Drugs to avoid in Myasthenia Gravis

About theCollege

Departments Research Education Faculty Rockford Campus Alumni

Drug Information GroupDepartment of PharmacyPracticeAbout Us

People

Publications

Contact Us

Frequently Asked Questions

What drugs should be avoided in myasthenia gravis?

Myasthenia gravis is a rare autoimmune disease occurring in 0.25 to 2 people per 100,000annually.1,2 Normally, for a synaptic transmission to occur at the neuromuscular junction, anaction potential must initiate depolarization of the presynaptic terminal. Once the presynapticterminal has been depolarized, there is an influx of calcium, which causes the release ofacetylcholine from vesicles. The acetylcholine then enters the synaptic cleft and binds to thepostsynaptic acetylcholine receptor (AChR). This interaction then causes a depolarization ofthe postsynaptic terminal, which allows the signal to propagate and eventually ends instimulation of the muscle. In myasthenia gravis, formation of antibodies directed against theAChR in the postsynaptic neuron form. The antibodies bind with the AChR, thus makingacetylcholine unable to complex with the AChR. This causes a decrease in the total number ofAChRs and muscle weakness due to diminished neurotransmission to the postsynapticmembrane. The disease may be limited to the external ocular muscles (a less severe form ofthe disease) or may be more generalized, involving muscles of the face, oropharyngeal areas,upper torso, and proximal extremities. Respiratory paralysis can also occur in very severeexacerbations. Although the disease is progressive, patients experience intermittent periodsof very active disease and remission.

Several medications are implicated in either inducing or worsening myasthenia gravis.1,3 Fourmechanisms have been described to explain the interaction of these drugs and the disease:(1) neuronal transmission may be inhibited at the presynaptic terminal; (2) lack ofacetylcholine release (possibly related to inhibition of calcium influx into the presynapticterminal); (3) blockade of the postsynaptic AChRs, therefore preventing the binding ofacetylcholine to the postsynaptic AChR; and (4) prevention of action potential transmissionpast the postsynaptic terminal secondary to changes in postsynaptic ion permeability.

More than 30 medications have been reported to have an effect on neuromusculartransmission.1,3 The agents suspected in exacerbations or first presentations of myastheniagravis have mainly been published in case reports, therefore, it is difficult to describe a trueincidence with each agent. In addition, questionable temporal relationships or otherconfounding factors sometimes make interpretation of the case reports difficult. Nonetheless,it is prudent to use precaution when using the medications that have been implicated inmyasthenia gravis.

A simple way to remember the drugs that should be used with caution in myasthenia gravis isthe "14 As":4-7

ACTH and corticosteroids prednisoneAnalgesics narcoticsAnesthetics, local cocaine, procaine, lidocaine, bupivacaine,

prilocaineAntacids or laxatives containing magnesium Maalox, MylantaAntiarrhythmics quinidine, lidocaine, procainamideAntibiotics aminoglycosides, quinolones, telithromycin,

azithromycin, erythromycin, clindamycin,ampicillin, imipenem, vancomycin,metronidazole

Anticonvulsants phenytoinAntihypertensives beta-blockers, calcium channel blockersAntimanics lithium salts

Antipsychotics chlorpromazineAntirheumatic chloroquineArthritis agents penicillamine-induced myasthenia gravisAll neuromuscular blocking agentsAntimalarials chloroquine, hydroxychloroquine

Approximately 1% to 7% of patients on penicillamine will develop myasthenia gravis.1,3Penicillamine has been reported to induce the formation of anti-AChR antibodies in 90% ofpatients who develop myasthenia gravis while on this agent. While penicillamine is very welldocumented to be a cause of myasthenia gravis, there are no reports of it causing anexacerbation in a patient already diagnosed with myasthenia gravis. Patients who developmyasthenia gravis while receiving penicillamine typically have a mild form of the disease,often limited to the extraocular muscles. Initial presentation of the disease varies occurringfrom 2 to 12 months after therapy has begun. Most patients have resolution of the diseasewithin 2 to 6 months following discontinuation.

Interferon alfa has also been implicated as the cause of myasthenia gravis in patients withleukemia or hepatitis C.3 Rat data suggest the proposed mechanism may be an autoimmune

Drug Information Group http://dig.pharm.uic.edu/faq/myasthenia.aspx

1 of 3 05/10/2015 20:51

response to the expression of interferon on motor endplates. The onset is from 6 to 9 months,and it has been reported to last up to 7 months after discontinuation.

Corticosteroids, although a mainstay in the management of moderate to severe myastheniagravis, can also cause an exacerbation of muscle weakness.1-3 Patients are generally startedon high doses of prednisone (60 to 100 mg/day) until the disease is in remission, then thedose is tapered to the lowest possible daily dose, and eventually switched to an everyother-day regimen. Approximately 20% to 50% of patients initiated on high dose prednisonewill have an exacerbation of their disease in the first days to weeks of therapy, which is thenfollowed by a period of remission.

Overdoses of cholinesterase inhibitors may also exacerbate myasthenia gravis.3 Excessivedoses can result in acetylcholine accumulation, which causes increased bronchial secretionsleading to difficulty swallowing or breathing. It has been suggested that weakness 1 hour afteradministration of pyridostigmine could indicate overdose, while weakness 3 or more hoursfollowing a dose could indicate a suboptimal response to therapy.

Aminoglycosides are cited in numerous case reports involving their concomitant use withneuromuscular blockers.1,3,4 Postoperative respiratory depression was reported in nearly allcases. Limb or facial weakness has also been reported. Aminoglycosides have also beendocumented to exacerbate preexisting myasthenia gravis, and have lead to worseningsymptoms within 1 hour of administration.

Summarized below are various medications that have been associated with exacerbations ofmyasthenia gravis.

Table 1. Medications to be used with caution in myasthenia gravis.3-7

Drug Onset (from initiation) ResolutionPrednisone 1 to 2 weeks 1 to 20 daysStreptomycin 15 min to 1.5 hours

Documents

Drugs to avoid in Myasthenia Gravis