PDF Antiviral Chemotherapy 5: New Directions for Clinical Application and Research

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JavaScript is currently disabled, this site works much better if you enable JavaScript in your browser. Biomedical Sciences Immunology. Buy eBook. Buy Hardcover. Buy Softcover. FAQ Policy. About this book The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. Show all. Lynn et al. Michael et al. The common theme that they share in their chemotherapy indication is that they interrupt cell division. The most important subgroup is the anthracyclines and the bleomycins ; other prominent examples include mitomycin C , mitoxantrone , and actinomycin.

Among the anthracyclines, doxorubicin and daunorubicin were the first, and were obtained from the bacterium Streptomyces peucetius. Other clinically used drugs in the anthracyline group are pirarubicin , aclarubicin , and mitoxantrone. The mechanisms of anthracyclines include DNA intercalation molecules insert between the two strands of DNA , generation of highly reactive free radicals that damage intercellular molecules and topoisomerase inhibition.

This occurs when bleomycin binds to a metal ion , becomes chemically reduced and reacts with oxygen. Mitomycin is a cytotoxic antibiotic with the ability to alkylate DNA. Most chemotherapy is delivered intravenously , although a number of agents can be administered orally e. There are many intravenous methods of drug delivery, known as vascular access devices. These include the winged infusion device , peripheral venous catheter , midline catheter, peripherally inserted central catheter PICC , central venous catheter and implantable port.

The devices have different applications regarding duration of chemotherapy treatment, method of delivery and types of chemotherapeutic agent. Depending on the person, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or an outpatient basis. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access.

These have a lower infection risk, are much less prone to phlebitis or extravasation , and eliminate the need for repeated insertion of peripheral cannulae. Isolated limb perfusion often used in melanoma , [63] or isolated infusion of chemotherapy into the liver [64] or the lung have been used to treat some tumors. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage.

Topical chemotherapies, such as 5-fluorouracil , are used to treat some cases of non-melanoma skin cancer. If the cancer has central nervous system involvement, or with meningeal disease, intrathecal chemotherapy may be administered. Chemotherapeutic techniques have a range of side-effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines.

Chemotherapy-related toxicities can occur acutely after administration, within hours or days, or chronically, from weeks to years. Virtually all chemotherapeutic regimens can cause depression of the immune system , often by paralysing the bone marrow and leading to a decrease of white blood cells , red blood cells , and platelets.

Anemia and thrombocytopenia may require blood transfusion. Neutropenia a decrease of the neutrophil granulocyte count below 0.

Antiviral Chemotherapy 4

In very severe myelosuppression , which occurs in some regimens, almost all the bone marrow stem cells cells that produce white and red blood cells are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. In autologous BMTs, cells are removed from the person before the treatment, multiplied and then re-injected afterward; in allogenic BMTs, the source is a donor.

However, some people still develop diseases because of this interference with bone marrow. In Japan , the government has approved the use of some medicinal mushrooms like Trametes versicolor , to counteract depression of the immune system in people undergoing chemotherapy. Due to immune system suppression, neutropenic enterocolitis typhlitis is a "life-threatening gastrointestinal complication of chemotherapy.

Typhlitis is a medical emergency. It has a very poor prognosis and is often fatal unless promptly recognized and aggressively treated. Nausea , vomiting , anorexia , diarrhoea , abdominal cramps, and constipation are common side-effects of chemotherapeutic medications that kill fast-dividing cells. This can result in rapid weight loss, or occasionally in weight gain, if the person eats too much in an effort to allay nausea or heartburn.

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Weight gain can also be caused by some steroid medications. These side-effects can frequently be reduced or eliminated with antiemetic drugs.

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Self-care measures, such as eating frequent small meals and drinking clear liquids or ginger tea, are often recommended. In general, this is a temporary effect, and frequently resolves within a week of finishing treatment. However, a high index of suspicion is appropriate, since diarrhea and bloating are also symptoms of typhlitis , a very serious and potentially life-threatening medical emergency that requires immediate treatment.

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Anemia can be a combined outcome caused by myelosuppressive chemotherapy, and possible cancer-related causes such as bleeding , blood cell destruction hemolysis , hereditary disease, kidney dysfunction, nutritional deficiencies or anemia of chronic disease. Treatments to mitigate anemia include hormones to boost blood production erythropoietin , iron supplements , and blood transfusions.

Medications that kill rapidly dividing cells or blood cells can reduce the number of platelets in the blood, which can result in bruises and bleeding. Extremely low platelet counts may be temporarily boosted through platelet transfusions and new drugs to increase platelet counts during chemotherapy are being developed. Fatigue may be a consequence of the cancer or its treatment, and can last for months to years after treatment.

Antiviral Chemotherapy

One physiological cause of fatigue is anemia , which can be caused by chemotherapy, surgery , radiotherapy , primary and metastatic disease or nutritional depletion. Nausea and vomiting are two of the most feared cancer treatment-related side-effects for people with cancer and their families. In , Coates et al.

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Since the s, several novel classes of antiemetics have been developed and commercialized, becoming a nearly universal standard in chemotherapy regimens, and helping to successfully manage these symptoms in many people. Effective mediation of these unpleasant and sometimes-crippling symptoms results in increased quality of life for the recipient and more efficient treatment cycles, due to less stoppage of treatment due to better tolerance and better overall health.

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Hair loss alopecia can be caused by chemotherapy that kills rapidly dividing cells; other medications may cause hair to thin. These are most often temporary effects: hair usually starts to regrow a few weeks after the last treatment, but sometimes with a change in color, texture, thickness or style.

Sometimes hair has a tendency to curl after regrowth, resulting in "chemo curls. Permanent thinning or hair loss can result from some standard chemotherapy regimens. Chemotherapy induced hair loss occurs by a non-androgenic mechanism, and can manifest as alopecia totalis , telogen effluvium, or less often alopecia areata. Scalp cooling offers a means of preventing both permanent and temporary hair loss; however, concerns about this method have been raised.

Development of secondary neoplasia after successful chemotherapy or radiotherapy treatment can occur. The most common secondary neoplasm is secondary acute myeloid leukemia, which develops primarily after treatment with alkylating agents or topoisomerase inhibitors. Some types of chemotherapy are gonadotoxic and may cause infertility. Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles.

People may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of semen, ovarian tissue, oocytes, or embryos.

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Potential protective or attenuating agents include GnRH analogs , where several studies have shown a protective effect in vivo in humans, but some studies show no such effect. Sphingosinephosphate S1P has shown similar effect, but its mechanism of inhibiting the sphingomyelin apoptotic pathway may also interfere with the apoptosis action of chemotherapy drugs. In chemotherapy as a conditioning regimen in hematopoietic stem cell transplantation, a study of people conditioned with cyclophosphamide alone for severe aplastic anemia came to the result that ovarian recovery occurred in all women younger than 26 years at time of transplantation, but only in five of 16 women older than 26 years.

Chemotherapy is teratogenic during pregnancy , especially during the first trimester , to the extent that abortion usually is recommended if pregnancy in this period is found during chemotherapy. In males previously having undergone chemotherapy or radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy. Between 30 and 40 percent of people undergoing chemotherapy experience chemotherapy-induced peripheral neuropathy CIPN , a progressive, enduring, and often irreversible condition, causing pain, tingling, numbness and sensitivity to cold, beginning in the hands and feet and sometimes progressing to the arms and legs.

Though the symptoms are mainly sensory, in some cases motor nerves and the autonomic nervous system are affected. The platinum-based drugs are the exception; with these drugs, sensation may continue to deteriorate for several months after the end of treatment. Some people receiving chemotherapy report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment , referred to as "chemo brain" in popular and social media.