466% increase in opioid prescribing
In England, the growing use of buprenorphine, oxycodone hydrochloride, and morphine sulphate increased annual costs for these three drugs by more than £10 million (US$12.98 million) between 2002 and 2013. Also, dispensing data reported by the UK National Health and Social Care Information Center show a 466% increase in opioid prescribing between 2000 and 2010.
However, in cancer patients, opioid prescribing has not increased as dramatically and represents only 16.1% of all opioid prescriptions issued in the United Kingdom, the authors say.
Reviewing a centralized UK prescriptions database, the authors extracted all prescriptions for analgesics issued to each patient in the cohort during the 12 months before death.
43.3% for strong opioids
The team also analyzed the extent and duration of strong-opioid treatment with respect to clinical and patient characteristics.
Strong-opioid prescribing was not influenced by cancer type, duration of illness, or sex but was adversely influenced by older age, they report.
Compared with patients who died in a hospice, those who died in a hospital were 60% less likely to receive a strong opioid in primary care before admission (relative risk ratio, 0.4; 95% confidence interval, 0.3 – 0.5; P < .01).
60 weeks survival
“Median survival for our sample from diagnosis was 60 weeks, suggesting that most opioid prescribing in fact occurred late in the trajectory between diagnosis and death, regardless of cancer duration,” summarized coauthor Mike Bennett, St. Gemma’s Professor of Palliative Medicine, University of Leeds, in a press statement.
Dr Ziegler also pointed out that more than 90% of all patients in the cohort had received some form of cancer treatment. “Therefore, it was not the absence of a cancer diagnosis or poor engagement with cancer services that hindered timely access to an opioid,” she said.
Number of deaths from opioid overdoses now exceeds the number of deaths caused by motor vehicle accidents
Nationally, the annual number of deaths from opioid overdoses now exceeds the number of deaths caused by motor vehicle accidents,” write Dr Califf and coauthors Janet Woodcock, MD, and Stephen Ostroff, MD, also from the FDA. “Regardless of whether we view these issues from the perspective of patients, physicians, or regulators, the status quo is clearly not acceptable. As the public health agency responsible for over-sight of pharmaceutical safety and effectiveness, we recognize that this crisis demands solutions. We are committed to action, and we urge others to join us.”
Activation of opioid receptors results in inhibition of synaptic neurotransmission in the central nervous system (CNS) and peripheral nervous system (PNS). Opioids bind to and enhance neurotransmission at three major classes of opioid receptors. It is also recognized that several poorly defined classes of opioid receptors exist with relatively minor effects.
The physiological effects of opioids are mediated principally through mu and kappa receptors in the CNS and periphery. Mu receptor effects include analgesia, euphoria, respiratory depression, and miosis. Kappa receptor effects include analgesia, miosis, respiratory depression, and sedation.
Two other opiate receptors that mediate the effects of certain opiates include sigma and delta sites. Sigma receptors mediate dysphoria, hallucinations, and psychosis; delta receptor agonism results in euphoria, analgesia, and seizures. The opiate antagonists (eg, naloxone, nalmefene, naltrexone) antagonize the effects at all four opiate receptors.
Common classifications divide the opioids into agonist, partial agonist, or agonist-antagonist agents and natural, semisynthetic, or synthetic. Opioids decrease the perception of pain, rather than eliminate or reduce the painful stimulus. Inducing slight euphoria, opioid agonists reduce the sensitivity to exogenous stimuli. The GI tract and the respiratory mucosa provide easy absorption for most opioids.
Peak effects generally are reached in 10 minutes with the intravenous route, 10-15 minutes after nasal insufflation (eg, butorphanol, heroin), 30-45 minutes with the intramuscular route, 90 minutes with the oral route, and 2-4 hours after dermal application (ie, fentanyl). Following therapeutic doses, most absorption occurs in the small intestine. Toxic doses may have delayed absorption because of delayed gastric emptying and slowed gut motility.
Most opioids are metabolized by hepatic conjugation to inactive compounds that are excreted readily in the urine. Certain opioids (eg, fentanyl, buprenorphine) are more lipid soluble and can be stored in the fatty tissues of the body. All opioids have a prolonged duration of action in patients with liver disease (eg, cirrhosis) because of impaired hepatic metabolism. This may lead to drug accumulation and opioid toxicity. Opiate metabolites are excreted in the urine. Impaired renal function can lead to toxic effects from accumulated drug or active metabolites (eg, normeperidine).
Long-acting opioids also may increase mortality from cardiorespiratory and other causes. In a retrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care, prescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, hazard ratios were 1.64 for total mortality, 1.65 for cardiovascular deaths, and 4.16 during the first 30 days of therapy.
Connie’s comments: Sublingual morphine is given to hospice seniors, who have less than few months to live. In the caregiving business, I saw how a droplet of this opioids behave similar to mercury. It arrests the muscles in the body.