Historically
baclofen was originally developed in the 1920's to treat epilepsy
and was a derivative of diazepam. Its clinical effect on epilepsy
was found to be disappointing but it was found to be beneficial
on lessening spasticity. Baclofen is called an agonist (mimic)
of a natural neurotransmitter found in the body called GABA -
an acronym for gamma-aminobutyric acid.
Baclofen is used to reduce muscle tone and needs to bind to receptors
located on the spinal cord to exert its clinical effect. The
spinal cord is a reflex system, a feedback loop. The most obvious
example of a reflex is the withdrawal to heat when you burn yourself.
This movement is brisk and not very well controlled. This is
similar to what happens in CP. 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”.
Baclofen works on this reflex circuit by inhibiting it (slowing
it down).
The first line pharmacological treatment is to administer baclofen
orally in tablet form. Baclofen is rapidly absorbed after oral
administration, and it is partially metabolised (broken down)
by the liver but largely excreted by the kidneys unchanged.
In the majority of children oral baclofen or other oral medications
provide adequate management of spasticity. But in a few children the dosages needed are extremely high resulting
in unwanted side-effects such as nausea, vomiting, sedation,
drowsiness, confusion, memory and attention problems. It is in
these children that a decision can be made to deliver a liquid
formulation of baclofen, called “intrathecal baclofen” directly
into the intrathecal space, a fluid filled cavity surrounding
the spinal cord, via an implantable programmable pump. Since
the ITB is delivered precisely to where the receptors are located
the dose of ITB necessary to slow down the reflex circuit is
generally 100 times smaller than the equivalent oral dose whilst
still giving a positive clinical effect and minimal, if any,
side-effects. |
