-life, is 3-10 hours for a low dose and 8-15 hours for a high dose.

Pharmacodynamics: Methotrexate reversibly inhibits the action of the enzyme dihydrofolate reductase. This blocks normal folic acid processing which inhibits DNA and RNA synthesis. The result is cell death.

Pharmacotherapeutics: Methotrexate is especially useful in treating: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">The drug is also prescribed in low doses to treat severe psoriasis, graft-versus-host disease, and rheumatoid arthritis that don’t respond to conventional therapy.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Acute lymphoblastic leukemia, the most common leukemia in children
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Acute lymphocytic leukemia; may be given as treatment and prophylaxix for meningeal leukemia
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">CNS diseases
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Choriocarcinoma
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Osteogenic sarcoma
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Malignant lymphomas
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Carcinomas of the head, neck, bladder, testis, and breast.

<span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Drug interactions: Metotrexate interacts with several other drugs: <span style="font-family: 'Comic Sans MS', cursive;"><span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Probenecid decreases methotrexate excretion, increasing the risk of methotrexatetoxicity, including fatigue, bone marrow suppression and stomatitis (mouth inflammation) <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Salicylates and NSAIDS, also increase methotrexate toxicity. <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Cholestyramine reduces the absorption of methotrexate from the GI tract. <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Concurrent use of alcohol and methotrexate increases the GI tract. <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Concurrent use of alcohol and mathotrexate increases the risk of liver toxicity <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Taking co-trimoxazole with methotrexate may produce blood cell abnormalities. <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Penicillin decreases renal tubular secretion of methotrexate, increasing the risk of methotrexate toxicity <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Monitor hematocrit; ALT, AST, LD serum bilirubin, serum creatinine, urine acid and BUN levels; platelet and total and differential leukocyte counts; and other values as required. <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Evaluate the patient’s and family’s knowledge of drug therapy. <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Pyrimidine analgues <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Inhibit production of pyrimidine nucleotides necessary for DNA synthesis.

Pharmacokinetics: Because pyrimidine analogues are absorbed poorly when given orally, they’re usually administered by other rountes. With the exception of cytarabine, pyrimidine analgues are distributed well throughout the body, including CSF. They’re metabolized extensively in the liver and are excreted in urine. Intrathecal cytarabine may be given with or without cranial radiation to treat CNS leukemia.

Pharmacodynamics: Pyrimienine analgogues kill cancer bells by interfering with the natural function of pyrimidine nucleotides.

Pharmacotherapeutics: Pyrimidine analogues may be used to treat many types of tumors. However, they’re primarly indicated in thetreatment of: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;"> Drug Interactions: No significant drug interactions occur with most of th pyrimidine analogues; however, several are possible with capecitabine ; <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;"> Adverse reactions: Like most antineoplastic drugs, phrimidine analogues can cause: <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Purine analogues <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Incorporated into DNA and RNA, interfering with nucleic acid synthesis and replication.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Acute leukemias
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">GI treact adnocarcinomas, such as colorectal pancreatic, esophageal and stomach cancers.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Carcinomas of the breat and ovaries
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Malignant lymphomas
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;"> Capecitabine may have increased absorption when coadministered with antacid <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">s
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Capecitabine can increase the pahrmacodynamic effects of warfarin, thereby increasing the risk of bleeding
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Capecitabine may increase serum phenytoin levels
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Fatigue
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Inflammation of the mouth, esophagus, and throat, leading to painful ulceration and tissue sloughing
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Bone marrow suppression
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Nausea
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Anorexia
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">High dose cytarabine can caus sever cerebellar neuotoxicity, chemical conjunctivitis, diarrhea, fever, and hand-foot syndrome. Crab erythema can be seen with high dose cytarabine and continuaous infusions of fluorouracil. Other adverse reactions with fluorouracil include diarrhea and hair loss.

Pharmacokinetics: Aren’t defined clearly. They’re largely metabolized in the liver and excreted in urine.

Pharmacodynamics: As with othe antimetabolites, fudarabine, mercaptopurine, and thioguanine first must undergo conversion via phosphorylation to the nucrleotide level to be active. The resulting nucleotides arethen incorporated into DNA and RNA synthesis as well as other metabolic reactions necessary for proper cell growth. Cladribine responds in a similar fashion. Pentostatin inhibits adenosine deaminase (ADA), causing an increase in intracellular levels of deoxyadenosine trphosohate. This leads to cell damage and death. The greates activity of ADA is in cells of lymphoid system, especially malignant T cells. This conversation to nucleotides is the same process that pyrimidine analogues experience but, in this case, it’s puridine nucleotides tha are affected. Purine analogues are cell cycle-specific as well, exerting their affect during that same S phase. <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;"> Pharmacotherapeutics: Purine analogues are used to treat acut and chronic leukemias and may be useful in the treatment of lymphomas.

Drug Interactions: No significant interactions occur with cladribine or thioguanine. Taking fludarabine andpentostatin together may cause severe pulmonary toxicity, with can be fatal. Taking pentostatin with allopurinol may increase the risk of rash. Takin pentostatin with vidarabine amy enhance the effect of vidarabine and increase the risk of toxicity. Concomitant administration of mercaptopurine and allopurinol may increase bone marrow suppression by decreasing meraptopurine metabolism.

Adverse Reactions: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Fludarabine, when used at high doses, may cause severe neurologic effects, including blindness, coma, and death.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Bone marrow suppression
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Nausea and vomiting
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Anorexia
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Mild diarrhea
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Stomatitis
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Rise in uric acid levels

<span style="font-size: 11pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Antibiotic antineoplatic drugs: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacokinetics: Because antibiotic antineioplastic drugs are usually administered IV no absorption occurs. Distribution of antibiotic antineoplastic drugs throughout the body varies as does their metabolism and elimation.

Pharmacodynamics: With the exception of mitomycin, antibiotic antineoplastic drugs intercalate, or insert themselves, between adjacent base pair of a DNA molecule, physically separating them. Remember, DNA looks like a twisted ladde with the rungs made up of pairs of nitrogenous bases. Antibiotic antineoplastic drugs insert themselves between these nitrogenous bases. Then, when DNA chain replicates, an extrea base is enserted opposite the intercalated antibiotic, resulting in a mutant DNA molecule. The overall effects s cell death. Mitomycin is activated inside the cell to a bifunctional or trifunctional alkylating drug. It produces single-stranded breakage DNA, cross links DNA nad inhibits DNA synthesis. Pharmacotherapeutics: Antibiotic antineoplastice drugs act against many cancers, including: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;"> Drug interactions: Antibiotic antineoplastic drugs interact with many others drugs: <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;"> Adverse reaction: The primary adverse reaction to antibiotic antineioplastic drugs is bone marrow suppression. Irreversible cardiomyopathy and acute ECG changes can also occur as well as nausal and vomiting. An antihistamine and antipyretic should be given before bleomycin to prevent fever and chills. An anaphylactic reaction can occur in patients receiving bleomycin for lymphoma so test doses should be given first. <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Doxorubicin, daunorubicin, and idarubicin may color urine red; mitoxantrone may color it blue-green. <span style="font-size: 11pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">Hormonal antineoplastic drugs and hormone modulators:
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Hodgkin’s disease and malignant lymphomas
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Testicular carcinoma
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Squamous cell carcinoma of the head, neck, and cervix
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Wilms’ tumor
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Osteogenic sarcoma and rhabdomayosarcoma
 * Ewing’s sarcoma and othe soft-tissue sarcomas
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Breast, ovarian, bladder, and lung cancer
 * <span style="font-family: 'Comic Sans MS', cursive;"><span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Melanom a
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Carcinomas of the GI trac
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Choriocarcinoma
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Acute leukemia
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Concurrent therapy with fludarabine and idarubicin isn’t recommended because of the risk of fatal lung toxicity.
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Bleomycin may decrease serum digoxin and serum phenytoin levels
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Doxorubicin may reduce serum digoxin levels
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Combination chemotherapies enhance leucopenia nad thrombocytopenia
 * <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Mitomycin and vinca alkaloids may cause acute respiratory distress.

<span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Aromatase inhibitors: prevent androgen from being converted into estrogen in postmenpausal women. This blocks estrogen’s ability to activate cancer cells by limiting the amount of estrogen reaching the cancer cess to promote growth. Aromatase inhibitors may be type 1 steroidal inhibitors or type 2 nonsteroidal inhibitors.

Pharmacokinetics: Aromatase inhibitors are taken orally in pill form and are well tolerated by most women. Steady state plasma levels after daily doses are reached in 2 to 3 weeks. Inactive metabolites are excreted in urine. <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacodynamics: In post menopausal women, estrogen is produced through aromatase, an enzyme that converts hormone precursors into estrogen. Aromatase inhibitors work by lowering the body’s production of the female hormone estrogen. In up to half of all patients with breast cancer, the tumors are dependent on this hormone to grow. Aromatase inhibitors are used in postmenopausal women because they lower the amount of estrogen that’s produced outside the ovaries in muscle and fat tissue. Because they induce estrogen deprivation, bone thinning and osteoporosis may develop in time. Type 1 inhibitors irreversibil inhibit aromatase enzyme, whereas type 2 inhibitors reversibly inhibit the aromatase enzyme/ It has also been suggested that type 1 might have some effect after the failure of a type 2. Exemestane selectively inhibits estrogen synthesis and doesn’t affect synthesis of adrenocorticosteroid, aldosterone, or thyroid hormones. Anastrozole and letrozole act by competitively binding to the heme of the cytochrome P450 subunit of aromatase, leading to decrease biosynthesis of estrogen in all tissues. They don’t affect synthesis of adrenocorticosteroid, aldosterone, or thyroid hormones. <span style="font-size: 10pt; font-family: 'Comic Sans MS', cursive;">Pharmacotherapeutics: <span style="font-size: 10pt; color: #6b8dd1; font-family: 'Comic Sans MS', cursive;"> Antiestrogens: <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Bind to estrogen receptors and block estrogen action. <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Pharmacokinetics: After oral dministration, tamoxifen is absorbed well and undergoes extensive metabolism in the liver before being excreted. IM injection of fulvestrant yields peak serum levels in 7-9 days and has a half life of 40 days. Toremifene is well absorbed and isn’t influenced by food. <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Pharmacodynamics: The exact antieoplastic action of these agents is unknown. However it’s known that they act as estrogen antagonists. Estrogen receptors, found in the cancer cell of half of premenopausal and ¾ of post menopausal women with breast cancer, respond to estrogen to induce tumor growth. DNA synthesis and cell growth are inhibited.

Pharmacotherapeutics: The antiestrogen tamoxifen citrate is used alone and as adjuvant treatment with radiation therapy and surgery in women with negative axillary lymph nodes and in postmenopausal women with positive axillary nodes. It’s also used for advanced breast cancer in postmenopausal women who have estrogen receptor-positive tumors. Tumors in postmenopausal women are more responsive to tamoxifen than those in pre-menopausal women. Tamoxifen may also be used to reduce the incidence of breast cancer in healthy women at high risk for breast cancer. Toremifene is used to treat metastatic breast cancer is post menopausal women with estrogen receptor-positive tumors. Fulvestrant is used in postmenopausal women with receptor-positive metastasis breast cancer with disease progression after treatment with tamoxifen.

Drug interactions: <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;"> Adverse reactions: <span style="font-family: 'Comic Sans MS', cursive;"><span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Hot flashes <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Mausea and vomiting <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Diarrhea and constipation <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Abdominal pain <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Headache <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Back pain <span style="font-size: 10pt; font-family: Symbol; mso-bidi-font-family: Symbol; msofareastfontfamily: Symbol; msobidifontfamily: Symbol; mso-fareast-font-family: Symbol; msolist: Ignore;">· Pharyngitis.
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Fulvestrant has no known drug interactions
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Tamoxifen and toremifene may increase the effects of warfarin sodium, increasing prothrombin time (PT) and risk of bleeding.
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Bromocriptine increases the effects of tamoxifen.
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Tamoxifen: **
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Hot flashes
 * <span style="font-size: 10pt; color: #000000; font-family: 'Comic Sans MS', cursive;">Nausea and vomiting
 * <span style="font-family: 'Comic Sans MS', cursive;">Diarrhea
 * <span style="font-family: 'Comic Sans MS', cursive;">Fluid retention
 * <span style="font-family: 'Comic Sans MS', cursive;">Leucopenia or thrombocytopenia
 * <span style="font-family: 'Comic Sans MS', cursive;">Hypercalcemia
 * <span style="font-family: 'Comic Sans MS', cursive;">Toremifene **
 * <span style="font-family: 'Comic Sans MS', cursive;">Hot flashes
 * <span style="font-family: 'Comic Sans MS', cursive;">Sweating
 * <span style="font-family: 'Comic Sans MS', cursive;">Nausea and vomiting
 * <span style="font-family: 'Comic Sans MS', cursive;">Edema
 * <span style="font-family: 'Comic Sans MS', cursive;">Fulvestrant **

<span style="color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">**Natural Products** <span style="color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">**Anthracycline Antibiotics**
 * **Drug:** **Bleomycin** (Bleo, Bleocin, Blenoxane ®) ||
 * **Drug Class: Antitumor Peptide** ||
 * **Mechanism of Action:** bleomycin is a small peptide that contains **a DNA binding region & an iron-binding domain** at opposite ends of the molecule. It acts by intercollating into DNA & reacts with ferous ions (Fe2+) to produce free radicals that cause DNA fragmentation, resulting in single & double strand breaks, and inhibition of DNA biosynthesis. Bleomycin is a cell-cycle specific drug that causes accumulation of cells in the G2 phase of the cell cycle. ||
 * **Indications:** **Hodgkin's disease**, **Non-Hodgkin's lymphoma**, **testicular carcinoma** ||
 * **Side Effects: little myelosuppression** (unusual for antineoplastics), and as a result it can be combined with other drugs that do produce myelosuppression (e.g. BACOP, ABVD, PEB). **Lung toxicity** that is dose -limiting, including reversible pneumonitis (8-10%) and, more rarely, a potentially fatal pulmonary fibrosis (1%). ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug:** **Actinomycin D** or **Dactinomycin** (Cosmegen ®) ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug Class: Antitumor Antibiotic** ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Mechanism of Action:** Dactinomycin intercolates into DNA & inhibits transcription, resulting in cell death. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Indications:** **Wilm's tumor** & as an alternative to methotrexate in **choriocarcinoma**. Its indications are limited due to its toxicity. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Side Effects:** A highly toxic drug. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug:** **Daunorubicin** or Daunomycin (Daunoxome, Cerubidine ®) ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug Class: Antitumor Antibiotic** ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Mechanism of Action:** 1) **inhibits topoisomerase II**, 2) high affinity **binding to DNA through** **intercalation**, resulting in blockade of DNA and RNA synthesis, and DNA strand scission; 3) alterations in cell membrane transport; 4) generation of semiquinone free radicals & oxygen free radicals that cause DNA strand breaks. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Indications:** **acute myelocytic leukemia (AML)** "only" ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Side Effects:** dose-limiting myelosuppression & cardiotoxicity ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Notes:** Daunorubicin was the first agent in this class to be isolated, and its current use is limited to the treatment of AML. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug:** **Doxorubicin** (**Adriamycin**, Doxil, Rubex ®) ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug Class: Antitumor Antibiotic** ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Mechanism of Action:** same as for Daunorubicin (above) ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Indications:** **broad spectrum** of clinical indications including solid tumors (e.g. breast cancer) and hematoligic malignancies. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Side Effects:** **myelosupression** and **cardiotoxicity** including acute transient ECG changes (reversible) and chronic cardiomyopathy leading to the development of **congestive heart failure**. The development of CHF is related to the cumulative dose taken over time: ~1% at 450-500 mg/m2; ~11% at 500-600 mg/mm2; ~33% at >600 mg/mm2.  ||

<span style="color: #6b8dd1; font-family: 'Comic Sans MS', cursive;">//**Vinca Alkaloids**// 
 * <span style="font-family: 'Comic Sans MS', cursive;">**Drug:** **Vinblastine** (Velban ®) ||
 * <span style="font-family: 'Comic Sans MS', cursive;">**Drug Class: Antineoplastic alkaloid** ||
 * <span style="font-family: 'Comic Sans MS', cursive;">**Mechanism of Action:** binds to microtubule protein in its dimeric form and **promotes depolymerization**. This results in **mitotic arrest** at metaphase, and interference with chromosome segregation. ||
 * <span style="font-family: 'Comic Sans MS', cursive;">**Indications:** has clinical acitivity against **Kaposi's sarcoma**, advanced carcinoma of the testis, lymophocytic lymphoma. ||
 * <span style="font-family: 'Comic Sans MS', cursive;">**Side Effects:** myelosuppression, nausea & vomiting ||
 * <span style="font-family: 'Comic Sans MS', cursive;">**Notes:** isolated from the periwinkle plant ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug:** **Vincristine** (Oncovin, Vincasar ®) ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Drug Class: Antineoplastic alkaloid** ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Mechanism of Action:** same as vinblastine (above) ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Indications: wider spectrum of clinical activity than vinblastine**. Used with prednisone for **acute lymphoblastic leukemia** **(ALL)** in children. Active in combination with other drugs (MOPP, CHOP, BACOP) to **treat various hematological malignancies** such as Hodgkin's & non-Hodgkin's lymphoma, multiple myeloma. ||
 * <span style="color: #000000; font-family: 'Comic Sans MS', cursive;">**Side Effects:** **allopecia**, **peripheral neuropathy**. Not as myelosuppressive as vinblastine. (Note: different than for vinblastine).

**VII. Drugs Used In Cancer Chemotherapy**

Excluding hormonal agents, more than 60 different anti-cancer drugs are used in various areas of the world, with more than 30 of them currently being used in man in the United States and Western Europe. Not all of these have been used or are suitable for use in veterinary medicine.

These agents undergo strongly electrophilic chemical reactions through formation of carbonium ion intermediates or transition complexes with the target molecules. The intermediates then react with strongly nucleophilic substituents (i.e., phosphate, amino, sulfhydryl, hydroxyl, carboxyl, imidazole groups) to form covalent bonds. The target molecule is then said to have been alkylated. Alkylation of the 7-nitrogen atom of guanine is an important site in the covalent cross-linking of DNA to a closely associated protein if the drug is a bifunctional alkylating agent. Also, alkylation may cause a shift of electron configuration of guanine so that its base pairs with thymine rather than cytosine. This results in the substitution of an adenine-thymine pair in place of a guanine-cytosine pair. The alkylating agents are effective against cells rapidly traversing the cell cycle and for this reason are more toxic to bone marrow cells than to such organs as liver and kidney. They may also cause infertility in males and females. They also resemble radiation as to their toxic effects. Tumors commonly develop resistance that may extend across the whole class of alkylating agents as a result of decreased permeability to drugs, increased production of nucleophilic substances and increased activity of DNA repair systems.
 * A. Alkylating Agents**

1. Nitrogen Mustards: These are bifunctional alkylating agents which include mechlorethamine (must be given intravenously), cyclophosphamide melphalan and chlorambucil. Chlorambucil and cyclophosphamide are so stable they can be given orally. Cyclophosphamide must be activated in the liver. The mustards are toxic to lymphocytes and bone marrow cells.

A severe vesicant and must be administered intravenously with great care. In contrast to the other mustards, it has significant G.I. toxicity. It has been used for lymphoreticular neoplasms and mast cell tumors. A dose of 5 mg/M2 as a single treatment or in 2-4 divided doses on successive days as appropriate has been recommended for dogs and cats.
 * a. Mechlorethamine Hydrochloride**

Widely used in veterinary medicine in combination with other drugs. It has been used for lymphoreticular neoplasms, sarcomas, carcinomas of the lung and mammary gland, and other tumors. The side effects of cyclophosphamide are bone marrow suppression, with both leukopenia and thrombocytopenia. Nausea and vomiting are rare. Sterile necrotizing hemorrhagic cystitis has been associated with chronic administration and is a cause of stopping therapy(bloody urine).
 * b. Cyclophosphamide**

Most widely used for treatment of mammary carcinoma, malignant melanoma, multiple myeloma, ovarian carcinoma, and testicular seminoma. It produces anorexia, nausea, and vomiting. Leukopenia, thrombocytopenia and anemia are the dose -limiting toxicities.
 * c. Melphalan**

Used in lymphoreticular tumors and ovarian carcinoma. It can be used orally and has a half-life in humans of 90 minutes. It is the slowest acting of the mustards. It produces bone marrow suppression, including leukopenia and delayed thrombocytopenia. High doses may cause cerebella necrosis and atrophy. Nausea, vomition, diarrhea, skin pigmentation, and pulmonary fibrosis are rare. The oral dose for dogs and cats is 8mg/M2 daily for 4 days. The drug is supplied as 2mg tablets. The number of cycles depends upon the cycle.
 * d. Chlorambucil**


 * 2. Nitrosoureas**: The nitrosoureas include carmustine, lomustine, semustine and streptozocin.


 * a. Lomustine**

Usually administerd orally as a single dose every 6 weeks at a dose of 100 mg/M2 in dogs, in which there is severe neutropenia within 7-9 days followed by a rebound neutrophilia. GI bleeding, nausea, and vomiting may be seen. Hepatotoxicity and renal toxicity are also observed.

The only triazine compound used in tumor therapy because of its structural resemblance to 5-aminoimidazole- 4-carboxamide (AIC), which can be converted to inosinic acid. Dacarbazine was thought to be an antimetabolite. However, the drug must be activated by a hepatic microsomal cytochrome P-450-dependent- N-demethylation. An alkylating moiety may then be spontaneously released in the target cells along with AIC. The drug appears to inhibit RNA and protein synthesis more than DNA synthesis. The drug is not cell cycle specific. Used to treat malignant melanomas, sarcomas, lymphoreticular neoplasms and neuroblastomas. Useful with other drugs such as doxorubicin, bleomycin and vinblastine. The drug is given intravenously slowly over 5 minutes. Extravasation may cause tissue damage. Nausea and vomiting are produced within a few hours of administration in more than 90% of human patients and may last up to 12 hours. Alopecia and an influenza have also been reported in humans. Anorexia, debility, and malaise have been observed in the dog. The dose is 200 mg/M2 intravenously on days 1 to 5 of a 3-week cycle.
 * b. Dacarbazine**


 * B. Antimetibolites**

These are compounds that compete with normal metabolites necessary for cell function and regulation. They are ultimately inhibitors of DNA synthesis. They all suppress bone marrow cells. Gastrointestinal toxicity is severe. They are cell cycle specific with the S phase being the most sensitive stage.

A folic acid analog used against a wide variety of neoplasms including lymphoreticular neoplasms, mammary carcinoma, bronchogenic carcinoma, choriocarcinoma (1st cure of cancer) medulloblastoma, osteogenic sarcoma, rhadbomyosarcoma, squamous cell carcinoma, sertoli cell carcinoma and uterine cervix carcinoma. Also, canine transmissible venereal tumor. Mechanism of action - blocks the cyclic regeneration of tetrahydrofolic acid (TFA) by competitively inhibiting dihydrofolate (DHF) reductase. This causes an accumulation of DHF at the expense of THF, which function as a donor of one carbon moieties of biochemical reactions related to RNA, protein and DNA synthesis.
 * a. Methotrexate**

The dose for dog is 2.5 to 5 mg/M2 for 4 days/week, with cycles repeated as indicated by the disease. The drug is supplied in 2.5 mg tablets. The drug may be given intrathecally, intramuscularly, or close interaterial injection into the tumor. C. Vinca alkaloids. D. Antibiotics. E. Hormones

The main problem with many cytotoxic drugs used in veterinary practice is bone marrow depression. Severe lymphopenia, granulopenia, and thrombocytopenia can lead to toxic signs such as pyrexia, infection, hemorrhages, and in some instances death. A particularly dangerous sign is a total white blood cell(WBC) count below ten per cent of normal values. Should this occur, all cytotoxic therapy is stopped and broad spectrum antibiotics are given. If petechiae occurs or the WBC count continues to fall, whole fresh blood collected in citrate phosphate dextrose in polyvinyl bags (to preserve platelets) is transfused to the affected animal following usual cross-matching procedures.
 * VIII. Treatment of Drug Toxicity**


 * Renal toxicity** - is not uncommon in old dogs and cats given alkylating agents and certain other cytotoxic agents. Therapy is stopped, the drugs are changed, and the standard therapy for nephritis is instituted.

Many cytotoxic drugs are teratogens and their use should be avoided in pregnant or breeding animals
 * Cyclophosphamide** - is a very useful drug in veterinary practice but has the disadvantage of producing cystitis, particularly after prolonged usage. The toxic effects can be mitigated by feeding extra salt and a watery diet and by giving interrupted drug therapy. Concurrent corticosteriod therapy in cases of lymphosarcoma promotes renal perfusion and urine production, which is beneficial. Once following sensitivity tests, antibacterial therapy is instituted. Severe cases of hemorrhagic cystitis have been reported to respond favorably to infusion with one percent formalin solution.

 || **Disorder** || **Some Examples** || || adapted from Table 39-2; Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 643. ||
 * Allergic reactions || angioneurotic edema, asthma, contact dermatitis, drug reactions, allergic rhinitis, urticaria ||
 * Collagen-vascular pathology || giant cell arteritis, lupus erythematosus, polymyositis, rheumatoid arthritis, temporal arteritis ||
 * Eye diseases || allergic conjunctivitis, optic neuritis ||
 * Gastrointestinal || inflammatory bowel disease than ||
 * Hematologic || acute allergic purpura, leukemia, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, multiple myeloma ||
 * Infections || gram-negative septicemia and ||
 * Inflammatory disorders of joints/bones || arthritis, bursitis,tenosynovitis ||
 * Neurologic || cerebral edema, multiple sclerosis ||
 * Organ Transplantation || prevention/treatment of rejection (immunosuppression) ||
 * Pulmonary || bronchial asthma, prevention of infant respiratory distress,sarcoidosis, aspiration pneumonia ||
 * Renal || nephrotic syndrome ||
 * Skin || atopic dermatitis, dermatoses, mycoses fungoides, seborrheic dermatitis ||
 * Thyroid || malignant exophthalmos, subacute thyroiditis ||