Controlled pain medications are commonly used in pain management and psychiatry.
Rules and regulations for controlled substances vary by state and federal law in the United States. Schedule II-controlled substance prescriptions cannot be refilled and expire after six months. Schedule III or IV prescriptions may not be filled or refilled more than six months after the written date or refilled more than five times, whichever comes first (Queremel Milani & Davis, 2023). Schedule V controlled substances may be refilled as authorized. Laws may vary by state. A complete list of scheduled drugs is available at Drugs of Abuse: A DEA Resource Guide.
The list of Schedule I substances includes marijuana, heroin, and lysergic acid diethylamide (LSD). We will discuss only the one currently being used for pain medication.
There are 38 states where all forms of medical marijuana are legal (Anderson & Rees, 2023); this is a controversial moment in the history of marijuana legalization by the states because the drug is still classified as Schedule I by the federal government. The VA and Federal Bureau of Prisons do not allow marijuana for their patients. If they have marijuana show up on a drug test, they will be penalized (VA, 2016). There is currently no consensus on what or when a change might be made, as marijuana could be reclassified (rescheduled), or perhaps as it is legal for recreational use in many states, it might be decriminalized federally (Celeste & Thompson-Dudiak, 2021).
These medications/drugs have the strictest regulations when compared to other prescription drugs because they are the most likely to be abused, diverted, or addicting. They include hydromorphone, meperidine, methadone, morphine, and oxycodone.
Morphine is used to treat soft tissue pain but also has been used to treat arthritis when other medications have failed.
Embeda® is a combination with naltrexone for the opioid-naïve patient, 20 mg/0.8 mg PO every 24 hours. Extended-release forms of morphine, such as MS Contin, should only be used for opioid-tolerant patients accustomed to ingesting over 400mg/day.
Morphine in selected forms should be used cautiously for patients with variable respiratory diseases such as COPD, obstructive asthma, hepatic or renal dysfunction, brain injury, increased intracranial pressure, or severe hypotension.
Hydromorphone (Dilaudid®) is a semisynthetic, phenanthrene opioid agonist. It is used for the treatment of persistent, severe pain that requires an extended treatment period with a daily opioid and for which alternative treatments are inadequate.
Fentanyl is supplied as a sublingual, transmucosal, nasal spray, transdermal patches, sublingual tablets, buccal lozenge, transmucosal lozenge, intramuscular injections, transmucosal tablets, intravenous injections, and electrically controlled transdermal patch. Different preparations of fentanyl are not interchangeable from microgram to microgram, even if administered via the same route. With the most popular clinic-level form, the transdermal 72-hour patch, providers should use a conversion table from other opiates used in the previous 24 hours to MMEs, then convert to fentanyl micrograms per hour.
Patients may use short-acting opioid agonists for the first 24 hours after stopping all other opiates at fentanyl patch initiation.
Hydrocodone/acetaminophen is a semisynthetic opiate agonist and a non-salicylate analgesic.
Opioid use requires an experienced clinician knowledgeable about the use of opioids, including the use of extended-release and long-acting opioids and how to mitigate the associated risks. All opiates have similar side effect profiles. From most to least severe, they cause all the obvious symptoms of CNS depression, such as decreased level of consciousness, increased respiratory depression, nausea, vomiting, constipation, slow gastric transit, and dry mouth. Unfortunately, hormonal and immunological dysfunction can happen with chronic use, physical dependence, tolerance, and rarely, hyperalgesia.
Schedule III drugs have a lower misuse and addiction potential than I and II. Medications in this category are often used for pain control or anesthesia. Drugs in this category may cause physical dependence but more commonly lead to psychological dependence. Examples of schedule III substances include ketamine, opioid analgesic products containing not more than 90 mg of codeine per dosage unit, and buprenorphine/naloxone oral film.
These drugs are considered to have less likelihood of dependence and abuse. Carisoprodol is a centrally-acting skeletal muscle relaxant and salicylate analgesic. It is used for musculoskeletal conditions such as muscle spasms. Tramadol is an opiate sometimes used for patients experiencing intractable pain because of its impact on peripheral pain pathways, partial inhibition of serotonin reuptake, and low affinity for opioid receptors. Tramadol is thought to result in less sedation, respiratory depression, and potential for tolerance; however, constipation can still be problematic because of anticholinergic adverse effects.
Medications containing codeine must have less than 200 mg of codeine per 100 milliliters (mL), such as cough syrups, Tylenol® #3, and Tylenol® #4. Tylenol® #3 and Tylenol® #4 are an oral combination of analgesics, which include an opioid agonist. Codeine as an opiate has all the same side effects and adverse effects as other opioids; this medication may mistakenly be less protected from children, pets, or other adults because of the Tylenol® name. Tylenol® #3 and Tylenol® #4 are acetaminophen mixed with codeine.
Tizanidine (Zanaflex®), a centrally acting muscle relaxant similar chemically to clonidine, works about as well as baclofen. Cyclobenzaprine (Flexeril®) is a muscle relaxant for acute musculoskeletal pain. Tizanidine causes dry mouth. It may cause orthostatic hypotension, especially in older adults.
Naloxone is an opioid antagonist, a derivative of oxymorphone employed for reversing the CNS and respiratory depression caused by opioid overdose. Auto-injectors and nasal formulations are available to treat or prevent an overdose outside of the healthcare setting. Naloxone nasal insufflation may be used in adults, children, and even infants at both the four and eight mg doses.
Medicaid, Medicare, and most insurance plans cover naloxone. There are free naloxone programs nationwide and prescription cards that can reduce the costs of prescribed naloxone to about $20.00 per kit. It should be remembered that as an opioid antagonist, it can precipitate a complete and sudden opioid withdrawal crisis for the patient. Too much naloxone can also remove all analgesic effects of the opioid being reversed; this can be extremely dangerous, even fatal, for an opioid-addicted infant and extremely uncomfortable for the opioid-addict in other age groups. Think severe instant withdrawal; a trip to the hospital to combat this may be necessary. The half-life of the nasal spray is comparable to the injection at about two hours. When given for fentanyl overdose, it may have to be repeated as fentanyl and other synthetic drugs, such as carfentanil, are 10,000 times stronger than morphine. Naloxone should be used cautiously with patients taking buprenorphine and cobicistat concurrently with protease inhibitors (Baker et al., 2010). As of this writing, naloxone has been made an over-the-counter medication by the FDA.
Buprenorphine is prescribed for patient support while tapering off opioid addiction and can be combined with naloxone to make a medication called Suboxone® (inSupport, 2023).
Methadone is structurally unrelated to morphine, and methadone is a Schedule II synthetic opiate agonist. Used in medically supervised opiate withdrawal and maintenance programs; also effective for relieving severe or chronic pain (Physicians' Desk Reference [PDR], n.d.a). For the treatment of opiate dependence, prescribers must register and comply with the Narcotic Addict Treatment Act (NATA) [21USC 823(g)].
Flumazenil (Romazicon®) is not available commercially in an intranasal spray. Therefore, the overdosed patient must be transported immediately to the hospital for care. It treats benzodiazepine overdose, reverses benzodiazepine-induced sedation, and antagonizes the actions of zolpidem. It does not reverse the actions of barbiturates, opiate agonists, or tricyclic antidepressants (PDR, n.d.b).