1
Q
Opioids vs Opiates
A
Opioid
- Medication that work at the opioid receptor
- Narcotics: Used to describe sleep agents, now for addictive drugs
- Associated with pain relief, diarrhea treatment and euphoria
Opiates
- Natural plant
- Active compounds: morphine, codeine
2
Q
Opioids MOA
A
Opioid receptor agonist; block release of pain neurotransmitters from the nociceptive fibers; activate presynaptic receptors on GABA neurons (inhibit GABA release)
3
Q
Opioid Receptors
A
Mu (Morphone= Mu agnoist): found in the brainstem and medial thalamus; responsible for analgesia, respiratory depression, euphoria, sedation, decreased GI motility and physical dependence
- Mu1: analgesia, euphoria and serenity
- Mu2 (OP3 or MOR– morphine opioid receptors): respiratory depression, pruritus, prolactin release, dependence, anorexia, and sedation
Kappa (OP2 or KOR– kappa opioid receptors): limbic and other diencephalic areas, brainstem, and spinal cord; responsible for analgesia, sedation, dyspena, dependence, dysphoria, and respiratory depression
Delta: located largely in the brain; effects are not well studies (may be psychomimetic and dysphoric effects)
4
Q
Opioid Agonist
A
Full agonist (complete response)
- Morphine
- Fentanyl
- Hydromorphone
- Codeine
- Oxycodone
- Methadone
- Heroin
Partial agonist (partial response or antagonist) - Analgesic ceiling effect: Buprenorphine (kappa receptor), Butorphanol
Antagonist (block response)
- Naloxone, Naltrexone
- Suboxone (buprenorphine + naloxone)
5
Q
Short Acting Opioids
- Codeine
- Hydrocodone
- Hydromorphone (Dilaudid)
- Morphine (MSIR, Raxanol)
- Oxycodone
- Oxymorphone (Opana)
- Fentanyl (Actiq)
A
USE
- Acute pain
- Incident pain
- Breakthrough pain
- For activity: post op, physical therapy, travel
6
Q
Long Acting Opioids
- Fentanyl (transdermal)
- Levorphanol
- Methadone
- Morphine (MS Contin, Kadian, Azinza)
- Oxycodone (Oxycontin)
- Oxymorphone (Opana ER)
A
Use
- Chronic pain
- Moderate to severe pain
7
Q
d
A
d
8
Q
Opioid ADR
A
- Sedation, lethargy
- Constipation
- Respiratory depression
- N/V
- Pruritus/urticaria (direct histamine response, can also cause bronchospasm)
9
Q
Opioid Overdose
A
Triad
- Miosis
- Loss of consciousness
- Respiratory depression
- Much worse with other CNS depressant (EtOH)
- Antidote: Naloxone (Narcan)
10
Q
Morphine
A
- Crosses BBB
- ADR: direct histamine release; respiratory depression; orthostasis; constipation; N/V
- Drug interactions rare
- t1/2= 2hrs
11
Q
Codeine
A
- MOA: weak mu agnoist
- Metabolized to morphine (50% potency of morphine)
- t1/2= 2.5-3hrs
- CYP 2D6 substrate: inhibited by bupropion, cimetidine, celecoxib, cocaine; warning for ultra-rapid metabolizers– lots of codeine!!!! (nursing infants, baby might be ultra rapid metabolizers)
12
Q
Oxycodone (Oxycontin, Percocet)
A
- Activity at mu and kappa receptors
- High potency analgesia
- t1/2= 2.5-3 hrs
- Metabolized by CYP 2D6 to oxymorphone
- Combo products: oxycodone/acetaminophen (percocet)
- highly abused
13
Q
Hydocodone
A
- Most commonly used opioid
- Weak activity at mu receptor
- t1/2= 4hrs
- Metabolized by CYP 2D6 to hydromorphone
- Combo products: hydrocodone/acetaminophen (Vicodin); hydrocodone/ibuprofen (Vicoprofen)
14
Q
Hydromorphone (Dilaudid)
A
- Activity at mu and delta receptors
- More potent than morphine
- t1/2= 4 hrs
- Metabolized by glucuronidation
15
Q
Oxymorphone (Opana)
A
- 10x more potent than morphine
- No P450 interactions
16
Q
Fentanyl (Actiq)
A
- Strong mu agonist (80x more potent than morphine)
- CYP 3A4 metabolism
- Transdermal: Long acting (steady state 3-6 days); clearance up to 24 hrs; dose dumping with heat; Don’t cut the patch!!!
17
Q
Codeine allergy
A
Can take fentanyl due to different compound and structure
18
Q
Meperidine (Demerol)
A
- Weak mu agonist (10% morphine potency)
- Anticholinergic properties (recommended to avoid elderly)
- Avoid with MAOIs (Respiratory depression)
- Neurotoxic metabolite (anxiety, tremors, seizures; not reversible with naloxone)
19
Q
Propoxyphene (Darvon, Darvocet)
A
- Weak mu agonist, NMDA antagonist
- CYP 3A4 inhibitor
- CNS effects: dizziness, sedation, weakness, falls, agitation, insomnia
- Recommended to avoid in elderly
- Neurotoxic: seizures, reversible with naloxone
- Cardiotoxicity
20
Q
Methadone
- Often used to help get ppl off heroin
- Helps pt ease through withdrawal
A
- High affinity mu agonist (Analgesic effect)
- NMDA antagonist (Neuropathic pain)
- Serotonin-norepinephrine reuptake inhibitor (SNRI)
- Analgesic effect 4-8 hrs
- Metabolized by CYP 3A4 and 2D6: initially induces 3A4 metabolism, then levels out; titrate slowly
- t1/2= 12-150hrs (highly lipophilic)
- Cardiotoxicity (Torsades)
21
Q
Buprenorphine
A
- Mu receptor partial agonist (ceiling effect)
- Kappa receptor antagonist
- Used for opioid/heroin addiction
- 3A4 metabolism
- ADR: sedation; N/V; dizziness, HA; respiratory depression
22
Q
Butorphanol (Stadol)
Levorphanol
A
- Partial Mu agonist
- USE: moderate to severe pain
- ADR: respiratory depression, euphoria, typical opioids ADRs
23
Q
Naloxone (Narcan)
A
- Mu receptor antagonist
- USE: reversal agent for opioid OD
- Reverses respiratory depression, sedation, hypotension (works in 2-5 mins, Lazarus effects)
- IM, subQ, IV, intranasal
24
Q
How to give nasal spray naloxone
A
- pull or pry off yellow caps
- pry off red cap
- grip clear plastic wings
- gently screw capsule of naloxone into barrel of syringe
- insert white cone into nostril, GIVE A SHORT, VIGOROUS PUSH on end of capsule to spray naloxone into nose; ONE HALF OF THE CAPSULE INTO EACH NOSTRIL
- if no reaction in 2-5 mins, give the second dose
25
Naltrexone (Vivitrol)
- Opioid receptor antagonist
- USE: opioid and alcohol addiction (MOA in EtOH abuse unknown)
- Contraindicated in pts using opioids
- Well tolerated: some associated with N, HA, dizziness, nervousness, fatigue
26
Tramadol
- Synthetic codeine analog; weak Mu receptor agonist; inhibits NE and 5HT uptake (SNRI)
- As effective as morphine for mild to moderate pain, labor pain
- Less effective for severe or chronic pain
- Warning for seizure risk at recommended and increased doses (higher incidence with SSRIs, TCAs, opioids, MAOI)
- Suicide risk
- Serotonin syndrome risk
- ADR: dizziness, vertigo, N/V/C, HA, somnolence, pruritis
- DRUG INTERACTIONS: CYP 2D6 and 3A4 inhibitors, serotonergic drugs, carbamazepine
27
Tapentadol (Nucynta)
- Mu opioid agonist, NE reuptake inhibitor
- 1st opioids specifically approved for diabetic neuropathy
- Stronger than tramadol
- No P450 metabolism
- Potentially fatal if taken with EtOH
- CII
- Same drowsiness/ dizziness as oxycodone with less N/V/C
28
Opioid Conversions
- Calculate 24 hr total dose
- Dividing by dosing schedule
- Reduce dose by 30-50%
- Titrate to goal
29
Opioid Drug Interaction
- Erythromycin
- Phenytoin
- Phenobarbital
- CY2D6 inhibitors (increase tramadol levels)
- CYP3A4 inhibitors (increase methadone levels)
30
Opioid withdrawal
Signs and symptoms
- mood lability (irritability, anxiety, restlessness)
- chills, sweating
- abd pain/N/D
- sneezing, rhinorrhea, dilated pupils
- muscle weakness, pains
- insomnia
- Begin 8-16 hrs following last dose, peak 2-4 days
- extremely unpleasant but not life threatening
- resolve 7-14 days
31
Opioid Dependence Treatment
Detoxification
- Necessary step for long term abstinence
- Slow taper: tapering of opioids through prescription of methadone
- Rapid: reversal med or d/c of opioids--Naltrexone or buprenorphine; other meds (clonidine-- help with noradrenergic hyperactivity; antidiarrheal meds, NSAIDs, muscle relaxants)
Goals
- prevent or reduce withdrawal sx
- prevent or reduce cravings
- avoid relapse
- restore normal physiological functions caused by opioid dependence
- improve impairments created by opioid dependence
Non-pharmacological treatments: support groups, psychotherapy, pain contracts, family counseling
Pharmacological treatments
- Methadone
- Buprenorphine
- Naltrexone
32
CDC Chronic Pain Guidelines
- Pain lasting > 1 yr
12 recommendations
- nonopioid and nonpharm treatments preferred (consider opioids when benefits outweigh risks)
- establish treatment goals before starting opioid therapy
- discuss risks and realistic benefits
- start with IR opioids
- start with lowest effective dosage
- for acute pain, lowest effective dose at limited duration (3-7 days)
- evaluate treatment q1-4 wks after starting or increasing dose; if dosing stable, evaluate q 3months (if harm> benefit, taper and d/c)
- evaluate risk for harms (sleep disorders, pregnancy, renal/liver insufficiency, >65 yrs old)
- review history of controlled substance prescriptions
- urine drug testing prior to initiation and annually thereafter
- avoid concomitant use of BZDs
- arrange treatment for opioid use disorders
Pharm
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