August 15, 2008

Spasmolytics, We Cure Your Sore Muscles

2008 Beijing Olympic games is underway in China. Many records will be broken and there is a chance that many a tendons will be torn too. Bones will be fractured and joints will be sprained. In cases of these sports related injuries, the athlete will suffer from pain and local muscle spasm. The spasms are of reflex origins arising out of pain, causing hyperactivity in type 1A sensory fibers. Mere treatment of pain or reduction (correction) of fractures will not do. The muscles need to be relieved of their spasms too, so that the vicious cycle of pain causing spasms--> and spasms causing pain, is interrupted.

It is then, spasmolytics will come to their rescue. They are used to relieve spasms in such cases and in cases of spasticity that occur in cerebral palsy, multiple mechanism of action of spasmolytics like diazepam and baclofen with respect to stretch reflex arcsclerosis, amyotrophic lateral sclerosis. In spasticity, the basal muscle tone is increased and there is an increase in tonic stretch reflex. Have a look at the stretch reflex arc on the left. A vital component of this is contributed by type 1a fibers, shown in red. They carry sensory information from muscle spindle that regulate muscle tone. Benzodiazepines like diazepam (valium) act by enhancing the GABA mediated inhibition of inhibitory interneurones, shown in green. These interneurons secrete a chemical substance, GABA, which bind with its receptors in the post-synaptic neuron. The receptor, called GABA(A)-benzodiazepine-chloride ion channel complex, have an integrated chloride ion channel. When a ligand such as the neurotransmitter GABA combines with the receptor, the conductance of chloride (Cl-) ion increases. (As in physics, conductance is the opposite of resistance.) Chloride rushes in to the interior of the cell, down its concentration gradient, through the channel. The cells becomes more negative (hyperpolarization), rendering them inconducive to signal propagation. Diazepam binds to this receptor and facilitates GABA-A action.

Baclofen, binds with GABA-B receptors and increases potassium conductance. K+ exits to the exterior, down the concentration gradient, making the cell negative (and non conductive) in the process. The march of spasm is halted. Baclofen is also used to fight cravings in recovering alcoholics, and in preventing migraine in some persons.

Other centrally acting drugs used to treat spasm include the anti-epileptic gabapentin which gives some relief in multiple sclerosis; riluzole and idrocilamide which are useful in symptom alleviation in amyotrophic lateral sclerosis, also called Lou Gehrig's disease, of which scientist par excellence, Stephen Hawking is a victim.

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Reference: Bertram Katzung, Basic and clinical Pharmacology, 9e, page 441-443

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