medication treatment of pain in eb: how to choose treatment of pain in eb: how to choose kenneth r....
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Medication treatment of pain in EB: how to choose
Kenneth R. Goldschneider, M.D.
Cincinnati Children’s Hospital Cincinnati Ohio, USA
Objectives
• Understand the strengths and weaknesses of basic analgesics as used for EB
• Be aware of the basic differences among the classes of medications used for pain and itching in EB
• Know a few questions that can help to guide which medicine to use for pain or itch
Classes of Pain Medications Commonly used for Pain in EB
• Opioids
• Nonsteroidal anti-inflammatory drugs (NSAIDs) and Acetaminophen
• Ketamine
• Neuropathic medications
– E.g. gabapentin, amitriptyline
Opioids
PROS
• Many routes
• Effective
• Many formulations
• No Ceiling Effect
CONS
• Side effects
• Social Stigma
• Variable availability
• Abuse potential
Theory: mu, kappa and delta opioid receptor mediate pain transmission Blockade of these receptor reduces pain of many types
Opioids: Routes and Formulations
Intravenous
Oral
Sublingual
Epidural
Intrathecal
Transbuccal
Transdermal
Subcutaneous
Intranasal
Rectal
Transpulmonary
Ceiling Effect
• A point beyond which increasing the dose will result in no further effect
0
1
2
3
4
5
6
DOSE
Opioid Side Effects
Important in EB
• Constipation
• Itching
Less important in EB
• Sedation
• Respiratory depression
• Nausea
• Mental clouding
Opioids: other considerations
Social stigma/abuse potential
• Leads to fear of use
• Leads to fear of prescribing
• Is a rare problem
• Opioids are a tool to do a job, no more and no less
Variable availability
• Opioids will vary in how easily they can be obtained depending on local law, regulation, manufacturing and prescribing patterns
Codeine
• Bad
• Yuck
• Phooey
• Ick
• Dangerous to some
• Ineffective for others
• Use something else unless the patient has a good history with it.
Opioids: how to choose
• What has worked before?
• What side effects have been experienced?
• What is the context?
– Is long-acting or short-acting needed?
• Avoid codeine unless the patient prefers it
– KRG preference
NSAIDs (nonsteroidal anti-inflammatory drugs)
PROS
Effective
Anti-inflammatory
Available
Several routes
Not sedating or respiratory depressant
Non-constipating
CONS
• Side effects
• Ceiling effect
Theory: Cyclooxegenases are key mediators of peripheral pain and inflammation NSAIDs block cycolooxygenase
NSAID Side Effects
Important in EB
• Increased bleeding risk
Less important in EB
• Kidney toxicity
• Liver toxicity
• GI effects
– Ulceration, reflux
Acetaminophen
PROS
• Effective for mild pain
• Availability
• Oral, rectal, Intravenous
CONS
• Cumulative toxicity risk
– Hidden exposures
Theory: It does something in the central nervous system, probably. Anyhow, it works.
www.addictionsearch.com/treatment_articles www.fda.gov/ForConsumers/ConsumerUpdates/ucm2 63989.htm www.canada.com/health/Study+links+acetaminophen +with+higher+risk+teenage+asthma/3394455/story.html
NSAIDs: how to choose
• Is the pain related to inflammation, bones or muscles?
• What are the ongoing bleeding issues?
• Are there any kidney problems?
• What other sources of acetaminophen are there?
Ketamine
PROS
• Effective
• Oral or intravenous
• Little respiratory effect
CONS
• Availability
• Regulations
• Side effects
• Bitter taste
Theory: Many receptors are involved in pain (e.g. AMPS, NMDA, opioid, 5-HT, adrenergic) Ketamine hits them all
Ketamine: how to choose
• Qualified personnel to administer it?
• Local regulations permit?
• Is there a place to test dose it?
Neuropathic Medications
• Anticonvulsants
– E.g. gabapentin, oxcarbazepine, carbamazepine
• Tricyclic antidepressants
– E.g. amitriptyline, doxepin, nortriptyline
• Newer antidepressants
– E.g. Duloxetine
Neuropathic Medications
PROS
• Helpful for some pain
• Helpful for some itching
• No tolerance
• No respiratory depression
• Some can help with sleep
CONS
• Less experience for general practitioners
• Potential interactions – Especially tricyclic
antidepressants
• Choices not always clear
Theory: Many chronic pain conditions involve overexcited nerves. Quieting those nerve can reduce pain
Neuropathic medications: how to choose
• Practitioner experienced with these medications?
• Is the pain related to nerves?
• Has the pain been poorly responsive to other treatments?
• Heart or kidney problems?
• Pain interfering with sleep?
• What other medications is the patient taking?
Drug Treatment of Itching
• Antihistamines – Sedating or non-sedating
• Change opioids – if that is a factor
• Ondansetron?
• Gabapentin?
• Doxepin or other tricyclic antidepressants?
• Mirtazepine?
Antihistamines
PROS
• Classic treatment for itch
• Effective for histamine mediated itching
• Low toxicity
CONS
• Role of histamine unclear in EB
• Variable effectiveness
Theory: histamine is a key mediator of itching Itch receptors respond to histamine, but not other painful stimuli
Opioid Rotation
PROS
• Opioids very in their itch – inducing properties
• Changing opioids is usually easy to do
• Little downside
• A common technique for general opioid side effect management
CONS
• No guarantee that the next opioid will be better
• Hence, trial and error
• May trade one side effect for another
• Limitations in medication or usable formulation
Theory: opioids cause itching; opioids overlap incompletely. Change from one to another to reduce dosing and side effects
Ondansetron
PROS
• Low toxicity
• Comes in dissolvable tablets
CONS
• Expensive
• Efficacy unclear
Theory: Serotonin is involved in itch Ondansetron is an 5-HT3 inhibitor
Gabapentin
PROS
• Low toxicity
• Comes as liquid
• No drug interactions
• Works in post-burn itching
CONS
• Side effects – Mood swings, sedation
• Variable success
Theory: itch transmitted via c-fibers, similar to pain Gabapentin is useful in neuropathic pain
Doxepin/Amitriptyline
PROS
• Combination antihistamine and neuropathic mechanisms
• Helps with sleep, if that is a problem
• Once a day dosing (bedtime)
CONS
• Low toxicity threshold
• Numerous drug interactions
• Variable response
• Potential prolonged QT issues, obtaining ECG not easy in EB
Theory: histamine and serotonin are involved in itch Block both and itch will be less
Mirtazapine
PROS
• Helpful in other types of itching
• Helps with sleep
CONS
• Little experience in EB – Dosing in kids?
Theory: Anti-H1, anti 5-HT and anti-noradrenaline Has helped in lymphoma and uremia related itch
Itch treatment: how to choose
• Did itch change with the new medication or treatment?
• Is the itch interfering with sleep?
• What other medications is the patient taking?
• Are there any heart or kidney problems?
• What has been tried before?
• Remember: non-medication treatments should always be used also
Conclusion
• Many pain medications and anti-itch medications are available
• The effectiveness of many of them has not been shown, or is variable
• Most commonly, medications are used in combination
• Best practice care guidelines for pain are being developed (almost done!) – The level of evidence is low – Research in this area is imperative