Friday, May 15, 2015

Anticholinesterase Therapy in the Treatment of Myasthenia Gravis

Anticholinesterase Therapy (Mestinon, Prostigmin, Mytelase)

Anticholinesterase drugs include:

- pyridostigmine (brand-name "Mestinon")
- neostigmine (brand-name "Prostigmin")
- ambenonium chloride (brand-name "Mytelase")

In order for a muscle to contract, the nerve sends a message to the muscle through a neurotransmitter chemical, acetylcholine (ACh). The nerve end releases a considerable amount of ACh, which then makes its way through the
neuromuscular junction (NMJ) (that's the gap between the nerve and the muscle) and then it binds to a receptor on the muscle membrane. In people who have MG, the attacking antibodies bind to the muscle's membrane and initiate a series of events that destroy the membrane and prevent ACh from binding. When that happens, ACh is unable to bind to the muscle, and the muscle doesn't receive the message from the nerve and will not contract. The result of this chain of events can be sudden and fluctuating muscle weakness.

Anticholinesterase drugs increase the body's ACh by blocking the enzyme which normally breaks down ACh. This allows the build up of ACh to concentrate at the muscle receptor, which is where it is needed to transmit messages from the nerves to the muscles, and its effect is prolonged. By increasing the quantity of ACh, more of it is able to bind to the membrane and allow the muscle to contract.

The most commonly used anticholinesterase is "Mestinon". It is available in 60 milligram (mg) or 10 mg tablets and is released immediately. “Mestinon TimeSpan" is a 180 mg tablet in which 60 milligrams is released immediately and the remaining 120 milligrams are released over several hours. TimeSpan is usually prescribed for patients who require medication throughout the night (this allows for comfortable, uninterrupted sleep and reasonable strength in the morning). Timespan's uneven release provides less predictable results than with ordinary Mestinon and is usually not recommended for day time use, but some myasthenics prefer taking it. Liquid "Mestinon" syrup is for children and for adults who have trouble swallowing pills.

There are no fixed dose or time schedules for anticholinesterases as muscle involvement and severity vary so much among myasthenics. An increase in muscle strength is usually noticeable within 20 to 40 minutes after taking the medication, and they produce their maximal effects about one to two hours after ingestion (although muscle strength rarely returns to normal). The effects start wearing off after three or four hours. The medication must be taken at regular intervals so that muscle strength is maintained throughout the day. For those myasthenics who have trouble chewing or swallowing, it is best to take medication at a time that will produce optimal strength during meals.

The need for anticholinesterases varies from day-to-day, and during the same day in response to infection, menstruation, emotional stress, and hot weather. Different muscles respond differently; with any dose, certain muscles get stronger, others do not change, and still others become weaker. A "brittle myasthenic" may be adequately medicated during one 3 to 4 hour period and over-dosed with the same dose in the next 3 to 4 hour period. Medication dosage may require frequent adjustment according to one's response to the drug and to hourly/daily activity level.

Anticholinesterases are the gentlest of the drugs available to treat MG. However, some people do experience side effects, including:

- stomach cramps
- queasiness and nausea
- gut hyperactivity and diarrhea
- vomiting
- increased perspiration
- increased salivation
- muscle twitching and muscle cramps
- palpitations
- increased urinary frequency
- the muscle controlling the pupil of the eye is also affected, and there may be difficulty in focusing
- there are Acetylcholine receptors in the heart and so Mestinon may cause a very slow heart beat, which can, in turn, cause dizziness.

The presence of these symptoms may be a sign of taking too much medication, in which case the medication should be taken at longer intervals or in lesser amount. Other symptoms of overdose could include the worsening of generalized weakness, swallowing difficulties and respiratory failure (in which case a doctor should be contacted immediately). The myasthenic who is prescribed large daily dosage of anticholinesterase and suffering severe side effects or a worsening of their condition should question their doctor about their therapy.

To lessen the side effects, the drug can be taken with bland foods such as crackers and milk. If the unwanted side effects are particularly intense, they can be prevented or reduced by simultaneously taking other drugs - either anticholinergics (atropine) and hydrozyzine (Vistaril). It is also important to emphasise that all the unwanted effects of Pyridostigmine are short-lasting, and that it does not cause any permanent or long-term problems.

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