Since each controlled-release tablet of oxycodone contains a large quantity of oxycodone to allow for prolonged action, those intent on abusing the old formulation have extracted crushed tablets and injected high doses, resulting in misuse and possible fatal overdose. In 2010, the FDA approved a new formulation of the controlled-release form of oxycodone that reportedly prevents the tablets from being cut, broken, chewed, crushed, or dissolved to release more oxycodone. It is hoped that this new formulation will lead to less misuse by snorting or injection. The FDA is now requiring a Risk Evaluation and Mitigation Strategy (REMS) that will include the issuance of a medication guide to patients and a requirement for prescriber education regarding the appropriate use of opioid analgesics in the treatment of pain. (See Box: Educating Opioid Prescribers.)
Propoxyphene is chemically related to methadone but has extremely low analgesic activity. Its low efficacy makes it unsuitable, even in combination with aspirin, for severe pain. The increasing incidence of deaths associated with its use and misuse caused it to be withdrawn in the United States.
Diphenoxylate and its metabolite, difenoxin, are not used for analgesia but for the treatment of diarrhea. They are scheduled for minimal control (difenoxin is Schedule IV, diphenoxylate Schedule V; see inside front cover) because the likelihood of their misuse is remote. The poor solubility of the compounds limits their use for parenteral injection. As antidiarrheal drugs, they are used in combination with atropine. The atropine is added in a concentration too low to have a significant antidiarrheal effect but is presumed to further reduce the likelihood of misuse.
Loperamide is a phenylpiperidine derivative used to control diarrhea. Due to action on peripheral μ-opioid receptors and lack of effect on CNS receptors, investigations are ongoing as to whether it could be an effective analgesic. Its potential for misuse is considered very low because of its limited access to the brain. It is therefore available without a prescription.
The usual dose with all of these antidiarrheal agents is two tablets to start and then one tablet after each diarrheal stool.
Care should be taken not to administer any partial agonist or drug with mixed opioid receptor actions to patients receiving pure agonist drugs because of the unpredictability of both drugs’ effects; reduction of analgesia or precipitation of an explosive abstinence syndrome may result.