McKenna's Pharmacology for Nursing, 2e

C H A P T E R 2 6 Opioids, opioid antagonists and antimigraine agents 405

• Keep this drug and all medications out of the reach of children. • Do not take any leftover medication for other disorders and do not let anyone else take your medication.

• Take this drug exactly as prescribed. Regular medical follow-up is necessary to evaluate the effects of this drug on your body.

Pharmacokinetics Intravenous (IV) administration is the most reliable way to achieve therapeutic levels of opioids. Intramus- cular (IM) and subcutaneous (SC) administration offer varying rates of absorption, and absorption is slower in females than in males because of the normal fat content of female muscles and tissue. These drugs undergo hepatic metabolism and are generally excreted in the urine and bile. Half-life periods vary widely, depending on the drug being used. These agents cross the placenta and are known to enter breast milk. Contraindications and cautions The opioid agonists are contraindicated in the follow- ing conditions: presence of any known allergy to any opioid agonist to avoid hypersensitivity reactions ; diar- rhoea caused by toxic poisons because depression of GI activity could lead to increased absorption and toxicity ; and after biliary surgery or surgical anastomoses because of the adverse effects associated with slowed GI activity due to opioids. Oxycodone is classified as pregnancy category B, whereas all of the other opioids agonists are in category C, so it might be the drug of choice if one is needed during pregnancy. Extended-release oxycodone ( OxyContin ) has been associated with abuse because when the tablet is cut, crushed or chewed, the entire dose of the drug is released at once. Pregnant women must be cautioned not to cut, crush or chew these tablets if they are prescribed this drug. Many sources recom- mend waiting 4 to 6 hours after receiving an opioid before breastfeeding the baby if an opioid is needed for pain control. Caution should be used in people with respira- tory dysfunction, which could be exacerbated by the respiratory depression caused by these drugs ; recent GI or genitourinary (GU) surgery, acute abdomen or ulcerative colitis, which could become worse with the depressive effects of the opioids ; head injuries, alco- holism, delirium tremens or cerebral vascular disease, which could be exacerbated by the CNS effects of the drugs ; liver or renal dysfunction, which could alter the metabolism and excretion of the drugs ; and during pregnancy, labour or breastfeeding because of potential adverse effects on the fetus or neonate, including res- piratory depression.

Adverse effects The most frequently seen adverse effects associated with opioid agonists relate to their effects on various opioid receptors. Respiratory depression with apnoea, cardiac arrest and shock may result from opioid-induced res- piratory centre depression. Orthostatic hypotension is commonly seen with some opioids. Gastrointesti- nal effects such as nausea, vomiting, constipation and biliary spasm may occur as a result of CTZ stimulation and negative effects on GI motility. Box 26.3 discusses a drug approved to treat opioid-induced constipation. Neurological effects such as light-headedness, dizziness, psychoses, anxiety, fear, hallucinations, pupil constric- tion and impaired mental processes may occur as a result of the stimulation of CNS opioid receptors in the cerebrum, limbic system and hypothalamus. GU effects, including ureteral spasm, urinary retention, hesitancy and loss of libido, may be related to direct receptor stim- ulation or to CNS activation of sympathetic pathways. In addition, sweating and dependence (both physical and psychological) are possible, more so with some agents than with others. One of the most uncomfortable side effects of opioid use is constipation. Frequently, when ordering a opioid for pain, a prescriber will also order a laxative to avert serious constipation discomfort. When a person is on long-term opioids for controlling pain in cases of cancer or in hospice settings where palliative care uses opioids to make people comfortable, constipation can be a real problem. In 2008, methylnaltrexone bromide ( Relistor ) was approved for the treatment of opioid-induced constipation in people who are receiving palliative care and who no longer respond to traditional laxatives. Relistor is a peripherally acting, mu-specific opioid antagonist. It blocks the mu-receptors responsible for constipation related to opioid use. Relistor is given by subcutaneous injection once each day. It is rapidly absorbed from the tissues, reaching peak levels in 30 minutes. It is excreted primarily unchanged in the urine with a half-life of 8 hours. The adverse effects associated with the drug are related to the increase in GI activity that occurs—diarrhoea, abdominal pain, flatulence and nausea. ■■ BOX 26.3  Laxative for dealing with opioid-induced constipation