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ORLANDO -- With attention focused on opioids and illicit drugs, the abuse potential of noncontrolled medications has flourished, according to a primary care practitioner who has worked extensively in the correctional system.

Commonly abused noncontrolled drugs range from the surprising (anticholinergics) to the perhaps not-so-surprising (antidepressants), and multiple categories in between. What all of the drugs have in common is one or more psychoactive effects or characteristics that feed into the potential for abuse.

The abuse potential for many of the drugs has its origin in the nation's prison system, said Renee Dahring, MSN, APRN, CNP, who practices in Minneapolis, during the American Association of Nurse Practitioners annual meeting. She cited examples of prisoners who would swallow a pill, pass an oral inspection, and then regurgitate the pill, dry it, and sell it or use it for trade. Another prisoner learned how to extract medication that had been dissolved in water to prevent diversion or misuse and then turn it into paste.

Only half in jest, Dahring quipped that some prisoners know more about pharmacology than pharmacists do.

"I'm not saying you should never use these drugs. They are great drugs that help many, many people," she said. "I'm just giving you some food for thought about when you might want to be a little bit cautious or alerting you to when it's going on."

"I don't want to make a situation worse," Dahring continued. "I want to leave people in better condition than when I found them, and in some of these cases, [abuse and misuse] can lead to more problems than we're trying to solve."

Building a Database

Data on abuse and misuse of noncontrolled medications are hard to come by, consisting primarily of case reports. As a result, statistics on prevalence and other common metrics of drug abuse are almost nonexistent. Complicating the lack of data is that healthcare professionals "aren't looking for it," said Dahring. "If you don't look for something, you're not going to see it."

"We've been really focused on opioids and tracking that problem," she continued. "But this type of prescription drug abuse has risen with the clamping down on opioids, as it sort of leads people to look for opioids. Sometimes maybe we think there is not a lot of harm in some of these drugs because they aren't controlled substances. My job is to point out that even though they're not controlled substances, there can be harm from them."

Misuse of noncontrolled drugs has special implications in the overdose setting. Because the drugs are not opioids, patients in overdose will not respond to naloxone.

Dahring cited five noncontrolled therapeutic categories with the potential for abuse or misuse: anticholinergics, antipsychotics, antidepressants, anticonvulsants, and muscle relaxers. The drugs within each category pose a risk because of sedating properties, stimulant effects, euphoric effects, hallucinatory/dissociative effects, augmentation of another drug's effects, synergism with another drug, self-medication, or the principle that "if a little is good, more is better."

"I don't see many people using just one drug anymore," she said. "That seems like a thing of the past. We've got a lot of polypharmacy going on. Sometimes the effects are synergistic, you get a little bit more [effect] than you would individually."

Common Sources of Unexpected Abuse

Dahring singled out five specific drugs among commonly abused noncontrolled medications.

• Oxybutynin -- An anticholinergic approved for overactive bladder, with side effects including dry mouth, blurred vision, and a hallucinogenic "rush." People try to "exacerbate" the hallucinogenic effect by taking the drug more often or at higher doses. The drug can also be ground up and dissolved for injection, which can lead to injection-site tissue damage with repeated use. Often used in combination with bupropion or diphenhydramine.
• Quetiapine -- Second-generation atypical antipsychotic that has serotonergic and dopaminergic effects, as well as adrenergic antagonism. Broad off-label use, which has increased the risk potential. Potentiates the effects of benzodiazepines, and chronic misuse/abuse can lead to dependence and withdrawal symptoms. Increasingly, the drug is found in people who overdose.
• Bupropion -- An antidepressant with broad off-label use, including ADHD and smoking cessation. A derivative of cathinone, which is an amphetamine analog. The drug targets the brain reward circuits, similarly to cocaine, methamphetamine, and nicotine. In the setting of abuse, high-dose bupropion is ground up for snorting and creates a euphoric high similar to cocaine.
• Gabapentin -- Indicated for seizures and neuropathic pain, the drug has off-label uses that include anxiety, bipolar disorder, and management of withdrawal symptoms. When ground up and snorted, the drug can produce a cocaine-like high. Additionally, gabapentin can potentiate the effects of buprenorphine and naloxone. The FDA and Drug Enforcement Administration recently have advocated to designate gabapentin as a to counter misuse.
• Clonidine -- An older antihypertensive that has come to be used in the treatment of childhood attention deficit-hyperactivity disorder. Structurally similar to the short-acting muscle relaxant tizanidine, clonidine is a centrally acting adrenergic agonist that decreases sympathetic activity. When used with opioids, clonidine can decrease the amount of opioid needed to obtain a high. Misuse of the drug has been associated with an increasing number of emergency department visits.

As an aside, Dahring and an unidentified member of the audience pointed out that clonidine is also structurally similar to the animal tranquilizer xylidine. When an increasing number of emergency department visits for overdose revealed xylidine in the patients' blood, Dahring began studying the issue more closely and found that clonidine often was involved in the overdose.

Misuse of other prescription drugs in combinations has given rise to catchy street names, such as Sextasy (sildenafil and cocaine), Deadly Duo (opioid and alprazolam), and the Unholy Trinity (benzodiazepine, opioid, and carisoprodol). All are associated with potentially fatal adverse effects.

Certain patient populations have been linked to abuse and misuse of noncontrolled medications, said Dahring, including patients with a history of mood disorders and substance use disorders, adolescents and young adults, and people living in controlled environments (such as prisons).

Behaviors associated with misuse are similar to those seen with opioid abuse: missed appointments, requests for early refills or dose increases, indifference to side effects, decreased functional ability despite increased dosage or more frequent prescriptions, and an atypical patient profile. As an example of the atypical patient profile, Dahring described a hypothetical 24-year-old man seeking a prescription for oxybutynin.

"That's not typical of the overactive bladder population," she said. "I've had children. I know what overactive bladder is."

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