Opioid Analgesics

鸦/片类镇痛剂
Opioid analgesics are the cornerstone of treatment for cancer pain . Although randomized studies（随机试验） have found that opioids are effective in noncancer pain conditions, several reviews have concluded they provide long-term improvement in only a minority of individuals and that their superiority to other analgesics and ability to improve function is inconclusive.For patients presenting to the emergency department with acute extremity pain, there was found to be no significant or clinically important difference in pain reduction at 2 hours among single-dose treatment with ibuprofen（布洛芬） and acetaminophen（对乙酰氨基酚） or with 3 different opioid and acetaminophen combination analgesics. Optimizing therapy with opioid analgesics requires carefully balancing the beneficial and undesirable effects, including addiction. Understanding the clinical pharmacology of opioids, including their relative potency, duration of action, bioavailability（生物利用度）, and pharmacokinetics（药物代谢动力学）, is essential for rational use. Their use for chronic pain management is limited primarily by myriad side effects that include nausea（恶性，呕吐是vomiting）, constipation（便秘）, sedation, itch, respiratory depression（呼吸抑制）, and endocrine deficiency（内分泌功能不足） leading to sexual dysfunction and accelerated osteoporosis（骨质疏松）. Opioids that are predominantly renally eliminated, such as morphine, should be used with caution in patients with renal dysfunction. Two metabolites of morphine, morphine-6-glucuronide, which contains analgesic properties, and morphine-3-glucuronide, which may amplify pain in certain contexts, can accumulate in patients with renal dysfunction. Alternative drugs include fentanyl（芬太尼） and methadone（美沙酮）.
The increasing use of prescription opioids for chronic pain has been associated with a more than 3-fold increase in opioid-related deaths in the early years of the 21st century. A synthesis（合成） of evidence suggests that among chronic pain patients on opioids, up to 40% exhibit aberrant drug-related behaviors, 20% abuse their drugs, and around 10% become addicted. These grave statistics have led to a recent Centers for Disease Control and Prevention (CDC疾控中心) guideline for prescribing opioids for chronic pain.The guidelines focus on three main areas:

1. Determining when to initiate or continue opioids for chronic pain;
2. Opioid selection, dosage, duration, follow-up and discontinuation; and
3. Assessing risks and addressing harms of opioid use.

The 12 primary recommendations in the CDC guideline are:

1. Nonpharmacologic and nonopioid pharmacologic therapy are preferred
   and should be utilized before initiating opioid therapy.
2. Establish realistic goals before starting opioid therapy and discuss how
   therapy will be discontinued if benefits do not outweigh risks.
3. Before initiating and periodically during opioid therapy, discuss known
   risks and realistic benefits of therapy.
4. Initiate therapy with immediate-release opioids.
5. Start with the lowest effective dose, carefully reassess benefits and risks when dosage is increased beyond 50 morphine mg equivalents (MME) per day, and try to avoid dosages greater than 90 MME per day.
6. The treatment of acute pain with opioids should be usually limited to 3
   days or less and rarely beyond 7 days.
7. Evaluate the patient within 1 to 4 weeks after starting opioids and reevaluate the benefits and harms of opioid therapy within 3 months.
8. Before starting opioid therapy and during treatment, risk factors for harm should be evaluated and strategies to mitigate risk, such as offering naloxone（纳洛酮）, should be considered.
9. Review the patient’s history of controlled substance prescriptions using
   state prescription drug monitoring programs.
10. Use urine drug screening tests before initiating opioid therapy and at least annually subsequently.
11. Try to avoid using opioids and benzodiazepines（苯二氮卓） concurrently.
12. For patients with opioid use disorder, offer or arrange treatment with
    buprenorphine or methadone in combination with behavioral therapies.
    In summary, when considering a trial with opioids, health care providers need to consider disease pathology, assess traits such as compliance and responsibility, perform risk stratification, and monitor for predefined treatment goals and aberrant drug-related behaviors .
    The long-term use of opioids can be associated with tolerance and physical dependence. Cross-tolerance（交叉耐受） among opioids is incomplete, and a strategy often used when tolerance is suspected is rotation to an alternative opioid, which may result in a 30 to 50% reduction in the equianalgesic dose. Tramadol（曲马多） and tapentadol（他喷他多） represent a class of analgesic drugs that have dual mechanisms of action. Tramadol is a weak agonist that inhibits the reuptake of norepinephrine（去甲肾上腺素） and serotonin（血清素，又叫五羟色胺）. Along with the typical opioid-related side effects, seizures have been reported. Tapentadol functions as a µ-opioid agonist and a norepinephrine reuptake inhibitor and is slightly stronger than tramadol.Butorphanol, nalbuphine, and pentazocine are opioid agonist-antagonist drugs that can antagonize the actions of µ-opioid agonists and cause psychotomimetic effects due to their actions on the κ-opioid receptor. These drugs should be used with caution, particularly in patients receiving other µ-opioid agonists, because they may precipitate withdrawal or reduce the effectiveness of pure opioid agonists. Buprenorphine, a partial agonist at the µ-opioid receptor and an antagonist at other opioid receptors, is available in various formulations, including a once-per-week transdermal patch for pain, and in combination with naloxone for the treatment of opioid addiction.