Opioids Update: Getting Away From The Too Poppyular Bad Press

19. April 2016

Even after years, opioids are still good at providing surprises. Side effects do not play the role which was widely feared. Nevertheless pain patients often end up slipping into long-term therapy. New active agents could solve many such problems.

Doctors and pharmacists employ opioid analgesics with older, multi-morbid patients often quite cautiously. Several studies now show that the risks are more minor than were feared. The focus here is people who are not suffering tumour-related pains. These include both acute pain and chronic non-cancer-related pain (CNTS) associated with diseases of the musculoskeletal system.

Heart-felt therapy

Doctors do not inject opioids into patients having had a heart attack merely as a remedy for pain and anxiety. By using the appropriate drugs, sympathetic nervous system activation and cardiac load are also reduced. However, older studies yielded evidence that clopidogrel, prasugrel and ticagrelor could potentially be hindered in their action. In order to provide clear facts, Etienne Puymirat of Université Paris Descartes has evaluated data from the French Myocardial Infarction Registry [Paywall]. Out of approximately 2,400 persons with ST-segment elevation myocardial infarction (STEMI), 453 had received opioids from the emergency physician. Their complication rates, as well as their one-year survival rates, did not differ from the control group which was not given the respective analgesics. Puymirat found no evidence of negative effects within the usual dosage range.

Pain and fall

Similarly positive is the evaluation of opioids with CNCP. Erin E. Krebs from Minneapolis VA Health Care System wanted to know the extent to which opioids suit use as analgesia for the elderly with pain in the back, in the hips or knees [Paywall]. She analysed data from the osteoporotic fractures in men study. 2,902 of close to 6,000 men over 65 had suffered from pain that could be attributed to diseases of the muscles or the skeleton. Doctors prescribed opioids to 309 patients as an analgesia. Within the follow-up period of more than nine years, 2,413 people reported to have had at least one fall. After correction for other factors, such as alcohol consumption, age, BMI and BMD, Erin E. Krebs came to a surprising conclusion. In the groups with and without opioids, patients suffered falls similarly often. Significant differences were, contrary to expectations, not to be seen. A few years earlier scientists, in view of a meta-analysis, warned against admininistering it [Paywall]. The current study does indeed have methodological limitations, especially with regard to the relatively small number of events. Doctors are, however, given greater scope in the prescription process.

It’s running ever so smoothly

Opioid-induced constipation leaves doctors today with fewer headaches. Depending on the dose and duration of treatment, up to 95 percent of patients suffer from the condition. It wasn’t always the case that laxatives produced the desired effect. With naloxegol there is now an oral, peripherally-acting opioid receptor antagonist available. The drug exhibits rapid first pass metabolisation and does not flood into the CNS. In one manufacturer-funded study program (KODIAC ) opioid patients already had bowel movement after 7.6 hours. Under placebo this figure was 41.1 hours.

Secure in the hand

Despite positive prevailing circumstances, there remains scepticism. This is in some part due to a Scandinavian study. Andreas Mellbye from St. Olav University Hospital, Trondheim, evaluated the prescribing and provision of opioids – a central register in Norway paved the way for this evaluation. 417,000 patients received the respective medications on the basis of having non-cancer-related pain. In almost every tenth case, this meant, according to Mellbye, long-term medication use – in other words more than 180 daily doses per year. This group has been followed by pain researchers in detail. Within six years, 47 percent were given continuous opioid treatment. More than a quarter needed the medications permanently. Dosage increases of up to 120 percent were involved here. Among all patients taking opioids permanently, almost every third person regularly needed benzodiazepines or Z substances. The proportion grew steadily.

Power forces from the body

It’s quite clear – opioids in practice still have drawbacks. James E. Zadina of the Tulane University School of Medicine, New Orleans, has now found possible ways to get out of the dilemma. He reports about a derivative of the endogenous molecule endomorphin [Paywall]. His experimental drug use in animal trials demonstrated the analgesic properties of morphine, without leading to undesired effects. When rodents received the substance, Zadina found neither respiratory depression nor impairment of their motor skills. In the next step, tests focused on its potential to be addictive. The animals by pressing a button were able to receive further doses of endomorphin. Here also, the substance fared significantly better than morphine. Whether or not the promising results are able to be reproduced in clinical trials will be seen in the coming years.

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