see also:

• acute kidney injury (AKI) / acute renal failure (ARF)

• quinine has a long history of medical usage as well as an additive to drinks to give a bitter taste as in tonic water and lemon, lime bitters
• it is possible that consumption of quinine as tonic water could create immune sensitivity to oral doses of quinine ¹⁾
• its main medical uses are:
  • as a prophylactic and Rx for malaria
  • to reduce leg cramps and restless leg syndrome - no longer used for this purpose
• quinine in tonic water is limited by the FDA to a dose of 83 mg/L, but the daily therapeutic dose of quinine for malaria prevention is up to 1000 mg

• late 17th century Spanish invaders in South America noted that the bark of the cinchona tree had medicinal qualities for a variety of tropical febrile illnesses.
• the bark was brought back by the Spanish to Europe as both a remedy for and prevention of malaria.
• 19th century, British leaders recognized the power of quinine powder as an antimalarial, and due to their interest in conquering India, began importing the bark in massive quantities, supplying their soldiers in India with over 700 tons of cinchona bark annually.
• the extracted quinine powder was effective, but very bitter, so it was soon made more palatable by mixing into drinks with soda and sugar
• in 1858, the first commercial tonic water became available (patented by Erasmus Bond), subsequently, Schweppes introduced “Indian Quinine Tonic,” turning a medical necessity into a commercial profitability. The tonic water was soon added to gin to create gin and tonic.
• Sir Winston Churchill even credited the gin and tonic with saving “more Englishmen’s lives, and minds, than all the doctors in the Empire.”
• in the mid 20th century, gin and tonic even reached popularity as a “radioactive” party favorite, as it fluoresces with exposure to UV light.
• independent of its antimalarial actions, it was also found to be effective at relieving muscle cramps, and was widely adopted by nephrologists to treat this painful condition associated with hemodialysis treatments.
• reports of quinine-associated fatalities from thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome (HUS), renal failure, and torsades de pointes and other arrhythmias led the FDA to ban most forms of this medication in 2007

• prolonged QTc and torsade de pointes VT
• autoimmune haemolytic anaemia
• rare but life threatening acute kidney injury (AKI) / acute renal failure (ARF) via:
  • immune-mediated thrombotic microangiopathy (TMA)
    • similar to peanut-related anaphylaxis, an initial exposure to quinine leading to sensitization and antibody production is necessary.
    • a repeat exposure is then enough to massively bind antigen to antibodies, which can then activate the glycoprotein (GP) IIb/IIIa receptor leading to platelet aggregation (this is the opposite to how clopidogrel works).
    • additionally, the quinine induced antibodies can also interact directly with endothelial cells, as well as neutrophils, which can lead to neutrophil adhesion to endothelial cells, causing direct vascular injury.
    • theoretically, only a miniscule amount of quinine would be needed to trigger the TMA if a prior exposure occurred, and therefore, a simple sip of tonic water could be enough to cause a patient to have severe AKI requiring dialysis
    • in a Oklahoma registry of TMA in USA from 1989-2015, quinine accounted for 4% of cases including 1 from tonic water alone and quinine-induced TMA clinically presented more like HUS than TTP, as it had a renal predominance of organ injury and less severe thrombocytopenia ²⁾
  • interstitial nephritis
  • thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome (HUS)