Download Schedule II Drugs: Pain Management

SCHEDULE II DRUGS:
PAIN MANAGEMENT
Rachel Beaty, PharmD
Clinical Pharmacy Specialist, Hematology
Thursday, April 14, 2016
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
DISCLOSURE DECLARATION
• The following declare they have no relevant financial interest in
relation to this activity:
• Rachel Beaty, presenter
• Off-label uses of medications will be disclosed during the
presentation
• Brand names, kept to a minimum, are used when necessary to
differentiate products
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
LEARNING OBJECTIVES
1.
Interpret common pain assessment tools and behaviors associated
with pain in pediatric patients
2.
Review the stepwise approach for the treatment of pain in
pediatric patients
3.
Describe the properties of various schedule II medications used
for the treatment of pain in pediatric patients
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
DEFINITION OF PAIN
• “An unpleasant sensory and emotional experience arising from
actual or potential tissue damage or described in terms of such
damage”
• “Sensory, emotional, cognitive, and behavioral components that are
interrelated with environmental, developmental, socio-cultural, and
contextual factors”
• Pain in children is a public health concern
• Chronic pain affects 20 - 35% of children and
adolescents worldwide
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Pain. 2008;137:473-477.
N Engl J Med. 1982;306:639-645.
Geneva: World Health Organization; 2012.
Pain. 2011;152(12):2729–2738.
Image from: http://contemporarypediatrics.modernmedicine.com/contemporary-pediatrics/news/neurologic-complications-influenza-children.
BARRIERS TO PAIN CONTROL IN PEDIATRICS
• Barriers to pediatric pain control
• Misconception that infants and children do not feel pain
• Lack of routine pain assessment in children
• Lack of knowledge
• Fears of respiratory depression or other adverse effects of analgesic medication
• Misconception that preventing pain takes too much time and effort
• Joint Commission on Accreditation of Healthcare Organizations (JCAHO)
considers pain “the fifth vital sign”
• Chronic pain that is left unaddressed can lead to emotional and
psychological scars
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Pediatrics. 2001;108:793-797.
Indian J Palliat Care. 2011;17:S70-S73.
BEHAVIORS ASSOCIATED WITH PAIN
Acute Pain
•
•
•
•
•
Facial expression
Body movement and posture
Inability to be consoled
Crying
Groaning
Chronic Pain
•
•
•
•
•
•
•
•
•
•
Abnormal posturing
Fear of being moved
Lack of facial expression
Lack of interest in surroundings
Undue quietness
Increased irritability
Sleep disruption
Low mood
Anger
Changes in Appetite
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Indian J Palliat Care. 2011;17:S70-S73.
PAIN ASSESSMENT
• Should involve one or a combination of the following approaches:
Self-reporting, validated observational measures, physiological
indicators, behavioral signs, and/or parent report
• Children’s self report should be the primary source
• Pain is primarily an internal experience
• Self reported tools: Visual analog scale
(VAS), numerical rating scale, faces
scale, color analogs scale (CAS),
poker chip scale
• Faces scales are usually preferred by children
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Can J Anaesth. 2014;61(2):180-7.
Pediatrics. 2010;126:e1168-e1198.
Image from: http://wongbakerfaces.org/faces-download/.
CASE
TS is a 3 YO female admitted for an appendectomy. She has been
crying, groaning, and unable to be consoled. Which of the following is
true:
A. The Wong-Baker Faces Pain Rating Scale should be used to assess
the patient’s pain
B. The parents should be questioned regarding whether or not they
feel their child is in pain
C. Her pain should be assessed utilizing the Visual Analog Scale
D. These actions are indicative of a normal toddler
E. Both A and B
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
TYPES OF PAIN
Pain
Nociceptive
Somatic
Neuropathic
Visceral
Sensory nerve
damage
Well-localized
Poorly- localized
Poorly-localized
Sharp
Stabbing
Cramping
Tightness
Burning
Tingling
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
J Pain Symptom Manage. 2011; 22(5):899-910.
Am J Manag Care. 2006;12:S256-S262.
NEUROPATHIC PAIN
• Abnormal excitability in the peripheral nervous system (PNS) or
central nervous system (CNS) that may persist after injury heals or
inflammation subsides
• Acute or chronic
• Burning, shooting, tingling, or stabbing quality
• Post-traumatic, post-surgical
• Responds poorly to opioids
• Complex regional pain syndrome
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Clin J Pain. 2006;22:443-448.
Arch Neurol. 2003; 60(11):1524-34.
MANAGEMENT OF NEUROPATHIC
PAIN IN CHILDREN
Medications listed are off label
indications
• No randomized controlled trials
• Least invasive to most invasive stepwise approach
• Identify and treat underlying cause
• Start non-pharmacologic therapies to help manage comorbidities
• Administer an opioid and/or non-steroidal anti-inflammatory (NSAID) if not
contraindicated
• If pain is localized, consider the addition of lidocaine 5% patch
• Add low dose tricyclic-antidepressant (nortriptyline or amitriptyline) or
gabapentin
• Begin NMDA-receptor channel blocker such as ketamine or methadone.
Consider addition of benzodiazepine, alpha agonist
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Nortriptyline. Lexi-Drugs Online.
Amitriptyline. Lexi-Drugs Online.
Curr Opin Support Palliat Care. 2013;7:131-138.
Arch Neurol. 2003; 60(11):1524-34.
MANAGEMENT OF NEUROPATHIC PAIN IN CHILDREN
WITH CANCER
Reference
Study Design
Outcome
Anghelescu DL et
al. J Opioid
Manag. 2011;
7:353–361.
• Retrospective, single-center
• Cancer patients over 5 years
N= 41
Methadone was effective in treating both neuropathic and nociceptive pain
unresponsive to other opioids (39% for neuropathic pain)
Anghelescu DL et
al. Pain Manag
Nurs. 2011;
12:82–94.
• Retrospective, single center
• Pediatric patients over 26
years
N= 151
Presence of complex pain syndrome of mixed nociceptive and neuropathic pain
following limb-sparing surgery for bone cancer
Therapies included opioids, NSAIDS, acetaminophen-opioid combinations, postoperative continuous epidural infusion, anticonvulsants, and tricyclic
antidepressants for neuropathic pain
Anghelescu DL et
al. Pediatr Blood
Cancer 2011;
57:1147–1153.
• Retrospective, single center
• Pediatric patients with acute
lymphoblastic leukemia over
20 years
N= 498
35% experienced vincristine-associated neuropathic pain. There was no evidence
gabapentin prevented recurrence of neuropathic pain at a mean dose of 15.5
mg/kg/day. However, that dose may have been too low to show effect (usual max
dose: 50-70 mg/kg/day)
Anghelescu DL et
al Pain Manage
Nurs.
2014;15(1):126131.
• Retrospective, single center
• Pediatric patients with
neuropathic and nonneuropathic pain who were
referred to the pain service
over 3 years
N= 323
56 (17%) had neuropathic pain
Median age: 16 years (range 2.2-28.3 years)
Majority had solid tumor diagnosis (37 of 56; 66.1 %)
All patients with neuropathic pain received at least one pharmacologic
intervention- most commonly opioids (97 %) followed by anticonvulsants, mainly
gabapentin (90.9 %)
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Medications listed are off label indications
ANALGESICS FOR NEUROPATHIC PAIN
• Gabapentin
• Binds to alpha-2-delta-1 subunit on presynaptic voltage-gated Ca2+ channels modulates release of excitatory neurotransmitters
• Dosed three times daily
• Significant improvement in pain in adults with 3600 mg/day compared to
placebo
• Amitriptyline
• Enhanced availability of monoamines within pathways that modulate
descending pain
• Inhibition of norepinephrine reuptake. Serotonergic and dopaminergic effects
may also play a role
• Dosed once daily
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Gabapentin. Lexi-Drugs Online.
Amitriptyline. Lexi-Drugs Online.
Anaesthesia. 2002;57:451-462.
Arch Neurol. 2003; 60(11):1524-34.
CASE
JT is a 19 YO AA male s/p treatment of Ewing’s sarcoma who is being
seen in your clinic for a follow up appointment. He received vincristine
as part of his chemotherapy regimen and has been complaining of
tingling pain in his hands and feet for the past 2 weeks. What should
you do?
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
NOCICEPTIVE PAIN
Acute
Perioperative
/ Procedural
Related
Pain
Chronic /
Persisting
Recurring
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
NONPHARMACOLOGIC TREATMENT
• Useful to prevent and treat pain
• Interfere with pain transmission along ascending pain pathway by
introducing other excitatory messages
Nonpharmacologic Treatment
Music
Hypnosis
Heat therapy
Massage therapy
Distraction
Aromatherapy
Physical therapy
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Emerg Med Clin North Am. 2005;23:393-414.
PHARMACOLOGIC TREATMENT: TWO-STEP
STRATEGY
• More effective than the three step ladder (WHO 1986)
• Three step ladder
• Recommended use of codeine and/or tramadol as a weak opioid for
the treatment of moderate pain
• Two step ladder
• Mild
• Acetaminophen and ibuprofen
• Moderate to Severe
• Opioids
• Morphine-drug of choice
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
MEDICATIONS FOR MILD PAIN
• Acetaminophen
• Inhibits synthesis of prostaglandins in the CNS and blocks pain impulse
generation
• 10 - 15 mg/kg every 6 hours
• Maximum daily dose: 75 mg/kg/day
• Ibuprofen
• Inhibits cyclooxygenase-1 and 2 enzymes, which results in decreased
formation of prostaglandin precursors thromboxane A2
• 10 mg/kg every 6 hours
• Maximum daily dose: 40 mg/kg/day
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
McNeil Consumer Healthcare, 2014.
Acetaminophen. Lexi-Drugs Online.
Ibuprofen. Lexi-Drugs Online.
OPIOIDS FOR MODERATE-SEVERE PAIN
• Use of strong opioids is recommended for the relief of moderate to
severe persisting pain in children
• No upper dosage limit: No ceiling analgesic effect
• Appropriate dose is the one that produces pain relief for the
individual child
• If pain is constantly present, analgesics should be administered
“around the clock” while monitoring side effects
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Clin Perinatol. 1987;14:911-30.
J Invest Dermatol. 1981;76:147-50.
Pediatrics. 2005;115:1494-500.
Geneva: World Health Organization; 2012.
ROUTE OF ADMINISTRATION
• Utilize simplest, most effective, and least painful route
• Recommend: Oral, intravenous,
subcutaneous
• Continuous infusions for patients requiring
more steady-state opioid concentrations
• Intramuscular is not preferred due to it
being painful
• Rectal has unreliable bioavailability
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Reg Anesth Pain Med. 1992;24:438-43.
Pediatr Anaesth. 1999;9:321-7.
Image from: http://www.nortongethealthy.com/prescription-safety.
GENERAL MECHANISM OF ACTION
• Work at opioid (µ) receptors in the CNS and PNS
• Binds to opioid receptors in the
CNS, causing inhibition of
ascending pain pathways, altering
the perception of and response to
pain
• Each opioid has different
affinities for different receptors
• Variability in response among patients
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Lexi-Drugs Online.
Image from http://opioidanalgesics.blogspot.com/2011/03/mechanism-of-action-of-opioid.html.
OPIOID PHARMACOKINETIC DIFFERENCES
• Different pharmacokinetics for different age groups
• First few years of life - significant changes in absorption, distribution,
metabolism, and excretion
• Neonates - thinner stratum corneum and greater hydration to the
epidermis compared with older children
• Neonates and infants - reduced ability to metabolize medications
hepatically
• Different pharmacokinetics for obese children
• Higher volume of distribution for lipophilic medication and increased
glomerular filtration rates
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Clin Perinatol. 1987;14:911-30.
J Invest Dermatol. 1981;76:147-50.
Pediatrics. 2005;115:1494-500.
SCHEDULE II OPIOIDS
• Opioids are one of the oldest drugs
• Opium poppy
Natural
Synthetic
Morphine
Fentanyl
Hydrocodone
Methadone
Oxycodone
Meperidine
Hydromorphone
Tapentadol
Oxymorphone
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Psychosomatics. 2009;50(2):169-76.
Image from: http://veryshareimg.com/opium-poppy-flower.html.
Off label use in pediatrics < 2 years
FENTANYL
• Availability: Injectable solution, *buccal tab, *lozenge, and
*transdermal patch
• Rapid onset, brief duration of action
• Starting dose for children 1 - 12 years
• IV injection: 1 - 2 mcg/kg/dose every 30 - 60 minutes
• IV infusion: 1 mcg/kg/hr
• Clinical pearls:
•
•
•
•
•
70-100x more potent than intravenous morphine
Prolonged half-life with continuous infusion
Side effect of rapid administration may produce chest wall rigidity
Boxed Warning: CYP3A4 interactions
The parenteral preparation may be given intranasal
*Should only be used in opioid tolerant patients
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Fentanyl. Lexi-Drugs Online.
Anesthesiology. 1996;85:1268-75.
Geneva: World Health Organization; 2012.
Image from: http://www.thepoisonreview.com/2011/06/30/whole-fentanyl-patch-ingestion-expect-the-worst/.
Off label use in pediatrics < 2 years
HYDROCODONE
• Availability:
• Formulated with acetaminophen; capsule, oral elixir, oral solution, oral tablet
• Also available as an ER abuse deterrent tablet
• Starting dose children 2 - 13 years
• 0.1 - 0.2 mg/kg/dose every 4 - 6 hours
• Clinical pearls:
• Rescheduled from Schedule III to Schedule II August 2014
• Since April 2014: ≤ 325 mg acetaminophen
• Boxed Warning: CYP3A4 interactions
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Hydrocodone. Lexi-Drugs Online.
Off label use in pediatrics
HYDROMORPHONE
• Availability: Tablet, suspension, injectable solution, suppository
• Starting dose for children 1 - 12 years
• IV injection: 0.015 mg/kg/dose every 3 - 6 hrs
• Oral: 0.03-0.08 mg/kg/dose every 3 - 4 hrs
• Clinical pearls:
• 5 x more potent than intravenous morphine
• Preferred for patients in renal failure due to decreased amount of metabolites
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Hydromorphone. Lexi-Drugs Online.
Pediatr Clin North Am. 2005;995-1027.
Off label use in pediatrics
METHADONE
• Availability: Tablet, suspension, injectable solution
• Starting dose for children 1 - 12 years
• Oral: 0.1 - 0.2 mg/kg/dose every 4 hrs for first 2 - 3 doses, then every 6 - 12 hrs
• IV: 0.1-0.2 mg/kg/dose every 4 hrs for first 2-3 doses, then every 6 - 12 hrs
• Clinical pearls:
•
•
•
•
•
Long half life and slow peak - steady state concentrations may take 12 days
Weak N-methyl-D-aspartate (NMDA) receptor antagonism
CYP3A4 interactions
Boxed Warning: QT prolongation
Structurally similar to verapamil - calcium channel blockade
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Pharmacotherapy. 2002;22:1196-9.
Methadone. Lexi-Drugs Online.
Off label use in pediatrics
MORPHINE
• Availability: Immediate release tablet, controlled release tablet,
suspension, sublingual tablet, suppository, injectable solution
• Starting dose for children 1 - 12 years
• Oral: 0.2 – 0.5 mg/kg/dose every 4 hrs
• IV: 0.1 – 0.2 mg/kg/dose every 4 hrs
• Clinical pearls:
• Metabolized by glucuronidation to morphine-6-glucuronide (active) and
morphine-3-glucuronide (inactive)
• Neonates: Reduced ability to produce morphine-6-glucuronide
• Renally eliminated
• Half life 1 - 3 hours in older children; 10 - 20 hours in preterm neonates
• Hypotension
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Morphine. Lexi-Drugs Online.
N Eng J Med. 2002;347:1094-103.
Pediatr Clin North Am. 2005;995-1027.
Geneva: World Health Organization; 2012.
Off label use in pediatrics
OXYCODONE
• Availability: Immediate release tablet, extended release tablet,
suspension
• Starting dose for children 1 - 12 years
• Oral: 0.125 – 0.2 mg/kg/dose every 4 hrs
• Clinical pearls:
• Most potent oral opioid
• Boxed Warning: CYP3A4 interactions
• Partially metabolized to an active metabolite, oxymorphone, via CYP2D6
pathway
• Slow or ultra-fast metabolizers may experience reduced or enhanced
analgesia and dose-related side-effects
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Oxycodone. Lexi-Drugs Online.
OPIOID HYPERSENSITIVITY
Phenanthrenes
Phenylpiperidines
Phenylheptanones
Morphine
Hydromorphone
Codeine
Hydrocodone
Oxycodone
Fentanyl
Remifentanyl
Methadone
• Cross-reactivity between agents of same structural class
• Investigate allergies
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
PAAPA. 2012;25(1):17.
GENERAL SIDE EFFECTS OF OPIOIDS
Respiratory
Depression
Urinary
Retention
Nausea /
Vomiting
Opioids
Pruritus
Sedation
Constipation
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Lexi-Drugs Online.
Pediatr Clin North Am. 2005;995-1027.
Geneva: World Health Organization; 2012.
SUPPORTIVE THERAPY
• Constipation: Prevention is Key
• Bowel regimen: Polyethylene glycol, docusate, bisacodyl, senna, lactulose,
magnesium citrate, oral naloxone
• Sedation: Switch to another agent
• Consider psychostimulant: Methylphenidate, dextro-amphetamie, caffeine
• Nausea/vomiting
• Antiemetics: Ondansetron, promethazine
• Pruritus
• Diphenhydramine, hydroxyzine, low-dose naloxone infusion
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Lexi-Drugs Online.
Pediatr Clin North Am. 2005;995-1027.
OTHER SCHEDULE II PAIN MEDICATIONS
• Meperidine
• Tapentadol
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Off label use in pediatrics
MEPERIDINE
• Not indicated or recommended for treatment of pain in pediatric
patients
• Availability: Tablet, solution, injectable solution
• Low bioavailability, short duration of action, formation of an active
metabolite
• Risk of seizures with accumulation of active metabolite normeperidine
• Higher risk with oral administration: First-pass metabolism decreases efficacy
while increasing normeperidine concentrations
• American Pain Society recommends restricting the use of
meperidine in adults to 600 mg/day and for < 48 hours
• Use in children: Drug induced rigors (off label indication), allergic to other
analgesics
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
J Pediatr Pharmacol Ther. 2011;16(3):185-190.
Meperidine. Lexi-Drugs Online.
Off label use in pediatrics
TAPENTADOL
• Indications: Moderate-severe acute pain in adults
• Availability: Immediate release tablets, extended release tablets
• µ opioid agonist and norepinephrine reuptake inhibitor
• Clinical pearls:
•
•
•
•
Lower affinity to µ opioid receptor than morphine
Less opioid receptor mediated side effects- nausea, constipation
1/3 analgesic potency as morphine
Norepinephrine reuptake inhibition also contributes to analgesia
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Anesth Prog. 2013;60:178-187.
Clinical trials.gov: NCT01134536.
TAPENTADOL PEDIATRIC TRIAL
Children 6 - < 18 years after
scheduled surgical procedures
• An efficacy and safety study of tapentadol in the treatment of post-operative acute
pain requiring opioid treatment in pediatric participants
< 20 kg: 4 mg/mL
Tapentadol 1 mg/kg
single dose
≥ 20 kg: 20 mg/mL
• Multi-center, single-arm, open-label, single-dose trial
• Primary outcome: Pharmacokinetic profile and the number of patients with adverse
events
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Clinical trials.gov: NCT01134536.
PATIENT CONTROLLED ANALGESIA (PCA)
• Programmable pump that allows patient control of intravenous
analgesia
• Patient can choose when to deliver a dose of opioid and achieve
relief quickly
• Inherent safety in the PCA - patient will fall
asleep when over sedated and is unlikely to
administer too much drug
• Teaching is integral and essential
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Image from: http://www.kroslakent.com/cgi-bin/shop/pid_1837.htm.
Randomized
PCA DOSING TRIAL
•
•
•
•
Higher demand dose with low
constant infusion (HDLI)
Total opioid utilization:
Pediatrics: 3.7 ± 1.0 mg/kg
Adults: 11.6 ± 2.6 mg/kg
Lower demand dose with
higher constant infusion
(LDHI)
Total opioid utilization:
Pediatrics: 5.8 ± 2.2 mg/kg
Adults: 4.7 ± 0.9 mg/kg
38 total patients with sickle cell disease enrolled
Reduction in pain intensity during PCA treatment observed in both groups
Time to improvement did not differ
Hospital durations were similar for children in both groups
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Am Jour Hematol. 2011;86(12):E70-E73.
Retrospective Review
PCA DOSING TRIAL #2
HDLI
Total morphine: 222.71 mg
Total length of PCA: 4.9 days
Total hospital days: 5.03 days
LDHI
Total morphine 355.58 mg
Total length of PCA: 6.16 days
Total hospital days: 7.18 days
• 26 patients 11-18 years with sickle cell pain crisis
• Total morphine and length of hospital stay less in high demand/low basal infusion
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
J of Pediatr Nurs. 1998;13(1):15-19.
Descriptive Design
PCA TRIAL #3
•
•
•
HDLI
No significant change in pain
rating scale
Morphine: 1.1-1.2 mg/kg/day
LDHI
Significant reduction in pain
rating scale
Morphine: 0.3-1 mg/kg/day
Nursing controlled analgesia:
high scheduled and low
infusion
No significant change in pain
rating scale
Morphine: 1.1-2.4 mg/kg/day
13 hospitalized pediatric sickle cell patients > 8 years
Amount of morphine administered was not significantly different
Patients had significantly lower pain scores in LDHI group
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
J Pain Manag. 2008;2(1):179-190.
MONITOR PATIENTS RECEIVING OPIOIDS
• Close observation of all patients receiving opioids
• Routine vital signs
• Sedation scales when indicated
• Particular close attention to patients
• History of obstructive sleep apnea
• Craniofacial anomalies
• Infants who are younger than 6 months or older infants with
history of apnea or prematurity
• Opioid-naïve patients with continuous infusions
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
BREAKTHROUGH PAIN
• Sudden onset, occurs for short periods of time and is severe
• Distinguish between end-of-dose pain episodes, incident pain
related to movement or procedure, and breakthrough pain is
needed
• Children with persisting pain should receive regular medication to
control pain and appropriate medication for breakthrough pain
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
NALOXONE
• Mechanism of action
• Opioid antagonist that competes and displaces opioids at opioid receptor sites
• Dose
• 0.1 mg/kg/dose (max: 2 mg) every 3 minutes IV,
IM, SubQ, intraosseous (off-label), endotracheal
(off-label)
• 4 mg intranasal nasal spray ; 1 mg per nostril of
1 mg/mL injection (off-label)
• Clinical pearls:
• Caution to avoid withdrawal syndrome after prolonged administration of
opioids and in opioid tolerant children, cardiovascular disease, post-operative
patients
• May be given continuously for treatment of opioid induced pruritus (off-label)
• Dose: 0.25 mcg/kg/hour
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Naloxone. Lexi-Drugs Online.
Image from: https://www.statnews.com/2015/11/18/fda-nasal-spray-overdose/.
PROLONGED RELEASE VS. IMMEDIATE RELEASE
• Immediate release: First line
• Prolonged release: Recommended to be available if patient can
afford medication
• Insufficient evidence to support prolonged release over immediate
release morphine. Studies in adults showed that immediate and
prolonged release morphine formulations are equivalent for pain
relief
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Cochrane Database Syst Rev. 2007;4:1-57.
OPIOID SWITCHING AND ROTATION
• Opioid Switching - changing to an alternative opioid because of an
inadequate analgesic effect and/or dose-limiting side-effects and to
improve outcomes
• Recommended in presence of inadequate analgesic effect with intolerable
side-effects
• Utilize the equianalgesic dosing table
• Opioid Rotation - changing between different opioids in a set
schedule to prevent potential adverse effects and limit dose
escalation
• Routine rotation of opioids is not recommended
• Optimal titration of opioids before switching to another agent
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
J Pain Sympton Manage. 2009;38(3):418-425.
CONVERTING BETWEEN OPIOIDS
• General process for switching opioids
• Determine 24-hr opioid requirement
• Calculate equianalgesic dose of new opioid
• Convert to desired formulation of new opioid
• Incomplete cross-tolerance
• Tolerance to opioids does not occur to the same extent with each drug
• If goal is true equianalgesic conversion, reduce dose by ~20% when switching
from one opioid to another
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
EQUIANALGESIC DOSING
Approximate Equianalgesic Dose (mg)
Agent
IV
PO
Morphine
10
30
Hydromorphone
1.5
7.5
Fentanyl
0.1
--
--
20
Oxycodone
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Lexi-Drugs Online.
PARENTERAL AND ORAL EQUIANALGESIC DOSES
Opioid
(Parenteral : Oral)
Morphine
1:2 – 1:3
Hydromorphone
1:2 – 1:5
Methadone
1:1 – 1:2
Example: 2 mg IV morphine = 4 to 6 mg PO morphine
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Geneva: World Health Organization; 2012.
Lexi-Drugs Online.
EXAMPLE CONVERSION
Hydromorphone PCA
Continuous 0.06 mg/hr + demand 0.2 mg q10 min PRN
Patient has received 12 demand doses in past 24 hr
Convert to equianalgesic oral morphine regimen
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
CASE
BC is a 15 yo male with HbSS admitted to the floor with a VOC. He was
started on a morphine PCA but has been complaining of itching. Which
of the following is appropriate:
A.
B.
C.
D.
Order a low dose naloxone infusion for the patient
Switch the PCA from morphine to hydromorphone
Scheduled hydroxyzine to be given with the morphine
Any of the above
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
TOLERANCE, DEPENDENCE, ADDICTION
• Tolerance: Body becomes accustomed to certain doses of the
medicine and needs a higher dose to obtain the same effect
• Patients who receive synthetic opioids are more likely to develop
tolerance
• Treatment: Increase the dose, decrease the interval, switch agents
• Dependence: Behavioral and cognitive phenomenon including a
strong desire to take the psychoactive drug
• Addiction: Persistent need to obtain an opioid medication for its
euphoric effects, which often involves criminal activity to obtain the
agent
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Crit Care Med. 2000;28:2122-32.
Geneva: World Health Organization; 2012.
WITHDRAWAL
• Withdrawal signs/symptoms: Tachypnea, tachycardia, fever,
sweating, hypertension, diarrhea
• 35-52% of critically ill children and infants develop withdrawal due
to long-term opioid use
• Risk for withdrawal increases with long duration and high dosages
of opioids
• To prevent: Taper opioid dose
• 7 - 14 days: Decrease by 10 - 20% of original dose every 8 hours
• > 14 days: Decrease dose by 10 - 20% of original dose weekly
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
Ann Pharmacother. 2009;431506-11.
Geneva: World Health Organization; 2012.
Image from http://www.roxyaddict.com/blog/.
REASSESSMENT OF PAIN
• How did the intervention impact the patient’s report of pain (or
behavior)?
• Is the patient experiencing adverse effects from opioids?
• Constipation - modify bowel regimen
• Pruritus with continuous opioid - low-dose naloxone drip
• Does patient require adjunctive agent in addition to opioids?
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
CASE
EF is an 18-yr old patient with refractory rhabdomyosarcoma who is
currently on palliative chemotherapy and was admitted for worsening
pain. His current pain medications include: Hydromorphone PCA and
Methadone PO. The provider initiated gabapentin for tingling/burning
sensations in lower extremities and the oral methadone dose was
increased 2 days ago, but patient’s pain is still not controlled. She
wants to increase the methadone dose. What do you tell her?
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
CASE
Patient AB is a 18 yo female who is followed in your clinic for sickle cell
disease. Of note, she has missed the majority of her appointments
over the past two years. Based on your exam and AB’s report of her
pain, she needs a pain medication for as-needed treatment of pain at
home. The patient states she responds well to Lortab®, you should
A. Have the MD write a prescription for Lortab®, as it is a Schedule-II
medication and requires a triplicate prescription
B. Inform the patient that Lortab® is formulated with 500 mg
acetaminophen and is no longer available
C. Call Lortab® in to the patient’s pharmacy
D. None of the above
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
SUMMARY
• Pain is subjective – not all patients are alike
• Pain should be assessed and managed consistently and with an
interdisciplinary approach
• A two-step approach to treating pain should be employed
• Selection of primary and adjunctive agents for pain depends on
medication properties… and the patient!
DEPARTMENT
NAME
DEPARTMENT
OF PHARMACY
COMMENTS/QUESTIONS?
DEPARTMENT NAME