Opioid respiratory effects

The large numbers of opioid receptors in areas of the brainstem such as the solitary tract and adjacent areas are probably related to respiratory effects of opiates, cough suppression and nausea and vomiting. Opiates acting in the brainstem reduce the sensitivity of the respiratory centres to pC02 and this is the most common cause of death from overdose with street use of opiates. 

Tramadol is an opioid analgesic, which acts by exerting an opioid effect and through the stimulation of adrenergic and serotonin pathways. Compared with the other opioids, tramadol is less likely to cause the typical opioid side-effects, such as respiratory depression, and constipation. It is also less likely to cause addiction. 

Reversal of opioid effects Complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Opioid overdose Management of known or suspected opioid overdose. 

Administration Nalbuphine should be given as a supplement to general anesthesia only by persons specifically trained in the use of IV anesthetics and management of the respiratory effects of potent opioids. 

Mechanism of Action A narcotic antagonist that binds to opioid receptors. Therapeutic Effect Prevents and reverses effects of opioids (respiratory depression, sedation, hypotension). 

Side-effects Typical side-effects of tramadol are nausea, sweating and dizziness. In rare cases seizures after high i.v. doses are reported, mostly in combination with other proconvulsant componds or in patients with reduced seizure theshold (Gardner et al., 2000). Tramadol shows a reduced level of opioid side-effects, especially respiratory depression and constipation are less frequent and severe than with standard opioids such as morphine. Tramadol has a very limited abuse potential and is not subject to narcotic control (Cossmann et al., 1997). 

Gerak LR, Butelman ER, Woods JH, France CP (1994) Antinociceptive and respiratory effects of nalbuphine in rhesus monkeys. J Pharmacol Exp Ther 271 993-999 Howell LL, Bergman J, Morse WH (1988) Effects of levor-phanol and several kappa-selective opioids on respiration and behavior in rhesus monkeys. J Pharmacol Exp Ther 245 364-372... 

Liguori A, Morse WH, Bergman J (1996) Respiratory effects of opioid full and partial agonists in rhesus monkeys. J Pharmacol Exp Ther 277 462-472... 

Opioid toxidrome effects include miosis, respiratory depression, and CNS depression. More serious... 

The efflux transporter P-gp is a major determinant of the pharmacokinetics and pharmacodynamics of loperamide, a potent opiate. The main reason that loperamide does not produce opioid CNS effects at usual doses in patients is a combination of slow dissolution, first-pass metabolism, and P-gp-mediated efflux, which prevents brain absorption, perhaps contributing to its low addiction potential. Loperamide produced no respiratory depression when administered alone, but when administered with a P-gp inhibitor, respiratory depression occurred, which could not be explained by increased plasma loperamide concentrations. This effect demonstrates the potential for important drug interactions by inhibition of P-gp efflux transporter. The lack of respiratory depression produced by loperamide, which allows it to be safely used therapeutically, can be reversed by a drug causing P-gp inhibition, resulting in serious toxic and abuse potential. 

NSAIDs are frequently used with opioids because of their lack of respiratory depression and opioid-sparing effects. However, this study demonstrates that there may be a risk of respiratory depression and other adverse effects due to persistently high levels of morphine-6-glucuronide for a number of hours after receiving an NSAID. During this time period, patients should be more closely monitored. ... 

The most common adverse events seen with fentanyl buccal tablets and fentanyl lozenges are typical of opioid side effects. The most serious adverse reactions with all opiods include respiratory depression, circulatory depression, hypotension, and shock. Other common opioid side effects include nausea, vomiting, fatigue, dizziness, drowsiness, constipation, and headache. Dental caries has been reported with the use of fentanyl oralet. A minor adverse event with fentanyl buccal tablets is mouth ulcer. 

Butorphanol has antagonistic activity at p opioid receptors. It is an agonist at K opioid receptors, effecting visceral and spinal analgesia. With this set of differential effects, it can provide pain relief, while blocking p-mediated respiratory depression. 

As an NSAID, diclofenac is easy to use, and has been shown to be efficacious in arthritic syndromes, as well as for acute treatment of migraines, and small procedures. A major advantage of diclofenac, as with other NSAIDs, is its use in multimodal analgesia. In patients who are post-operative or with certain chronic pain syndromes, diclofenac can be used to provide additive analgesia and an opioid-sparing effect. Diclofenac has decreased side effects when compared to opioids in terms of nausea, respiratory depression, sedation, and constipation. 

As adjuvant therapy clinically significant opioid-sparing effect. It may be useful in elderly debilitated patients in whom respiratory and CNS depression due to narcotic overdose needs to be avoided. 

Use caution in opioid-naive patients (monitor for central nervous system and respiratory effects)... 

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