Adverse reactions from over-the-counter medications present a challenge to physicians. Homeopathic medicine is an alternative practice, originating in Germany and gaining popularity in the United States. It utilizes dilute preparations of substances in order to treat and cure disease. Patients may potentially suffer serious effects from the use of these products as the contents and concentrations are often unclear. Here, we describe a case of suspected atropine toxicity due to the overuse of a topical homeopathic cream, Topricin, which contains belladonna, a plant containing atropine

Deeb, L.

Jesin, R. C.

Krzyzak, M.

Majlesi, N.

Regina, A.

Steinberg, E.

English

Hofstra Northwell Academic Works (Hofstra Northwell School of Medicine)

Journal Articles 2018 Anticholinergic Toxicity Secondary to Overuse of Topricin Cream, a Homeopathic Medication. M. Krzyzak Zucker School of Medicine at Hofstra/Northwell A. Regina R. C. Jesin L. Deeb Zucker School of Medicine at Hofstra/Northwell E. Steinberg See next page for additional authors Follow this and additional works at: https://academicworks.medicine.hofstra.edu/publications  Part of the Gastroenterology Commons Recommended Citation Krzyzak M, Regina A, Jesin RC, Deeb L, Steinberg E, Majlesi N. Anticholinergic Toxicity Secondary to Overuse of Topricin Cream, a Homeopathic Medication.. . 2018 Jan 01; 10(3):Article 4357 [ p.]. Available from: https://academicworks.medicine.hofstra.edu/publications/4357. Free full text article. This Article is brought to you for free and open access by Donald and Barbara Zucker School of Medicine Academic Works. It has been accepted for inclusion in Journal Articles by an authorized administrator of Donald and Barbara Zucker School of Medicine Academic Works. For more information, please contact academicworks@hofstra.edu. Authors M. Krzyzak, A. Regina, R. C. Jesin, L. Deeb, E. Steinberg, and N. Majlesi This article is available at Donald and Barbara Zucker School of Medicine Academic Works: https://academicworks.medicine.hofstra.edu/publications/4357 Received 02/02/2018 Review began  02/09/2018 Review ended  02/28/2018 Published 03/05/2018© Copyright 2018Krzyzak et al. This is an open accessarticle distributed under the terms ofthe Creative Commons AttributionLicense CC-BY 3.0., which permitsunrestricted use, distribution, andreproduction in any medium,provided the original author andsource are credited.Anticholinergic Toxicity Secondary toOveruse of Topricin Cream, a HomeopathicMedicationMichael Krzyzak  , Angela Regina  , Raphael C. Jesin  , Liliane Deeb  , Eric Steinberg  , NimaMajlesi 1. Medicine, Staten Island University Hospital 2. Emergency Medicine, St Barnabas Health System 3.Internal Medicine, Holyoke Medical Center 4. Department of Gastroenterology, Staten Island UniversityHospital 5. Emergency Medicine, Mount Sinai Beth Israel Medical Center 6. Emergency Medicine, StatenIsland University Hospital Corresponding author: Michael Krzyzak, mkrzyzakmd@outlook.com Disclosures can be found in Additional Information at the end of the articleAbstractAdverse reactions from over-the-counter medications present a challenge to physicians.Homeopathic medicine is an alternative practice, originating in Germany and gainingpopularity in the United States. It utilizes dilute preparations of substances in order to treatand cure disease. Patients may potentially suffer serious effects from the use of these productsas the contents and concentrations are often unclear. Here, we describe a case of suspectedatropine toxicity due to the overuse of a topical homeopathic cream, Topricin, which containsbelladonna, a plant containing atropine.Categories: Emergency MedicineKeywords: anticholinergic toxicity, homeopathic, alternative medicineIntroductionAtropine is a reversible antagonist of muscarinic anticholinergic receptors. It causes higherfiring of the sinoatrial node, decreases bronchial secretions, and decreases firing of the vagusnerve. It has several medicinal uses, including treatment of severe bradycardia, anesthesiaadjunct to dry oral secretions, and organophosphate and carbamate poisoning [1]. Differentforms of plants and herbs that have atropine-like properties are also used in homeopathicremedies like Topricin, a topical preparation to treat pain [2].Homeopathy relies on the principle of “similars”, which attempts to use one compound to treatthe entire host of symptoms. In 1796, Samuel Hahnemann proposed ‘like may be cured withlike’. This statement means that a disease that is cured by a remedy whose drug picture is mostsimilar to the disease itself. This pharmacotherapy relies on exact observation and experiencerather than to evidence-based medicine [3]. The manufacture of homeopathic medicineinvolves dilution of an extracted substance in decimal and centesimal stages. The dilution levelis based on the experience of homeopathy and on a patient’s symptoms [3]. Newer agentsinvolve combinations of different diluted substances in small quantities, as in the case ofTopricin [2].Homeopathic medicine use should be a concern to a clinician when evaluating for possible drugside effects. Approximately one million children and five million adults use some sort of1 2 3 4 56 Open Access CaseReport  DOI: 10.7759/cureus.2273How to cite this articleKrzyzak M, Regina A, Jesin R C, et al. (March 05, 2018) Anticholinergic Toxicity Secondary to Overuse ofTopricin Cream, a Homeopathic Medication. Cureus 10(3): e2273. DOI 10.7759/cureus.2273homeopathic substances in the United States [4]. The United States Food and DrugAdministration has regulated substances sold as homeopathic remedies since 1988. Substancesfor self-limiting conditions can be sold over the counter, but substances for moreserious conditions need to be prescribed by a homeopathic clinician [5].Herein, we report a case of anticholinergic toxicity secondary to a topical homeopathic painrelief remedy.Case PresentationA 40-year-old man presented with family to the emergency department complaining ofheadache and blurry vision of one day's duration. His wife also noticed a change in mentationfor two hours prior to presentation when he repeatedly asked the same questions and did notrecognize family members. His past medical history included hypertension and dyslipidemia.His daily medications were pravastatin, metoprolol, enalapril, and non-steroidal anti-inflammatories for musculoskeletal pains. Social history and family history were non-contributory. Two days prior to presentation, he had developed severe pain in his left footwhich he treated with over-the-counter Topricin (topical pain relief) cream. He applied thecream liberally without respecting the recommended dosage. The exact quantity and frequencywere unknown.On physical exam, his vital signs were significant for sinus tachycardia at 135 beats per minutebut otherwise was normal without fever. He was lethargic, yet arousable; his orientation couldnot be assessed. His pupils were small and no gross focal motor deficits could be elicited. Astroke code was initially called in the emergency room due to his altered mental status, and asubsequent computed tomography scan was negative for any intracranial pathology.Thrombolytics were not given. Laboratory studies showed hypercholesterolemia with a low-density lipoprotein of 114 mg/dL and a creatine kinase (CK) initially of 98 IU/L, whichsubsequently rose up to 1,837 IU/L on repeat lab testing. A troponin level and creatine kinasemuscle-brain (CK-MB) were within normal limits. Urine drug screen was negative. Blood ureanitrogen and creatinine were 29 mg/dL and 1.59 mg/dL, respectively.In the emergency department, the patient was disoriented and incontinent to urine. A Foleywas placed and drained 950 mL of clear urine in one hour, with his incontinence likelyrepresenting overflow. Lorazepam was administered for acute delirium. A toxicology consultwas obtained. At that point, the possibility of anticholinergic toxicity secondary to the overuseof the Topricin cream was suspected, given the favorable complex of presenting signs andsymptoms. A review of the ingredients revealed belladonna. Physostigmine was thenrecommended as a diagnostic tool. However, due to the recent use of a benzodiazepine and thelack of imminent need, a decision was taken to withhold. The patient was admitted forobservation and intravenous (IV) hydration. On the second day, his mental status had returnedto baseline, his kidney functions improved, and his CK level approached normal limits. He wasdischarged home after extensive education regarding the use of over-the-counter andhomeopathic remedies.DiscussionTopricin is a topical homeopathic cream used for rapid relief of pain and stiffness. It iscomprised of the following active ingredients: Aesculus hippocastanum, Arnica montana,belladonna, Crotalus horridus, echinacea, Graphites, Heloderma, Lachesis mutus, Najatripudians, Rhus toxicodendron, and Ruta graveolens. The belladonna concentration is “6X in170 g” of Topricin [2]. Belladonna is a component isolated from the herbaceous plant Atropabelladonna. The name "belladonna" is derived from Italian and means "pretty woman" becausethe herb, which has anticholinergic properties, was used in eye-drops by women to dilate the2018 Krzyzak et al. Cureus 10(3): e2273. DOI 10.7759/cureus.2273 2 of 4pupils of the eyes to make them appear seductive [6]. It is commonly used as an herbal remedyto combat pain, reduce secretions, and alleviate muscle spasms. In large quantities, belladonnacan induce anticholinergic toxicity. Patients with anticholinergic toxicity may present withflushing, dry skin and mucous membranes, mydriasis with loss of accommodation, alteredmental status, fever, sinus tachycardia, decreased bowel sounds, functional ileus, urinaryretention, hypertension, tremulousness, and myoclonic jerking leading to rhabdomyolysis. Aslittle as 2 mg of atropine ingestion has been reported to produce those symptoms [7].Identifying a patient with anticholinergic toxicity can be difficult since its presentation is oftensimilar to delirium caused by other conditions (e.g., infections, substance withdrawal,metabolic disturbance). The correct diagnosis of anticholinergic toxicity depends on thetreating physician's awareness of the condition and recognition of its symptoms. Diagnosis ofatropine toxicity is mainly clinical. Some commonly prescribed medications have detectable anticholinergic effects. Beta blockers,such as the metoprolol which our patient was prescribed, are known to have low anticholinergicactivity [8]. On the other hand, the temporal relationship between the institution ofTopricin and symptoms, imply it as the sole agent. In addition, metoprolol has minimalanticholinergic properties; thus, it is unlikely to play a role in the patient’spresentation. Further studies are needed to explore the relationship between prescribedmedications with anticholinergic activity and atropine-containing medications.Treatment of anticholinergic toxidrome is based on the severity of the symptoms. Mild casescan be treated supportively, and benzodiazepines can be used for agitation, as they were usedin this case. However, the definitive antidote for anticholinergic toxicity is physostigmine,which is used in moderate to severe cases to reverse the central effects of coma, seizures,severe dyskinesias, hallucinations, and severe agitation [9]. Gastrointestinal decontaminationmay be necessary after anticholinergic poisoning by ingestion.The patient improved significantly with supportive treatment. Although our case lacked ablood test and physostigmine trial for a definitive diagnosis, the presenting symptoms ofdelirium, antimuscarinic effects, and the elevation of creatine kinase secondary to musclebreakdown are hallmarks of atropine toxicity. In addition, the possibility of surreptitiousingestion also was considered, although the family stated they witnessed the patient apply thistopically. Although often advertised as “natural and safe”, adverse reactions to homeopathic treatmentsare rare but do exist. Often, they occur due to the lack of proper diagnosis and therapy providedby conventional medicine. A systematic review done in 2012 in the United Kingdom showed themost common adverse reaction of homeopathy was allergic reactions [10]. Adverse reactions tohomeopathic therapies are likely to be under-reported and a true incidence is unknown.ConclusionsOur case illustrates the importance of emphasizing the side effects of natural homeopathicremedies and over-the-counter preparations. Obtaining a detailed history, especially use ofnon-prescribed medications, is vital when an overdose of a substance issuspected. Theoretically, the amount of substances in homeopathic medications are intendedto contain minimal concentrations. Physicians and pharmacists alike should be aware ofalternative medications, including homeopathy, in patients presenting with new and unusualsymptoms.Additional Information2018 Krzyzak et al. Cureus 10(3): e2273. DOI 10.7759/cureus.2273 3 of 4DisclosuresHuman subjects: Consent was obtained by all participants in this study. Conflicts of interest:In compliance with the ICMJE uniform disclosure form, all authors declare the following:Payment/services info: All authors have declared that no financial support was received fromany organization for the submitted work. Financial relationships: All authors have declaredthat they have no financial relationships at present or within the previous three years with anyorganizations that might have an interest in the submitted work. Other relationships: Allauthors have declared that there are no other relationships or activities that could appear tohave influenced the submitted work.References1. Katzung BG, Trevor AJ: Basic & Clinical Pharmacology, 13th Edition . Weitz M, Lebowitz H(ed): McGraw-Hill Education, New York, NY; 2015.2. TOPRICIN - aesculus hippocastanum, arnica montana, belladonna, calendula officinalis,crotalus horridus, echinacea, graphites, heloderma horridum, lachesis mutus, naja tripudians,phosphorus, rhus toxicodendron, ruta graveolens, sulfur cream. (2012). Accessed: January 28,2016: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=321e83de-71e8-20b4-e054-00144ff8d46c.3. Righetti M, Ammon K, Mattmann P, Thurneysen A: Introduction to the speciality ofhomeopathy – principles and definition. Homeopathy in Healthcare – Effectiveness,Appropriateness, Safety, Costs. Bornhöft G, Matthiessen PF (ed): Springer-Verlag, Berlin,Heidelberg; 2011. 9–14. 10.1007/978-3-642-20638-2_34. Righetti M: Aims of homeopathy research, 1994 and 2015. Homeopathy. 2015, 104:343–44.10.1016/j.homp.2015.10.0045. Podolsky SH, Kesselheim AS: Regulating homeopathic products - A century of dilute interest .N Engl J Med. 2016, 374:201–203. 10.1056/NEJMp15133936. Kuhn C, Swartzwelder S, Wilson W: Buzzed. The Straight Facts about the Most Used andAbused Drugs from Alcohol to Ecstasy. WW Norton & Company, New York, NY; 2008.7. Glatstein M, Alabdulrazzaq F, Scolnik D: Belladonna alkaloid intoxication: the 10-yearexperience of a large tertiary care pediatric hospital. Am J Ther. 2016, 23:e74–77.10.1097/01.mjt.0000433940.91996.168. Lanctôt KL, O'Regan J, Schwartz Y, et al.: Assessing cognitive effects of anticholinergicmedications in patients with coronary artery disease. Psychosomatics. 2014, 55:61–68.10.1016/j.psym.2013.04.0049. Burns MJ, Linden CH, Graudins A, et al.: A comparison of physostigmine and benzodiazepinesfor the treatment of anticholinergic poisoning. Ann Emerg Med. 2000, 35:374–81.10.1016/S0196-0644(00)70057-610. Posadzki P, Alotaibi A, Ernst E: Adverse effects of homeopathy: a systematic review ofpublished case reports and case series. Int J Clin Pract. 2012, 66:1178–88. 10.1111/ijcp.120262018 Krzyzak et al. Cureus 10(3): e2273. DOI 10.7759/cureus.2273 4 of 4

Anticholinergic Toxicity Secondary to Overuse of Topricin Cream, a Homeopathic Medication.

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Anticholinergic Toxicity Secondary to Overuse of Topricin Cream, a Homeopathic Medication.

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