综述：阿片类镇痛药：管理可预测的不良反应

这篇综述全面阐述了阿片类镇痛药在癌症相关疼痛治疗中的常见可预测不良反应，包括便秘、恶心呕吐、镇静、内分泌异常和瘙痒等，同时介绍了相应的管理策略，强调临床医生应充分了解并在用药前后对患者进行适当评估和监测。

　　

Opioid analgesics have been used for thousands of years, remaining a crucial treatment for cancer - related pain. However, they cause a range of predictable adverse effects.

Opioid induced constipation (OIC) is the most common form of opioid - induced bowel dysfunction, affecting up to 97% of people prescribed opioids for cancer - related pain. Opioids bind to μ - receptors in the gastrointestinal tract, inhibiting neurotransmitters and causing constipation. The Rome IV criteria are used for diagnosis. NICE recommends stimulant laxatives at the start of opioid therapy, with osmotic laxatives if there's no response within 3 - 4 days. Rectal interventions are a last resort. Peripherally acting μ - receptor antagonists (PAMORAs) like naloxegol and naldemedine are useful for OIC unresponsive to conventional laxatives. Importantly, tolerance doesn't develop to OIC.

Opioid induced nausea and vomiting (OINV) affects approximately 25 - 40% of patients. Opioids stimulate the chemoreceptor trigger zone (CTZ) and directly stimulate the vestibular apparatus. The CNS adapts over time, reducing these effects. Management should be individualized based on the pathophysiology of nausea. Anti - emetic therapy should be prescribed if nausea persists, and an opioid switch can be considered after anti - emetic optimization fails.

Opioid induced sedation (OIS) occurs in around 40% of people taking opioids for cancer pain, commonly at initiation or dose titration. Sedation is due to depression of the reticular activating system in the brainstem. Patients develop a tolerance over time. Clinicians should counsel patients about the risks, especially regarding driving. An opioid switch may be considered if sedation persists, and there is weak evidence for psychostimulants.

Endocrinopathies associated with opioids are common but under - reported. Hypogonadism prevalence can be up to 50% in chronic opioid users. Opioids disrupt the hypothalamic - pituitary - adrenal (HPA) and hypothalamic - pituitary - gonadal (HPG) axes, leading to reduced gonadal sex steroid production and increased osteoporosis risk. There is also a risk of secondary adrenal insufficiency. A thorough history and examination are needed to identify endocrinopathies, and management strategies include opioid discontinuation or switch, and appropriate replacement therapies.

Pruritis is a less common but troublesome adverse effect. Opioids act centrally and peripherally to cause itching through various neurotransmitters. Measures such as menthol - based creams and H₁ receptor antagonists can be used for management.

Clinicians often worry about addiction risk when prescribing opioids, but in advanced illness, ensuring adequate pain control is the priority. Dependence is an expected physiological response, while addiction is a complex syndrome. Patients with pre - morbid opioid misuse may need specialist input.

Opioid switching can be a useful tool to mitigate intolerable adverse effects. Individualized prescribing should consider comorbidities and concomitant medications. Partial μ - receptor agonists like buprenorphine may cause fewer adverse effects than full μ - receptor agonists like morphine.

In conclusion, clinicians must understand the common adverse effects of opioids, counsel patients before initiation, and regularly reassess them. Most adverse effects improve over time except constipation, and laxatives should be prescribed at the start of opioid therapy. Opioid switch can be used to manage intolerable adverse effects, with decisions based on opioid pharmacology and individual patient factors.