Opioid receptor antagonists-naloxone and naloxone are very similar to morphine in chemical structure, the main difference is that the methyl group on the tertiary nitrogen is replaced by allyl group, and the 6- hydroxyl group is changed into keto group. Naloxone has antagonistic effect on opioid receptor type 4. It has no obvious pharmacological action and toxicity, and does not produce any symptoms after injection of 12mg. Injection of 24 mg only caused slight drowsiness. However, for patients with morphine poisoning, low dose (0.4 ~ 0.8 mg) intramuscular or intravenous injection can quickly reverse the effect of morphine, eliminate respiratory depression and increase respiratory frequency within 1 ~ 2 minutes. It can quickly induce the withdrawal symptoms of morphine addicts, indicating that naloxone competes with morphine for the same receptor in vivo. Clinically, it is suitable for acute poisoning caused by morphine analgesics, relieving central depression symptoms such as respiratory depression, and making coma patients recover quickly. Naloxone is an important tool for the theoretical study of analgesic drugs.
The effect of naltrexone is the same as that of naloxone, but its oral bioavailability is high and its action lasts for a long time.
Opioid receptor agonists mainly include methadone, buprenorphine and dihydroetorphine. Its main feature is that it can quickly detoxify, but it will be addictive.
Methadone, also known as methadone, phenacetin and amiodarone, is an opioid receptor agonist and belongs to narcotic analgesics. It was first synthesized by German chemists during World War II.
The chemical structure of methadone is far from that of morphine, but its pharmacological action is very similar to that of morphine. Its outstanding characteristics are strong analgesic effect, effective oral administration, lasting inhibitory effect on withdrawal symptoms of opioid addicts, sustainable and effective repeated application, and suitable for drug rehabilitation treatment of addicts.
Methadone has a strong analgesic effect, which is 2-3 times as effective as morphine. It takes effect slowly and lasts for a long time. It is suitable for chronic pain, but its curative effect on acute pain is slightly worse. Methadone can cause sedation, respiratory depression and constipation. The effect on smooth muscle and cardiovascular system is similar to morphine, but weaker than morphine; It has similar effects on mydriasis, antitussive and pituitary hormones as morphine. It has respiratory inhibition effect on fetus, so it is not suitable for obstetric analgesia.
Methadone is absorbed quickly and completely by subcutaneous or intramuscular injection, and is easy to be absorbed from gastrointestinal tract. After oral administration for 30 minutes, it can be measured in blood, and the concentration reaches the peak in 4 hours, and the half-life is 10- 18 hours, with an average of 15 hours. For long-term drug users, the half-life is 13-47 hours, with an average of 25 hours, and 85% of them bind to plasma protein. The biotransformation of methadone is mainly carried out in the liver, and most of it is excreted in urine and feces in the form of metabolites.
In the mid-1960s, methadone was used to treat opioid addiction. It was first discovered in the United States that methadone can control the withdrawal symptoms of heroin. In recent 30 years, this drug has become the main drug for detoxification in western countries in Europe and America. In the early 1970s, Hong Kong began to implement methadone treatment program, and achieved satisfactory results. 1993, China's Ministry of Health promulgated the Guiding Principles of Common Drugs for Opioid Addiction, and methadone is the first choice for drug treatment.
Methadone, like morphine, is a narcotic analgesic, so it can be addictive and has physiological dependence, psychological dependence and tolerance. Therefore, methadone should be used reasonably and not abused, otherwise it will lead to the same consequences as heroin. Methadone is also the target of drug addicts and must be strictly managed to avoid being lost to drugs.
Dihydroetorphine hydrochloride (DHE) is a new and highly effective narcotic analgesic developed in China in recent years. Most of them are tablets, which are chemically synthesized opioid receptor agonists. Taking dihydroetorphine hydrochloride will cause physical and psychological dependence, which is more addictive than heroin, so it is listed as a strictly controlled narcotic drug.