Quinine in Otology and Neurotology: Ototoxicity and Historic Role in Therapy

Abstract

Objectives/Hypothesis: Quinine, a cinchona bark-derived antimalarial alkaloid, is a known ototoxic. Isolated and named in 1820 by the French scientists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou, it has since been employed in the treatment of different maladies. Quinine was also recommended as a local anesthetic in surgical procedures in the early 20th century. This article aims to identify early ototoxicity reports regarding quinine and to investigate if quinine was previously used in otology as an anesthetic agent or as an actual therapy. Method: Historical review of medical and pharmaceutical literature from the 19th and 20th centuries in databases (PubMed; Web of Science), as well as medical books on ototoxic drugs, quinine, and therapies in otology. Results: The first identified reference of quinine ototoxicity was from 1824. Quinine also had a therapeutic role in otology and neurotology and was employed for its analgesic properties. It was used in Menière's disease, vertigo, otalgia, purulent otitis media, neuralgia of the plexus tympani, furuncles in the auditory canal, and herpes zoster in the auricle. Conclusion: Quinine was acknowledged as an ototoxic drug in the 19th century. Quinine was used in several otologic disorders, both as an analgesic (for herpes zoster, otalgia) and as a therapeutic agent (Menière's disease, vertigo, purulent otitis media, furuncles in the auditory canal). This research demonstrates that, analogously to gentamicin, quinine was used in Menière's disease specifically due to its ototoxic effects.

The Ototoxicity of Antimalarial Drugs—A State of the Art Review

“…Chloroquine (CQ) and hydroxychloroquine (CHQ) are derivatives of quinine (QN), obtained from the bark of the Peruvian Cinchona tree. QN was first isolated in 1820 by the French scientists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou (9). CQ was first synthesized in 1934, and hydroxychloroquine sulfate (Plaquenil) was developed in 1946 as a less toxic chloroquine analog (10,11).…”

“…Antimalarials are used not only for the treatment of malaria but also for a range other dermatological, immunological, rheumatological, and severe infectious diseases. In the past, quinine has been used to treat otologic conditions (Menière's disease, herpes zoster, vertigo, purulent otitis media, furuncles in the auditory canal) due to its analgesic as well as ototoxic properties (9). Nowadays, chloroquine and hydroxychloroquine are used to treat autoimmune and connective tissue diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, palindromic rheumatism, eosinophilic fasciitis, dermatomyositis, cellulitis, mixed and undifferentiated connective tissue disease (11,13,14).…”

Investigação científica em rede de Portugal para a Europa: o caso da descoberta da cinchonina (1810)

“…Mais tarde, com a identificação da etiologia da malária, a quinina tornou-se o tratamento preferencial contra a malária até síntese e vulgarização dos antimaláricos sintéticos, como a cloroquina. Entre os usos propostos para a quinina incluiu-se igualmente o tratamento da gripe ou de patologias otológicas, como a doença de Ménière 86 . A quinina foi também aplicada militarmente (designadamente em campanhas do exército 87 e nas marinhas britânica e americana 88 ), foi incluída em campanhas de saúde pública destinadas à erradicação da malária, e fez parte do dia a dia, designadamente, de colonos ingleses 89 e portugueses 90 em África.…”