Tropicamide: Difference between revisions

{{Short description|Chemical compound}}

{{Infobox drug

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| verifiedrevid = 409089198

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| pronounce =

| tradename = Mydriacyl, others

| Drugs = {{drugs |monograph|tropicamide}}

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| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->

| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->

| DailyMedID = Tropicamide

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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

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| pregnancy_US = <!-- A / B / C / D / X / N -->

| pregnancy_US_comment =

| pregnancy_category = C

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| routes_of_administration = Topical [[Ophthalmic drug administration|eye drops]]

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<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | url=https:// ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=25356&agid=%28PrintDetailsPublic%29&actionid=1 | title=Summary for ARTG Entry: 25356 Mydriacyl tropicamide 0.5% eye drops bottle | access-date=5 June 2023 |website=[[Therapeutic Goods Administration]] |archive-url=https://web.archive.org/web/20230605204727/https:// ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=25356&agid=%28PrintDetailsPublic%29&actionid=1 |archive-date=5 June 2023 }}</ref>

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| legal_NZ = <!-- Class A, B, C -->

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| legal_UK = POM

| legal_UK_comment = <ref>{{cite web | title=Mydriacyl 1% eye drops, solution - Summary of Product Characteristics (SmPC) | website=[[Electronic Medicines Compendium]] | date=12 February 2020 | url=https:// medicines.org.uk/emc/product/1610/smpc | access-date=29 July 2020 |archive-url=https://web.archive.org/web/20220627153935/https:// medicines.org.uk/emc/product/1610/smpc |archive-date=27 June 2022}}</ref>

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| legal_status = <!-- For countries not listed above -->

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| protein_bound = 45%

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<!-- Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 1508-75-4

| IUPHAR_ligand = 7319

|DrugBank_Ref= {{drugbankcite|changed|drugbank}}

| DrugBank = DB00809

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 5391

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| UNII = N0A3Z5XTC6

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| ChEMBL = 1200604

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<!-- Chemical and physical data -->

| IUPAC_name = (''RS'')-''N''-Ethyl-3-hydroxy-2-phenyl-''N''-(pyridin-4-ylmethyl)propanamide

| SMILES = CCN(Cc1ccncc1)C(=O)C(CO)c1ccccc1

| StdInChI = 1S/C17H20N2O2/c1-2-19(12-14-8-10-18-11-9-14)17(21)16(13-20)15-6-4-3-5-7-15/h3-11,16,20H,2,12-13H2,1H3

| StdInChI_comment =

| StdInChIKey = BGDKAVGWHJFAGW-UHFFFAOYSA-N

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<!-- Definition and medical use -->

'''Tropicamide''', sold under the brand name '''Mydriacyl''' among others, is a medication used to [[mydriatic|dilate the pupil]] and help with [[examination of the eye]].<ref name=AHFS2016/> Specifically it is used to help examine the [[fundus (eye)|back of the eye]].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free |page=314}}</ref> It is applied as [[Ophthalmic drug administration|eye drops]].<ref name=AHFS2016/> Effects occur within 40 minutes and last for up to a day.<ref name=AHFS2016/>

<!-- Side effects and mechanism -->

Common side effects include [[blurry vision]], [[increased intraocular pressure]], and [[photosensitive|sensitivity to light]].<ref name=AHFS2016/> Another rare but severe side effect is [[psychosis]], particularly in children.<ref name=AHFS2016/> It is unclear if use during [[pregnancy]] is safe for the fetus.<ref>{{cite web|title=Tropicamide ophthalmic Use During Pregnancy |url=https:// drugs /pregnancy/tropicamide-ophthalmic.html|website=[[Drugs ]] |access-date=28 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161228195917/https:// drugs /pregnancy/tropicamide-ophthalmic.html|archive-date=28 December 2016}}</ref> Tropicamide is in the [[antimuscarinic]] part of the [[anticholinergic]] family of medications.<ref name=AHFS2016/> It works by making the muscles within the eye unable to respond to nerve signals.<ref name=AHFS2016/>

<!-- History and culture -->

Tropicamide was approved for medical use in the United States in 1960.<ref name=AHFS2016>{{cite web|title=Tropicamide|url=https:// drugs /monograph/tropicamide.html |website=[[Drugs ]] |publisher=[[American Society of Health-System Pharmacists]] |access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161228200117/https:// drugs /monograph/tropicamide.html|archive-date=28 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name= "WHO21st" >{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>

==Medical use==

[[Image:Anizokoria.JPG|thumb|upright=1.3|alt=Right eye was instilled with tropicamide, leading to [[mydriasis]] and therefore [[anisocoria]] (unequal pupil size)|[[Anisocoria]] caused by tropicamide instilled into the subject's right eye only.]]

Tropicamide is an [[Muscarinic antagonist|antimuscarinic]] drug that produces short acting [[mydriasis]] (dilation of the [[pupil]]) and [[cycloplegia]]<ref name= "pmid11431435" >{{cite journal | vauthors = Manny RE, Hussein M, Scheiman M, Kurtz D, Niemann K, Zinzer K | title = Tropicamide (1%): an effective cycloplegic agent for myopic children | journal = [[Investigative Ophthalmology & Visual Science]] | volume = 42 | issue = 8 | pages = 1728–35 | date = July 2001 | pmid = 11431435 | url = http:// iovs.org/cgi/pmidlookup?view=long&pmid=11431435 | archive-url = https://archive.today/20130112222624/http:// iovs.org/cgi/pmidlookup?view=long&pmid=11431435 | url-status = dead | archive-date = 2013-01-12 }}</ref> when applied as [[Ophthalmic drug administration|eye drops]]. It is used to allow better examination of the [[lens (anatomy)|lens]], [[vitreous humor]], and [[retina]]. Due to its relatively short duration of effect (4&ndash;8 hours), it is typically used during [[eye examination]]s such as the [[dilated fundus examination]], but it may also be used before or after [[eye surgery]]. Cycloplegic drops are often also used to treat anterior [[uveitis]], decreasing risk of posterior [[Synechia (eye)|synechiae]] and decreasing inflammation in the anterior chamber of the eye.

Tropicamide is occasionally administered in combination with [[4-Hydroxyamphetamine|''p''-hydroxyamphetamine]] (brand name [[Paremyd]]), which is a [[sympathomimetic]]. The use of the sympathomimetic drug causes the iris dilator muscle to be directly stimulated, causing increased dilation. In the United States, the sympathomimetic drop most commonly used along with tropicamide, is 2.5% [[phenylephrine]] hydrochloride (brand name AK-Dilate).

==Side effects==

Tropicamide induces transient stinging and a slight and transient rise in [[intraocular pressure]] in the majority of patients. It may cause redness or [[conjunctivitis]] (inflammation) and also [[Defocus aberration|blurs]] near vision for a short while after instillation (care must be taken, and the patient must only drive when vision returns to normal). Tropicamide may, in very rare cases,<ref name= "pmid16399709" >{{cite journal | vauthors = Liew G, Mitchell P, Wang JJ, Wong TY | title = Fundoscopy: to dilate or not to dilate? | journal = [[British Medical Journal|BMJ]] | volume = 332 | issue = 7532 | pages = 3 | date = January 2006 | pmid = 16399709 | pmc = 1325111 | doi = 10.1136/bmj.332.7532.3 }}</ref> cause an attack of [[Glaucoma#Classification|acute angle-closure glaucoma]]. This tends to be in patients with narrow [[anterior chamber]] [[trabecular meshwork|angles]], and closure risk must be assessed by the practitioner prior to instillation.

Tropicamide is often preferred to [[atropine]] because atropine has a longer [[half-life]], causing prolonged dilation and blurry vision for up to a week. Atropine has less [[sting effect]], but can be toxic or fatal if ingested in large quantities by children or adults.

With [[Ophthalmic drug administration|eye drops]], [[systemic circulation|systemic effect]]s are minimal to nonexistent due to very low absorption into the bloodstream.<ref>{{cite journal | vauthors = Vuori ML, Kaila T, Iisalo E, Saari KM | title = Systemic absorption and anticholinergic activity of topically applied tropicamide | journal = Journal of Ocular Pharmacology | volume = 10 | issue = 2 | pages = 431–437 | date = 1994-01-01 | pmid = 8083562 | doi = 10.1089/jop.1994.10.431 }}</ref>

==Pharmacology==

===Pharmacodynamics===

Tropicamide is an [[anticholinergic]].<ref name= "LakstygalKolesnikovaKhatsko2019" >{{cite journal | vauthors = Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV | title = DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens | journal = ACS Chem Neurosci | volume = 10 | issue = 5 | pages = 2144–2159 | date = May 2019 | pmid = 30566832 | doi = 10.1021/acschemneuro.8b00615 | url = }}</ref> It is specifically an [[antimuscarinic]], acting as a [[binding selectivity|selective]] [[muscarinic acetylcholine receptor|muscarinic acetylchline]] [[M1 receptor|M₁]] and [[M4 receptor|M₄ receptor]] [[receptor antagonist|antagonist]].<ref name= "LakstygalKolesnikovaKhatsko2019" /> However, it has also been reported to be a non-selective antagonist of all five muscarinic acetylcholine receptors.<ref name= "LavradorCabralVeríssimo2023" >{{cite journal | vauthors = Lavrador M, Cabral AC, Veríssimo MT, Fernandez-Llimos F, Figueiredo IV, Castel-Branco MM | title = A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity | journal = Pharmaceutics | volume = 15 | issue = 1 | date = January 2023 | page = 230 | pmid = 36678858 | pmc = 9863833 | doi = 10.3390/pharmaceutics15010230 | doi-access = free | url = }}</ref> As with other antimuscarinics, tropicamide can produce [[deliriant]] effects.<ref name= "LakstygalKolesnikovaKhatsko2019" />

==Recreational use==

Tropicamide is sometimes abused (injected intravenously e.g. by [[insulin syringe]]) as an inexpensive recreational [[deliriant]] drug (along with [[naphazoline]]). This was initially reported in Russia, but has subsequently spread to various other countries in the former Soviet Union and around Europe, and later in the United States.<ref>{{cite journal | vauthors = Bersani FS, Corazza O, Simonato P, Mylokosta A, Levari E, Lovaste R, Schifano F | title = Drops of madness? Recreational misuse of tropicamide collyrium; early warning alerts from Russia and Italy | journal = [[General Hospital Psychiatry]] | volume = 35 | issue = 5 | pages = 571–3 | year = 2013 | pmid = 23706777 | doi = 10.1016/j.genhosppsych.2013.04.013 }}</ref><ref name= "pmid26216560" >{{cite journal | vauthors = Bersani FS, Imperatori C, Prilutskaya M, Kuliev R, Corazza O | title = Injecting eye-drops: a mini-review on the non-clinical use of tropicamide | journal = Hum Psychopharmacol | volume = 30 | issue = 4 | pages = 262–4 | date = July 2015 | pmid = 26216560 | doi = 10.1002/hup.2481 | s2cid = 190289 }}</ref><ref name= "pmid35739063" >{{cite journal | vauthors = Bellman V, Ukolova A, Erovichenkova E, Lam S, Srivastava HK, Bruce J, Burgess DM | title = Abuse of tropicamide eye drops: review of clinical data | journal = [[Revista Brasileira de Psiquiatria|Braz J Psychiatry]] | volume = 44 | issue = 5 | pages = 522–531 | date = November 2022 | pmid = 35739063 | pmc = 9561840 | doi = 10.47626/1516-4446-2021-2446 }}</ref>

Tropicamide severely destroys internal organs when injected.<ref>{{cite journal |title=Bellman, V., Ukolova, A., Erovichenkova, E., Lam, S., Srivastava, H. K., Bruce, J., & Burgess, D. M. (2022). Abuse of tropicamide eye drops: review of clinical data. Revista brasileira de psiquiatria (Sao Paulo, Brazil: 1999) |journal=Braz J Psychiatry |date=2 Nov 2022 |volume=44}}</ref><ref>{{cite web | title=Krokodil: Russia's Deadliest Drug (NSFW) | website=[[YouTube]] | date=17 May 2012 | url=https://youtube /watch?v=JsUH8llvTZo}}</ref>

==Stereochemistry==

Tropicamide has a [[chiral center]] and two [[enantiomers]]. Medications are [[racemates]].<ref name= "Rote Liste" >{{cite book | publisher = Rote Liste Service GmbH | title = Rote Liste | year = 2017 | quote = Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte)| location = Frankfurt/Main | volume = 57 | isbn = 978-3-946057-10-9 | page = 224 | language = de }}</ref>

{| class= "wikitable" style= "text-align:center"

|-

!colspan= "2" |Enantiomers

|-

| [[File:(R)-Tropicamid Structural Formula V1.svg|200px]]<br />(''R'')-Tropicamid<br /><small>CAS: 92934-63-9</small>

| [[File:(S)-Tropicamid Structural Formula V1.svg|200px]]<br />(''S'')-Tropicamid<br /><small>CAS: 92934-64-0</small>

|}

{{Reflist|32em}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/tropicamide | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Tropicamide }}

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