Therapeutic Drug-Induced and Cancer-Related Neuropathies

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Introduction:
Therapeutic drug trials and drug legislation cannot anticipate every interaction or side effect a medication may have on the general population, and therefore, these interactions may go unnoticed until they have developed into full-blown difficulties themselves. (Arnold, 1979)

Definitions for italicized words can be found in the Glossary.

DRUG – INDUCED NEUROPATHIES

What does it mean to have a drug-induced neuropathy?
Drug-induced means that an individual’s neuropathy was caused primarily by his/her medication(s). Although these neuropathies only affect 2-4% of individuals who take specific prescription medications, the complex issues of resulting symptoms, drug continuation, and pain treatment proves very frustrating for many individuals.

What types of therapeutic drugs may lead to neuropathy? And what types of neuropathy do they lead to?
Although many powerful drugs have the potential to create serious side effects like neuropathy, there are around seven main categories of medications that have shown to do so. These are: chemotherapy drugs, antifungal drugs, antibiotics, drugs involved in the treatment of infectious disease, cardiovascular and cholesterol drugs, hypnotics, and psychotherapeutic drugs used to treat addictions. Please see the table provided for examples of such drugs, as well as for more information on what types of neuropathy they may cause. (Critchley, 1979)(Flatters, 2006)

Click here to read a short story from a man who developed peripheral neuropathy after getting treatment for colon cancer.

What are some symptoms of drug-induced neuropathy?
Since most drug-induced neuropathies tend to be peripheral, their side effects are similar to neuropathies not induced by medication. You should consult with your doctor if you have any of the following side effects from a prescribed medication(Leonard, 2005):

How do these drugs potentially cause neuropathy?
The ways in which these drugs cause neuropathy is, for the most part, still being studied. However, research has found evidence that appears promising. One is that, most often, the individual has an underlying cause that makes them more susceptible to getting neuropathy. These causes can be from, for example, cancer (read more about this below) or other disabling ailments (such a rheumatoid arthritis, diabetes, or alcoholism), or they can be from a predisposition in one’s genetic makeup or genetic malfunction. The drugs that are used in treatments continue where the ailments “left off”. For example, sometimes giving penicillin injections to a person who is unknowingly allergic to penicillin may result in a type of nerve damage called brachial plexus neuropathy – in a case such as this, it was not necessarily the drug that caused the neuropathy, but instead, the patient’s genetic predisposition to have an allergenic response to the drug that causes such adverse side effects. (Argov, 1979)

In addition, the very ways in which these prescription medications function can lead to neuropathy. There are six ways in which therapeutic drugs have been thought to cause neuropathy and the various symptoms that come with it (most notably pain and numbness).

A quick recap: Nerve axons are very sensitive. The myelin sheathes that cover axons are important not only for making communication between neurons fast and efficient, but also for protecting these highly sensitive areas. Numbness occurs when myelin is temporarily or permanently destroyed. Temporary demyelination makes a cell less efficient and less responsive to changes in the environment until the axon’s Schwann cells regenerate new myelin. On the other hand, permanent demyelination, which often occurs in axonal degeneration, leaves the highly sensitive axon completely exposed, and, in the case of Schwann cell damage, the axon is unable to regenerate myelin, resulting in permanent numbness and high pain sensitivity. In any case, if a nerve axon dies, the communication network that that nerve cell is a part of becomes completely disrupted, since there is no axon to relay messages from the body to the brain. The process of axonal degeneration is extremely painful, but ending result is a permanent numbness.

Photo courtesy of www.myelitis.org

CANCER- RELATED NEUROPATHIES

How can neuropathies be cancer-related? (Eade, 1975)(Benson, 1979)
As mentioned, neuropathies can be indirectly related to cancer if the patient is taking a medication that may cause some nerve damage. However, neuropathy can also be directly caused by cancer.

It is unknown why many blood cancers, like leukemia, sometimes cause neuropathy; however, it is better understood why cancers that either develop into solid tumors or have a great affect on bone often cause neuropathy. Cancers that develop into tumors, for example, may cause neuropathy by cancer cells themselves taking over, damaging, or killing a nerve cell, or more likely, by cancer tumors developing on or around main nerves, thus compressing the nerve as the tumor grows, causing symptoms of pain and numbness.

Bone cancers work differently and more indirectly. Since these cancers slowly degrade bone tissue, they have a grave and often quicker impact on our vertebrae bones, which protect our spinal cord. When such a bone or bones weaken, there occurs what is called a vertebral collapse, in which the spinal cord gets compressed. Although not directly due to interaction with cancer, such compression has a profound and excruciating effect on our nerves. Neuropathies resulting from these types of cancers are almost always irreversible.

What are some examples of cancers in which a patient would be more prone to developing neuropathy? (Eade, 1975)(Benson, 1979)
Two examples of cancers often linked to neuropathies are lymphomas and multiple myeloma. Lymphomas (which are cancers involving lymphocytes, the white blood cells in the vertebrae immune system) affect the nervous system in the first way mentioned above – as lymphatic tumors begin to crowd the space of surrounding neurons, the individual may begin to experience slight neuropathy. Multiple myeloma, in contrast, works like the latter type of possible cancer-nerve interactions. It is a bone cancer that not only is known for leading to spinal compression-induced neuropathies, but also, to peripheral neuropathies caused by the infiltration of amyloid, a type of protein found in excess in many neurological disorders. Click here to read a short story from a woman who has multiple myeloma and peripheral neuropathy.

What are some symptoms of cancer-related neuropathies?
You should consult with your oncologist if you have any of the following (same probable symptoms as those involved in drug-induced neuropathies)(Leonard, 2005):

Are there any treatments for drug-induced or cancer-related neuropathies?
There is no specific treatment or “cure” for these types of neuropathies. This is a complex issue because the course of drug treatments for and the progression of cancer in affected individuals varies. This variation is due to the amount of time and dosage of medication that nerves were exposed to or the amount of damage caused by direct and indirect involvement of cancer cells. There is current research about how to control the pain and discomfort that comes with neuropathy, and in some trials, there is work being done on how to reverse and prevent such debilitating effects. These include, but are not limited to:

Why are issues surrounding drug-induced and cancer-caused neuropathies so complex?
In many cases, therapeutic drugs that can cause neuropathy are often combating diseases that prove to be more life-threatening, such as cancer. In the drug treatment many cancer patients undergo, neuropathy remains a serious dose-limiting side effect if the treatment is causing neurological discomfort. If the resulting neuropathy is too painful for the patient, his/her doctors might have to lower doses or stop treatment. This can be a very difficult decision, as lowering the doses may allow the cancer to regenerate, but stopping treatment does not guarantee the reduction of pain due to the damage that has already been done. (Flatters, 2006)

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