PHA 535 Opioid Use Disorder

• Opioid Use Disorder is covered in Human Behavior & Psychiatry PHA 535, Spring 2025.

Opioids

• Scheduled drug, classification depends on strength.
• Natural opioids are derived from the poppy plant.
• Examples of natural opioids include heroin (diacetylmorphine), morphine, codeine, oxycodone, hydrocodone, and hydromorphone.
• Synthetic opioids include meperidine, methadone, fentanyl, and carfentanil.
• Opioids mechanism of action (MOA) is Mu receptors 1 and 2 agonist.
• Fentanyl is a synthetic opioid 50-100x stronger than morphine.
• Sufentanil and remifentanil are 250-1000x stronger than morphine and can displace buprenorphine.
• Carfentanil, a fentanyl analog, is 10,000x stronger than morphine and is used as a veterinarian dose for large animals.

Opioid Epidemic

• Pain scale and marketing contributed to the opioid epidemic.
• 75% of 106,699 drug overdose deaths in 2021 involved an opioid.
• More people die from opioids than car accidents as of 2021.
• In 2021, there were 42,915 MVA deaths versus 80,411 opioid deaths.
• National overdose deaths involving any opioid show a significant increase from 1999 to 2021.
• In 2021 there were 80,411 deaths.

Improper Marketing Lawsuits

• Improper marketing and distributing of opioids lawsuits pending include Allergan, Cardinal Health Inc., Costco, CVS, Endo Health Solutions, Mallinckrodt LLC, Purdue Pharma.
• Rite-Aid Corporation, Rochester Drug Cooperative Inc., Teva Pharmaceuticals USA Inc., Walgreens, Wal-Mart, McKesson, Cardinal Health, Amerisource Bergen, Johnson & Johnson lawsuits pending.

Opioid Effects

• Heroin use is part of a larger substance abuse problem.
• People addicted to alcohol are 2x more likely to be addicted to heroin.
• People addicted to marijuana are 3x more likely to be addicted to heroin.
• People addicted to cocaine are 15x more likely to be addicted to heroin.
• People addicted to Rx opioid painkillers are 40x more likely to be addicted to heroin.
• Opioid effects include analgesia, respiratory depression (most common cause of death), miosis (pinpoint pupils), pruritus, euphoria, nausea, constipation, drowsiness/ paradoxical insomnia, ARM PEN CD.
• Anyone can become addicted to opioids.
• Taking opioids > 5 days increases risk of being on opioids for 1 year and becoming accustomed to euphoria.
• Cells internalize mu and delta receptors with opioid use ("down regulation").
• Increase sense of pain after stopping long-term opioids may occur.
• With chronic use, pain can actually increase.

Opioid Use

• Opioids can be swallowed, smoked, snorted, or injected.
• Heroin IV use leads to track marks caused chronic abuse, old needles, or impure drugs.

Associated Opioid Related Conditions

• Associated opioid-related illnesses and deaths include Hepatitis (B and C), HIV, abscesses, sepsis, right-sided endocarditis, HIV/AIDS.
• No standard dosing, illicit drugs "laced" with fentanyl/ other drugs, overdose (respiratory arrest), and suicide are associated with opioid use.
• New users of SSPs are 5x more likely to enter drug treatment.
• Needle Exchange Programs/Syringe Services Programs (SSP) are 3x more likely to stop using drugs.
• Providing naloxone through SSP decreases opioid overdose deaths.
• SSP programs protect the public, first responders, protects through safe disposal of used needles/ syringes, cost-effective, and does not increase drug use.
• Opioid withdrawal is typically not life-threatening unless severe medical illness is present, it is discomforting.
• More fragile patients can die during opioid withdrawal.
• "Fluids coming out everywhere" and Piloerection with a cold clammy feeling are associated with opioid withdrawal.
• Opioid withdrawal mnemonic "STOP TRYING Joints" includes sweating, tremors, O looks like a pupil, mydriasis or yawning, Piloerection, Tachycardia, Restlessness, Yawning, Irritability or anxiety, Nose running or eyes tearing, GI upset (vomiting / diarrhea/ pain), Joint pain or bone pain.
• The Clinical Opiate Withdrawal Scale (COWS) - Symptoms include resting pulse rate, Sweating, Restlessness, Pupil Size, Bone or Joint aches, Runny Nose or tearing.
• Gl upset, Tremor, Yawning, Anxiety & irritability, and Gooseflesh skin are also signs to measure withdrawal.
• Replace opiate, symptoms start 8-12 hours after the last dose, see PDF in Canvas, perform at regular intervals per protocols.

Treatment

• FDA-approved medications for opioid addiction, overdose, and withdrawal work in various ways.
• Opioid Receptor Agonist and Partial Agonist both reduce opioid use and cravings.
• Opioid Receptor Antagonist reverses opioid overdoses.
• Adrenergic Receptor Agonist treats withdrawal symptoms.
• Medications include Naloxone, Naltrexone, Methadone, Buprenorphine, Lofexidine.
• Central alpha 2 agonist (used for HTN) for autonomic dysfunction.
• Lofeidine is safer but is around $2000 for 96 tablets as an initial 7-day amount and Clonidine is only $8/month but can cause more hypotension & dizziness.
• Clonidine for 14 weeks increased abstinence from heroin.
• NSAIDs for muscle cramps and Dicyclomine (Bentyl), anticholinergic for GI symptoms are for symptom management but will not completely control all withdrawal symptoms in all patients.

Medication Assisted Treatment

• OUD (Opioid Use Disorder) MAT (Medication Assisted Treatment) shows Full Agonist, Partial Agonist, and Antagonist effects vs. Log dose.
• OUD MAT: Buprenorphine, partial opiate agonist (ceiling effect reduces chances for overdose), schedule III drug, works as well as methadone in high enough doses.
• Buprenorphine displaces opioids on Mu receptors except sufentanil.
• Buprenorphine is available as SL, film, IM/IV, Sublocade®: Once/month injection.
• Buprenorphine side effects are similar, less severe than opioids but have lethal interactions with other drugs is an effective treatment.
• Patients are 1.82 X more likely to stay in treatment than placebo-treated patients and decreased the number of opioid-positive drug tests by 14.2%.
• OUD MAT: Buprenorphine + Naloxone Use, Suboxone® (and others) for out-patient.
• If drug is tampered with, naloxone (Narcan) is released: sequestered antagonist and is poorly absorbed Sublingually and orally but is well-absorbed IV.
• Initial treatment is begun using buprenorphine monotherapy under supervision, but then switched to maintenance combination and is not recommended for use during induction period for long-acting opioids or methadone.
• Buprenorphine and Naloxone should not be recommended with liver disease: due to naloxone has increased bioavailability.

ER Initation

• ER Initiated Buprenorphine and Naloxone (Suboxone) & Referral to Treatment - Symptom start 8-12 hours after last dose or right after naloxone.
• Treat short-acting opioids (for example, heroin) that require 12 hours since last use for sufficient withdrawal to safely give Suboxone without causing withdrawal.
• Some opioids such as fentanyl may require greater than 12 hours & long-acting opioids, such as methadone, require 48-72 hours since last use before initiating buprenorphine.
• In ED Initiated Buprenorphine and Naloxone, if COWS>8, start buprenorphine/naloxone and monitor every hour or known if known heavy user and/or already using Suboxone or COWS>12.
• Perform brief negotiating interview (BNI) and assess their willingness to stop and abstain from illicit opioids then send home with buprenorphine/naltrexone (Suboxone®) and RTC or ER in 1 day.
• Tapering of Suboxone requires a high relapse rate and intense therapy and discussion and possible naltrexone.

DEA

• DEA Deferred Practitioners Who Can Prescribe Buprenorphine, qualified practitioners include physicians, ARNPs, PAs, Clinical Nurse Specialists, CNRA, and CNMs.
• Deferred means a setting other than in opioid treatment centers.
• As of June 2023, all practitioners with a DEA license must now complete an 8- hour free nationwide training where AAPA is an eligible provider.
• OUD MAT: Methadone, full mu receptor agonist with delayed onset of action and longer half-life (opposite addiction characteristics).
• Methadone continues dependence without causing the usual opioid abuse-related harms.
• Methadone is administered once daily and must be obtained legally.
• Once tolerance develops, has little impact on mood, judgment, and psychomotor skills.
• Physician needs to be enrolled to prescribe methadone under a certified opiate substitution program, but as of September 2024, PAs who work for an opioid treatment program may prescribe methadone.
• Methadone side effects are similar to other opioids but are more severe including effects: cardiac arrhythmias (prolonged QT), hyperalgesia, lethal interactions with other drugs, and overdose.
• Methadone Effectiveness includes reduced opioid use, decreased opioid use-associated transmission of infectious disease, and crime.
• Patients on methadone have 33% fewer opioid-positive drug tests is more effective at controlling use and are 4.44 X more likely to stay in treatment compared to controls
• Methadone significantly improves long term outcomes, even without counseling and has similar results to buprenorphine when treating at the same dose.

Opioid Antagonist

• OUD MAT: Naltrexone is a Vivitrol® long acting injection or Revia ® daily pill.
• Naltrexone is a full opioid receptor antagonist: prevents the effect of further opioid use and works slower and longer than naloxone.
• Naltrexone not used for acute opioid intoxication; the patient must have gone through withdrawal first.
• Treatment of Opioid Use Disorder: includes the FDA-approved app program in conjunction with therapy reSET O.
• Prescription Drug Monitoring Programs where all 50 states have a program.
• Florida uses Electronic-Florida Online Reporting of Controlled Substance Evaluation Program, E-FORCSE®.
• The purpose is to prevent prescription abuse and to be aware and know the requirements and consequences.
• In Florida, it is a first-degree misdemeanor for not consulting E-FORCSE®.
• Opioid Overdose Treatment includes Naloxone (Narcan®), full opioid receptor antagonist causing rapid onset of withdrawal symptoms.
• Naloxone is used to counteract life-threatening opioid overdose in the CNS/respiratory depression to awaken the patient.
• May need multiple doses for higher strength/higher doses of opioids with continued life support until the patient awakens.

Opioid Overdose

• Opioid overdose history includes unconsciousness, pinpoint pupils +/-, IV tracks, vomiting, and respiratory arrest.
• Administer -0.4 mg IV/ IM/ SC/ ETT of naloxone and may need multiple/ higher doses.
• The patient should be observed for rebound for 2 hours after treatment until their vital signs are stable.
• Give home community naloxone: for abuse/ Rx of opioids or give intranasal 2 mg or 4 mg every 2-3min.
• Acute Treatment of Opioid Overdose can be given to an unconscious patient.
• The patient requires to be observed for recurrent opioid toxicity for at Least 2 hours for post naloxone care.
• Safe discharge criteria includes being clear of adverse events within 24 hours, a normal gait, baseline SpO2 >92% on RA, Respiration Rate between 10 and 20, Temperature between 35.0°C and 37.5°C, Heart Rate between 50 and 100, and a Glasgow Coma Scale of 15.
• Substance Use: Urine Drug Screen is Always presumptive until confirmed with a specific drug assay and is done using Immunoassays via antibodies.
• Confirmation is done via gas chromatography-mass spectrometry or serum tests: but these are costly and difficult to perform,
• Urine Drug Screen can contain Amphetamines, MDMA, Barbiturates, Benzodiazepines, Cannabinoids, Cocaine, Methadone, Opiates, Oxycodone, Phencyclidine (PCP) Tricyclic antidepressants, Heroin, and Anti-epileptics.
• Urine Drug Tests - include Cocaine: benzoylecgonine has virtually no cross-reactivity with other substances.
• Opiates are 3-morphine-glucuronide and 6-morphine-glucuronide.
• Codeine: morphine, norcodeine
• Heroin: 6-monoacetylmorphine (6-MAM), morphine, and morphine glucuronide.
• Beware that poppy seeds: bagel: 1.5 mg morphine, 0.1 mg codeine can cause a false positive.
• Four Drugs Not Detected on Routine Urine Screen include Fentanyl, Tramadol, Oxycodone, and Buprenorphine.
• Fentanyl test strips can be used to test illicit drugs if suspected of being laced in that drug.
• Various Drugs and the time they are detectable are listed in Table 2 that is meant to be referred to, but not memorized
• There are also false positives via other drug that is important to recognize through patient history.
• Serum Drug Screens Panels tests cover Above drugs and Acetaminophen, Salicylates, Carbon monoxide (carboxyhemoglobin), Pesticides (cholinesterase) and Iron.
• Involuntary Drug Treatment exists in 37 states in the US where it is important to Know your state laws .
• Florida law: is the Hal S. Marchman Alcohol and Other Drug Services Act of 1993.

Marchman Act

• Marchman Act Criteria for involuntary admission: a person is substance abuse impaired and has lost self-control of substance use.
• 2a. Has inflicted, threatened, or threatened or attempted to inflict, physical harm on himself or herself or another.
• Is in need of substance abuse services and his/her judgment is so impaired that they are incapable of understanding that need.
• Refusal to receive such services does not constitute evidence of lack of judgment with respect to his or her need for such services.
• Giving money, posting bail, calling in sick, doing their work/ responsibilities, and making excuses for drug/ alcohol use are forms of enabling.
• How Families/ Friends Can Interact with Loved Ones: through talking, avoiding Judgmental and "guilt ing", avoiding nag or scold.
• There should be a Family Plan and it must be emphasized that "Some people will die from their disease.”
• Getting Support for Family includes family counseling, involvement in a program of "recovery."
• Altered Mental Status should be remembered with: A,E,I,O,U, TIPS
• P.A. Groups and Associations include Impaired Practitioners Resource Committee, Society of Physician Assistants in Addiction Medicine, Caduceus Caucus, and Assoc. of PA's in Psychiatry (APAP).
• Useful Websites include:
• www.al-anon.alateen.org (for families)
• www.aa.org (Alcohol anonymous)
• www.na.org (Narcotics anonymous)
• www.drugabuse.gov (Nat'l Institute on Drug Abuse)
• www.samhsa.gov (Substance Abuse & Mental Health)