Cinchona ledgeriana" had a yield of 8 to 13 percent quinine in bark grown in Dutch Indonesia which effectively out-competed the British Indian production. It was only later that the English saw the value and sought to obtain the seeds of "C. ledgeriana" from the Dutch. During World War II, the Japanese conquered Java and the United States lost access to the cinchona plantations that supplied war-critical quinine medication. Botanical expeditions – called Cinchona Missions – were launched in 1942-1944 to explore promising areas of South America in an effort to locate cinchona species that contained quinine and could be harvested
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