Editing Myasthenia gravis (section)

==Causes==
===Medications that cause or worsen myasthenia gravis===
[[Antibiotics]]: In the [[macrolide]] family of [[antibiotics]], [[azithromycin]], [[telithromycin]] (which is no longer available in the U.S. market), and [[erythromycin]] are reported to exacerbate MG. In the [[fluoroquinolone]] antibiotic family, [[ciprofloxacin]], [[norfloxacin]], [[ofloxacin]], and [[moxifloxacin]] are reported to exacerbate MG.<ref name="pmid33917535">{{Cite journal |vauthors=Sheikh S, Alvi U, Soliven B, Rezania K |date=April 2021 |title=Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update |journal=Journal of Clinical Medicine |volume=10 |issue=7 |page=1537 |doi=10.3390/jcm10071537 |pmc=8038781 |pmid=33917535 |doi-access=free}}</ref> And, In the [[aminoglycoside]] family of antibiotics, [[gentamicin]], [[streptomycin]], and [[neomycin]] are reported to exacerbate MG.<ref name="pmid4568132">{{Cite journal |vauthors=Hall DR, McGibbon DH, Evans CC, Meadows GA |date=December 1972 |title=Gentamicin, tubocurarine, lignocaine and neuromuscular blockade. A case report |journal=British Journal of Anaesthesia |volume=44 |issue=12 |pages=1329–32 |doi=10.1093/bja/44.12.1329 |pmid=4568132}}</ref> The aminoglycoside [[tobramycin]] has not been reported to exacerbate MG and may be used in people that require aminoglycoside treatment.<ref name="pmid33917535" /> Because of the rarity or absent reports on their exacerbation of MG, the following antibiotics are considered safe to use in people with myasthenia gravis: the [[cephalosporin]] class of drugs, [[sulfa drug]]s, the [[Tetracycline antibiotics|tetracycline group of drugs]], [[clindamycin]], [[polymyxin B]], and [[nitrofurantoin]].<ref name="pmid33917535" />

[[Checkpoint inhibitor|Immune checkpoint inhibitors]]: Immune checkpoint inhibitors promote certain types of autoimmune responses by blocking checkpoint pathways that inhibit these responses. They are used to treat cancers that promote their own growth and spread by stimulating checkpoint pathways. These checkpoint inhibitors include [[pembrolizumab]], [[nivolumab]], [[ipilimumab]], [[avelumab]], [[atezolizumab]], and [[durvalumab]]. From a total 5,898 patients who received these drugs, 52 developed new onset MG and 11 had a flare of their preexisting MG. The symptoms of MG developed within 6 days to 16 weeks (median time 4 weeks). Their medicine-induced MG symptoms were often severe with 29 patients developing [[respiratory failure]] that required [[mechanical ventilation]].<ref name="pmid31753014">{{Cite journal |vauthors=Safa H, Johnson DH, Trinh VA, Rodgers TE, Lin H, Suarez-Almazor ME, Fa'ak F, Saberian C, Yee C, Davies MA, Tummala S, Woodman K, Abdel-Wahab N, Diab A |date=November 2019 |title=Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature |journal=Journal for Immunotherapy of Cancer |volume=7 |issue=1 |pages=319 |doi=10.1186/s40425-019-0774-y |pmc=6868691 |pmid=31753014 |doi-access=free}}</ref> Other studies have reported that these checkpoint inhibitors cause respiratory failure in 45% and death in 25–40% of patients with MG.<ref name="pmid33917535" /><ref name="pmid30638612">{{Cite journal |vauthors=Puwanant A, Isfort M, Lacomis D, Živković SA |date=February 2019 |title=Clinical spectrum of neuromuscular complications after immune checkpoint inhibition |journal=Neuromuscular Disorders |volume=29 |issue=2 |pages=127–133 |doi=10.1016/j.nmd.2018.11.012 |pmid=30638612}}</ref>

[[Statin]]s: Statins are drugs that lower blood [[cholesterol]] levels in order to reduce the risk of developing a [[cardiovascular disease]] due to [[atherosclerosis]] In a 2019 review of 169 patients who were reported to develop myasthenia gravis or had worsened myasthenia gravis symptoms while taking a statin (i.e., [[simvastatin]], [[atorvastatin]], [[rosuvastatin]], [[pravastatin]], [[lovastatin]], or [[fluvastatin]]), 138 had developed generalized myasthenia gravis, 13 had developed ocular myasthenia gravis, and 18 had worsening of their myasthenia gravis. Following discontinuance of the statin and treatment of their myasthenia gravis, 63 patients fully recovered, 27 patients were recovering, 19 patients had not yet recovered, 5 patients recovered but had ongoing symptoms, 1 patient had died, and there was no follow-up data for 54 patients. Among these cases, 56% were considered to be serious.<ref name="pmid31298743">{{Cite journal |vauthors=Gras-Champel V, Batteux B, Masmoudi K, Liabeuf S |date=October 2019 |title=Statin-induced myasthenia: A disproportionality analysis of the WHO's VigiBase pharmacovigilance database |journal=Muscle & Nerve |volume=60 |issue=4 |pages=382–386 |doi=10.1002/mus.26637 |pmid=31298743}}</ref> A 2024 study evaluated 593 individuals who had myasthenia gravis and 790,399 individuals who did not have myasthenia gravis after being treated with one of the previously cited statins or with [[pitavastatin]] or [[pravastatin]]. The statin-treatment caused small but statistically significant increases in numbers of exacerbations of myasthenia gravis as well as new onsets of myasthenia gravis in individuals without the disorder. The development of myasthenia gravis in individuals without myasthenia gravis appeared to be more likely in individuals over 60 years of age.<ref name="pmid39609410">{{cite journal | vauthors = Xu W, Yan VK, Zhang Z, Fung KK, Chan KH, Lau KK, Chui CS, Lai FT, Li X, Chan EW, Wong IC, Wan EY | title = Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study | journal = Nature Communications | volume = 15 | issue = 1 | pages = 10317 | date = November 2024 | pmid = 39609410 | pmc = 11604770 | doi = 10.1038/s41467-024-54097-1 }}</ref> Six non-statin cholesterol-lowering drugs, [[nicotinic acid]], [[cholestyramine]], [[colestipol]], [[colesevelam]], [[alirocumab]], and [[evolocumab]], have been used in patients without causing or worsening myasthenia gravis.<ref name="pmid33917535" /> 

[[Antiarrhythmic agents|Ia antiarrhythmic agents]]: A type Ia antiarrhythmic agent (see [[Antiarrhythmic agent#Vaughan Williams classification|Vaughan Williams classification]]), i.e., [[procainamide]], which is used to treat [[cardiac arrhythmia]]s, has caused [[respiratory failure]] in people with myasthenia gravis who, prior to being treated with it, did not have respiratory symptoms. Furthermore, this drug has caused MG-like symptoms in patients who have kidney failure but do not have MG. And, procainamide worsened muscle dysfunction in a rat model of human MG.<ref name="pmid33917535" />

[[Neuromuscular-blocking drug#Depolarizing blocking agents|Depolarizing neuromuscular blockers]]: Depolarizing neuromuscular blockers suppress the neurons' signaling at neuromuscular junctions thereby reducing the affected skeletal muscles contractibility. These blockers are used as muscle relaxants in patients undergoing surgery.<ref name="pmid35322378">{{Cite journal |vauthors=van den Bersselaar LR, Gubbels M, Riazi S, Heytens L, Jungbluth H, Voermans NC, Snoeck MM |date=June 2022 |title=Mapping the current evidence on the anesthetic management of adult patients with neuromuscular disorders-a scoping review |journal=Canadian Journal of Anaesthesia |volume=69 |issue=6 |pages=756–773 |doi=10.1007/s12630-022-02230-3 |pmc=9132812 |pmid=35322378}}</ref> [[Succinylcholine]] is the only depolarizing neuromuscular blocker available in the U.S. market.<ref name="pmid33917535" /> Succinylcholine's ability to induce or worsen MG is unclear. It has been suggested to cause life-threatening side effects such as [[rhabdomyolysis]], [[myotonia]], and [[hyperkalemia]] in patients with muscle disease although the role of succinylcholine in causing these side effects also remains unclear.<ref name="pmid35322378" /> Until more evidence on these issues becomes available and since there are other neuromuscular blocking agents without these deleterious side effects, the use of succinylcholine in MG (and other neuromuscular disorders) should probably be avoided where feasible.<ref name="pmid33917535" /><ref name="pmid35322378" />

[[Inhalation anesthetics]]: Inhalation anesthetics are [[general anesthetic]]s that are delivered by inhalation generally for patients undergoing surgery. People with myasthenia gravis undergoing surgery with inhaled anesthetics (i.e., [[halothane]], [[isoflurane]], [[enflurane]], and [[sevoflurane]]) may develop neuromuscular blockage and have an increased incidence of developing a life-threatening myasthenia crisis which must be treated by prolonged mechanical ventilation. In a study of 795 people with myasthenia gravis undergoing surgical removal of their thymus under general anesthesia, [[sugammadex]], a [[neuromuscular-blocking drug]] (i.e., a drug that reverses neuromuscular blockade) significantly reduced the development of this crisis.<ref name="pmid33917535" /><ref name="pmid31124838">{{Cite journal |vauthors=Mouri H, Jo T, Matsui H, Fushimi K, Yasunaga H |date=February 2020 |title=Effect of Sugammadex on Postoperative Myasthenic Crisis in Myasthenia Gravis Patients: Propensity Score Analysis of a Japanese Nationwide Database |journal=Anesthesia and Analgesia |volume=130 |issue=2 |pages=367–373 |doi=10.1213/ANE.0000000000004239 |pmid=31124838}}</ref>

[[Glucocorticoids]]: Glucocorticoids are anti-inflammatory agents that in initial studies were used at high dosages and found to worsen MG in 25-75% of cases.<ref name="pmid25069701">{{Cite journal |vauthors=Hoffmann S, Kohler S, Ziegler A, Meisel A |date=October 2014 |title=Glucocorticoids in myasthenia gravis - if, when, how, and how much? |journal=Acta Neurologica Scandinavica |volume=130 |issue=4 |pages=211–21 |doi=10.1111/ane.12261 |pmid=25069701 |doi-access=free}}</ref> However, further studies found that glucocorticoids do have favorable effects on MG when taken long-term. Two glucocorticoids, oral [[prednisone]] and [[prednisolone]], are now the first line [[immunosuppressive]] treatment for MG. To avoid exacerbation of MG, it is recommended that the corticosteroids should be started at a low dose and gradually increased to the dose achieving maximal responses. To achieve a faster therapeutic responses in cases with severe MG symptoms, it has been recommended to start with high doses of oral or intravenous glucocorticoids after first treating patients with plasmapheresis or intravenous immunoglobulin therapy, each of which reduces the chance of having a severe reaction to the corticosteroids.<ref name="pmid33917535" /><ref name="pmid35350948">{{Cite journal |vauthors=Dalakas MC, Meisel A |date=April 2022 |title=Immunomodulatory effects and clinical benefits of intravenous immunoglobulin in myasthenia gravis |journal=Expert Review of Neurotherapeutics |volume=22 |issue=4 |pages=313–318 |doi=10.1080/14737175.2022.2057223 |pmid=35350948 |doi-access=free}}</ref><ref name="pmid38306763">{{Cite journal |vauthors=Ghimire A, Kunwar B, Aryal B, Gaire A, Bist A, Shah B, Mainali A, Ghimire B, Gajurel BP |date=March 2024 |title=Assessing the comparative efficacy of plasmapheresis and Intravenous immunoglobulin in myasthenia gravis treatment: A systematic review and meta-analysis |journal=Journal of Clinical Neuroscience |volume=121 |pages=1–10 |doi=10.1016/j.jocn.2024.01.025 |pmid=38306763}}</ref>

[[Calcium channel blocker]]s: Calcium channel blockers (e.g., [[felodipine]], [[nifedipine]], and [[verapamil]]) are drugs that lower [[blood pressure]] in patients with [[hypertension]]. Felodipine and nifedipine are reported to worsen MG and nifedipine and verapamil are reported to cause respiratory failure in patients with severe generalized MG.<ref name="pmid33917535" />

[[Penicillamine]]: Penicillamine is a [[chelation therapy]] drug used to treat various diseases (e.g., [[Wilson's disease]]). About 1-2% of individuals treated long term with penicillamine develop MG and/or develop low concentrations of antibodies to AChR.<ref name="pmid11445126">{{Cite journal |vauthors=Vincent A, Palace J, Hilton-Jones D |date=June 2001 |title=Myasthenia gravis |journal=Lancet |volume=357 |issue=9274 |pages=2122–8 |doi=10.1016/S0140-6736(00)05186-2 |pmid=11445126}}</ref> Their MG is often mild and predominantly ocular MG, becomes evident usually 6–7 months (range one month to 8 years) after starting the drug, and goes into complete remission in 70% of the cases within 6–10 months after discontinuing the drug. It is recommended that penicillamine be discontinued and thereafter avoided in patients who develop MG symptoms when treated with it.<ref name="pmid33917535" />

[[Botulinum toxin|Botulinum toxin A]]: Botulinum toxin A (sold under the brand name Botox, Jeuveau, and Xeomin) blocks transmission at [[neuromuscular junction]]s to paralyze the muscles into which it is injected. Local botulinum toxin A injections for cosmetic purposes have on occasion caused weaknesses in distant muscles, symptoms resembling ocular or generalized MG in individuals with subclinical MG, and exacerbations of previously controlled MG. Botulinum toxin A has also been used to treat [[spasmodic torticollis]] (i.e., involuntarily neck turning), [[blepharospasm]] (involuntary contraction of the eye lids), and other uncontrolled facial muscle spasms in people with myasthenia gravis without side effects or with only short-lived [[dysphagia]] or [[diplopia]]. Botulinum toxin A treatment, it is suggested, is best avoided in people with myasthenia gravis but may be offered with caution to patients with mild or stable MG using gradual increases in its dosages and close monitoring.<ref name="pmid33917535" />

[[Magnesium]]: Magnesium is a [[chemical element]] that blocks skeletal muscle contraction by inhibiting the release or [[acetylcholine]] at the neuromuscular junction and also by lowering the sensitivity of these muscles to acetylcholine.<ref name="pmid33917535" /> Respiratory failure has occurred after systemic use of magnesium (mainly in the form of intravenous [[magnesium sulfate]] injections) for [[pre-eclampsia]] and after magnesium replacement during the course of a hospitalization in patients with underlying MG.<ref name="pmid33917535" /><ref name="pmid38235027">{{Cite journal |vauthors=Petrucelli N, Barra ME, Koehl JL |date=January 2024 |title=Evaluation of Medication Exposure on Exacerbation of Disease in Patients With Myasthenia Gravis |journal=The Neurohospitalist |volume=14 |issue=1 |pages=52–57 |doi=10.1177/19418744231206256 |pmc=10790617 |pmid=38235027 }}</ref> It is suggested that magnesium when given intravenously or when given orally at high doses should be used with extreme caution in people with myasthenia gravis.<ref name="pmid33917535" />

[[Local anesthetics]]: Local anesthetics cause absence of pain and all other sensations in a specific body part without loss of consciousness. There are two broad classes of these anesthetics: esters (i.e., [[procaine]], [[cocaine]], [[tetracaine]] [[benzocaine]], and [[chloroprocaine]]) and amides (i.e. [[lidocaine]], [[bupivacaine]], [[etidocaine]], [[levobupivacaine]], [[mepivacaine]], [[prilocaine]], and [[ropivacaine]]). Ester local anesthetics are metabolized by [[pseudocholinesterase]]s which in people with myasthenia gravis taking anticholinesterase drugs may lead to excessive levels of these ester anesthetics. Amide local anesthetics are not metabolized by psuedocholineesterases. Based on these considerations, amide local anesthetics are strongly preferred over ester local anesthetics in patients with MG.<ref name="pmid29980408">{{Cite journal |vauthors=Muckler VC, O'Brien JM, Matson SE, Rice AN |date=February 2019 |title=Perianesthetic Implications and Considerations for Myasthenia Gravis |journal=Journal of PeriAnesthesia Nursing |volume=34 |issue=1 |pages=4–15 |doi=10.1016/j.jopan.2018.03.009 |pmid=29980408}}</ref><ref name="pmid30859135">{{Cite journal |vauthors=Prabhu SS, Khan SA, Doudnikoff AL, Reebye UN |date=February 2019 |title=Anesthetic considerations for a patient with myasthenia gravis undergoing deep sedation in an outpatient oral surgery setting |journal=Journal of Dental Anesthesia and Pain Medicine |volume=19 |issue=1 |pages=67–72 |doi=10.17245/jdapm.2019.19.1.67 |pmc=6405345 |pmid=30859135}}</ref>

Other Drugs: Rare cases of MG exacerbations have been reported in patients treated with: '''1)''' [[penicillins]], i.e., [[ampicillin]] and [[amoxicillin]]; '''2)''' anti-cancer medications, i.e., [[lorlatinib]], [[nilotinib]], [[imatinib]] (these three drugs are [[tyrosine kinase inhibitor]]s that may also cause MG), [[dabrafenib]], and [[trametinib]]; '''3)''' [[antipsychotic]] drugs, i.e., [[chlorpromazine]], [[pimozide]], [[thioridazine]], [[clozapine]], [[olanzapine]], [[haloperidol]], [[quetiapine]], [[risperidone]], and [[olanzapine]]; '''4)''' [[Interferon type 1#IFN-α|IFN-α]] (may also cause MG); and '''5)''' the chemical element, [[lithium]]. These agents can be used in people with myasthenia gravis because reports on their exacerbation (or induction) of MG are rare.<ref name="pmid33917535" />