Pyridostigmine, neostigmine, and ambenonium are the standard anti-ChE drugs used in the symptomatic treatment of myasthenia gravis. All can increase the response of myasthenic muscle to repetitive nerve impulses, primarily by the preservation of endogenous ACh. The optimal single oral dose of an anti-ChE agent is determined empirically. Baseline recordings are made for grip strength, vital capacity, and a number of signs and symptoms that reflect the strength of various muscle groups. The patient then is given an oral dose of pyridostigmine (30-60 mg), neostigmine (7.5-15 mg), or ambenonium (2.5-5 mg). The improvement in muscle strength and changes in other signs and symptoms are noted at frequent intervals until there is a return to the basal state. After an hour or longer in the basal state, the drug is readministered at 1.5 times the initial amount, and the functional observations are repeated. This sequence is continued, with increasing increments of one-half the initial dose, until an optimal response is obtained.
The interval between oral doses required to maintain a reasonably even level of strength usually is 2-4 hours for neostigmine, 3-6 hours for pyridostigmine, and 3-8 hours for ambenonium. However, the required dose may vary from day to day; physical and emotional stress, infections, and menstruation usually necessitate an increase in the frequency or size of the dose. In addition, unpredictable exacerbations and remissions of the myasthenic state may require adjustment of dosage. Patients can be taught to modify their dosage regimens according to their changing requirements.
Pyridostigmine is available in sustained-release tablets containing a total of 180 mg, of which 60 mg is released immediately and 120 mg over several hours; this preparation is of value in maintaining patients for 6-8-hour periods but should be limited to use at bedtime. Muscarinic cardiovascular and GI side effects of anti-ChE agents generally can be controlled by atropine or other anticholinergic drugs (see Chapter 7), remembering that anticholinergic drugs mask many side effects of an excessive dose of an anti-ChE agent. In most patients, tolerance develops eventually to the muscarinic effects, so that anticholinergic medication is not necessary.
A number of drugs, including curariform agents and certain antibiotics and general anesthetics, interfere with neuromuscular transmission (see Chapter 9); their administration to patients with myasthenia gravis is hazardous without proper adjustment of anti-ChE dosage and other appropriate precautions. Glucocorticoids and immunosuppressant therapies are also used in the treatment of myasthenia gravis.
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