Spasticity

A deficiency of niacin also affects the nervous system. Numbness is initially observed and later, paralysis, particularly in the extremities is common. Severe cases are characteri2ed by tremor and a spastic or ataxic gait and are frequentiy associated with peripheral neuritis. Left untreated, severe thought disorders can ensue (1). 

For hookworms, treatment is continued for three days. In roundworms, muscle tissue is stimulated continuously, resulting in spastic paralysis. The dmg was introduced in veterinary medicine in 1966 and then appHed to clinical medicine three years later. 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

Currently, baclofen is the only clinically used GAB Ab receptor agonist. It is used as a muscle relaxant for treatment of spasticity in spinal injury and multiple sclerosis. The cloning of GABAb receptors has renewed the interest in the search for more selective diugs and novel therapeutic indications. 

Peripheral vasodilating drugs are chiefly used in the treatment of peripheral vascular diseases, such as arteriosclerosis obliterans, Raynaud s phenomenon, and spastic peripheral vascular disorders. Short-term use is rarely beneficial or permanent. Improvement, if it occurs, takes place gradually during weeks of therapy. 

The enantiomerically pure 3-arylglutaric ester are precursors for the synthesis of (—)-paroxetine [10], a selective serotonin reuptake inhibitor used in the treatment of depression, obsessive compulsive disorder, and panic, and (i )-Baclofen [11], a GABAb receptor agonist, which is used cHnically in the treatment of spasticity (Chart 5.1). 

Homocarnosine (Figure 31-2), present in human brain at higher levels than carnosine, is synthesized in brain tissue by carnosine synthetase. Serum carnosinase does not hydrolyze homocarnosine. Homocarnosinosis, a rare genetic disorder, is associated with progressive spastic paraplegia and mental retardation. 

There have been a number of studies to evaluate the therapeutic effect of carmabinoids against spastic disorders, including multiple sclerosis and spinal cord injury. For example, a randomised placebo-controlled trial in more than... 

Irritable bowel syndrome (IBS) is a disorder of the gastrointestinal tract that interferes with the normal functions of the colon. At various points in the past, IBS has been referred to as mucous colitis, spastic colon, irritable colon, or nervous stomach. IBS is generally described as afunctional disorder rather than a disease per se. A functional disorder involves symptoms that cannot be attributed to a specific injury, infection, or other physical problem. A functional disorder occurs because of altered physiologic processes rather than structural or biochemical defects and may be subject to nervous system influence. IBS is associated with frequent fluctuation in symptoms, loss of productivity, and decreased quality of life. Although IBS has been referred to as functional bowel disease, true functional bowel disease may be more indicative of widespread gastrointestinal involvement including (but not limited to) the colon. 

Multiple sclerosis patients must be treated with agents specific for upper motor neuron spasticity. 

Spasticity 60% Falls, care difficulties, pain, gait problems... 

MS patients develop many symptoms that require treatment. The symptoms most unique to MS are fatigue and spasticity ... 

After 3 years of treatment, CN has had one additional relapse, but otherwise is doing fairly well. At her routine clinic appointment, she describes some difficulty walking due to leg spasticity and urinary incontinence episodes that occur about twice a week. 

What treatment options are available for spasticity, and which would you choose ... 

The goals of treating spasticity can be patient-specific. For ambulatory patients, reducing spasticity may improve mobility. For bed-bound patients, treating spasticity may relieve pain and... 

MS patients usually have upper motor neuron spasticity. This type of spasticity cannot be treated with muscle relaxants such as carisoprodol. MS patients must be treated with agents specific for upper motor neuron spasticity (Table 26—8).48 MS spasticity is classified as focal or generalized. If the spasticity primarily involves only one muscle group, it is focal and may benefit from botulinum toxin administration.11 Systemic medications are used for generalized spasticity. No clear conclusion can be reached regarding the superiority in efficacy of one antispasticity agent over another medication selection is usually based on adverse effects (see Table 26-8).11,48... 

Focal spasticity Botulinum toxin Prevents release of acetylcholine in the neuromuscular junction Individualized... 

Spasticity A motor disorder characterized by an increase in muscle tone with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex. 

Spastic colon A synonym for irritable bowel syndrome. 

Baker D, Pryce G, Croxford JL. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 2000 404 84-87. 

Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo V. Endocanna-binoids control spasticity in a multiple sclerosis model. FASEB J 2001 15 300-302. 

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