Jump to content

User:Lowkeyvision/sandbox

From Wikipedia, the free encyclopedia
Lowkeyvision/sandbox
Clinical data
Trade namesBenadryl, Unisom, Sominex
AHFS/Drugs.comMonograph
MedlinePlusa682539
Pregnancy
category
  • AU: A
Dependence
liability		Very low
Routes of
administration		Oral, parenteral (IM and IV), topical, suppository
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability40–60%[1]
Protein binding98–99%
MetabolismVarious cytochrome P450 liver enzymes: CYP2D6 (80%), 3A4 (10%)[4]
Elimination half-life8 hours (children)[2]
9 to 12 hours (adults)[2]
17 hours (elderly)[2]
Excretion94% through the urine, 6% through feces[3]
Identifiers
  • 2-(diphenylmethoxy)-N,N-dimethylethanamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC17H21NO
Molar mass255.355 g/mol g·mol−1
3D model (JSmol)
  • O(CCN(C)C)C(c1ccccc1)c2ccccc2
  • InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3 checkY
  • Key:ZZVUWRFHKOJYTH-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Diphenhydramine (/ˌdaɪfɛnˈhaɪdrəmiːn/; abbreviated DPH, sometimes DHM) is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties that is mainly used to treat allergies. It is also used in the management of drug-induced parkinsonism and other extrapyramidal symptoms. The drug has a strong hypnotic effect and is FDA-approved as a non-prescription sleep aid, especially in the form of diphenhydramine citrate. It is produced and marketed under the trade name Benadryl by McNeil-PPC (a division of Johnson & Johnson) in the U.S., Canada and South Africa (trade names in other countries include Dimedrol and Daedalon). It is also available as a generic or store brand medication.

Medical uses

[edit]

Diphenhydramine is a first generation antihistamine used to treat a number of conditions including allergic symptoms and itchiness, the common cold, insomnia, motion sickness, and extrapyramidal symptoms.[5][6]

Diphenhydramine is significantly more potent in treatment of allergies than newer generation of antihistamines.[7] Consequently, it is frequently used when an allergic reaction requires fast, effective reversal of a massive histamine release. Diphenhydramine is available as an over-the-counter (OTC) or prescribed HCl injectable. In addition, injectable diphenhydramine can be used for life-threatening reactions (anaphylaxis) to allergens such as bee stings, peanuts, or latex, as an adjunct to epinephrine.[8]

It is a potent antagonist to acetylcholine affecting muscarinic receptors and as a result is used to treat parkinson's disease like extrapyramidal symptoms caused by typical antipsychotics. The muscarinic receptor antagonism leads to correction of dopamine, the neurotransmitter responsible for control of motor function in the brain, similar to other antimuscarinic agents such as atropine. [9] Diphenhydramine can cause strong sedation and has also been used as an anxiolytic as a result.[10]

File:Benadryl Diphenhydramine.jpg
Diphenhydramine in the United States

Diphenhydramine sedative properties make it widely used in nonprescription sleep aids for insomnia. The maximum recommended dose of 50 mg (as the hydrochloride salt) being mandated by the U.S. FDA. Diphenhydramine has been shown to build tolerance against its sedation effectiveness very quickly, with placebo-like results after a third day of common dosage.[11] The drug is an ingredient in several products sold as sleep aids, either alone or in combination with other ingredients such as acetaminophen (paracetamol). An example of the latter is Tylenol PM. Examples of products having diphenhydramine as the only active ingredient include Unisom, Tylenol Simply Sleep, Nytol, ZzzQuil, and Sominex (the version sold in the US and Canada; that sold in the UK uses promethazine).

Diphenhydramine also has antiemetic properties which make it useful in treating the nausea that occurs in motion sickness. As it causes marked sedation in many individuals, newer generation antihistamines including Loratadine, Cetirizine, and Dimenhydrinate may be preferred for this purpose.[12]

There are also topical formulations of diphenhydramine available, including creams, lotions, gels, and sprays. They are used to relieve itching, and have the advantage of causing much less systemic effect (i.e. drowsiness) than oral forms.[13] Diphenhydramine also has local anesthetic properties, and has been used for patients allergic to common local anesthetics like lidocaine.[14]

Adverse effects

[edit]

Diphenhydramine has potent anticholinergic agent, leading to the side-effects of dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, hallucinations or delirium. Other side-effects include motor impairment (ataxia), flushed skin, blurred vision at nearpoint owing to lack of accommodation (cycloplegia), abnormal sensitivity to bright light (photophobia),sedation, difficulty concentrating, short-term memory loss, visual disturbances, irregular breathing, dizziness, irritability, itchy skin, confusion, decreased body temperature (in general, in the hands and/or feet), erectile dysfunction, excitability, and, although it can be used to treat nausea, higher doses may cause vomiting.[15] Some side-effects, such as twitching, may be delayed until the drowsiness begins to cease and the person is in more of an awakening mode.

Torsade De Pointes can occur as a side effect of Diphenhydramine

Acute poisoning can be fatal leading to cardiovascular collapse and death in 2-18 hours and is treated general using a symptomatic and supportive approach.[16] Diagnosis of toxicity is based on history and presentation of the patient and specific levels are generally not useful.[17] There are several levels of evidence strongly indicating diphenhydramine (similar to chlorpheniramine) can block the delayed rectifier potassium channel and consequently prolong the QT-interval, leading to cardiac arrhythmias, such as torsade de pointes.[18]

There is no specific antidote for diphenhydramine toxicity, but the anticholinergic syndrome has been treated with physostigmine for severe delirium or tachycardia.[17]

Some patients have an allergic reaction to diphenhydramine in the form of hives.[19][20] Paradoxically restlessness or akathesia can also be a side effect that is made worse by increased levels of diphenhydramine.[21] As diphenhydramine is extensively metabolized by the liver, caution should be exercised when giving the drug to individuals with hepatic impairment.

Special populations

[edit]

Diphenhydramine is not recommended for patients older than 65 or children under the age of six, unless a physician is consulted.[22] These populations should be treated with second-generation antihistamines such as loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine, and azelastine.[16] Due to its strong anticholinergic effects, diphenhydramine is on the "Beers list" of drugs to avoid in the elderly.[23]

Diphenhydramine is Category B in the FDA Classification of Drug Safety During Pregnancy.[24] Diphenhydramine is also excreted in breast milk.[25] Paradoxical reactions to diphenhydramine have been documented, particularly among children, and it may cause excitation instead of sedation.[21]

Measurement in body fluids

[edit]

Diphenhydramine can be quantitated in blood, plasma, or serum.[26] Gas chromatography with mass spectrometry (GC-MS) can be used with electron ionization on full scan mode as a screening test. GC-MS or GC-NDP can be used for quantification.[26] Rapid urine drug screens using immunoassays based on the principle of competitive binding may show false-positive methadone results for patients who have ingested diphenhydramine.[27] Quantitation can be used monitor therapy, confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest, or assist in a death investigation.[26]

Mechanism of action

[edit]
Overview of diphenhydramine targets and effects
Biological target Mode of action Effect
H1 receptor
(Peripheral)		 Inverse agonist Allergy relief
H1 receptor
(Central)		 Antagonist Sedation
M Receptors Antagonist Anticholinergic
Antiparkinson
Na channel Inhibitor Local anesthetic
SERT Inhibitor
μ,δ, κ Receptors Potentiator
of morphine		 Analgesia

Diphenhydramine is an inverse agonist of the histamine H1 receptor.[28] It is a member of the ethanolamine class of antihistaminergic agents.[16] By blocking the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. Diphenhydramine also crosses the blood–brain barrier (BBB) and antagonizes the H1 receptors centrally. Its effects on central H1 receptors cause drowsiness.[29]

Like many other first-generation antihistamines, diphenhydramine is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors), and, as such, at high doses can cause anticholinergic syndrome.[30] The utility of diphenhydramine as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.

Diphenhydramine also acts as an intracellular sodium channel blocker, which is responsible for its actions as a local anesthetic.[31] Diphenhydramine has also been shown to inhibit the reuptake of serotonin.[32] Finally, diphenhydramine has been shown to be a potentiator of analgesia induced by morphine in rats.[33]

Pharmacokinetics

[edit]

Oral bioavailability of diphenhydramine is in the range of 40–60% and peak plasma concentration occurs approximately 2–3 hours after administration.[1] The primary route of metabolism is two successive demethylations of the tertiary amine. The resulting primary amine is further oxidized to the carboxylic acid.[1] The half-life is as short as 8 hours in children to 17 hours in the elderly.[2]

History

[edit]
Diphenhydramine ball and stick model

Diphenhydramine was discovered in 1943 by Dr. George Rieveschl, a former professor at the University of Cincinnati.[34] In 1946, it became the first prescription antihistamine approved by the U.S. Food and Drug Administration (FDA).[35] Diphenhydramine, N,N-dimethyl-(diphenylmethoxy)ethylamine, was synthesized by a simple reaction of benzhydryl bromide and 2-dimethylaminoethanol.[36][37][38]

synthesis of Diphenhydamine

In the 1960s, diphenhydramine was found to inhibit reuptake of the neurotransmitter serotonin.[32] This discovery led to a search for viable antidepressants with similar structures and fewer side-effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI).[32][39] A similar search had previously led to the synthesis of the first SSRI, zimelidine, from brompheniramine, also an antihistamine. [40]

Society and culture

[edit]

Diphenhydramine is sometimes abused as a deliriant, or as a potentiator of alcohol,[41][42] opiates[43] and other depressants. Diphenhydramine is deemed to have limited abuse potential in the United States due its potentially serious side effect profile and limited euphoric effects, and is not a controlled substance. Since 2002, the U.S. FDA has required special labeling warning against use of multiple products that contain diphenhydramine.[44] In some jurisdictions, diphenhydramine is often present in postmortem specimens collected during investigation of sudden infant deaths; the drug may play a role in these events.[45][46]

Diphenhydramine is among the prohibited and controlled substances in the Republic of Zambia.[47] Travelers are advised not to bring this drug into the country. Several Americans have been detained by the Zambian Drug Enforcement Commission for possession of Benadryl and other over-the-counter medications containing diphenhydramine.[48]

See also

[edit]

References

[edit]
  1. ^ a b c Paton DM, Webster DR (1985). "Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines)". Clin. Pharmacokinet. 10 (6): 477–97. doi:10.2165/00003088-198510060-00002. PMID 2866055. S2CID 33541001.
  2. ^ a b c d Simons KJ, Watson WT, Martin TJ, Chen XY, Simons FE (1990). "Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children". J. Clin. Pharmacol. 30 (7): 665–71. doi:10.1002/j.1552-4604.1990.tb01871.x. PMID 2391399. S2CID 25452263. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Garnett WR (1986). "Diphenhydramine". Am. Pharm. NS26 (2): 35–40. doi:10.1016/s0095-9561(16)38634-0. PMID 3962845. {{cite journal}}: Unknown parameter |month= ignored (help)
  4. ^ "Showing Diphenhydramine (DB01075)". DrugBank. Retrieved 5 September 2009.
  5. ^ "Diphenhydramine Hydrochloride Monograph". Drugs.com. The American Society of Health-System Pharmacists.
  6. ^ Brown HE, Stoklosa J, Freudenreich O (2012). "How to stabilize an acutely psychotic patient" (PDF). Current Psychiatary. 11 (12): 10–16. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Raphael GD, Angello JT, Wu MM, Druce HM (2006). "Efficacy of diphenhydramine vs desloratadine and placebo in patients with moderate-to-severe seasonal allergic rhinitis". Ann. Allergy Asthma Immunol. 96 (4): 606–14. doi:10.1016/S1081-1206(10)63557-0. PMID 16680933. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Young WF (2011). "Chapter 11: Shock". In Roger L. Humphries RL, Stone CK (ed.). CURRENT Diagnosis and Treatment Emergency Medicine. LANGE CURRENT Series)\ (Seventh ed.). McGraw-Hill Professional. ISBN 978-0-07-170107-5.
  9. ^ Aminoff MJ (2012). "Chapter 28. Pharmacologic Management of Parkinsonism & Other Movement Disorders". In Katzung B, Masters S, Trevor A (ed.). Basic & Clinical Pharmacology (12th ed.). The McGraw-Hill Companies, Inc. pp. 483–500. ISBN 978-0-07-176401-8.{{cite book}}: CS1 maint: multiple names: editors list (link)
  10. ^ Dinndorf PA, McCabe MA, Frierdich S (1998). "Risk of abuse of diphenhydramine in children and adolescents with chronic illnesses". J. Pediatr. 133 (2): 293–5. doi:10.1016/s0022-3476(98)70240-9. PMID 9709726. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T (2002). "Tolerance to daytime sedative effects of H1 antihistamines". J. Clin. Psychopharmacol. 22 (5): 511–5. doi:10.1097/00004714-200210000-00012. PMID 12352276. S2CID 19773705. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Katzung B (2012). "Chapter 16. Histamine, Serotonin, & the Ergot Alkaloids". In Katzung B, Masters S, Trevor A (ed.). Basic & Clinical Pharmacology (12th ed.). The McGraw-Hill Companies, Inc. pp. 274–277. ISBN 978-0-07-176401-8.{{cite book}}: CS1 maint: multiple names: editors list (link)
  13. ^ MedlinePlus Encyclopedia: Diphenhydramine Topical
  14. ^ Smith DW, Peterson MR, DeBerard SC (1999). "Local anesthesia. Topical application, local infiltration, and field block". Postgrad. Med. 106 (2): 57–60, 64–6. doi:10.3810/pgm.1999.08.650. PMID 10456039. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ "Diphenhydramine Side Effects". Drugs.com. Retrieved 6 April 2009.
  16. ^ a b c Brunton L, Chabner B, Knollmann B (2011). "Chapter 32. Histamine, Bradykinin, and Their Antagonists". In Brunton L (ed.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (12e ed.). McGraw Hill. pp. 242–245. ISBN 978-0-07-162442-8.{{cite book}}: CS1 maint: multiple names: authors list (link)
  17. ^ a b Manning B (2012). "Chapter 18. Antihistamines". In Olson K (ed.). Poisoning & Drug Overdose (6th ed.). McGraw-Hill. ISBN 978-0-07-166833-0. Retrieved 19 March 2013.
  18. ^ Nia AM, Fuhr U, Gassanov N, Erdmann E, Er F (2010). "Torsades de pointes tachycardia induced by common cold compound medication containing chlorpheniramine" (PDF). Eur. J. Clin. Pharmacol. 66 (11): 1173–5. doi:10.1007/s00228-010-0875-5. PMID 20676621. S2CID 26312358. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  19. ^ Heine A (1996). "Diphenhydramine: a forgotten allergen?". Contact Derm. 35 (5): 311–2. doi:10.1111/j.1600-0536.1996.tb02402.x. PMID 9007386. S2CID 32839996. {{cite journal}}: Unknown parameter |month= ignored (help)
  20. ^ Coskey RJ (1983). "Contact dermatitis caused by diphenhydramine hydrochloride". J. Am. Acad. Dermatol. 8 (2): 204–6. doi:10.1016/S0190-9622(83)70024-1. PMID 6219138. {{cite journal}}: Unknown parameter |month= ignored (help)
  21. ^ a b de Leon J, Nikoloff DM (2008). "Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports". CNS Spectr. 13 (2): 133–5. doi:10.1017/s109285290001628x. PMID 18227744. {{cite journal}}: Unknown parameter |month= ignored (help) Cite error: The named reference "pmid18227744" was defined multiple times with different content (see the help page).
  22. ^ Medical Economics (2000). Physicians' Desk Reference for Nonprescription Drugs and Dietary Supplements, 2000 (21st ed.). Montvale, NJ: Medical Economics Company. ISBN 1-56363-341-8.
  23. ^ "High risk medications as specified by NCQA's HEDIS Measure: Use of High Risk Medications in the Elderly" (PDF). National Committee for Quality Assurance (NCQA).
  24. ^ Black RA, Hill DA (2003). "Over-the-counter medications in pregnancy". Am. Fam. Physician. 67 (12): 2517–24. PMID 12825840. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ Spencer JP, Gonzalez LS, Barnhart DJ (2001). "Medications in the breast-feeding mother". Am. Fam. Physician. 64 (1): 119–26. PMID 11456429. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  26. ^ a b c Pragst F (2007). "Chapter 13: High performance liquid chromatography in forensic toxicological analysis". In Smith RK, Bogusz MJ (ed.). Forensic Science (Handbook of Analytical Separations). Vol. 6 (2nd ed.). Amsterdam: Elsevier Science. p. 471. ISBN 978-0-444-52214-6. {{cite book}}: More than one of |pages= and |page= specified (help)
  27. ^ Rogers SC, Pruitt CW, Crouch DJ, Caravati EM (2010). "Rapid urine drug screens: diphenhydramine and methadone cross-reactivity". Pediatr. Emerg. Care. 26 (9): 665–6. doi:10.1097/PEC.0b013e3181f05443. PMID 20838187. S2CID 31581678. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Yamashiro K, Kiryu J, Tsujikawa A, Nonaka A, Honjo M, Tanihara H, Nishiwaki H, Honda Y, Ogura Y (2001). "Suppressive effects of histamine H1 receptor antagonist diphenhydramine on the leukocyte infiltration during endotoxin-induced uveitis". Exp. Eye Res. 73 (1): 69–80. doi:10.1006/exer.2001.1008. PMID 11428864. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  29. ^ Reiner PB, Kamondi A (1994). "Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current". Neuroscience. 59 (3): 579–88. doi:10.1016/0306-4522(94)90178-3. PMID 8008209. S2CID 17151260. {{cite journal}}: Unknown parameter |month= ignored (help)
  30. ^ Lopez AM (10 May 2010). "Antihistamine Toxicity". Medscape Reference. WebMD LLC.
  31. ^ Kim YS, Shin YK, Lee C, Song J (2000). "Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine". Brain Research. 881 (2): 190–8. doi:10.1016/S0006-8993(00)02860-2. PMID 11036158. S2CID 18560451. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ a b c Domino EF (1999). "History of modern psychopharmacology: a personal view with an emphasis on antidepressants". Psychosom. Med. 61 (5): 591–8. doi:10.1097/00006842-199909000-00002. PMID 10511010.
  33. ^ Carr KD, Hiller JM, Simon EJ (1985). "Diphenhydramine potentiates narcotic but not endogenous opioid analgesia". Neuropeptides. 5 (4–6): 411–4. doi:10.1016/0143-4179(85)90041-1. PMID 2860599. S2CID 45054719. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Hevesi D (29 September 2007). "George Rieveschl, 91, Allergy Reliever, Dies". The New York Times. Retrieved 14 October 2008.
  35. ^ Ritchie J (24 September 2007). "UC prof, Benadryl inventor dies". Business Courier of Cincinnati. Retrieved 14 October 2008.
  36. ^ US patent 2397799, Martin H, Hafliger F, Gatzi K, Grob A, "Amino-ethers and a process for their manufacture", published 1946-04-02, assigned to JR Geigy AG 
  37. ^ US patent 2421714, Riveschl G, "Dialkylaminoalkyl benzhydryl ethers and salts thereof", published 1947-06-03, assigned to Parke Davis & Company 
  38. ^ US patent 2427878, Riveschl G, "Dialkylaminopropyl ethers of benzhydrol", published 1947-09-23, assigned to Parke Davis & Company 
  39. ^ Awdishn RAL, Whitmill M, Coba V, Killu K (2008). "Serotonin reuptake inhibition by diphenhydramine and concomitant linezolid use can result in serotonin syndrome". Chest. 134 (4 Meeting abstracts). {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  40. ^ Barondes, Samuel H. (2003). Better Than Prozac. New York: Oxford University Press. pp. 39–40. ISBN 0-19-515130-5.
  41. ^ "Diphenhydramine and Alcohol / Food Interactions". Drugs.com.
  42. ^ Zimatkin SM, Anichtchik OV (1999). "Alcohol-histamine interactions". Alcohol Alcohol. 34 (2): 141–7. doi:10.1093/alcalc/34.2.141. PMID 10344773.
  43. ^ Sandor I (30 July 2000). "Using Antihistamines, Anticholinergics, and Depressants To Potentiate Opiates, And Dealing With Opiate Side Effects". Antihistamine Aficionado Magazine.
  44. ^ Food and Drug Administration, HHS (2002). "Labeling of Diphenhydramine-Containing Drug Products for Over-the-Counter Human Use". Federal Register. 67 (235): 72555–9. PMID 12474879. Retrieved 14 October 2008.
  45. ^ Marinetti L, Lehman L, Casto B, Harshbarger K, Kubiczek P, Davis J (2005). "Over-the-counter cold medications-postmortem findings in infants and the relationship to cause of death". J. Anal. Toxicol. 29 (7): 738–43. doi:10.1093/jat/29.7.738. PMID 16419411. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  46. ^ Baselt RC (2008). Disposition of Toxic Drugs and Chemicals in Man. Biomedical Publications. pp. 489–492. ISBN 978-0-9626523-7-0.
  47. ^ "List of prohibited and controlled drugs according to chapter 96 of the laws of Zambia" (DOC). The Drug Enforcement Commission ZAMBIA.
  48. ^ "Zambia". Country Specific Information. Bureau of Consular Affairs, U.S. Department of State.

Further reading

[edit]
[edit]

Category:Antiemetics Category:Deliriants Category:H1 receptor antagonists Category:Muscarinic antagonists Category:Sedatives Category:Hypnotics Category:Ethers Category:Amines Category:Serotonin reuptake inhibitors

Retrieved from "https://wiki.riteme.site/w/index.php?title=User:Lowkeyvision/sandbox&oldid=983256394"