Opioid-Related Disorders

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Narcotic
comes from Greek word stupor and originally referred to as a variety of substances that dulled the senses and relieved pain
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Opioid
Opioid: natural, synthetic, or semi-synthetic chemicals that interact with opioid receptors on nerve cells in the body and brain and reduce pain signals

Opiate: naturally occurring opioid ex. Morphine, codeine

Semi-synthetic: Heroin, oxycodone

Synthetic: fentanyl, methadone
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DSM-5: Opioid-Related Disorders
Opioid Intoxication

Opioid Withdrawal

Opioid Use Disorder
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DSM-5: Opioid Intoxication
Recent use of an opioid.

Clinically significant problematic behavioral or psychological changes that developed during, or shortly after, opioid use.

Pupillary constriction and one (or more) of the following signs or symptoms developing during, or shortly after, opioid use:
Drowsiness or coma.
Slurred speech.
Impairment in attention or memory.

The signs or symptoms are not attributable to another condition or intoxication with another substance
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DSM-5: Opioid Withdrawal
Presence of either of the following:
Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e., several weeks or longer).
Administration of an opioid antagonist after a period of opioid use.

Three (or more) of the following developing within minutes to several days after Criterion A:
Dysphoric mood.
Nausea or vomiting.
Muscle aches.
Lacrimation or rhinorrhea.

Pupillary dilation, piloerection, or sweating.
Diarrhea.
Yawning.
Fever.

Insomnia
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DSM-5: Opioid-Use Disorder
A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:
11 symptoms in total, highlights seen below:
Opioid are often taken in larger amounts or over a longer period than was intended
Unsuccessful efforts to cut down or control opioid use
Cravings
Recurrent opioid use resulting in a failure to fulfill major role obligations
Tolerance
Withdrawal
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Etiology and Pathophysiology
Multifaceted
Biological
Environmental
Genetic
Psychosocial factors
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Racial Disparities
Black patients are half as likely to obtain follow up appointments for opioid use disorder care after discharge from the emergency room

Death Rates
Opioid overdose death rates have increased in black populations while leveling off in other populations

Access to Care
Counties with more black and Hispanic communities had more methadone clinics per capita
Counties with more white communities had more buprenorphine use per capita
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Naloxone
Class:
Opioid antagonist

Place in therapy:
Opioid overdose

Mechanism of action:
Competitive antagonist at opioid receptors
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Naltrexone
Class:
Opioid antagonist

Place in therapy:
Opioid use disorder
Alcohol use disorder

Mechanism of action:
Antagonist at opioid receptors

Dosing:
Naltrexone tablet (Revia®): 50 mg oral daily
Naltrexone LAI (Vivitrol®): 380 mg IM every 4 weeks

Onset of action:
Can work within a few days, but maximum effects may not be seen for a few weeks

Pharmacokinetics:
Extensive first pass metabolism but the major metabolite (6-beta-naltrexol) is active
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Buprenorphine
Class:
Opioid

Place in therapy:
Opioid withdrawal
Opioid use disorder

Mechanism of action:
Mu-opioid partial agonist

Only start if the patient is already in withdrawal (*at standard dosing), otherwise may cause withdrawal symptoms
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Buprenorphine and Naloxone Combination
Class:
Opioid

Place in therapy:
Opioid withdrawal
Opioid use disorder

Mechanism of action:
Mu-opioid partial agonist and mu-opioid antagonist

Dosing:
Buprenorphine/naloxone sublingual (Suboxone®): 2/0.5 mg – 32/8 mg films and tablets
Buprenorphine/naloxone sublingual (Zubsolv®): 0.7/0.18 mg – 11.4/2.9 mg tablets

Onset of action:
Depends on product used

Pharmacokinetics:
Depends on product used

Side effects
Constipation
Headache
Nausea

Contraindications
Hypersensitivity
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Methadone
Class:
Opioid

Place in therapy:
Opioid withdrawal
Opioid use disorder

Mechanism of action:
Mu-opioid agonist

Dosing:
2.5 – 120 mg oral concentrate daily

Onset of action:
0.5 – 2 hours

Pharmacokinetics:
Duration of action 24 – 36 hours for cravings

Side effects
Dizziness
Lightheadedness
Nausea/vomiting
Sweating

Contraindications
Acute or severe asthma
Paralytic ileus
Respiratory depression
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Lofexidine (Lucemyra)
Alpha-2 receptor agonist
Less side effects than clonidine
hypotension, fatigue and weakness
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Opioid intoxication/overdose guidelines
First line — APA and ASAM recommend Naloxone
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Clinical Opiate Withdrawal Scale
5-12 mild; 13-24 moderate; 25-36 moderately severe; 36+ severe withdrawal
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Bernese Method
consists of initiating a low dose of 0.2 mg sublingual buprenorphine and slowly increasing the dose while continuing full opioid agonist therapy. Once buprenorphine has reached a sufficient dose, the full opioid agonist is discontinued without tapering.
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Microinduction Protocol
method that includes starting with a low dose of buprenorphine that overlaps with other opioid use. The small buprenorphine dose increases over time and then tapering or cessation of opioid use at sufficient dose of buprenorphine (or sometimes an abrupt cessation). The goal is to transition patients to buprenorphine therapy without opioid withdrawal.
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Practical Guidance for OUD
Provide low threshold rapid access to treatment
Provide non-punitive care
Check the Prescription Monitoring Program (PMP)
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Harm Reduction
Reduces the risks of addiction
Maintains physiological need for opioid agonism
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Naloxone Statistics
A study in Massachusetts showed
No difference in rates of opioid-related emergency department visits
No difference in hospital admissions in communities with low or high implementation of overdose education and naloxone distribution programs

Naloxone distribution programs were shown to:
prevent overdose deaths,
increase quality-adjusted life years (QALYs)
be highly cost-effective.
naloxone distribution was predicted to prevent 6 percent of overdose deaths
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Cost Effectiveness of Treatments for Opioid Use Disorder
All forms of medications for the treatment of opioid use disorder were associated with cost savings compared with no treatment

\$25,000 – \$105,000 savings in lifetime costs per patient
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Healthcare Professionals Perspectives
Generally negative
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Pharmacists with SUD
1 in 10 pharmacists will suffer from a substance use disorder at some point during their lifetime
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