Oxycodone respiratory depression

Oxycodone CR tablets are not intended for use as an as-needed analgesic. Oxycodone 80 and 160 mg CR tablets are for use in opioid-tolerant patients only. These tablet strengths may cause fatal respiratory depression when administered to patients not previously exposed to opioids. 

Codeine, one of the principal alkaloids of opium, has an analgesic efficacy much lower than other opioids, due to an extremely low affinity for opioid receptors. It is approximately one-sixth as potent as morphine. It has a low abuse potential. In contrast to other opioids, with the exception of oxycodone, codeine is relatively more effective when administered orally than parenterally. This is due to methylation at the C3 site on the phenyl ring (Figure 7.3), which may protect it from conjugating enzymes. It is used in the management of mild-to-moderate pain, often in combination with non-opioid analgesics, such as aspirin or paracetamol. It is valuable as an antitussive and for the treatment of diarrhoea. Side effects are uncommon and respiratory depression, even with large doses, is seldom a problem. 

Side-effects Oxycodone has a morphine-like side-effect profile. Respiratory depression has been found in children. The compound has a relevant abuse and dependence potential and illicit use of the retarded preparations has been reported. 

Postmortem findings suggested severe nervous system and respiratory depression produced by high concentrations of clonazepam and oxycodone, including collapsed lungs, aspirated mucus, and heart failure. 

IMATINIB ANALGESICS-OPIOIDS May cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol Inhibition of CYP2D6-mediated metabolism of these opioids Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise or anorexia. Measure amylase and lipase levels if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts, and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider 1 dose. Methadone may cause Q-T prolongation the CHM has recommended that patients with heart and liver disease who are on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG as they may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily and thus an t in plasma concentrations necessitates close monitoring of cardiac and respiratory function... 

OPIOIDS ANTICANCER AND IMMUNOMODULATING DRUGS - CYTOTOXICS 1. Imatinib may cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol 2. Unpredictable reactions may occur associated with hypotension and respiratory depression when procarbazine is co-administered with alfentanil, fentanyl, sufentanil or morphine... 

E Oxycodone/acetaminophen would be the most appropriate drug to start for this patient s acute postsurgical pain. The onset of action is rapid, and it can be titrated to effect. Morphine and meperidine have active metabolites that can accumulate in this patient with renal dysfunction, increasing the risk for seizures, sedation, and respiratory depression. The fentanyl patch is primarily indicated in chronic pain. The onset is slow, and the patches cannot be titrated up rapidly to cover acute pain, nor titrated down as the patient recovers and requires less opioid. 

CODEINE In contrast to morphine, codeine is -60% as effective orally as parenteraUy as an analgesic and as a respiratory depressant. Codeine analogs such as levorphanol, oxycodone, and methadone have a high ratio of oral-to-parenteral potency. The greater oral efficacy of these drugs reflects lower first-pass metabolism. Once absorbed, codeine is metaboUzed by the liver, and its metabolites are excreted chiefly as inactive forms in the urine. A relatively small fraction (-10%) of administered codeine is O-demethylated to morphine, and free and conjugated morphine can be found in the urine after therapeutic doses of codeine. Codeine has an exceptionally low affinity for opioid receptors, and the analgesic effect of codeine is due to its conversion to morphine. However, its antitussive actions may involve distinct receptors that bind codeine itself. The tj of codeine in plasma is 2-4 hours. 

Dexamfetamine increased the analgesic effect of morphine and reduced its respiratory depressant effects to some extent in studies during postoperative analgesia and in healthy subjects. Methylphenidate 15 mg daily similarly increased the analgesic effects of various opioids (morphine, hydromorphone, ievorphanol, oxycodone) and reduced the sedative effects in patients with chronic pain due to advanced cancer. Therefore, the analgesic dose of an opioid may be lower than expected in patients on these drugs. 

NSAIDs are often administered with opioids because they usually reduce the opioid requirements and some of the opioid-induced Averse effects. Enhanced pain relief has been reported with various combinations including dextromethorphan with ketorolac or tenoxicam, oxycodone with ibuprofen, and tramadol with ketorolac without increased adverse effects. See also coxibs , (p.l79). However, cases of respiratory depression have been reported, see Morphine below. Myoclonus has been reported with high does of morphine administered with NSAIDs, see C3pioids Morphine + Miscellaneous , p.l90. 

Drug overdose Severe leukoencephalopa-thy occurred in a 46-year-old man after an overdose of oxycodone (35 x 10 mg tablets) and oxycontin (5 x 80 mg capsules) [154" ]. He developed respiratory depression, and brain imaging showed a non-vascular distribution of diffusion positive lesions in both cerebellar hemispheres and globi pallidi, with preserved cerebral perfusion. 

Oxycodone should be used with caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses may decrease respiratory drive to the point of apnea. 

Absolute contraindications for both opioids and NSAIDS include hypersensitivity reactions, such as development of shortness of breath, severe rash, etc. Oxycodone and hydrocodone are contraindicated in patients with risk for significant respiratory depression. Because of the inhibition of GI motility by narcotic medications, oxycodone and hydrocodone are contraindicated in the setting of paralytic ileus. 

Comparative studies In 14 patients using controlled-release oxycodone for postoperative pain and nine using patient-controlled morphine, there was a lower incidence of postoperative nausea and vomiting with oxycodone (14% versus 20%) [135 ]. There was no somnolence, respiratory depression, confusion, or pruritus in either group. 

Breast-Feeding A case report of a 4-day-old infant who presented witix respiratory depression and pinpoint pupils after breast-feeding from the mother who had used oxycodone prior to Caesarean section highlights the risk of transmission of oxycodone through breast milk [65 ]. 

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