Opioids adverse effects

Yuan CS. (2007) Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects. Ann Pharmacother 41 984-993. 

Efficacy and clinical use Naltrexone (Crabtree, 1984 Gonzalez and Brogden, 1988) is a pure opioid antagonist and has no analgesic activity. It is used for the treatment of opioid adverse effects, for opioid detoxification and as maintenance treatment for former addicts to avoid a relapse. In chronic opioid users, naltrexone may precipitate an acute withdrawal reaction. 

In a prospective, open, uncontrolled study 50 patients with a history of cancer taking daily oral morphine (90-800 mg) but with uncontrolled pain with or without severe opioid adverse effects were switched to oral 8-hourly methadone in a dose ratio of 1 4 for patients receiving less than 90 mg of morphine daily, 1 8 for patients receiving 90-300 mg daily, and 1 12 for patients receiving more than 300 mg daily (5). Methadone was effective in 80% of the patients when comparing analgesic... 

Butorphanol is a synthetic 14-hydroxymorphinan analogue with a low dependence potential and a low propensity to cause opioid adverse effects (1). It is a synthetic OP2 (k) receptor agonist and OP3 ( ) receptor antagonist. 

Data on the incidence of adverse effects after usual doses of oral ciramadol are conflicting. In one study there was a low incidence of mild adverse effects (1), but in another, in which ciramadol 60 mg was more effective than codeine 60 mg or placebo, there was a high incidence of opioid adverse effects (2) some other workers have had the same experience. 

Fentanyl citrate is a sjmthetic opioid 1000 times more potent than pethidine. It has a relatively short duration of action, and its effects are rapidly reversed by opioid antagonists (1). It is useful (2) but has typical opioid adverse effects. 

The analgesic effect of fentanyl 1.5 pg/kg has been compared with that of tramadol 1.5 mg/kg in 61 patients receiving standardized anesthetics for day-case arthroscopic knee surgery (3). Opioid adverse effects and analgesia were similar in the two groups. 

Transdermal fentanyl has an adverse effects profile similar to that associated with parenteral administration (SEDA-20, 77). Local erythema and rash have been reported (43), as well as the usual opioid adverse effects. However, an unusual reaction, with progressive agitation to acute delirium, has occurred (SEDA-20, 79). 

The strategies used in managing the adverse effects of oral morphine have been reassessed in another special article compiled by the Expert Working Group of the European Association of Palliative Care Network (5). Factors that predict opioid adverse effects include ... 

Four different approaches to the management of opioid adverse effects were described in the review ... 

Patient-controlled analgesia with epidural pethidine or a single bolus of epidural morphine 4 mg during the 24 hours after cesarean section has been studied in 78 women (91). There were no differences in the degree of analgesia or opioid adverse effects profiles. 

The role of tramadol in the treatment of rheumatologi-cal pain has been reviewed (33). Tramadol causes fewer opioid adverse effects for a given level of analgesia compared with traditional opioids. Common adverse effects, such as nausea and dizziness, usually occur only at the beginning of therapy, abate with time, and are further minimized by up-titrating the dosage over several days (34). 

The use of modified-release tramadol in chronic malignant pain has been examined in an open, prospective study in 146 patients with moderate to severe cancer pain 90 patients completed the 6-week trial (53). Dropouts were due to opioid adverse effects (20%), inadequate pain relief (9%), or both (2.5%). There was at least one adverse effect in 86%. Overall, 433 adverse effect events were reported but some reduced in frequency over the 6 weeks. Modified-release tramadol (400 mg/day) provided fast and efficient pain relief in almost 60% of patients both during initial dosing and long-term treatment. 

Ritonavir increases the piasma levels of loperamide. Tipranavir, aione and combined with ritonavir, reduces the bioavailability and piasma ieveis of ioperamide and its metabolites. No central opioid adverse effects are seen when loperamide is given with ritonavir aione, tipranavir aione, or tipranavir/ritonavir. 

Drug-drug iuteractious Oxycodone In 11 healthy subjects telithromycin clearly reduced the 7V-demethylation of oxycodone to noroxycodone by inhibiting CYP3A4 [108 ]. Thus, telithromycin may increase the risk of opioid adverse effects in patients taking multiple doses of oxycodone for pain relief it may be appropriate to reduce the dose of oxycodone by 25-50%, followed by readjustment according to clinical response. 

The pharmacological and/or adverse effects of a drug can be reversed by co-administration of drugs which compete for the same receptor. For example, an opioid receptor antagonist naloxone is used to reverse the effects of opiates. Drugs acting at the same site with opposite effects also can affect each other, e.g. the reduction in the anticoagulant effect of warfarin by vitamin K. 

Prophylactic, continuous use of antibiotics has no effect on the frequency of exacerbations antibiotics should only be used for treating infectious exacerbations. Antitussives are contraindicated because cough has an important protective role. Opioids may be effective for dyspnea in advanced disease but may have serious adverse effects they may be used to manage symptoms in terminal patients. 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

Opioid rotation is the switch from one opioid to another to achieve a better balance between analgesia and treatment-limiting adverse effects. This practice is often used when escalating doses (greater than 1 g of morphine per day) become ineffective. In some settings opioid rotation is utilized routinely to prevent the development of analgesic tolerance.48... 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Treating adverse effects of opioids is part of pain management... 

Opioid-like adverse effects such as nausea, vomiting, dizziness, constipation, headache, and somnolence are common. 

Equianalgesic doses, dosing guidelines, histamine-releasing characteristics, major adverse effects, and pharmacokinetics of opioids are shown in Tables 54-2, 54-3, and 54-4. The equianalgesic doses are only a guide, and doses must be individualized. 

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