Respiratory depression is a serious and debilitating disease. It may affect the patient’s ability to breathe. Fortunately, there are ways to treat this disorder. One such method is opioid therapy. Opioids like morphine, levorphanol, and naloxone have been used to treat respiratory depression.
Impact of opioids on respiratory depression
Respiratory depression can be a lethal side effect of opioids, a class of drugs that have become a mainstay of pain management. Opioids bind to the respiratory network in the brainstem and induce a profound sedative state. This sedation leads to distinct changes in the electrocortical activity. These changes are, correlated with the magnitude of respiratory depression.
The respiratory depression, caused by opioids is, measured as changes in breathing frequency and oxygen saturation. In the outpatient setting without underlying pulmonary disease, this phenomenon is rare, but it is more common in the perioperative setting. Respiratory depression is, caused by the decreased respiratory drive mediated by opioids, which shift the ventilation-arterial carbon dioxide partial pressure response curve. Patients with respiratory depression are more sensitive to the respiratory depressant effects of opioids. Although respiratory depression is, easily reversed with naloxone, it is often a precursor to opioid withdrawal in opioid-dependent patients.
The respiratory control system is critical to the human body. Opioid analgesics are highly potent, and they depress respiratory rate and ventilation by acting on the m-opioid receptor expressed in respiratory neurons in the brainstem. This sedative effect is potentially life-threatening and is, associated with substantial morbidity. Fortunately, respiratory stimulants are available to counteract this effect. By activating non-opioid pathways in the respiratory system, they promote breathing and offset opioid-induced respiratory depression.
Effects of naloxone on respiratory depression
In a recent study, researchers showed that naloxone reversed the effects of opioids on respiratory depression. In this study, 16 healthy volunteers were, given intravenous morphine at a dose of 0.15 mg/kg. This opioid reuptake is, known to be the cause of respiratory depression.
In this study, naloxone reversed respiratory depression and improved opioid analgesic efficacy. However, 5HT selective agonists did not reverse respiratory depression in humans. This was likely because they were not able to reach sufficient concentrations at the receptor site and did not exhibit sufficient receptor selectivity. In contrast, ampakines, which act on AMPA receptors, increased respiratory drive and reversed alfentanil-induced respiratory depression.
In addition to naloxone’s effects on respiratory depression, studies show that multiple sequential naloxone doses can improve clinical reversal.One study shows, Faul et al. evaluated emergency medical providers from 2012 to 2015 and found a significant increase in the number of multiple sequential naloxone treatments in 2015. They concluded that these increases were likely related to the rise in the prevalence of higher potency opioids. Another study, Klebacher et al., investigated the frequency of redosing naloxone in the New Jersey Emergency Medical System.
Although multiple naloxone administrations have been increasing, some concerns still remain. One concern is that naloxone may not reverse opioids that have high mu-opioid receptor affinity and slow kinetics. Another concern is that naloxone can lead to renarcotisation, which is the return of respiratory depression. In addition, high-dose naloxone may cause opioid withdrawal and loss of analgesia.
Effects of morphine on respiratory depression
To determine the effects of morphine on respiratory depression, a randomized controlled trial was, conducted in mice. Specifically, the study examined whether morphine could avert respiratory arrest and thereby prolong survival time. The mice were, housed in chambers with a piezoelectric grid and were, given food and water daily. During the experiment, their breath rates were, recorded from four-s intervals during low activity and averaged over a period of 24 min. To determine the recovery time, a respiratory rate baseline was, determined over the first 24 h of treatment with morphine.
The opioid respiratory effect is quantified by determining changes in respiratory rate and oxygen saturation. The threshold for respiratory depression is Spo 2 90% or lower, with a moderate hypoxemia defined as less than 85%. However, the definition of respiratory depression is subjective. Some experts consider breathing rates lower than eight to 10 breaths/minute to be severe.
Respiratory depression is an undesirable effect of morphine, especially in PCA-based opioid delivery devices. However, this effect is rare. Studies conducted on postoperative patients using PCA devices have shown that morphine-induced respiratory depression is uncommon (0.2 to 0.5%). A recent study involving more than 1,600 patients in the United Kingdom found that only 8 patients suffered from respiratory depression and four required intravenous naloxone.
Effects of levorphanol on respiratory depression
Levorphanol is an orally available opiate that is used to treat respiratory depression. The duration of its action and half-life are longer than those of other opioids, which makes it a long-acting opioid. However, there are some concerns related to its pharmacology.
The main side effects of levorphanol include respiratory depression and increased risk of cardiovascular and respiratory complications. The drug should be administered with caution in patients with impaired respiratory reserve, or respiratory depression caused by other conditions. In addition, patients with obstructive respiratory conditions, severe infections, or chronic bronchial asthma should not take levorphanol.
Further research is, needed to determine whether levorphanol is a useful treatment option for cancer pain and palliative care. However, the long terminal half-life and low toxicity suggest that it is a suitable choice for this use. The drug may also help reduce the use of postoperative analgesics.
While levorphanol has respiratory depressant properties, it can also cause an increase in cerebral spinal fluid pressure. These effects can complicate the neurological evaluation and complicate its use in cardiac and myocardial infarction patients.
Effects of pentazocine on respiratory depression
Pentazocine is an opioid antagonist that inhibits the activity of mu-opiate receptors. As a result, it reduces respiratory depression and is less likely to cause severe adverse effects than morphine. However, it may cause gastrointestinal effects, including vomiting, diarrhea, and abdominal pain. It can also cause circulatory depression and syncope, and may lead to hypertension. Pentazocine is, also associated with increased systemic arterial pressure and vascular resistance in patients with acute myocardial infarction.
Effects of pentazocine on respiratory disorders should be closely monitored. This drug can increase blood pressure and cardiac workload and should be used with caution in patients with heart failure, renal failure, or severe hepatitis. In addition, smoking tobacco may increase the drug’s bioavailability, reducing its clinical efficacy. If possible, patients should avoid smoking. Pentazocine can also increase the rate of urinary excretion in some patients.
The drug is, well absorbed from the gastrointestinal tract, with peak concentrations occurring between 0.5 and four hours after oral administration. It is, then metabolized in the liver and excreted in urine. The drug is, eliminated from the body within 24 hours. Pentazocine can be fatal if administered to an infant.
Effects of fentanyl on respiratory depression
This study investigated the effects of fentanyl on respiratory depression. In the study, participants were, given different doses of the opioid. The highest doses reduced locomotor activity. However, lower doses enhanced locomotor activity. This means that fentanyl can lead to respiratory depression even in healthy individuals.
There are several mechanisms that influence respiratory depression after opioids are, administered to healthy adults. One mechanism involves opioid-induced changes in the reticular formation, which modulates nociceptive pathways and induces opioid analgesia. This region comprises the periaqueductal gray and rostral ventromedial medulla. These structures regulate pain and express m-opioid receptors. However, fentanyl inhibits these neurons, thereby contributing to respiratory depression.
The drug also induces a sedative state. Its effect was similar to that of ketamine, but fentanyl-induced sedation was less fragmented than that of ketamine. It also induced fewer arousals than in the control group.
In humans, sedation is, assessed with the help of medical scoring systems and responsiveness to external stimuli. Objective measurements of sedation could be more reliable, but they are difficult to interpret and are not widely used in clinical studies. For example, it is possible to assess sedation in rats by assessing loss of the righting reflex. This method, however, requires manipulating the animals. It is not possible to use this method in free-behaving rodents. Hence, researchers employed a combination of electrocortical recordings and behavioural assessments to determine the sedative effect of fentanyl.
Effects of fentanyl on respiratory depression in larval zebrafish
A recent study has found that fentanyl, a commonly used opioid analgesic, reduced respiratory rate in larval zebrafish. This effect was observed at a concentration of 1 uM, whereas the control group showed no change in respiratory rate. The researchers conclude that fentanyl decreases lower jaw movement, which is a key determinant of respiratory rate in zebrafish.
The findings of this study show that fentanyl reduces the respiratory mandible movement rate and induces analgesia in larval zebrafish, and that this effect is reversed in these animals by treatment with mu-opioid receptor antagonists. These results suggest that zebrafish represent evolutionary conserved mechanisms of opioid drug action, and make them suitable models for phenotypic-based drug discovery.
The findings of this study also point to the importance of using zebrafish larvae as a model animal for pharmacotoxicology. Unlike mice, zebrafish larvae are useful for studying respiratory depression in humans. They provide an excellent source of behavioural and metabolic information.
Respiratory rate and mandible movements were, measured in larvae at 12-14 days post-fertilization using a 4K high-definition camera. The data was, then normalized according to mandible rates to reduce the high variability among larvae. As larvae differ greatly in their development rates and access to food and other nutrients, they may also present differing behaviors. To avoid this problem, larvae were chosen at similar stages of development.
