CV - Opioids, strong: morphine, oxycodone

Question 1

Opioids, strong: morphine, oxycodone

Common indications

Answer 1

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

Question 2

Opioids, strong: morphine, oxycodone

Mechanisms of action

Answer 2

• 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.

Question 3

Opioids, strong: morphine, oxycodone

Important adverse effects

Answer 3

• 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 µreceptors 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

Question 4

Opioids, strong: morphine, oxycodone

Warnings

Answer 4

• 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.

Question 5

Opioids, strong: morphine, oxycodone

Important interactions

Answer 5

• 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.

Question 6

Opioids, strong: morphine, oxycodone

Px and Administration

Answer 6

• When treating acute severe pain in high dependency areas, morphine is given IV for rapid effect (onset at about 5 minutes).
• An initial dose of 2–10 mg, tailored to pain, age and other individual factors is prescribed in the once-only section.
• On a general ward, IM or SC administration is preferred. For chronic pain, the oral route is safest and usually most appropriate.
• Immediate-release oral morphine is preferred initially (e.g. Oramorph® 5 mg orally every 4 hours).
• Then, having found the optimum dose, this is converted to a modified-release form (e.g. MST Continus® 15 mg every 12 hours).
• Alongside regular treatment, ‘breakthrough analgesia’ should be prescribed.
• Prescribe immediate-release morphine at a dose of about one-sixth of the total daily regular dose (e.g. Oramorph® 5 mg 2-hrly) in the as-required section.