Pyridostigmine is an acetylcholinesterase inhibitor and is used for therapy in myasthenia gravis (muscle weakness). Pyridostigmine is also used for urinary retention and bowel paralysis resulting from decreased muscle tone. Pharmacologically, it is applied as a bromide salt in the form of tablets.
What is pyridostigmine?
Pyridostigmine is an acetylcholinesterase inhibitor and is used for therapy in myasthenia gravis (muscle weakness). As a drug, pyridostigmine belongs to the group of indirect parasympathomimetics. It thus indirectly activates acetylcholine activity at the receptors of the parasympathetic nervous system by inhibiting the enzyme acetylcholinesterase. The active ingredient is a quaternary amine complex present in drugs as bromide. Undissolved, pyridostigmine bromide is a white crystalline powder. It dissolves very well in water. The drug is administered in the form of tablets when needed. Pyridostigmine bromide cannot cross the blood–brain barrier because its salt-like structure makes it non-lipophilic. Its plasma half-life is approximately 1.5 hours. After use, the drug is partially metabolized and partially excreted renally (via urine) unchanged.
Pharmacologic Action
Pyridostigmine acts indirectly by inhibiting the enzyme acetylcholinesterase. This enzyme is responsible for the breakdown of the neurotransmitter acetylcholine in the synaptic cleft to acetate and choline. Inhibition of acetylcholinesterase in turn causes an increase in acetylcholine concentration at the motor endplate. The acetylcholine receptors present there are cation channels, which stimulate the muscles by cation currents triggered by acetylcholine. This increases the tone (tension) of certain muscles, increasing the likelihood of muscle contraction. In general, the activity of the parasympathetic nervous system, which is responsible for bodily processes during rest, also increases. The parasympathetic nervous system controls muscle tone and metabolic processes including bowel and bladder function. In autoimmune myasthenia gravis, disturbances occur at the receptors for acetylcholine, so that sufficient muscle contractions can only be induced by a higher concentration of acetylcholine. Bladder or bowel muscles are also stimulated. This property also makes pyridostigmine a good agent for treating paralysis of the bladder or bowel muscles. The increase in acetalcholine concentration also causes displacement of antagonistic muscle relaxants from acetylcholine receptors, which are drugs used to calm muscles. If needed, pyridostigmine is used to reverse the effects of these drugs.
Medical application and use
Pyridostigmine is mainly used to treat the disease myasthenia gravis. Depending on the severity of the disease, the individual dose of the drug must be determined by the physician. Treatment begins with the administration of pyridostigmine alone, but if there is no improvement, treatment can be continued in combination with guanine. The drug is applied in the form of tablets. Due to the wide range of possible side effects and the possibility of interaction with various other drugs, treatment should always be under medical supervision. The use together with other parasympathomimetic agents leads to the enhancement of the effect. The effect of muscle relaxant medications is reversed. If necessary, pyridostigmine must be used in this context in case of overdose with muscle relaxants or other problems that arise. Another area of use is application in urinary retention or intestinal atony (bowel paralysis). Here, however, it must be noted that pyridostigmine is absolutely contraindicated in cases of mechanical bowel obstruction or mechanically induced bladder voiding dysfunction. Stimulation of the bladder or bowel muscles in this case can lead to serious complications. Prophylactically, pyridostigmine was also used in the “Second Gulf War in 1991” against poisoning by cholinesterase inhibitor-based chemical warfare agents.
Risks and side effects
The use of pyridostigmine, as with all medications, carries the risk of side effects, which may or may not occur.As the activity of the parasympathetic nervous system is increased, this results in varying degrees in such typical symptoms as diarrhea, vomiting, abdominal cramps, increased salivation, increased mucus formation in the bronchi, bradycardia, drop in blood pressure, and adaptation disorders of the eye. Since bronchoconstriction may also occur, application is contraindicated in patients with obstructive airway disease. The same applies to mechanical intestinal and bladder obstruction. Overdose of the drug may cause weakening of the airway muscles as a result of a cholinergic crisis. Other side effects include increased perspiration and increased urination. Application with pyridostigmine should be avoided if the patient is pregnant or breastfeeding.
