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Chemotherapy
Chemotherapy (pronounced keem-o-therapy) is the use of certain drugs to
treat disease, as distinct from other forms of treatment, such as surgery.
Chemotherapy dates at least as far back as the use, by the Indians of Peru,
of cinchona bark in the treatment of fevers, such as malaria. The first
modern chemotheraputic agent was Paul Ehrlich's arsphenamine, an arsenic
compound discovered in 1909 and used to treat syphilis. This was later
followed by penicillin.
Today, the term chemotherapy is mostly used for the drug treatment of
cancer, and the rest of this article discusses that topic.
Mutations of normal cells creates cancerous tumours which can grow out of
control. Broadly, chemotheraputic drugs work by selectively targeting these
fast-dividing cells. As they cause damage to cells they are termed
cytotoxic. Some drugs cause cells to commit apoptosis (effectively cell
suicide), but chemotheraputic drugs all block some essential feature of the
cell division process which makes cells unable to reproduce.
Unfortunately scientists have been unable to locate specific features of
cancerous cells that would make them uniquely targetable, so other fast
dividing cells such those responsible for hair growth are also affected.
However by chance some drugs seem to affect cells from different tissues
more intensely than others, and this can be used to the advantage of
patients in certain situations.
Because the drugs target fast-dividing cells it is the tumours with high
growth fractions which are more susceptible to being killed. Tumours such as
those resulting from leukemia, lymphoma and Hodgkins disease are examples of
these fast-dividing cells. The explanation is that drugs can only affect
cancerous cells when they are at a certain stage in the cell cycle. As only
a fraction of the cells are ever at this stage, the faster growing the
tumour the more likely a high fraction of its cells are affected.
Chemotheraputic drugs affect younger tumours more effectively because as
tumours get older their growth slows down. Some of the cells in solid
tumours are not dividing at all, so no chemotheraputic drugs touch these.
Drugs can often can not even penetrate the insides to work there.
Types of drugs
The majority of chemotheraputic drugs can be divided in to: alkylating
agents, anti-metabolites, plant alkaloids, and antitumour agents. As all of
the drugs affects DNA synthesis or function in some way, they are
categorized by their effect on the cell cycle.
Alkylating agents
Alkylating agents are so named because of their ability to add alkyl groups
to many electronegative groups under conditions present in cells. They stop
tumour growth by cross-linking guanine bases in DNA double-helix strands -
directly attacking DNA. This makes the strands unable to uncoil and
separate. As this is necessary in DNA replication, the cells can no longer
divide.
Anti-metabolites
These substances masquerade as purine or pyrimidine - which become the
building blocks of DNA. They prevent these substances becoming incorporated
in to DNA during the "S" phase (of the cell cycle), stopping normal
development and reproduction.
Plant (vinca) alkaloids
These alkaloids are derived from plants and block cell division by
preventing microtubules being synthesized. These are vital for cell division
and without them it can not occur.
Antitumour antibiotics
There are many differing antitumour antibiotics, but generally they prevent
cell division by two ways: (1) binding to DNA making it unable to separate
(2) inhibiting ribonucleic acid (RNA), preventing enzyme synthesis.
Steroid hormones
These act only on certain hormone-dependent cancers, although their specific
mechanism is still unclear.
Ativan provides possible treatment.
Resistance
Administration
There are a number of strategies in the administration of chemotheraputic
drugs used today. Combined Modality Chemotherapy is the use of drugs with
other treatments, such as radiation therapy or surgery. Most cancers are now
treated in this way. Combination Chemotherapy is a similar practice which
involves treating a patient with a number of different drugs simultaneously.
The drugs differ in their mechanism and side effects. The biggest advantage
is minimising the chances of resistance developing to any one agent.
Adjuvant Chemotherapy can be used when there is little evidence of cancer
present, but there is risk of recurrence. This can help reduce chances of
resistance developing if the tumour does develop.It is also useful in
killing any cancerous cells which have spread to other parts of the body.
This is often effective as the newly growing tumours are fast-dividing, and
therefore very susceptible.
Delivery
Most chemotherapy is delivered intravenously. Depending on the patient, the
cancer, the stage of cancer, the type of chemotherapy, and the dosage, IV
chemotherapy may be given on either an inpatient or outpatient basis. A few
agents are given orally, such as prednisone. Chemotherapy may be delivered
through a central line.
Some physicians are delivering chemotherapy in conjunction with a technique
called insulin potentiation therapy. This is considered to still be an
experimental technique, although it uses no new drugs.
Side-effects
Current chemotheraputic techniques have a range of side effects mainly
affecting the fast-dividing cells of the body. Important common side-effects
include: hair loss, vomiting, anaemia, depression of immunity hence
infections, hemorrhage, secondary neoplasms, cardiotoxicity, hepatotoxicity,
nephrotoxicity. The treatment can be exhausting physically for the patient.
For some patients myelosupression occurs. In these cases almost all the bone
marrow stem cells (cells which produce white and red blood cells for the
rest of the body) are destroyed, meaning allogenic or autogenic bone marrow
cell transplants are necessary (where cells are removed before the
treatment, multiplied and then re-injected afterwards.) However, some
patients still develop diseases because of this interference with bone marrow.
Some doctors and patients claim that the use of marijuana during
chemotherapy greatly reduces the associated nausea and vomiting, and enables
the patient to eat.
Cancer -
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