{"id":1156,"date":"2012-11-01T00:00:42","date_gmt":"2012-11-01T07:00:42","guid":{"rendered":"http:\/\/rhochistj.org\/RhoChiPost\/?p=1156"},"modified":"2014-02-19T12:12:28","modified_gmt":"2014-02-19T19:12:28","slug":"safety-efficacy-atropine-salivary-hypersecretion","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/safety-efficacy-atropine-salivary-hypersecretion\/","title":{"rendered":"Safety and Efficacy of Atropine for Salivary Hypersecretion"},"content":{"rendered":"

By: Elsa Thomas, PharmD Candidate c\/o 2013<\/span><\/p>\n

–<\/p>\n

Atropine is an anticholinergic used to treat various conditions, such as bradycardia, neuromuscular blockade, mydriasis, nerve agent poisoning, and salivary hypersecretion.1,2<\/sup>\u00a0 Pharmacologically, it inhibits smooth muscle and glands innervated by postganglionic cholinergic nerves.1,2<\/sup>\u00a0 It also has functions in the central nervous system (CNS); it could stimulate or depress it based on the administered dose.1,2<\/sup>\u00a0 Its utility for treating salivary hypersecretion (i.e. <\/i>sialorrhea) is a result of muscarinic antagonism of acetylcholine, resulting in dry mouth and reduction of salivary, bronchial, gastric, and sweat gland secretions.1,2<\/sup>\u00a0 For adults, to reduce salivation and bronchial secretions, an oral dose of 0.4 mg is suggested, which may be repeated every 4 to 6 hours as needed.1,2<\/sup>\u00a0 In the form of an injection, 0.4 to 0.6 mg may be administered intramuscularly (IM), intravenously (IV), or subcutaneously (SC) over 30 to 60 minutes, and repeated every 4 to 6 hours as needed.1,2<\/sup>\u00a0 Interestingly a 1% ophthalmic solution of atropine has also been widely used, sublingually, for the treatment of the same.1,2<\/sup><\/p>\n

Sublingual atropine sulfate appears to have several advantages over the conventional IM route, including better bioavailability, rapid onset of action, and early \u201catropinization.\u201d3<\/sup>\u00a0 It is a relatively safe and effective procedure (with the aim of substituting conventional IM injections), and is readily available in the form of ophthalmic drops.1-3<\/sup>\u00a0 Yet, there are very few clinical studies on the safety and efficacy of sublingually delivered atropine for the treatment of sialorrhea.3-7<\/sup><\/p>\n

A single randomized controlled trial investigated the efficacy of atropine to reduce salivary hypersecretion with 2 drops of 0.5% SL atropine (0.5 mg total dose).4<\/sup>\u00a0 In the 22 adults who were receiving palliative care in the trial, the drug failed to show any benefit versus placebo.3<\/sup>\u00a0 The authors of this study suggested that their findings might have been a result of inadequate dosing.4<\/sup>\u00a0 In contrast, sublingual atropine was a simple and inexpensive treatment for sialorrhea, as reported by an open-label pilot study of sublingual atropine drops for the treatment of sialorrhea in seven patients (six with Parkinson’s disease, one with progressive supranuclear palsy).5<\/sup>\u00a0 Participants demonstrated statistically significant declines in saliva production, both objectively and subjectively, and the majority of patients did not experience any anticholinergic side effects.5<\/sup><\/p>\n

In 2000, there was a case report of a 44 year old female with chronic schizophrenia with hypersalivation secondary to clozapine.6<\/sup>\u00a0 It cited resolution of persistent symptoms after administration of atropine 1% eye drops, 1 to 2 drops (0.5 to 1 mg) administered sublingually in the morning.6<\/sup>\u00a0 The patient also reported no adverse effects from the treatment, which appeared to be the benefit of local administration of atropine versus systemic use (e.g.<\/i> IM, IV).6<\/sup>\u00a0 An updated report on the benefit of atropine drops for the treatment of sialorrhea induced by clozapine described that several patients experienced rebound sialorrhea due to the short duration of atropine, which necessitated repeat dosing.7<\/sup><\/p>\n

Although atropine does not require any specialized skill for use, unlike surgical removal, and has reversible effects, it is still contraindicated in patients with cognitive impairment, dementia, or hallucinations.1,2,4<\/sup> These patients are at higher risks for overdose due to mishandled dropper bottles.1,2,4<\/sup>\u00a0 Some patients reported difficulty in manipulating the dropper to ensure proper dosing.6<\/sup>\u00a0 In addition, dropper sizes are not standardized; ideally, 1 drop of 1% atropine solution should contain 500 micrograms of atropine (if 20 drops are in 1 mL of solution).1,2<\/sup>\u00a0 The potential for accidental overdose with drops is therefore, worrisome.6 <\/sup><\/p>\n

Drug-related adverse effects caused by atropine include dry mouth, blurred vision, urinary hesitancy and retention, tachycardia, palpitation, and constipation.1,2<\/sup>\u00a0 It may also produce CNS disturbances, ataxia, hallucinations, and delirium, but these effects are more common with systemic doses of atropine (exceeding 10 mg) and are rare with local administration.1,2<\/sup> \u00a0Therefore, it is necessary that a patient\u2019s heart rate, blood pressure, and mental status be monitored closely while on extended and high daily dose therapy with this drug.1<\/sup><\/p>\n

Hence, even with limited trial data, it seems that 1-2 drops (0.5 to 1 mg) of 1% ophthalmic atropine sulfate every 4 to 6 hours (not exceeding 10 mg daily) may be both effective and safe in the treatment of sialorrhea.1-7 <\/sup><\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. Lexi-Comp OnlineTM<\/sup>.\u00a0 Atropine (Lexi Drugs).\u00a0 Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; Accessed May 19, 2012.<\/li>\n
  2. Drug Facts and Comparisons.\u00a0 Facts & Comparisons [database online].\u00a0 Atropine Sulfate.\u00a0 St.\u00a0 Louis, MO: Wolters Kluwer Health, Inc.; April 2011.\u00a0 Accessed May 19, 2012.<\/li>\n
  3. Rajpal S, Ali R, Bhatnagar A, Bhandari SK, et. al.<\/i>\u00a0 Clinical and bioavailability studies of sublingually administered atropine sulfate.\u00a0 Am J Emerg Med.<\/i> 2010 Feb;28(2):143-50.<\/li>\n
  4. De Simone GG, Eisenchlas JH, Junin M, et al.<\/i>\u00a0 Atropine drops for drooling: a randomized controlled trial.\u00a0 Palliat Med <\/i>2006; 20: 665-71.<\/li>\n
  5. Hyson HC, Johnson AM, Jog MS.\u00a0 Sublingual atropine for sialorrhea secondary to parkinsonism: a pilot study.\u00a0 Mov Disord.<\/i>\u00a0 2002 Nov;17(6):1318-20.<\/li>\n
  6. Comley C, Galletly C, Ash D.\u00a0 Use of atropine eye drops for clozapine induced hypersalivation.\u00a0 Aust N Z J Psychiatry.<\/i>\u00a0 2000 Dec;34(6):1033-4.<\/li>\n
  7. Tessier P, Antonello C.\u00a0 Clozapine and sialorrhea: update.\u00a0 J Psychiatry Neurosci.<\/i>\u00a0 2001 May;26(3):253.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: Elsa Thomas, PharmD Candidate c\/o 2013 – Atropine is an anticholinergic used to treat various conditions, such as bradycardia, neuromuscular blockade, mydriasis, nerve agent poisoning, and salivary hypersecretion.1,2\u00a0 Pharmacologically, it inhibits smooth muscle and glands innervated by postganglionic cholinergic nerves.1,2\u00a0 It also has functions in the central nervous system (CNS); it could stimulate or…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[343,95,81,22,198,15,163,13,2229,2227,446,314,20,39,407,725,207,363,968,349,1625,657,19,2260,671,1820,1679,187,350,21,320,539,2252,453,1161,16,17,1061],"class_list":["post-1156","post","type-post","status-publish","format-standard","hentry","category-clinical","tag-and","tag-april","tag-atropine","tag-blood","tag-daily","tag-disease","tag-dose","tag-drug","tag-drugs","tag-ebola-virus-disease","tag-extended","tag-for","tag-health","tag-heart","tag-injection","tag-mg","tag-minutes","tag-of","tag-one","tag-ophthalmic","tag-or","tag-oral","tag-patient","tag-pressure","tag-r","tag-reduction","tag-short","tag-side","tag-solution","tag-study","tag-sublingual","tag-sulfate","tag-symptoms","tag-system","tag-therapy","tag-treatment","tag-trial","tag-with"],"views":55677,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1156","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=1156"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1156\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=1156"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=1156"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=1156"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}