Episode #6- Barking Up the Wrong Tree (Cinohonism, Quinine & Quinidine)

The Poison Lab

• Historical perspective on use of cinchona bark powder for malaria
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973170/
• Evolutionarily pressure of malaria on beta thalassemia (sickle sell) traits
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499995/
• Cinchonism
  • Classic toxicities causes by ingestion of quinoline derivatives found in the bark of the cinchona tree
  • Brief review- https://pubmed.ncbi.nlm.nih.gov/32644745/
• Etiology
  • Powdered cinchona bark
    • Used by people to make tonic water, treat restless legs, or viruses
  • Prescription quinoline derivatives may cause cause similar effects
    • Quinine
    • Quinidine
    • Hydroxychloroquine
    • Chloroquine
• Clinical effects
  • Dizzy
  • Flushed
  • Head ache
  • Tinnitus
  • Potential for vision loss
• Laboratory assessment
  • Hypoglycemia
  • Hypokalemia
  • Long QRS
• Treatment
  • Supportive care for ABCs
    • Potential role for epinephrine as preferred pressor from animal data and chloroquine data
  • Correct endocrine/metabolic abnormalities
  • Hypertonic sodium for wide QRS (be careful of worsening hypokalemia)
  • Consider multi dose activated charcoal
• More on toxicity/studies from the episodes
  • Incidence of caridac arryhmias in patients taking quinine alone
    • Padmaja UK, Adhikari P, Periera P. Experience with quinine in falciparum malaria. Indian J Med Sci. 1999 Apr;53(4):153-7. PMID: 10695226.
  • Negative inotropic effects of quinidine
    • Hoffmeister HM, Hepp A, Seipel L. Negative inotropic effect of class-I-antiarrhythmic drugs: comparison of flecainide with disopyramide and quinidine. Eur Heart J. 1987 Oct;8(10):1126-32. doi: 10.1093/oxfordjournals.eurheartj.a062178. PMID: 3119341
  • Occular toxicity, can be permanent
    • Treatment is debated, not clear what is preferred , HBO used often
    • Vision may recover centrally first, than peripheral
    • Vision loss usually delayed from initial symptoms
    • Quinine >15 associated w/ more ocular tox- https://pubmed.ncbi.nlm.nih.gov/3983356/
      • Hall AP, Williams SC, Rajkumar KN, Galloway NR. Quinine induced blindness. Br J Ophthalmol. 1997;81(12):1029. doi:10.1136/bjo.81.12.1029
      • Dyson EH, Proudfoot AT, Prescott LF, Heyworth R. Death and blindness due to overdose of quinine. BMJ 1985; 291:31–3.
  • Otooxicity -A hall mark toxicity of tinnitus appears to be caused by
    • Additionally, vasoconstriction and local prostaglandin inhibition within the organ of Corti contributes to decreased hearing.
    • Microstructural lengthening of the outer hair cells of the cochlea and organ of Corti occurs.
      • Jastreboff PJ, Brennan JF, Sasaki CT. Quinine-induced tinnitus in rats. Arch Otolaryngol Head Neck Surg. 1991 Oct;117(10):1162-6. doi: 10.1001/archotol.1991.01870220110020. PMID: 1910705
      • Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am. 1993 Oct;26(5):791-810. PMID: 8233489.
      • Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am. 1993 Oct;26(5):791-810. PMID: 8233489.
      • Roche RJ, Silamut K, Pukrittayakamee S, et al. Quinine induces reversible high-tone hearing loss. Br J Clin Pharmacol. 1990;29(6):780-782. doi:10.1111/j.1365-2125.1990.tb03704.x
      • Jarboe JK, Hallworth R. The effect of quinine on outer hair cell shape, compliance and force. Hear Res. 1999 Jun;132(1-2):43-50. doi: 10.1016/s0378-5955(99)00031-3. PMID: 10392546.