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Objectives. Define different types of painReview general guidelines for the pharmacological management of painCompare and contrastNon-opioid analgesicsOpioid analgesicsTopical agentsMiscellaneous analgesicsCalculate equianalgesic opioid doses using conversion guidelines Discuss management strategies for treating adverse effects associated with opioid therapyRecognize major drug interactions with analgesic agentsDiscuss medication safety issues with analgesic agentsDevelop patient-spec9441
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1. Pediatric Pain Management Liza Li, PharmD
Pediatric Pharmacy Resident
Department of Pharmacy
Childrens Hospital Boston
3. Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.
International Association for the Study of Pain
Pain is an inherently subjective multi-factoral experience and should be assessed and treated as such.
American Academy of Pediatrics and American Pain Society
4. Misconceptions That Can Lead to Under Treatment of Pain in Children Children, especially infants do not:
Feel pain the way adults do
Remember pain
Lack of assessment for presence of pain
Lack knowledge in pediatric analgesics
Use
Dosing
Adverse effects
Preventing pain takes too much time
5. Consequences of Inadequate Analgesia During Painful ProceduresWeisman, SJ et al. Arch Pediatr Adolesc Med 1998; 152: 147-149 Background/Method
21 patients documenting the efficacy of oral transmucosal fentanyl citrate (OTFC) for painful procedures rated the pain associated with subsequent procedures performed with open labeled OTFC
Results
Children <8 yo, mean pain ratings ? for those who had received placebo in the original study compared to those who received OTFC
6. Components of Pain Nociception
Sensation of pain
Perception of pain
Triggered by a noxious stimulus
Suffering
Negative response induced by pain, fear, anxiety, stress and other psychological states
Pain behaviors
Results from pain and suffering and are things a person does or does not do that can be ascribed to the presence of tissue damage
7. Types of Pain Acute
Elicited by substantial injury of body tissue
Activation of nociceptive transducers at the site of local tissue damage
Chronic
Commonly triggered by an injury or disease, but may be perpetuated by factors other than the cause of the pain
8. Types of Pain Transient
Elicited by the activation of nociceptive transducers in skin or other tissues of the body in the absence of any tissue damage Neuropathic
Pain sustained by abnormal processing of sensory input by the peripheral or central nervous system
9. I have a boo boo < 6 months
Do not express anticipatory fear
6 to 18 months
Begin to develop fear of painful experiences and withdraw when pain is anticipated
18 to 24 months
Express pain with words such as hurt or boo boo
3 years Children
Begin to localize pain and identify external causes
5 to 7 years
Improve understanding of pain, ability to localize and cooperate
Adolescence
Able to qualify/quantify pain and develop cognitive coping strategies that may help diminish pain
10. Measurement of Pain in Children Self-reported
Gold standard
Behavioral
Crying, facial expressions, general body movements
Physiological
HR, BP, RR, O2 saturation
11. Pain Assessment Tools PAINS
Place
Amount
Intensity
Nullifiers
Side Effects
PQRST
FLACC
Face
Legs
Activity
Cry
Consolability
N-PASS
12. Pain Scales
13. Treatment Goals Minimize physical pain and discomfort
Alleviate anxiety
Prevent potentially deleterious physiologic responses due to pain
14. Non-Pharmacologic Pain Treatment Communication
Psychological treatment
Physical therapy
Distraction
Biofeedback
Transcutaneous electrical nerve stimulation (TENS)
Acupuncture
15. Pharmacologic Pain Treatment Non-Opioids
Opioids
Adjuvant analgesics
Topical anesthetics
Routes of administration
Epidural
Intravenous
Intramuscular
Intrathecal
Oral
Nasal
Suppository
Topical
17. Ideal Analgesic Therapy Continuous analgesia
No/minimal adverse effects
Non-invasive mode of administration
No cumbersome equipment
18. Non-Opioid Analgesics
19. Acetaminophen MOA:
Inhibits the synthesis of prostaglandins in the CNS
Peripherally blocks pain impulse generation
Produces antipyresis from inhibition of hypothalamic heat-regulating center
NOT an anti-inflammatory
Adverse reactions
Blood dyscrasias
Hepatic necrosis w/ overdose
Renal injury w/ chronic use
20. Acetaminophen Dosage Forms
21. Non-Steroidal Anti-inflammatory Drugs NSAIDs are analgesic, anti-inflammatory, anti-platelet, and antipyretic
Side effects
Renal
Hematological
Gastric mucosal damage Examples
Aspirin
Choline magnesium trisalicylate
Diclofenac
Ibuprofen
Indomethacin
Ketorolac
Naproxen
Sulindac
22. NSAIDs MOA
23. Ibuprofen Special Notes
May cause allergic reactions in susceptible individuals
Junior Strength Motrin caplets contain tartrazine
Motrin IB gelcaps contain benzyl alcohol
Some products contain sodium benzoate (metabolite of benzyl alcohol)
Large amounts of benzyl alcohol (>99 mg/kg/day) have been associated with gasping syndrome
24. Ketorolac Only IV NSAID for pain management
Contraindicated
Coagulopathy
Gastropathy
Hypovolemia
Max duration=5 days
25. COX-2 Inhibitors Reduce risk of gastric irritation and bleeding
Inhibits prostaglandin synthesis
Indications
Signs/symptoms of osteoarthritis
Management of acute pain in adults
Treatment of menstrual cramps
Rheumatoid arthritis in adults and children Examples
Celocoxib (Celebrex)
Valdecoxib (Bextra)
Rofecoxib (Vioxx)
Voluntarily withdrawn from market:? risk CVD
Clinical evidence
VIGOR- VOIXX GI Outcomes Research
APPROVe- Adenomatous Polyp Prevention on VOIXX
26. PK/PD Properties of Non-Opioid Analgesics
27. Relative Side Effects of Non-Opioid Analgesics
28. Opioid Analgesics
29. Opioid Analgesics Morphine-Like Opioids
Morphine
Hydromorphone
Codeine
Oxycodone
Hydrocodone
Meperidine-Like Opioids
Meperidine
Fentanyl
Methadone-Like Agonists
Methadone
Propoxyphene
30. Opioid Analgesics Binds to opiate receptors in the CNS
Inhibits ascending pain pathways, altering the perception of and response to pain
Produces generalized CNS depression
31. Pharmacokinetics of Opioid Analgesics
32. Opioid Analgesic Route of Administration
33. Combination Analgesics Consider content of combination products
DO NOT exceed acetaminophen or aspirin maximum daily doses!
Examples:
Codeine/Acetaminophen (Tylenol #2,3,4)
Hydrocodone/Acetaminophen (Vicodin , Narco)
Oxycodone/Acetaminophen (Percocet )
Oxycodone/Aspirin (Pecodan )
Propoxyphene/Acetaminophen (Darvocet )
34. Conversions Between Opioids Calculate total milligrams of opioid administered for the past 24 hr.
Convert 24 hr dose to chosen equivalent dose.
Divide 24 hr daily dose into appropriate dose per time interval.
When switching from one opioid to another, dose reductions should be considered if the patient has stable, controlled pain.
Effective pain management may be achieved at 50-70% of the calculated equianalgesic dose because there is incomplete cross-tolerance among these drugs.
Most patients benefit from availability for a short-acting opioid for breakthrough pain.
35. Opioid Analgesics: Equianalgesic Dose Conversion
36. Case 1 KG is a 5 yo girl w/ sickle cell disease whos pain is controlled on 10mg of morphine solution po q3h. Her team is preparing for her discharge and would like to simplify her therapy to allow for fewer daily doses.
As her primary nurse, the team looks to you for guidance in dosing MS Contin (long acting morphine) which is available in 15mg and 30mg tablets.
37. Answer to Case 1 Total daily dose:
10mg of Morphine po q3h
= 80mg/day of morphine
Sustained release morphine:
MS Contin is available in 15mg, 30mg tabs
Possible recommendations:
Aggressive management
MS Contin 30mg po q12H + Morphine 10mg po q4h prn for breakthrough
Conservative management
MS Contin 45mg po q12H + Morphine 15mg po q4h prn for breakthrough
38. Case 2 DB is a 9 yo boy s/p spinal fusion. His fentanyl PCA requirement has ?ed significantly. He is only requiring on average 60 mcg/12 hr.
The physician would like to convert DB to oxycodone po and has asked you for assistance in the calculations.
39. Answer to Case 2 Total daily dose:
60mcg/12hr ? 120 mcg/24hr
Conversion to equivalent dose:
Fentanyl = 100mcg = 120mcg
Oxycodone 20mg xmg
Fentanyl = 0.1mg = 0.120mg
Oxycodone 20mg xmg
x= 24mg/day of Oxycodone
40. Answer to Case 2 Remember incomplete CROSS-TOLERANCE and effective pain management at 50-75% of calculated equianalgesic dose!
Possible Recommendations:
Aggressive management (50% of calculated dose)
Oxycodone 3mg po q6h prn
Conservative management (75% of calculated dose)
Oxycodone 4.5mg po q6h prn
41. Case 3 SO is a 17 yo male s/p ACL repair on OxyContin (long acting oxycodone) 20mg po q12h and Percocet (oxycodone 5mg/325mg acetaminophen) 1 tab po q3-4h PRN. The patients pain has been well controlled on this regimen (only requiring 1 Percocet tab daily).
Oral administration has become a contraindication in this patient and therefore you have been asked to convert the patient to a continuous infusion of morphine.
42. Answer to Case 3 Daily requirements:
OxyContin (long acting oxycodone) 20mg po q12h
Percocet (oxycodone 5mg/325mg acetaminophen) 1 tab/day
Total of oxycodone 45mg/day
Conversion to equivalent dose:
Morphine = 10mg = xmg
Oxycodone 20mg 45mg
X= 22.5mg/day of morphine
43. Answer to Case 3 Remember incomplete CROSS-TOLERANCE and effective pain management at 50-75% of calculated equianalgesic dose!
Possible Recommendations
Aggressive management (50% of calculated dose)
Morphine IV 11.24mg/day? ~ 0.5mg/hr
Conservative management (75% of calculated dose)
Morphine IV 16.9mg/day? 0.7mg/hr
44. Opioid Antagonists Antagonist
Competes and displaces narcotics at narcotic receptor sites
Example
Naloxone
Mixed Agonist/Antagonist
Binds to opiate receptors in the CNS
Cause inhibition of ascending pain pathways
Alters the perception of and response to pain
Produces generalized CNS depression
Opiate antagonistic effect may result from competitive inhibition at the opiate mu site
Example
Nalbuphine
45. More Definitions
Tolerance
Present when increasing amounts of drug are required to produce an equivalent level of efficacy
Physical Dependence
With rapid discontinuation of a drug following prolonged administration, results in withdrawal symptoms
Addiction
A form of psychological dependence and refers to the extreme behavior patterns that are associated with procuring and consuming drugs
46. Opioid Tolerance Opioids have no MAXIMUM dose
Doses are titrated to adverse effects and control of pain
Rate of development of opioid tolerance varies among patients
Earliest sign is reduction in duration of analgesic effect
Requirement for opioids ? as a log function of dose
Switch to an alternate opioid at half of the equianalgesic dose
47. Tapering of Opioids Scheduled opioid taper is not essential unless
Opioid use is prolonged
Total daily requirement is in excess of 160mg of oral morphine (or its equivalent)
Reduce by 10-15% each day
48. Opioid WithdrawalSigns and Symptoms Lacrimation
Rhinorrhea
Sweating
Yawning
Restlessness
Pupillary dilation
Nausea/Vomiting
Diarrhea ? irritability
Insomnia
Abdominal cramping
? BP
Hyperthermia
Chills
Flushing
49. Management of Adverse Effects Associated with Opioid Therapy Allergic Reactions
Stop opioid and switch to another class
Confusion Delirium or Hallucinations
Dose reduction, opioid rotation within in class
Haldoperidol, risperidone
Myoclonic jerking
Dose reduction, opioid rotation, benzodiazepines
Sedation
Hold dose, dose reduction, stimulant therapy
50. Management of Adverse Effects Associated with Opioid Therapy Nausea/Vomiting (Tolerance develops over time)
Ondansetron
Metoclopramide
Prochlorperazine
Promethazine
Pruritis
Diphenhydramine
Nalbuphine
Respiratory Depression
Stop drug, supportive measures (oxygen)
Naloxone
51. Management of Adverse Effects Associated with Opioid Therapy Bowel Regimen
Stool softener
Docusate
Laxatives
Bisacodyl
Lactulose
Milk of Magnesia
Senna
Polyethylene glycol
52. Case 4 JW is a 10 yo girl s/p a left tibia fracture. She is complaining of itching from her morphine, but shows no sign of rash.
What treatment can be initiated to alleviate JWs discomfort?
What other adverse effects from morphine should be monitored?
What are the 2 components of a bowel regimen that should be initiated for JW?
53. Answers to Case 4 JW is a 10 yo girl s/p a left tibia fracture. She is complaining of itching from her morphine, but shows no sign of rash. What treatment can be initiated to alleviate JWs discomfort?
Pruritis treatment w/ diphenhydramine or nalbuphine
What other adverse effects from morphine should be monitored?
Nausea/vomiting, sedation, respiratory depression
What are the 2 components of a bowel regimen that should be initiated for JW?
Stool softener and laxative
54. Misc. Opioid Clinical Pearls Morphine
Active metabolite may accumulate in patients with ? renal function
Meperidine
Toxic metabolite can accumulate with high doses or in patients with ? renal function
May precipitate tremors or seizures
Fentanyl Patches
Steady state levels of are not achieved until 72 hours after application of the patch
Patients with elevated temperatures may have ? fentanyl absorption transdermally
OxyContin (oxycodone sustained release)
Swallow tablets whole; do not crush, chew, or break
Empty tablet shell may appear in stool after medication is absorbed
55. Patient Controlled Analgesia (PCA) Opioid medications are administered using a pre-programmed infusion pump
Patient
Nurse
Parent PCA Order Components
Bolus dose (optional)
PCA dose
Lockout interval
Basal dose (optional)
Four hour limit
56. Pain Management with PCA Agents: Morphine, Hydromorphone, and Fentanyl
Pain assessment
Inadequate pain relief
Excessively pushing PCA button
Adequate pain relief
Utilize ordered or less than ordered PCA dose
Assess pain quality and severity
57. Advantages and Disadvantages of PCA
58. Regional Analgesia
59. Regional Anesthesia Epidural
Moderate-to-severe pain relief
Caudal, lumbar, thoracic, cervical
60. Epidurals Administration
Bolus
Continuous
Patient Controlled Epidural Administration (PCEA)
Greater analgesia than other modes of pain therapy
Agents
Opioids
Local Anesthetics
Clonidine Use caution in patients that are anticoagulated
Increase risk of hematoma
Analgesic Effect
Onset
Lipophilic > Hydrophilic
Duration
Lipophilic < Hydrophilic
Area
Lipophilic < Hydrophilic
61. Epidural Solutions Chloroprocaine 1.5%
clonidine
fentanyl
Bupivacaine 0.1% or 0.125%
clonidine
fentanyl
hydromorphone
Ropivacaine
Mepivacaine
62. Local Anesthetics MOA: Blocks nociceptive transmission and interrupting sympathetic reflexes
63. Infiltration of Local Anesthetics Indications
Large wounds
Mucous membranes involved
Need for immediate anesthetic effect
Route
Intradermal
Subcutaneous Amides
Lidocaine, mepivicaine, bupivacaine
Esters
Procaine, chloroprocaine, tetracaine, benzocaine
Rarely used
Diphenhydramine
May be used in patients allergic to amides
64. Topical Agents
65. Topical Analgesics Temporary pain relief
Most commonly used for osteoarthritis
66. Topical Anesthetic Preparations EMLA (lidocaine/prilocaine)
Concentrated in micron-sized droplets
Maybe used in infants 32 weeks gestation and older
Cream is applied to the skin and then covered with an occlusive dressing
Application time: 1 hour
Adverse effects
Methemoglobinemia L-M-X (lidocaine)
Lidocaine encapsulated in liposomes
Use in children <3 yo
Available without a prescription
No covering required
Application time: 30 min
67. Topical Anesthetic Preparations SyneraTM
Patch
lidocaine 70 mg and tetracaine 70 mg
Age: > 3 yrs
Skin: Intact only
Onset of Action: as little as 20 minutes
Duration of Analgesia: 2 hours Pain Ease Mist SprayTM
Counterirritant/skin vaporcoolent
Age: > 3 yrs
Skin: Intact or non-intact
Onset of Action: 10 seconds
Duration of Analgesia: 1 minute
68. Miscellaneous Analgesics
69. Concentrated Sucrose Diminishes pain response
MOA: unknown
Most effective when administered intra-orally
Need to use in conjunction with other pain relievers
No apparent adverse effects Dose
0.012g-0.12g/dose
Single vs. multiple dose
Product
Multiple
Childrens Hospital Boston
Sucrose 24% solution (Sweet-Ease)
70. Clonidine MOA: a2-adrenergic agonist
Sedation and analgesia
Effective analgesia in burn and surgical patients
Reduces post-operative vomiting, and attentuates symptoms of opioid withdrawal
Dosage forms
Transdermal patch (TTS-1, 2, 3)
Delivers 0.1-0.3mg/24 hours
Onset of action:2-3 days
Patch changed every 7 days
Tablets 0.1mg; 0.2mg; 0.3 mg
Must taper dose slowly
71. Neuropathic Pain
72. Muscle Spasms
73. Major Drug Interactions
74. Medication Safety with Analgesics Range orders
Frequency: PRN vs standing
Dose
Look-alike; Sound-alike
Oxycodone and Oxycontin
Hydromorphone and Hydrocodone
Clonidine and Klonopin
Morphine sulfate (MSO4) and magnesium sulfate (MgSO4)
Celebrex and Celexa
75. Pain Management
76. Multimodal Analgesia Several analgesic agents
Different mechanism of action
Different mode of administration
Minimizes adverse effects
Improves pain control
Labor-intensive for caregiver
77. Interdisciplinary Pain Management Team
Physician
Nurse
Pharmacist
Physical and occupational therapist
Psychologist
78. Recommendations from American Academy of Pediatrics and American Pain Society Expand knowledge about pediatric pain and management principles and techniques
Provide a calm environment for procedures that reduce distress producing stimulation
Anticipate predictable painful experiences, intervene, and monitor accordingly
Use a multi-modal (pharmacologic, cognitive, behavioral, physical) to pain management and multidisciplinary approach when possible
Involve families and tailor child specific interventions
Advocate for the effective use of pain medications in children to ensure compassionate and complete management of their pain
79. General Guidelines for the Pharmacological Management of Pain Individualize each patients treatment regimen
Simplify the dosage schedule and the least invasive modality should be utilized
Pain prevention is always easier than relieving pain
Medication for persistent acute or chronic pain should be administered Around the Clock vs. PRN
Meperidine has a toxic metabolite and generally should be avoided for long-term pain management
Naloxone and mixed agonists/antagonists should be used cautiously in patients on chronic opioid therapy
Constipation is a preventable problem associated with the use of opioids
Pain management issues should always be addressed when a patient is transferred from one setting to another
80. Questions