3.3 Dependence, Addiction, MAT, Prescribing Safely

Question 1

What are the two main theories that describe opioid tolerance?

Answer 1

Decreased receptor sensitivity with repeated exposure; Receptor downregulation at the nerve junction –> Higher doses of opioid required to get same effect

Question 2

Describe the physiology of opioid withdrawal

Answer 2

Opioids suppress cell signaling and neurotransmitter release, and the body responds by upregulating downstream pathways. In the abscence of opioids, now there’s lots of downstream pathways leading to enhanced neural excitability

Question 3

Describe initial withdrawal, peak day, and relation to chronic opioid use

Answer 3

Initial withdrawal: 6-12h after short acting stopped, 30h after long-acting stopped.
Peak day: 2-3, dissipates after day 5.
Withdrawal acts longer with chronic use. Withdrawal is rarely fatal.

Question 4

What is the COWS scale?

Answer 4

Use to quantify patient’s withdrawal symptoms by nursing, titrate meds to treat withdrawal.
5-12 mild, 13-28 mod, 25-36 mod severe, >36 severe

Question 5

How does a person become opioid dependent?

Answer 5

Opioids suppress NE production, causing sedation. Brain overproduces NE to compensate.
Brain finds homeostasis and maintains alertness, needs opioids to feel normal.

Question 6

What are pharm treatments for symptoms of opioid withdrawal? Describe each

Answer 6

Clonidine: alpha 2 adrenergic agonist, suppresses release of NE.

NSAIDs: COX1/2 inhibitor, good for myalgias, decreases prostaglandin production and reduces inflammation.

Diarrhea: treat with Loperamide, mu receptor agonist in GI tract.

Nausea/vomiting: metoclopramide and prochlorperazine: dopamine adrenergic receptor antagonist; ondansetron: 5Ht receptor antagonist.

Insomnia/agitation: BZDs (gaba agonist) - decreases neurotransmission, leads to sedation, anxiolysis, muscle relaxation

Question 7

How do we treat opioid addiction?

Answer 7

CBT, support groups, inpatient/outpatient models, pharmacotherapy (MAT) - methadone, buprenorphine/naloxone, naltrexone.

Goals of MAT: prevent withdrawal, block effects of opioids, reduce cravings, promote recovery

Question 8

Describe methadone

Answer 8

Slow acting, full mu agonist.
Half-life and absorption vary greatly from 8-59h.
Excretion: liver.
Admin: PO/IV.
Dose: initial 10-30mg, titrate to efficacy over 1-3 weeks. 60-120mg effective maintenance dose for most people, but have to start 30 or lower.
Better outcomes and program retention with higher doses.

Question 9

What precautions must you take with methadone?

Answer 9

QT interval prolongation, respiratory disorder, liver disease, may be diverted, avoid concurrent sedatives.

High potential for OD - 1/3 of opioid related deaths.

NOT recommended for routine use in acute and chronic pain.

Question 10

Describe buprenorphine/naloxone (suboxone)

Answer 10

Buprenorphine: partial mu agonist, delta agonist, kappa antagonist; binds competitively with high afinity - sits on receptors and gives low level of stimulation no matter how much is in your system, just enough to reduce cravings and prevent withdrawal but not enough to give CNS effects.

Naloxone is added bc if suboxone is injected, will induce withdrawal symptoms. Excretion: liver, use caution in hepatic impairment. Half-life: 2-3 days.

Administration: sublingual film.

Induction dose: wait until no opioids in system, 2-4mg every 60-90min until withdrawal controlled.

Maintenance: 8-24mg daily.

DATA 2000 waiver: 3 day emergency rule if pt cannot get to clinic.

Question 11

What are key takeaways about suboxone?

Answer 11

May induce withdrawal.
Ceiling effect.
Significantly lower risk of OD compared to methadone.
High-dose buprenorphine reduces illicit opioid use and promotes retention in recovery programs.
Wean buprenorphine prior to surgery.
Causes clinically significant hyperalgesia.

Question 12

Describe naltrexone

Answer 12

Not as effective as buprenorphine or methadone, think of as long-acting narcan. 
Long-acting opioid antagonist. 
Daily oral vs monthly injectable. 
Dose: 380mg injection Q4wks. 
Will precipitate withdrawal if opioid in system. 
Poor adherence with PO. 
Use for etoh as well, and weight loss. 
Wean prior to surgery.

Question 13

When prescribing opioids safely, what MME do you start with, and what is your max titration?

Answer 13

Start at <50 MME/day and titrate to max of 90 MME/day

Question 14

For acute pain, how many days and what dose of opioids do you prescribe?

Answer 14

No more than 3-7 days at lowest dose

Question 15

Describe hyperalgesia

Answer 15

Opioid receptors expressed on mast cells and non-neuronal support cells - opioids lead to increased production of pro-inflammatory cytokines.

Adjunct therapy should target this pathway and bypass mu receptors to control pain.

Question 16

What are considerations for the following populations: pregnant women, adults over 65, mental health d/o, substance use d/o

Answer 16

Pregnant: opioids safe for limited use, under supervision of OB. Rate of miscarriage higher in withdrawal.

Adults over 65: often contraindications to non-opioid therapies, but also sensitive to SEs of opioids.

Mental health: Rx with caution in anxiety, depression, PTSD.

Substance: give naloxone take home kit

Question 17

Describe Naloxone

Answer 17

Competitive opioid antagonist.

Onset: 2-13 min. 
Duration 30-120m, repeat as needed. 
Dose: route dependent. 
No renal/hepatic adjustment. No Max Dose. 
Safe for patients to self-administer.