Opioids, strong

Key examples

• Morphine
• Oxycodone

 

Common indications

1. For rapid relief of acute severe pain, including post-operative pain and pain associated with acute myocardial infarction.
2. For relief of chronic pain, when paracetamol, NSAIDs and weak opioids are insufficient (‘rung 3’ of the WHO pain ladder).
3. For relief of breathlessness in the context of end-of-life care.
4. To relieve breathlessness and anxiety in acute pulmonary oedema, alongside oxygen, furosemide and nitrates.

 

Mechanisms of action

• The term opioids encompasses naturally-occurring opiates (e.g. morphine) plus synthetic analogues (e.g. oxycodone). Morphine and oxycodone are strong opioids. 
• The therapeutic action of opioids arises from activation of opioid µ (mu) receptors in the central nervous system. 
• Activation of these G protein-coupled receptors has several effects that, overall, reduce neuronal excitability and pain transmission. 
• In the medulla, they blunt the response to hypoxia and hypercapnoea, reducing respiratory drive and breathlessness. 
• By relieving pain, breathlessness and associated anxiety, opioids reduce sympathetic nervous system (fight or flight) activity. 
• Thus, in myocardial infarction and acute pulmonary oedema they may reduce cardiac work and oxygen demand, as well as relieving symptoms. 
• That said, although commonly used, the efficacy and safety of morphine in acute pulmonary oedema is not firmly established.

 

Important adverse effects

• Opioids cause respiratory depression by reducing respiratory drive. They may cause euphoria and detachment, and in higher doses, neurological depression. They can activate the chemoreceptor trigger zone, causing nausea and vomiting, although this tends to settle with continued use. 
• Pupillary constriction occurs due to stimulation of the Edinger–Westphal nucleus. In the large intestine, activation of µ receptors increases smooth muscle tone and reduces motility leading to constipation. In the skin, opioids may cause histamine release, leading to itching, urticaria, vasodilatation and sweating. 
• Continued use can lead to tolerance (a state in which the dose required to produce the same effect increases over time) and dependence. Dependence becomes apparent on cessation of the opioid, when a withdrawal reaction occurs (see Clinical tip).

 

Warnings

• Most opioids rely on the liver and the kidneys for elimination, so doses should be reduced in hepatic failure and renal impairment and in the elderly. 
• Do not give opioids in respiratory failure except under senior guidance (e.g. in palliative care). 
• Avoid opioids in biliary colic, as they may cause spasm of the sphincter of Oddi, which may worsen pain.

 

Important interactions

• Opioids should ideally not be used with other sedating drugs (e.g. antipsychotics, benzodiazepines and tricyclic antidepressants). Where their combination is unavoidable, close monitoring is necessary.