Maximus Gage
Opioids are a class of drugs that include illegal drugs such as heroin and prescription painkillers like oxycodone and morphine. They work by binding to opioid receptors in the brain, which blocks pain signals and produces a euphoric effect. While opioids are effective in managing pain, they can also cause several side effects, including muscle spasms and involuntary muscle hyperactivity. This is known as opioid-induced myoclonus, which is defined as sudden, brief, and involuntary muscle jerks that can occur with all routes of opioid administration. Higher doses of opioids more frequently result in myoclonus, but the dose relationship is variable and dependent on several factors.
| Characteristics | Values |
|---|---|
| Opioids | Morphine, Hydromorphone, Fentanyl, Meperidine, Sufentanil, Oxycodone, Methadone |
| Adverse Effects | Involuntary muscle hyperactivity, multifocal myoclonus, seizures, sedation, respiratory depression |
| Treatment | Opioid dose reduction, opioid switching, 5-HTP |
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What You'll Learn
Opioid-induced myoclonus
Myoclonus is a relatively common adverse effect of opioid therapy, particularly with high-dose therapy. It has been observed with several opioids, including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. The risk of developing myoclonus is higher with higher doses, although the dose relationship is variable. It can occur with all routes of administration, including oral, intravenous, and transdermal.
The pathophysiology of opioid-induced myoclonus is not yet fully understood. However, current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects. In some cases, myoclonus may not develop until a neurotoxic threshold is surpassed. Co-morbid factors for neurotoxicity include renal failure, electrolyte disturbances, and dehydration.
The treatment of opioid-induced myoclonus may involve opioid dose reduction or opioid switching. In some cases, discontinuing the opioid may be necessary for the resolution of myoclonus. There is currently no definitive treatment or avoidance measures for opioid-induced myoclonus.
It is important to note that myoclonus can also occur during opioid withdrawal, although this is less commonly reported. In these cases, novel treatments or applications of existing medications may be required to manage the muscle spasms associated with withdrawal.
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Opioid-induced hyperalgesia
OIH is associated with analgesic tolerance, which corresponds to a progressive decrease in analgesia produced by a given dose of opiates upon chronic administration. This results in the need to increase the opioid dosage to maintain the initial analgesic effect. However, the increase in dosage can, in turn, induce an enhancement of OIH, leading to a conflicting situation in the clinic.
The mechanisms of OIH are complex and involve μ-opioid receptor signalling pathways. Several factors have been shown to influence OIH, including the genetic background and sex differences of experimental animals, as well as the opioid regimen. At the cellular level, both neurons and glia play a major role in the development of OIH.
The treatment for OIH involves tapering off the opioid medication completely when possible. During a period of abstinence, the brain changes induced by the medication should resolve, and the patient's pain may improve or even resolve. During this time, other non-opioid pain medications can be used safely, such as acetaminophen, non-steroidal anti-inflammatory drugs, or adjunctive pain medications.
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Opioid withdrawal and muscle spasms
Opioids are often used to manage chronic pain, but they can also cause involuntary muscle hyperactivity, known as myoclonus. This is characterised by uncontrollable twitching and jerking of muscles or muscle groups, often starting with occasional random jerking movements. Myoclonus can occur with all routes of opioid administration, although higher doses more frequently result in myoclonus.
In some cases, opioid withdrawal can also induce muscle spasms. For example, a patient who was being weaned off opioids experienced refractory muscle spasms as a withdrawal symptom. This was successfully treated with the serotonin precursor 5-hydroxytryptophan (5-HTP).
In another case, a patient developed spastic paraparesis with prominent extensor spasms in the legs while receiving a high dose of intravenous methadone. The patient was unable to rise from a chair without support and could not walk due to weakness and spasticity in the legs. This patient's muscle spasms were reversible, and the condition was likely induced by the toxic effects of intraspinal opioids.
It is important to note that the selection of adjuvants to assist in weaning patients off opioids can become exhausted by side effects or ineffective attenuation of withdrawal symptoms. In such cases, novel drugs or novel applications of currently available medications must be sought.
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High-dose intravenous methadone and spastic paraparesis
Opioids are well-known to produce side effects such as sedation and respiratory depression. However, high doses of parenteral opioids can also cause multifocal myoclonus and seizures. Myoclonus is defined as sudden, brief, involuntary muscle jerks that can be either irregular or rhythmic.
Spastic paraparesis results from restless muscle activity in the lower limbs that hinders leg movements, causing impaired gait. In a case study published in 2001, a patient developed reversible spastic paraparesis with prominent extensor spasms in the legs while receiving an infusion of intravenous methadone at 100 mg/hr. The patient also experienced mild arm weakness, tinnitus, and anxiety. When the methadone was discontinued, the patient's symptoms resolved within 24 hours. The authors of the study suggested that high opioid doses and underlying subclinical spinal cord pathology were risk factors for developing this syndrome.
Another case study describes a patient who developed opioid-induced myoclonus and hyperalgesia following a short course of low-dose oral morphine. The patient complained of ongoing chest pain and developed brief symmetrical involuntary jerking movements of his arms, legs, and neck. All dyskinetic movements and hyperalgesia resolved within 24 hours of discontinuing the oral morphine.
In some cases, opioid withdrawal can also induce refractory muscle spasms. In one case report, a patient who was intolerant to clonidine, a drug used to treat opioid withdrawal symptoms, was successfully weaned off chronic opiates by treating the muscle spasms with the serotonin precursor 5-hydroxytryptophan (5-HTP).
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Intraspinal opioid administration and muscle spasms
Opioids are a class of drugs that include illegal drugs such as heroin and prescription painkillers like morphine, fentanyl, and oxycodone. While they are effective at blocking pain signals between the brain and the body, they also have a range of side effects, including muscle spasms.
Spasticity has been reported in patients receiving intraspinal opioids. Intraspinal opioid administration is used to treat cancer pain that is refractory to systemic opioids, non-opioid analgesics, and other nonpharmacologic pain treatments. IT administration is preferred over the epidural route as the drug doses required via epidural are approximately ten times higher and increase systemic side effects. When spinal opioids are administered for postoperative pain, a decision is required to perform the spinal before or after surgery. Performing the spinal before surgery helps mitigate the stress response and lower the doses of anesthetics and analgesics required during the operation. However, performing the spinal after surgery would prolong the length of postoperative analgesia.
In a case study, a patient developed reversible spastic paraparesis with prominent extensor spasms in the legs while receiving an infusion of intravenous methadone at 100 mg/hr. The patient exhibited marked spastic tone in both legs and weakness in the iliopsoas and tibialis anterior bilaterally. The patient experienced intermittent extensor spasms in both legs and was unable to rise from a chair without support. Another case study describes a patient who developed transient muscular spasm after a large dose of intrathecal sufentanil.
Muscle spasms can also occur during opioid withdrawal. In a study by Dais, Khosia, and Doulatram (2015), opioid withdrawal-induced refractory muscle spasms were successfully treated with an over-the-counter supplement that is not typically used for the attenuation of opioid withdrawal symptoms. The patient was intolerant to the side effects of clonidine, so the serotonin precursor 5-hydroxytryptophan (5-HTP) was used to successfully wean them off chronic opiates.
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Frequently asked questions
Opioid therapy may cause myoclonus, which is defined as sudden, brief, involuntary muscle jerks that can be irregular or rhythmic. Higher doses more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur with all routes of administration.
Co-morbid factors for neurotoxicity, which is linked to myoclonus, include renal failure, electrolyte disturbances, and dehydration.
In one case, a patient was successfully weaned off opioids by treating refractory muscle spasms with the serotonin precursor, 5-hydroxytryptophan (5-HTP).
