Anja St Clair Jones
For one young man, the aftermath of a high school shooting in the USA involved treatment with large amounts of prescribed opioids and the development of addiction, attendees at a satellite symposium heard.
Austin Eubanks was a clean-living, 17-year-old high school student who liked nothing better than going fishing with his best friend. His life changed dramatically on 20 April 1999 when his best friend was shot and killed at his side as they hid under a table in the library at Columbine High School. Austin also had gunshot wounds and after undergoing surgery to his hand and knee, he received oxycodone (together with alprazolam and methylphenidate). Although his physical pain subsided fairly quickly, he continued to experience extreme emotional pain and he found that the medication enabled him to cope with it. He recalled that he quickly learned how much to take to make himself feel better. He had no previous experience of drugs of any kind and was unaware that he was becoming addicted to the opioid.
After discharge from hospital, he entered a downward spiral of addiction involving the use of alcohol, marijuana and illicit narcotics. Over the next 12 years – and multiple failed attempts at withdrawal and rehabilitation – he eventually overcame his addiction. He now runs a substance abuse treatment centre and talks about his experience “to put a face behind the statistics”.
Hospital pharmacists in the USA trace the increase in opioid use back to the 1990s when the concept of pain as the ‘fifth vital sign’ was widely embraced, explained Dianna Gatto (Clinical Pharmacy Manager, Multicare Health Systems, University of Washington, USA). The Joint Commission (the hospital accreditation body in the USA) expected nurses to ask patients to score their pain using a visual analogue scale (VAS) and then administer analgesics accordingly. Patients’ satisfaction levels with their pain treatment were recorded (together with other aspects of their care) and the scores were linked to funding for institutions. No institution wished to get low scores, so opioids for pain relief were readily available. Now that the potential problems are better understood, post-operative pain is discussed with patients in advance and expectations are managed. For example, patients are told that “zero pain is an unrealistic expectation” but that pain can be kept to the minimum, explained Dr Gatto.
Another contributory factor to the US opioid problem was the increasing availability of black tar heroin from Mexico, said Dr Gatto. The drug is cheaper than white powder heroin and can be taken by smoking or snorting, making it attractive to some users who might not wish to inject. Furthermore, Mexican suppliers have targeted suburban and rural areas. Thus, it was possible for a respectable student, with no previous exposure to alcohol or drugs, to become addicted to opioids.
In 2015 there were just over 33,000 deaths due to opioid overdoses in the USA, according to Jeffrey Bratberg (Clinical Professor, University of Rhode Island, USA). Deaths due to opioid overdose are increasing, are usually associated with heroin or synthetic opioids such as fentanyl, and are usually unintentional. Opioid misuse is now most prevalent in 18–29-year age group. The most common sources of opioids for these people are prescribed medicines, or opioids that are given by, sold by, or stolen from, friends or relatives.
Routine prescribing of naloxone together with opioids is now recommended. Studies have shown that providing naloxone and explaining how and when to use it reduces the number of visits to hospital emergency departments for opioid overdoses (in patients prescribed opioids for chronic, non-cancer pain). “Co-prescribing of naloxone is a prudent clinical and legal decision”, emphasised Dr Bratberg.
Pharmacists should educate patients and other people about use of naloxone. Patients are sometimes reluctant to have naloxone as it has been associated with heroin use in the past, but if explained as a measure to optimise opioid safety rather than to treat overdose, it is often better accepted, said Dr Bratberg. Intranasal naloxone is readily available in the USA, unlike the UK. Studies show that it takes no more than five minutes to train someone to use naloxone nasal spray. “Pharmacists should be prepared to administer the naloxone by nasal spray or intramuscular injection”, he added.
The literature shows that less than 5% of patients treated with opioids go on to develop addictions. However, one of the strongest risk factors is opioid misuse by peers, said Kelly Matson (Clinical Professor, University of Rhode Island, USA). In turn, misuse of opioid painkillers is a strong predictor of future heroin use.
There is a widespread lack of awareness and understanding of drugs effects among young people and ‘accidental’ overdoses are commonplace. “The only effective prevention strategy appears to be life-skills training”, said Dr Matson. Interactive sessions covering topics such as safe use and disposal of opioids, signs and symptoms of misuse and withdrawal and recognising and responding to overdoses have been developed at the University of Rhode Island. These programmes also cover alternatives to drug use and how to refuse offers of drugs, she added.
Pharmacogenomics in practice
Precision medicine is about designing drugs for groups of people, based on their genetic makeup, rather than for individuals – and patients are now learning about the topic and asking for gene sequencing, Marylyn Ritchie (Director, Biomedical and Translational Informatics Institute, Geisinger Health, Philadelphia, USA) told the audience. She illustrated the value of genomic information using the example of a 57-year-old woman with acute angina who underwent cardiac catheterisation, had a stent inserted and was prescribed clopidogrel. The patient subsequently suffered nine further acute angina episodes. “It was as if she was not taking the clopidogrel at all”, said Dr Ritchie. It was then discovered she had a genetic variation in CYP2C19 that meant she could not metabolise clopidogrel to its active form. Changing her prescription to prasugrel “completely changed her life”, said Dr Ritchie.
The cost of genomic typing has fallen from about $100,000 in the early days to $1500–3000 today, but it still requires supercomputing centres to process the information. So far, 33 gene–drug pairs that significantly affect the response to drug treatment have been identified. This information is available through the Clinical Pharmacogenetics Information Consortium (CPIC) scheme that also provides treatment information, said Dr Ritchie. Prescribing software could be programmed in such a way that, if the patient’s genetic profile is known, alerts pop up when potentially risky medicines are prescribed, she suggested. At present, treatment guidelines commonly recommend first-, second- and third-line treatment but this gene-based approach would enable the best treatment for the individual to be started immediately. For example, if the variant CYP2C19 were present, ticagrelor or prasugrel should be prescribed rather than clopidogrel. “It could be seen as a safety issue if this was not done”, she said.
These developments could also be good for the pharmaceutical industry. Although it might reduce the market for blockbuster drugs, DNA-based dosing will make drugs look better because they will be effective in every case. Medicines would need to be labelled as “suitable for people with or without specific genetic variations” said Dr Ritchie. It might also prompt reappraisals of some drugs with very variable responses, or even make it possible to rescue some older drugs, she added. In conclusion, she said that “you don’t have to know everything to figure out what to do” – some parts of the pharmacogenomics story are well-understood and should be put into practice immediately.
An evaluation of a compounding robot concluded that if more than 27 products were made per day then the robot created extra pharmacy technician capacity, according to Daniel Schenkat (Clinical Manager, Central Inpatient Pharmacy, UNC Healthcare, Chapel Hill, North Carolina, USA). The University of Wisconsin Hospital pharmacy prepared 80–85 doses of hazardous drugs each day. Baseline measurements showed that 85% were accurate (± 5%) but 15% were out of range. On average each dose took 7.4 minutes to prepare and 1.9 minutes for the pharmacist to check (for doses in IV bags). After the installation of a compounding robot 100% of doses were accurate (± 5%). This was because the robot rejected any doses that were out of range and remade them, acknowledged Dr Schenkat. Robotic preparation of a dose took 13.5 minutes from start to finish, of which 7.8 minutes was robotic compounding. “It required significantly less technician time than the manual process”, said Dr Schenkat. However, an additional 34.5 minutes per day were required for cleaning of the robot.
A breakeven analysis showed that when 27 or more preparations were made using the robot, technician capacity was released. Strategies to maximise efficiency included using only IV bags, making small doses and, if possible making small batches. It was also useful to load as much as possible into the robot at the beginning of the day, added Dr Schenkat.
A scheme to improve adherence to complex oral cancer treatment with capecitabine was described by Jenny Tsang (Clinical Pharmacist, Princess Margaret Hospital, Hong Kong). The oral capecitabine regimen is difficult to follow because the dose is calculated according to body surface area – 1000mg/m2, twice a day for 14 days of a 21-day cycle (14 days on, 7 days off). The doses are made up using 150mg and 500mg tablets. Unsurprisingly non-adherence is a common problem, said Ms Tsang. Intensive pharmacy support improved adherence to 96%. In future, dose-banding to simplify the capecitabine dosing might help to improve adherence, she said.
FarmAventura is the name of a pharmacy service tailored to needs of children with chronic diseases. It is designed to engage children through gaming. Children are given an ‘adventure backpack’ with 30 days’ treatment and an animal picture puzzle piece for each day. Patients ‘earn’ the puzzle pieces as rewards for taking medicines.
At critical stages in their treatment, they receive letters of congratulation from the animals and after one year, they receive free admission tickets for the zoo.
A review of the first 38 patients showed that during 178 hospital visits 62 medication errors were intercepted, 27 of which were potentially harmful. Non-adherence fell from 26% to 6% and patient/carer satisfaction increased significantly. The gaming approach was the key to success, according to presenter Alvaro Gimenez (Pharmacy Officer, Gregorio Marañon University Hospital, Madrid, Spain).
Multidisciplinary care is essential for effective management of patients with chronic diseases, according to Anja St Clair Jones (Consultant Pharmacist, Gastroentrology, Brighton and Sussex University Hospitals NHS Trust, UK). Ms St Clair Jones works in a gastroenterology multidisciplinary team (MDT) and is responsible for all prescribing and monitoring of immunosuppressant therapy and for biologics infusions. She also manages therapeutic drug monitoring and therapy individualisation. Treatment optimisation is an important part of her routine work. One example was optimisation of thiopurine treatment (for inflammatory bowel disease) through the addition of allopurinol and reduction in the thiopurine dosage. It was a good way “to get the best out of a cheap drug”, she said. Another example was switching from branded infliximab to a biosimilar product. As a result of having a pharmacist in the team, patients benefited because the MDT shifted its focus to medicines optimisation and the pharmacist shifted her focus to compassionate patient care, she concluded.