Opiates adverse effects

Geriatric Considerations - Summary Diphenoxylate is an analog of meperidine and can cause opiate adverse effects. When discontinued, physical dependence and withdrawal symptoms can occur. Adverse GI effects such as constipation, nausea/vomit-ing, and abdominal pain may result from normal doses. Afropine is added to discourage abuse but can cause anticholinergic adverse effects in the older adult. The benefits of f his drug combination for older adulfs are limifed by fhe risk of adverse effects. 

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. 

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... 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

Codeine, which is an opium alkaloid is most commonly opiate used as antitussive and more selective for cough centre. Like morphine, it depresses cough centre but is less constipating and abuse liability is low. It is relatively safe drug used in cough along with analgesic property and it s only important adverse effect is constipation. 

In Table 1.3 I have included the areas of physical and psychological health, which often do not feature in reviews. Methadone has significant adverse effects, as discussed below, and by no means do all patients report subjective improvements in health on the drug, as opposed to when taking street heroin or other opiates. However, if methadone treatment is adhered to, there is normalization of various circadian rhythms and endocrine effects... 

In the course of clinical treatment with methadone, certain situations relating to adverse effects are characteristic. Nausea is a general opiate effect, but complaints most frequently relate to the methadone mixture. This preparation does have a syrupy consistency, but the problem for clinicians is that the alternatives - sugar-free mixture or methadone tablets - are both more injectable, and therefore requests or implied requirements for these are often manipulative. So are requests for the antiemetic cyclizine tablets, which are crushed and injected by drug misusers along with injected methadone. As indicated in Chapter 4, thankfully these particular claims have become less common now that guidelines are much more discouraging of any use of methadone tablets. 

As indicated, buprenorphine can offer a quicker option than methadone, with a three-day course reported to be effective for withdrawal from heroin (Cheskin et al. 1994). The side-effects of clonidine which render it unsuitable for community treatment can be manageable in the inpatient setting, although the drug is being superseded by lofexidine where that is available. Controlled studies have found clonidine and lofexidine to be equally effective in alleviating withdrawal symptoms in inpatient detoxification from heroin (Lin et al. 1997) and from methadone (Khan et al. 1997), with lofexidine resulting in less hypotension and fewer adverse effects. Another double-blind controlled study found lofexidine to be broadly as effective as a ten-day methadone detoxification in inpatient opiate withdrawal (Bearn et al. 1996). 

Analogue of clonidine with fewer adverse effects, used in opiate detoxification... 

Some of the commonly used antitussives are listed in Table 26-1. As shown in the table, codeine and similar opiate derivatives suppress the cough reflex by a central inhibitory effect.21,124 Other nonopioid antitussives work by inhibiting the irritant effects of histamine on the respiratory mucosa or by a local anesthetic action on the respiratory epithelium. The primary adverse effect associated with most antitussives is sedation. Dizziness and gastrointestinal upset may also occur. 

Adverse effects Methadone can produce dependence like that of morphine. The withdrawal syndrome is much milder but is more protracted (days to weeks) than with opiates. 

An analysis of the balance of benefit to harm during methadone maintenance treatment for diamorphine dependence has shown lower mortality and morbidity with improvement in quality of life (7). The risks of methadone treatment include an increased risk of opiate overdosage during induction into treatment, and adverse effects of methadone in some patients. However, with careful management the benefits of prescribing methadone outweigh the risks. 

Buprenorphine has been suggested to be useful for the treatment of cocaine and opiate dependence. In a study designed to assess its safety for this purpose (SEDA-18, 85) there were no adverse effects or serious interactions with a single dose of intravenous morphine or cocaine during daily maintenance on buprenorphine. 

Flupirtine is a non-opiate, centrally acting analgesic, with muscle relaxant properties. It causes predominantly nervous system adverse effects (visual, disorientation, confusion, tremor). About 26% of patients develop minor adverse reactions (1). 

Gustafsson LL, Schildt B, Jacobsen K. Adverse effects of extradural and intrathecal opiates report of a nationwide survey in Sweden. Br J Anaesth 1982 54(5) 479-86. 

Eriksen HO, Jensen FM. Bivirkninger ved anvendelse af opiater epidwalt og opinalt. [Adverse effects of epidural and spinal opiates.] Ugeskr Laeger 1982 144(36) 2627-30. 

In seven patients (median age 7 years), limb and jaw muscle pain, starting at days 3-5 of an intravenous infusion of vincristine and requiring opiate analgesia, was the most pronounced adverse effect (68). 

Due to hydromorphone s potency, numerous adverse effects have been reported. CNS depression is the most frequently reported clinical effect. The typical overdose patient may present with extreme somnolence and may progress to coma. Miosis is usually present unless the individual is acidotic or has suffered hypoxic brain injury. Respiratory depression can occur and may progress to respiratory arrest. Pulmonary edema may be seen. Bradycardia, hypotension, and hyperthermia can develop. Available opiate immunoassays cross-react unreliably with hydromorphone. 

It has been reported that the serious adverse effects of opiate analgesia such as depression of breathing are caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. Serotonin 4(a) or 5-HT4(a) receptors are strongly expressed in these neurons and their selective activation protects spontaneous respiratory activity. Rats treated with a 5-HT4 receptor specific agonist overcame the fentanyl-induced respiratory depression, and reestablished stable respiratory rhythm without loss of fentanyl s analgesic effect. 

FIG. 5. The number of errors on an inclined plane response flexibility problem (Thompson et al 1990) is shown for the same groups of animals as seen in Fig. 4. Saline-treated controls made the fewest errors. Animals exposed to the neurotoxin MAM were slower to abandon a previously learned solution to try new routes to food. However, animals treated postnatally with naltrexone, an opiate receptor antagonist reported to induce dendritic arborization and spine formation, showed performance similar to controls. Decreases in neuron number, such as seen with MAM exposure prenatally, have adverse effects on tests of rat intelligence. Treatments that induce dendritic arborization and synapse formation can ameliorate these deficits. The ability to modify brain structure permits direct testing of the causal role of variation in brain structure and behavioural performance. 

Buprenorphine increases intracholedochal pressure to a similar degree as the other opiates. The adverse effects of buprenorphine are sedation, dizziness, vertigo, hypotension, hypoventilation, and miosis. Although naloxone is able to reverse several of the adverse effects of buprenorphine, it may not be as effective in reversing the respiratory depression requiring mechanical assistance of respiration. 

What adverse effects of opiates are seen on the cardiovascular system ... 

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