Adverse effects with long-term use of opioids

A significant proportion of patients using an opioid long term develop adverse effects. The risk of many adverse effects (eg opioid abuse, overdose, death) increases with the use of higher doses. See Adverse effects with long-term use of opioids for adverse effects with long-term use of opioids.

Table 1. Adverse effects with long-term use of opioids

System

Adverse effects with long-term use

respiratory

opioid-induced ventilatory impairment—manifests as sedation or reduced respiratory rate; risk increases with concomitant administration of sedatives (eg benzodiazepines, sedating antihistamines, gabapentinoids, alcohol, cannabis)

increased risk of sleep-disordered breathing (eg central sleep apnoea, obstructive sleep apnoea)

cardiovascular

myocardial infarction

fluid retention

dose-dependent QT-interval prolongation with methadone and to a lesser extent with buprenorphine and oxycodone

neurological

sedation, impaired cognition, delirium, dysphoria, euphoria, miosis—monitor patients and caution them not to drive, especially when opioids have recently been initiated, opioid dose has been increased, high doses are used, or opioids are combined with other sedatives (eg benzodiazepines, alcohol, cannabis)

impaired learning (in children and adolescents)

impaired coordination, which can result in falls and fractures

muscle rigidity, myoclonus or seizures can be idiosyncratic, or occur in patients taking a high dose of opioids or who have renal impairment, due to accumulation of neurotoxic metabolites

gastrointestinal

chronic constipation is common and requires pre-emptive use of laxatives

nausea and vomiting

musculoskeletal

osteoporosis and increased risk of fractures

neuroendocrine

opioids suppress hormone release from the hypothalamus and pituitary gland causing:

  • adrenal insufficiency—fatigue, nausea, vomiting, weight loss, dizziness, muscle aches, postural hypotension, reduced cortisol secretion in response to stress (eg surgery, trauma)
  • androgen deficiency leading to secondary testosterone deficiency—sexual dysfunction, osteoporosis, muscle weakness, obesity, insulin resistance, glucose intolerance, low mood, depression, fatigue; less common with opioids with reduced mu-receptor agonism (eg tramadol, tapentadol, buprenorphine)
  • hyperprolactinaemia—gynaecomastia, galactorrhoea

urinary

urinary retention

immunological

immunosuppression