Baclofen chemical structure
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Baclofen

Baclofen (brand names Kemstro® and Lioresal®) is a derivative of gamma-aminobutyric acid, and is an agonist specific to mammalian but not fruit fly (Drosophila) GABAB receptors. It is used for the treatment of spastic movement, especially in instances of spinal cord injury and in multiple sclerosis. Its beneficial effects result from actions at spinal and supraspinal sites. Baclofen can also be used to treat hiccups. more...

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Description of compound

Baclofen is a white to off-white, odorless or practically odorless crystalline powder, with a molecular weight of 213.66. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform.

Routes of administration

Baclofen can be administered either orally or intrathecally (directly into the spinal fluid). Intrathecal administration is often indicated in spasticity patients, as very little of the oral dose actually reaches the spinal fluid.

Intrathecal administration is particularly used in patients with multiple sclerosis who have severe painful spasms which are not controllable by oral baclofen. A test dose is given to assess the effect, and if successful a chronic intrathecal catheter in inserted and connected to a computer-controlled implanted pump. The reservoir in the pump can be replenished by percutaneous injuection. These pump systems are quite sophisticated and expensive so careful patient selection is required.

History

Historically Baclofen was designed to be a drug for epilepsy in the 1920’s, and was derived from diazepam (Valium©). The effect on epilepsy was disappointing but it was found that in certain patients spasticity decreased. Baclofen was and is still given orally with variable effects. In the severely affected children, the oral dose is so high that side effects appear and the treatment loses its benefit. How and when Baclofen came to be used in the spinal sack is not really clear but this is now an established method for the treatment of spasticity in many conditions.

How Baclofen works

Baclofen has its effect in the spinal cord, which is the main connection between the brain and then rest of the body. The spinal cord is a reflex system, a feedback loop. The most obvious reflex is the withdrawal to heat. This movement is brisk and not very well controlled. This is what happens in Cerebral Palsy. Without adequate control from the brain, every movement is like a reflex, being rough and uncontrolled. The reflex can spread through the body causing spasms or “arching”. These spasms can be painful and interrupt sleep.

Baclofen works on this reflex circuit. The reflex circuit in the spinal cord contains the Renshaw cells. These cells are very sensitive to a natural chemical produced by the nervous system: GABA, gamma-amino-butyric-acid. GABA slows the reflex circuit down and Baclofen acts like GABA. The dose of intrathecal Baclofen necessary to slow down the reflex circuit is variable but is generally one thousand times smaller than the oral dose.

Pharmacokinetics

The drug is rapidly absorbed after oral administration and is widely distributed throughout the body. Biotransformation is low and the drug is predominantly excreted in the unchanged form by the kidneys.

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letters
From PT Magazine, 10/1/05

Physical Therapy Needs More Inventors

To the Editor:

I was pleased to read the article "PT & PTA Inventors: What a Great Idea!" in the July issue of PT Magazine. It is vital for our profession to encourage each other to create innovations to improve assessment, treatment, and quality of life (both functional and recreational) for our patients. I applaud those individuals mentioned in the article (as well as those who were not highlighted) for pursuing the journey to turn an idea into a useful product. While the article primarily focuses on the inventors and describes some of the challenge they encountered, I want to convey the dire need for more inventors and more acceptance of inventions within our profession.

There are three main ways in which inventions typically are created in our profession. 1) A PT, PTA, patient, or patient family member recognizes a need and seeks to create a prototype (either self pursuant or requesting assistance from a technician/engineer) to address it; 2) An engineer or technician creates a prototype and seeks the guidance of a PT or PTA for application; or 3) A PT or PTA is introduced to new and creative technologies being used in other medical disciplines (or other fields entirely) and adapts existing technology to address a clinical need.

The article wonderfully provided examples of how inventions come to fruition using the first mechanism. I believe our profession could greatly benefit from inventions that also start from the adaptation of existing and evolving technology. In order to recognize the power of innovation, we need to be open to how technology can enhance our skills as PTs/PTAs. My colleagues and I visited and developed working relationships with MIT's Media Lab, where engineers of today (and tomorrow) are working on many creative technologies ranging from various modes of entertainment to lifesaving medical devices. Basic sensors like accelerometers and pressure sensors perform more complicated tasks such as monitoring movement and creating interactive machines. Microprocessors handle large bits of information and return output faster and faster using "real time" feedback. Wireless systems continue to expand. And all these technologies and others are becoming smaller and easier to use, afford, and build.

Being exposed to such technology development has allowed my colleagues and me new opportunities. We have worked with a group from the Media Lab to adapt and modify an existing technology called the Cyber Shoe that creates music based on a set of shoe-based on-board sensors. The sensors transmit data wirelessly to a base station that converts the output to digital sounds. The resulting musical environment is therefore created by the movement/dancing of the performer. We adapted and modified the Cyber Shoe to create a prototype of a portable, wireless gait analysis tool that has kinematic and kinetic data output with the ability to have real time auditory feedback for improving gait.

While a small number of patient populations are seeing advancing technologies assist in their care and daily lifestyle (for example: patients with spinal cord injury) many patient groups have seen limited application of innovative technology growth generating from the rehabilitation specialists. I believe PTs and PTAs should expose themselves to emerging technologies and make opportunities to meet engineers and technicians working with technology. This indeed will allow more creative inventions to be generated within our profession.

Another key point in the process of inventing new tools is the need to work with other disciplines. The Key Assessment invention mentioned in the July PT Magazine article appears to be an example of how working with other disciplines-in this case vocational rehabilitation counselors-can lead to development of new tools.

My colleagues and I have found it very important to have multidisciplinary input for development of our invention, mentioned above. Neurologists and engineers are involved with our project. It has been crucial in our development to include the physicians who eventually may refer patients for use of the equipment, review data from the tool, or possibly run the equipment. We have received helpful feedback from our team during all phases of development.

I am involved with other multidisciplinary groups that are meeting to create new tools to benefit patients through new mechanisms of providing and monitoring care. It is vital that many disciplines be involved for such advances. I highly encourage multidisciplinary product development. PTs and PTAs can lead such projects.

Finally, funding support of new inventions, as briefly mentioned in the July article, often is difficult to find. I am amazed at how many ideas are not even written down out of fear that there are no funding resources. My team has been especially fortunate to receive vital funding support during the early prototype development phases through a multi-center research consortium called The Center for Integration of Medicine and Innovative Technology (CIMIT). CIMIT fosters collaboration of disciplines to bring technology to health care. The early funding was crucial to prototype development and validation testing.

Although CIMIT is unique, other resources are available for clinicians with new ideas for improving health care. Our hospital and its affiliated university provide small start up grants for innovative ideas. Often networking within the research community at institutions will lead to startup or seed monies that can be used for innovation development. Department funds also often are available for seed, money. I hope that PTs and PTAs will seek such funding sources and petition for resources to be allocated for such purposes. We need to promote continued growth of innovations as well as hands-on treatment approaches.

Our patients see new tools and technology in other areas of medical care. They are surrounded by new sensors being built into their kitchen appliances and in cars (such as air bags using pressure gradation based on weight sensors within car seats). Voice activated sensors also are used in a growing number of commercial items. Our patients increasingly are accepting technology in daily life and medicine. They will expect to see new technologies in rehabilitation. We need to embrace innovations-including integrating technology-into our assessments, treatments, and adaptive equipment for activities of daily living.

Every PT and PTA can play a role in inventions, whether as the inventor, part of a team creating an invention, encouraging a co-worker to pursue an innovative idea, developing a fund within a department for innovations, or by offering financial support to existing funding resources. In the words of Ralph Waldo Emerson: "Be an opener of doors."

Donna Moxley Scarborough, PT, MS

Assistant Clinical Director

Biomotion Laboratory

Massachusetts General Hospital

Boston, MA

Returning to Physical Therapy's Roots

To the Editor:

After 23 years of clinical practice as a licensed physical therapist (PT), I retired in 2000 due to disabilities related to my diagnosis of primary lateral sclerosis (PLS), a very rare neuro-muscular disease. Needless to say it has been very frustrating dealing with a disease about which few physicians, let alone PTs, are knowledgeable and for which the prognosis is not decisive.

Essentially, the symptoms consist of spasticity in the extremities and facial muscles and can affect speech as well as swallowing. Chronic fatigue and obviously depression also are related to this disorder. The medical treatments vary from oral baclofen and Valium to intrathecal baclofen (ITB) pumps and botox injections.

I have been involved with the Spastic Paraparesis Foundation, which provides support groups and organizes fundraisers to study this disease. As a result, I frequently meet people who have been told by PTs that, because they aren't familiar with the disease, they are unable to treat them effectively.

Recently I spoke, as a fellow patient and retired PT, at a seminar for people with PLS and hereditary spastic paraparesis on the topic of exercise. I was appalled to hear from the number of people who were advised not to seek physical therapy because it would not be beneficial. Others had sought physical therapy only to be turned away because the PT didn't know what to do!

What is going on with our profession? In an issue of the PT Journal of Neurology last year, the editor wrote a great letter about the importance of evaluating the patient and treating the symptoms. Who cares if the spasticity (muscle shortening and tightness) is due to MS, ALS, CP, or an orthopedic problem? Do a complete physical therapy evaluation. Identify the muscles involved, stretch the tight ones, and strengthen the antagonist if possible.

Analyze the gait. This will help to determine not only which muscles are involved but also if there are balance and/ or coordination issues to be addressed. Recommend only the necessary assistive devices and teach the patient to use them appropriately. Excessive weight bearing on a walker can aggravate spasticity and pain in the upper extremities and weaken trunk muscles. Any patientneurological, orthopedic, pediatric, or other-who has been walking with an abnormal gait is going to demonstrate balance problems. Address these just as you would for the athlete-with therapy ball exercises, mat exercises, and so forth.

I could go on and on. Fortunately, with my background as a PT I was able to work in conjunction with Jennifer Bolster, PT, who researched the disease. Although her "specialty" is orthopedics and shoulder athletes, she developed a thorough and effective program for me.

I can't muscle test myself. I can't analyze my gait myself. I can't evaluate my balance myself. I needed a PT to evaluate me, assist me in developing the appropriate exercise program, and observe me exercising to make sure I was doing the exercises correctly.

As a result, she has been able to advise my physician regarding the effectiveness of dosage changes in my ITB pump. And most of all has encouraged me to approach my program with a positive outlook, greatly decreasing the depression. And, God bless her, she didn't forget my cardiovascular system. As a result of a thorough physical therapy program, my endurance has improved so that I can do my exercises on a regular basis.

We risk a public perception of the lazy PT who states, "... Uh, I am not familiar with that disease so I don't think I can help you." How dare we send lobbyists to Capitol Hill or state capitals when too many PTs turn away patients with chronic illnesses because joint mobilization is more exciting or sports PT is really fun. PTs must remember our origin and fundamentals.

No you can't make a lot of money providing hands-on treatment to a neurologically involved patient. But physical therapy wasn't meant to be a highincome field. Physical therapy began as a field to rehabilitate anyone who had physical disabilities that limited his or her functional activities. We have made many advances from the days of our foremothers-the reconstruction aides who cared for their patients. Have we become too haughty as we moved from our origins?

I look forward to speaking to more groups of people with rare neuromuscular diseases and being able to look them in the eye and assure them that they can enter any physical therapy office in the country and receive a thorough evaluation, be treated by PTs who will research what they don't know, and enthusiastically assist them in reaching their maximum level of functional ability.

Until then, I will have to agree with their physicians that they may find more help from a fitness instructor at a gym, a massage therapist, or a yoga class.

Our profession must get back to its roots. Million of dollars spent on marketing and lobbying is wasted if any individual clinical PT is unable or unwilling to perform to the fullest capacity that his or her licensure permits.

Julie O'Brien Thompson, PT

PT welcomes your letters. We will consider letters that relate to specific articles in the magazine and letters of general interest to the physical therapy profession. Letters may be edited for clarity, style, and space.

Send letters to PT Magazine, 1111 North Fairfax Street, Alexandria, Virginia 22314-1488; fax 703/706-3169; e-mail ptmag@apta.org. In all correspondence, please include your full name, city, and state.

Published letters do not necessarily reflect the positions or opinions of PT or the American Physical Therapy Association.

Copyright American Physical Therapy Association Oct 2005
Provided by ProQuest Information and Learning Company. All rights Reserved

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