Transmission Boosting: Anti-Acetylcholinesterase Agents
Acetylcholinesterase, seen left, breaks down the neurotransmitter acetylcholine, eliminating it from the synaptic cleft. Anti-acetylcholinesterase agents are the first line of treatment in myasthenia gravis, and may be given initially to enhance the function of the remaining normal acetylcholine
receptors. The use of anti-acetylcholinesterase drugs is limited to the treatment
of mild myasthenia.
Drugs that may be used alone for mild symptoms, or as adjuncts in patients
not adequately controlled by other measures such as thymectomy, treatment with corticosteroids, or other immunosuppressive agents, include:
ambenonium chloride (Mytelase)
These drugs act by reversibly inhibiting acetylcholinesterase (Inhibition by Fasciculin II shown below). Acetylcholinesterase
is an enzyme which deactivates acetylcholine. Thus with acetylcholinesterase
inhibition, acetylcholine is not destroyed as quickly, and therefore remains
active for a longer duration at the motor endplate. With this increased
duration of action, the number of interactions between the transmitter and
receptors is increased, and muscular strength and response to repetitive
nerve stimulation is improved.
The optimal dose and timing of administration of anticholinesterase drugs
must be determined empirically for each individual. A beneficial affect
is dose dependent.
Pyridostigmine Bromide (peer-id-oh-STIG-meen) [Mestinon, Regonol], given
orally, is the most widely used anticholinesterase agent for the treatment
of myasthenia gravis. It is given alone for mild muscle weakness, or in
combination with corticosteroids for moderate to severe impairment. Dosage
requirements vary among patients because of differences in absorption ,
metabolism, and excretion of the drug. Therefore, the dosage and timing
of administration must be determined empirically.
Other anticholinesterase agents include ambenonium (am-be-NOE nee-um) chloride
[Mytelase] and Neostigmine (nee-oh-STIG-meen) Bromide, Neostigmine Methylsulfate
All of the anticholinesterase agents are given by mouth or by injection. Before the myasthenic patient begins
the use of any of these drugs, the risks of taking the medicine must be
weighed against the good it will do. This decision is made by the patient
and their doctor, prior to which the following must be considered:
Allergies- any previous unusual or allergic reaction to ambenonium,
bromides, neostigmine, or pyridostigmine as well as allergies to other substances
such as foods, preservatives or dyes must be brought to the doctorís
Pregnancy- although these drugs have not been reported to cause birth
defects muscle weakness has occurred temporarily in some newborn babies
whose mothers took anticholinesterase agents during pregnancy, thus this
factor must be taken into consideration.
Breast-feeding- thusfar anticholinesterase agents have not been reported
to cause problems in nursing babies.
Age- these medicines are not expected to cause different side effects
or problems in children than they do in adults, nor are they expected to
cause different side effects or problems in older people than the do in
younger people, however there is no specific information comparing the use
of anticholinesterase agents among various age groups.
Concurrent use of Other Medications- inform your doctor if you are using
any of the following:
- Malathion: combination of these medicines with anticholinesterase agents
may result in SERIOUS side effects.
- Trimethaphan: the effects of these medicines may interfere with the
actions of the anticholinesterase agents.
Other medical problems- may affect the use of the anticholinesterase
- Intestinal blockage
- Urinary tract blockage
- Urinary tract infection
Side Effects- the most common adverse reactions to anticholinesterase
agents are caused by excessive cholinergic stimulation and include both
muscarinic and nicotinic effects.
Symptoms of overdose:
blurred vision; clumsiness or unsteadiness; confusion; convulsions (seizures);
diarrhea (severe); increase in bronchial secretions or watering of mouth
(excessive); increasing muscle weakness (especially in the arms, neck, shoulders,
and tongue); muscle cramps or twitching, nausea or vomiting (severe); shortness
of breath, troubled breathing, wheezing, or tightness in chest; unusual
irritability, nervousness, restlessness, or fear; unusual tiredness or weakness.
redness, swelling, or pain at place of injection (for pyridostigmine injections
only); skin rash (does not apply to ambenonium)
Other side effects may occur that usually do not need medical attention
because they usually subside further into the treatment as the body adjusts
to the medicine. However, if the following symptoms are found to persist,
the doctor must be informed.
More common symptoms:
diarrhea; increased sweating; increased watering of mouth; nausea or vomiting;
stomach cramps or pain; frequent urge to urinate; increase of in bronchial
secretions; unusually small pupils; unusual watering of eyes
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