Do Not Be an Oblivious Drug Dealer: Part 2

Written with Ashley Stokes and Mary Claire Blackmon, PharmD Candidates 2017 at the Auburn University Harrison School of Pharmacy

Prescription medications are a significant source of drug abuse. Abusers may abuse their own personal prescriptions, or get them from members of their family such as close relatives or even pets. More recently, medication abuse has expanded from more common opioid or pain-killer medications, to less common culprits, such as medications used to treat depression, diarrhea, and Parkinson’s disease.

Pharmacists have an important role in preventing prescription drug abuse by being alert and attentive to their customer base. Common signs of medication abuse include patients attempting to fill prescriptions early on several occasions, practicing polypharmacy, not filling prescriptions through insurance, the patient using an excuse of traveling out of the area on multiple occasions, and even accusing the pharmacy of miscounting a previous prescription. Filling prescriptions as scheduled, encouraging patient autonomy and understanding in handling their own medications, and proper counseling could help to decrease prescription drug abuse.

Fluoxetine

Fluoxetine is a selective serotonin reuptake inhibitor that can be used used for multiple mental health conditions.¹ Those who abuse fluoxetine often break open the capsules and snort the drug much like one would do cocaine. When used this way, a person may experience such effects as an increase in energy, talkativeness, and mood elevation. Fluoxetine abuse can produce many psychologic and physiologic responses such as depression, suicidal ideation, hallucinations, anxiety, and even paranoia. If abused often, it can become addictive.

Antipsychotics

Second-generation antipsychotics, such as quetiapine and olanzapine, are often abuse for their sedative and anxiolytic effects. ^2,3 Addicts seek out the calming and hallucinogenic effects caused by quetiapine and olanzapine. Oftentimes, they are even combined with cocaine or heroin to get a euphoric and hallucinogenic effect, or combined with opiates and benzodiazepines for an enhanced sedative and calming effect. The usual dosage range of quetiapine is from 400-800 mg daily, while oral abuse occurs at consuming 800-1200 mg at a time. Comparatively, olanzapine is usually dosed from 10-15 mg daily when taken by mouth; abuse and sedative effects can be witnessed at 40-50 mg, or 4-5 tablets, per day.

Mild-to-moderate symptoms of antipsychotic abuse include dry mouth, constipation, and somnolence. In higher concentrations, QT prolongation, seizure, delirium, arrhythmias, and sinus tachycardia can occur. Death is rare and usually due to polysubstance abuse.⁵ Additionally, olanzapine can cause nystagmus, and central diabetes insipidus. Illicit use of both has been reported, but more often with quetiapine. Quetiapine is known under the nicknames of “quell," “Susie-Q," and “baby heroin."⁴ These antipsychotics will be abused by individuals inhaling crushed tablets, dissolving the tablets and injecting the solution, and ingesting the pills by mouth. Abuse of these agents, once only common in the general public, has increased in the correctional facility population.

Loperamide

Loperamide is an OTC and prescription medication used to treat diarrhea, and traveler’s diarrhea. Its mechanism of action is to prolong transit time, increase bulk density, and improve stool frequency and consistency. It also is an opioid-receptor agonist. The OTC dose of loperamide is 8 mg per day, whereas the prescription dosage is 16 mg daily.⁵ At therapeutic doses, it does not cross the blood brain barrier (BBB). However, at supertherapeutic doses (approximately greater than a gram), it has been reported to cross the BBB and cause euphoria and other opioid-like effects. Loperamide is either abused for the euphoric effects or to self-treat opioid withdrawal symptoms. Other substances of abuse are often used in combination with loperamide to inhibit its metabolism, and enhance its ability to penetrate the BBB. Signs of and symptoms of loperamide abuse include QT prolongation, torsades de pointes, ventricular arrhythmia, and cardiac arrest. ⁵

Diphenoxylate/Atropine

Diphenoxylate/Atropine is another prescription medication that has recreational abuse potential. Diphenoxylate/Atropine is a combination medication that is used to treat diarrhea, with 2.5 mg of diphenoxylate and 0.025 mg of atropine within each pill. Diphenoxylate is a centrally-acting phenylpiperidine opioid that exhibits its pharmacologic activity by slowing the motility of the intestinal tract.⁶ Diphenoxylate is metabolized in the body to difenoxin, another opioid derivative that is 250-400 times the strength of diphenoxylate. Diphenoxylate has the potential to cross the blood-brain barrier and therefore has the potential to become habit-forming. The atropine and the diphenoxylate together produce unpleasant anticholinergic effects, nausea, and vomiting when taken in higher than recommended amounts and deter from abuse. The euphoria gained from abusing diphenoxylate/atropine is said to mimic the effects of more highly-regulated medications such as heroin and oxycodone. Usually dosed at a total of 5 mg of diphenoxylate by mouth 3-4 times daily, toxicity can begin at 75-100 mg per day.⁵ Overdosing on diphenoxylate/atropine can have serious side effects of seizure, flushing, drowsiness, respiratory depression and coma, particularly if combined with other respiratory depressants. A common dose of atropine, when used alone, 1 mg. This means that abusers can take up to 40 tablets of diphenoxylate/atropine, according to the atropine dose, without gaining appreciable anticholinergic effects.

Clonidine

Clonidine is an alpha-2 agonist used as an antihypertensive agent. Individuals abuse clonidine to self-treat opioid withdrawal and for its psychoactive potential. Particularly patients use clonidine with methadone to “boost” the central nervous system effects. Patients will appear to be drunk on this combination, yet will have no measurable blood alcohol concentrations. Other individuals abuse clonidine for its sedating properties. The average dose for abuse reported is 0.6 mg, significantly higher than the dose used to manage hypertension. Clonidine is often chosen as a drug of abuse due to its relative easiness to acquire.⁷

Parkinson’s drugs

Many drugs to treat Parkinson’s disease affect the dopamine receptors. Apomorphine is a D₂ receptor agonist. This can generate psychiatric symptoms that patients describe as pleasant sensations of awakening, activating, and hypersexuality.⁸ Levodopa is another commonly abused drug. A case report reported that 2 patients increased their levodopa dosage to 1500-2000 mg/day to achieve euphoria despite side effects such as hyperkinesis and hallucinations.⁹ The dopamine pathway is associated with the reward effect. Therefore, the addiction potential for these drugs is great. However, a small minority of patients with Parkinson ’s disease have considered or have increased their medication to feel good.¹⁰

Pharmacists have a particularly important role in combatting abuse in that oftentimes they are the frontline in providing essential counseling and other tools to the community. We can make the largest impact in identifying and helping individuals with substance abuse.

Pharmacists can help by knowing the resources available in your community, and utilizing prescription drug monitoring programs for drug abuse prevention. With each new medication that reaches the market, there is the potential for great therapeutic interventions in the community, but there underlies an opportunity to abuse its effects. Understanding the pharmacology of each new agent keeps pharmacists ahead of drug abusers, thus limiting the amount of adverse drug events and death experienced within each community.

References

1. Fluoxetine [2017].

In: DRUGDEX® System (Micromedex 2.0). [AUHSOP Intranet]. Greenwood Village, CO: Truven Health Analytics Inc. [updated 2017, cited 2017 Apr 10]. Available from:

http://www.micromedexsolutions.com/micromedex2/librarian/

2.

Klein L, Bangh S, Cole JB Intentional Recreational Abuse of quetiapine compared to other second-generation antipsychotics. West J Emerg Med.

2017 Feb;18(2):243-250. doi: 10.5811/westjem.2016.10.32322. Epub 2016 Dec 6.

3. Sansone RA, Sansone LA. Is seroquel developing an illicit reputation for misuse/abuse? Psychiatry (Edgmont). 2010;7(1):13-16.

4.

Seroquel abuse [Internet]. Integrated treatment of substance abuse & mental illness; c2016 [cited 2017 Apr 5]. Available from:.

http://www.dualdiagnosis.org/seroquel-abuse/

5.

Quetiapine [2017]. Olanzapine [2017], Loperamide [2017], Lomotil [2017]. In: DRUGDEX® System (Micromedex 2.0). [AUHSOP Intranet]. Greenwood Village, CO: Truven Health Analytics Inc. [updated 2017, cited 2017 Apr 5]. Available from: http://www.micromedexsolutions.com/micromedex2/librarian/

6.Lomotil Addiction [Internet]. Elements Behavioral Health Drug Addiction Treatment. c2013 [cited 2017 Apr 10]. Available from:http://www.drugaddictiontreatment.com/types-of-addiction/prescription-drug-addiction/lomotil-addiction/

7. Beuger M, Tommasello A, Schwartz R, Clinton M. Clonidine use and abuse among methadone program applicants and patients. J Subst Abuse Treat. 1998;15(6):589-93.

8. Téllez C, Bustamante M, Toro P, Venegas P. Addiction to apomorphine: a clinical case-centred discussion. Addiction [serial online]. November 2006;101(11):1662-1665. Available from: Academic Search Premier, Ipswich, MA. Accessed March 22, 2017.

9. Spigset, O. and von Scheele, C. (1997), Levodopa dependence and abuse in parkinson's disease. Pharmacotherapy: J Human Pharmacol Drug Therapy. 17: 1027—1030. doi:10.1002/j.1875-9114.1997.tb03794.x

10. Mursaleen LR, Stamford JA. Drugs of abuse and Parkinson's disease. Prog Neuropsychopharmacol Biol Psych. 2016;64:209-17.