Pharmacy students weigh in: Understanding sundowning, opioid abuse, Abuse Deterrent Formulations and medication synchronization.

Sundowning (also known as sundown syndrome) is the emergence of neuropsychiatric symptoms in the late afternoon, evening or night. Typical symptoms include agitation, confusion, anxiety and aggression. Sundowning is not a psychiatric diagnosis, but is a broadly used term to describe a group of behaviors that occur at a specific time of day. These behaviors can include disorientation, pacing, wandering, erratic movement and screaming.

Sundowning most often occurs among the cognitively-impaired or institutionalized elderly patients; however, sundowning may be observed in elderly patients without dementia.

While the exact etiology is unclear, several factors have been identified that might play a role in causing the clinical sundown phenomenon.

? Low lighting and increased shadows: Unfamiliar surroundings such as a nursing home, coupled with low lighting and shadows created in the late afternoon and early evening, make it more difficult for a cognitively-impaired individual to reorient to his surroundings, which aggravates late-day confusion.

? Disruption of circadian rhythm: The suprachiasmatic nucleus (SCN) is an area in the brain that regulates circadian rhythms. It is affected by senile plaque formation. SCN size decreases in persons between 80 and 100 years of age. This could disrupt the sleep-wake cycle and exacerbate disorientation. Fatigue, sleep apnea, and daytime napping can also contribute to disruption of circadian rhythms.

? Medication: Benzodiazepines and lowpotency antipsychotics are among medications used to manage the symptoms of sundowning. Akathisia, tardive dyskinesia, muscle rigidity, anticholinergic toxicity and orthostatic hypotension are among side effects caused by these medications. These effects can further contribute to the development of sundowning.

Dyskinesias secondary to the on-off effect of anti-parkinsonian medications can also contribute to sundowning. In dement ia patients, physical discomfort and illness may be expressed as behavior abnormalities. Patients with cognitive impairment are not able to react to pain or other physical discomfort in standard ways; they often use aggression, yelling, screaming or refusing to eat to express physical symptoms.

Before considering any specific treatment for sundowning, it is reasonable to gather a careful history, thorough physical examination, and laboratory analysis to assess the patient to rule out other medical conditions.

Pharmacologic and non-pharmacologic options are available for management of sundowning. The most effective pharmacologic options include melatonin and acetylcholinesterase inhibitors and antipsychotics. There are many non pharmacologic options to try as well.

Abuse Deterrent Formulations
New focus has been placed on drug formulations which can minimize opioid abuse potential by deterring this type of behavior. A 2007 study found 13.2 percent of individuals reported nonmedical use of pain relievers at some point during their lives.

This startling finding supports the need for drug formulations that minimize abuse potential of opioids. Abuse deterrent formulations (ADFs) are developed by altering one of three different mechanisms: physical barriers, added antagonists and added adverse components.

Physical barriers prevent crushing, chewing or dissolution in liquids. Antagonists neutralize opioid effects in the event the dosage form is altered. Adverse components create unwanted effects if the drug product adulterated.

Drug abusers often manipulate dosage forms for faster onset of action. Physical barriers can reduce this behavior. There are many existing products that make use of this ADF and more drugs in the approval pipeline, such as Remoxy, OxyContin, Oxecta and Opana ER.

Medications that have agents that cause adverse effects when manipulated are known as sequestered aversive agents. These agents may be irritating to tissues if ingested or inhaled. For example, when Oxecta is crushed or chewed, adverse effects result, making this medication an unlikely choice for abusers.

Before Oxecta was approved, Acurox was developed using niacin as the irritating agent. A compromise to the dosage form resulted in dizziness, flushing, nausea, vomiting and pruritus (itching). This type of ADF is also useful in preventing patients from taking intact tablets in excessive doses.

The last ADF often used is incorporation of a low-dose antagonist. The antagonist is not meant to neutralize the opioid active drug, unless the product is adulterated. Examples include Suboxone and Embeda, which are not without risk and have resulted in opioid withdrawal symptoms in some patients.

A number of abuse deterrent formulations have developed of late that minimize the abuse potential of opioid medications. They are not without risk, but care is taken in the manufacturing and design of these formulations to maintain safety and integrity of the active ingredient.

Extended-Release Opioids
Individuals who suffer from chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain isn’t properly controlled. Because of the risk of abuse, many doctors shy away from treating patients with highdose opioid analgesics.

However, in 2014 and 2015, new hydrocodone formulation with tamper-resistant features have been approved. These new dosage forms may lessen the abuse potential.

Tolerance is an unfortunate result of long-term opioid use. The analgesic effect diminishes, resulting in a need to increase dosing to maintain pain control. Until recently, none of the formulations of hydrocodone offered the ability to deliver medication over a prolonged period of time, which is preferred for the management of chronic pain.

The FDA recently approved Hysingla ER (hydrocodone bitartrate), an extended-release opioid analgesic indicated to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment. The delivery system of Hysingla ER has abuse-deterrent properties.

Hysingla ER can prevent abuse of the drug when chewed, crushed, snorted, or injected. The tablet is difficult to crush, break or dissolve. It also forms a thick gel and cannot be easily injected when dissolved.

Medication Synchronization
Medication synchronization is not a new term among pharmacists;  however, implementation has always been problematic. Medication synchronization, or med sync, is a service for pharmacy patients to allow them to refill all chronic medications on one appointed day every month. Pharmacies are challenged with reduced reimbursements from third party payers. This reduction in resources necessitates exploration of alternative revenue streams.

Pharmacies compete to maintain life-long relationships with patients. Med sync is a service valuable to patients, and to the pharmacy, as well. This service gives patients the convenience of one trip to the pharmacy every month, easier budgeting for monthly prescriptions and time saved by only calling the pharmacy one time every month.

Pharmacists can use this scheduled monthly appointment with the patient to discuss adherence issues, disease state counseling, and to answer questions. Medications can now be ordered in advance, reducing the number of out-ofstock medications, allowing better inventory control. The pharmacy no longer has to contact patients and prescribers multiple times every month.

Controlled medications typically cannot be refilled early. Most pharmacies have a two-day grace period when filling them. This poses a problem when trying to sync the complete medication patient profile. The American Pharmacists Association (APhA) suggests a controlled substance prescription be the anchor medication. It serves as the medication around which other noncontrolled medications are scheduled.

Insurance companies only allow medications to be refilled so many days early every month. APhA suggests calculating how many doses of each medication the patient needs to sustain until the agreed upon refill date.

Organizations such as APhA and the National Association of Student Personnel Administrators (NASPA) have online resources that assist with development. Pharmacist’s Letter has a step-by-step plan derived from the Appointment Based Model (ABM).

Online software such as Ateb’s Time My Meds, Simplify My Meds, and Synchro-Script facilitate the med sync setup, too. Careful planning and use of web-based resources can provide a seamless implementation of the medication synchronization service.

Jeremy Foster, Matt Burke and Jeremy Newton are a PharmD candidates at Sullivan University College of Pharmacy. Amber Cann, PharmD, MBA is director of the Drug Information Center at the Sullivan University College of Pharmacy.


Related posts