Morphine Morphine is quickly absorbed into the bloodstream regardless of the administration route, and the peak concentration depends on the route:
- 7-10 minutes for intravenous;
- 30 minutes for subcutaneous;
- 60 minutes for oral.
About 10% of morphine is excreted unchanged, and 90% as conjugates, primarily through the kidneys, with only 7-10% via the gastrointestinal tract.
Morphine should be administered with caution in patients with renal dysfunction.The duration of analgesia is determined by morphine's biotransformation in the liver, its elimination, and the genetically determined activity of its active metabolite.
Morphine suppresses the cough reflex and has notable antitussive properties. It stimulates chemoreceptors in the brainstem's trigger zones, causing nausea and vomiting.
Morphine does not cause clinically significant respiratory depression in cancer patients, as pain acts as a physiological antagonist to its central depressive effects. Thus, those with chronic pain do not typically experience respiratory suppression or develop dependency.
Significant side effect: respiratory centre depression related to reduced sensitivity to CO2. The peak depressive effect occurs at:
- 7-10 minutes post-intravenous administration,
- 30 minutes post-intramuscular administration,
- 60-90 minutes post-subcutaneous administration of a therapeutic dose.
Respiratory activity typically resumes within 4-5 hours. This is crucial for patients with comorbid conditions like chronic obstructive pulmonary disease, who already have reduced sensitivity to CO2. Always begin morphine treatment with low doses and gradually increase.
Gold standard for chronic cancer pain treatment: Morphine is a pure μ-receptor agonist, and its binding to peripheral and CNS receptors results in analgesia. The half-life for short-acting morphine is 4 hours; for extended-release forms, it's 8-12 hours. For patients with chronic kidney disease, the half-life may extend by 2.5 to 7.5 times.
For opioid-naive patients start with the minimum effective dose—2.5-5 mg orally every 4 hours for adults. For previously treated patients, initial doses of 10 mg short-acting every 4 hours can be used until a balance between analgesia and side effects is achieved. Have extra doses available for breakthrough pain. Once stabilised, switch to extended-release or alternative routes while observing equianalgesic principles.
Increasing dose for tolerance or other reasons: Increase the single dose by 30-50%. For instance, if the patient takes 10 mg every 4 hours, increase to 13-15 mg every 4 hours, equaling a total daily dose of 78-90 mg.
How to manage breakthrough pain with morphine? Assume you have achieved effective analgesia, and for the past 10 days, your patient has been on a stable dose of 90 mg of morphine per day with minimal or no pain. Suddenly, the patient reports that they are experiencing intense pain episodes that they can no longer manage. As we know, breakthrough pain can be spontaneous, more severe than baseline pain, and short-lived. It may be so intense that the patient finds it unbearable.
First, it is essential to correctly diagnose whether this is indeed breakthrough pain and determine whether it is related to the patient's underlying condition. If confirmed, the patient can be administered 50-100% of their single dose of short-acting opioids or 1/6 of their total daily dose of short-acting opioids. For instance, if the patient is on 10 mg of short-acting morphine, they may be given 5-10 mg to manage the breakthrough pain.
If the patient experiences more than 4-5 breakthrough pain episodes, the pain management strategy should be reviewed, and the total daily dose should be recalculated to include the additional opioid doses. For example, if the patient were taking 60 mg of short-acting morphine plus an additional 30 mg for breakthrough pain, the new total daily dose would be 90 mg. This should then be divided into six doses, resulting in a new single dose of 15 mg.
Tapering and discontinuing morphine: In cases where the patient's pain has subsided, such as following tumour reduction, discontinuing analgesia may be necessary. The morphine dose can be reduced gradually or discontinued by decreasing the total daily dose by 25-30% every 2-3 days to avoid withdrawal symptoms (abstinence syndrome).