Cinchona lost their plants when a wave took them off their ship. The Dutch sent Justus Hasskarl who brought plants that were then cultivated in Java from 1854. The English explorer Clements Markham went to collect plants that were introduced in Sri Lanka and the Nilgiris of southern India in 1860. The main species introduced were "Cinchona succirubra" or red bark, as its sap turned red on contact with air, and "Cinchona calisaya". The alkaloids quinine and cinchonine were extracted by Pelletier and Caventou in 1820. Later two more key alkaloids, quinidine and cinchonidine were identified and it became a routine
Analgesic tolerance, which may be of particular concern regarding patients suffering with chronic pain and requiring an analgesic over long periods. Opioid tolerance is often addressed with opioid rotation therapy in which a patient is routinely switched between two or more non-cross-tolerant opioid medications in order to prevent exceeding safe dosages in the attempt to achieve an adequate analgesic effect. Opioid tolerance should not be confused with opioid-induced hyperalgesia. The symptoms of these two conditions can appear very similar but the mechanism of action is different. Opioid-induced hyperalgesia is when exposure to opioids increases the sensation of pain (hyperalgesia) and can