MSK/Migraine Case Review Dobbs (Final) Flashcards
Goals of pain management therapy
- Decreased pain
- Decreased healthcare utilization
- Improved functional status
- Improved quality of life
Name some non-pharmacologic pain treatment options
- Heat/cold
- Meditation/Relaxation
- Guided imagery
- Acupressure/Acupuncture
- TENS units
- Physical Therapy
- Chiropractic Care
- Behavioral Therapy
- Cognitive/Behavioral Therapy
- Therapeutic Massage
Name some Pharmacologic pain treatment options
- NSAIDs
- Non-opioid analgesics
- Anti-seizure medications
- Anti-depressants
- Opioid analgesics
- Local anesthetics
What are some invasive therapies in the treatment of pain?
- Trigger Point Injections
- Joint Injections
- Regional Nerve Blocks
- Epidural Injection
- VArious Surgeries
MOA of Acetaminophen (APAP)
Dobbs said to know the MOAs of the various meds
- Inhibit the syntheses of prostaglandins in the CNS
- Works peripherally to block pain impulse generation
- Poor inhibitor of platelet function
- Very little anti-inflammatory properties
Dosage of APAP/Tylenol
- Comes in 326mg, 500mg (extra strength) and 650mg (Arthritis)
- Max recommended dose is 4g daily
- In elderly Pts some clinicians have recommended lowering the max dose to 3 grams daily
What is APAP most commonly recommended for?
- Anti-pyresis
- Relief of pain from:
- Osteoarthritis
- Migraine headaches
- Skeletal pain
- Muscular pain
- Pain in pregnant women
What is the antidote for APAP?
N-acetylcystine (Mucomyst)
MOA of Salicylates (Aspirin/ASA)
- Reduces prostaglandin and thromboxane A2 synthesis
- Reduces platelet aggregation
- Irreversibly inhibits platelet function for the life of the platelet, interfering with homeostasis and prolonging bleeding time
Dosage of ASA
- Comes in:
- 81mg (Baby)
- 325mg
- 500mg (Extra-strength)
S/E of ASA
- Gastrointestinal tact injury/upset
- Renal injury
- Viral syndromes in children and teenagers
- Risk of Reye’s syndrome
- A single dose of aspirin can precipitate asthma in aspirin-sensitive patients
ASA is most commonly recommended for?
- Ant-coagulation
- Anti-pyresis
- Relief of pain from
- Osteoarthritis
- Migraine headaches
- Muscular pain
Name some common Nonselective NSAIDs
- Ibuprofeb
- Naproxen
- Naproxen sodium
- Indomethacin
- Etodolac
- Diclofenac
- Sulindac
What is the one selective NSAID we need to know?
Celecoxib
If a Pt does not respond to one NSAID should you throw out the entire class?
No, some Pts respond better to one NSAID than another
NSAIDs are most commonly recommended for?
- Anti-pyresis
- Relief of pain/inflammation from:
- Dysmenorrhea
- Migraine/tension headaches
- Muscular/tendinous pain from strain/sprain
NSAIDs are NOT recommended for?
- Fracture pain
- Can delay bone healing
- Pregnant women
- Known history of PUD
- Renal dysfunction
- Bleeding disorders
- Uncontrolled HTN
- Use caution in Pts with
- Current nausea/vomiting
- GERD
Name two parenteral NSAIDs and how long can they be used for?
- Ketorolac (Toradol)
- Most commonly used injectable
- IV ibuprofen (Caldolor)
- Recently approved for use in people 6 months and older
- Approved as an antipyretic and for use in moderate to severe pain either alone or in conjunction with opioid therapy.
- Recently approved for use in people 6 months and older
- Short-term use
- Up to 5 days
S/E of Ketorolac (Toradol)
- Severe GI toxicity
- Especially in the elderly
- Acute renal failure has been observed
- In every age group from as little as a single dose IM
- No additional analgesic benefit to giving 60 mg vs 30 mg
- 60 mg dose only lasts longer
- High-risk patients for Toradol
- > 65 with known vascular or renal disease
- Dosage should be but in half or not given at all
- > 65 with known vascular or renal disease
Parenteral NSAIDs are recommended for?
- Outpatient relief of pain/inflammation from
- Migraine headaches
- Severe pain
MOA of NSAIDs
The main mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. [9] The therapeutic effects of NSAIDs are attributed to the lack of these eicosanoids.
S/E of Non-Selective NSAIDs
- Exacerbation or development of CHF
- Increased BP
- Can precipitate asthma and anaphylactoid reaction in aspirin-sensitive Pts
- Reversible inhibition of platelet aggregation
- GI Problems
- Bleeding
- Ulceration and perforation
- High doses, prolonged use, previous peptic ulcer disease, excessive EtOH use, and advanced age increases the risk of these complications.
- Ibuprofen can interfere with the antiplatelet effect of Aspirin
- Do not give to Pts taking Aspirin for CV protection, if need to give, give 2 hours after taking aspirin.
How can NSAIDs cause HTN and renal disease?
- NSAIDs decrease the synthesis of renal vasodilator prostaglandins and decrease renal blood flow, which can lead to fluid retention and may cause renal failure or HTN
- Risk factors include advanced age, congestive heart failure, renal insufficiency, ascites, volume depletion and concurrent diuretic therapy
- Hepatotoxicity can occur
Dosing guidelines for Ibuprofen
- Ibuprofen
- Comes in 200 mg, 400 mg, 600 mg, and 800 mg tabs
- Usual Doses
- 200-600 mg
- 800 mg (Rx)
- Dose Frequency
- Q4-6 hrs
- Q8hr if 800mg
- Max dose
- 2400 mg
- 3200 mg if taking 800mg Q8
Dosing guidelines for Naproxen
- Naproxen
- Comes in 250 mg, 375 mg, and 500 mg tabs
- Dose
- 250-500 mg
- Dose Frequency
- Q6-8 hrs
- Q12hr if taking 500 mg
- Max dose
- 1000 mg
Dosing guidelines for Naproxen Sodium (Aleve)
- Naproxen
- Comes in 220 mg, and 550 mg tabs
- Dose
- 220-550 mg
- Dose Frequency
- Q6-8 hrs
- Q12hr if taking 550 mg
- Max dose
- 1100 mg
Dosing for Selective COX-2 inhibitors (Celebrex)
100-200 mg BID
S/E of Selective COX-2 inhibitors (Celebrex)
- Less GI toxicity and non-selective NSAIDs
- Increased MI and CVA risks
- No inhibition of platelet aggregation or increase bleeding time
- May cause increased INR/PT if given with warfarin
- Unlikely to be clinically significant
- Similar S/E to non-selective NSAIDs
Antidote for NSAIDs
None exist
When using opioids for short term relief of pain should you use short or long-half life opioids?
Short half-life
Which opioid when given with cyclobenzaprine greatly increases the risk of seizure?
Tramadol
Which of the opioids are considered “stronger”?
- Fentanyl
- Hydromorphone
- Levorphanol
- Meperidine
- Methadone
- Morphine
- Oxycodone
- Oxymorphone
Which of the opioids are considered “weaker”?
- Hydrocodone
- Codeine
- Tramadol
Do Opioids have a ceiling for their analgesic effectiveness?
No unlike NSAIDs, opioids generally have no ceiling for their analgesic effectiveness except that imposed by their adverse effects
Which opioids do you need to use caution when prescribing with NASAIDs or APAP?
- Vicodin
- Vicoprofen
- Percocet
These meds contain an NSAID or APAP and when given with NSAIDs or APAP increase the risk of overdose on NSAID or APAP
Describe Oxycodone (Percocet, OxyContin)
- Semi0synthetic derivative of morphine
- Only available in oral formulations
- High oral bioavailability
- 2.5-3 hour half-life
- 9.5 times more potent than oral codeine
- 1.5 time more potent than oral morphine
Describe Hydromorphone
- The one that starts with “D” - Dilaudid
- Available in IV, IM, SubQ, rectal, and short- and long-acting oral formations
- Maybe more safe than morphine in Pts with renal failure
- Morphine can lead to toxic metabolite accumulation
- Immediate-release oral preparations have an onset of 30 minutes and a duration of 4 hours
Describe Fentanyl
- Available in IV, intrathecal, epidural, transdermal, and oral transmucosal preparations
- Also available in buccal soluble film, sublingual tablet, nasal spray, sublingual spray, and as a lozenge on a stick for breakthrough pain, especially in cancer patients.
- 80 times more potent than morphine
- Highly lipophilic and binds strongly to plasma proteins
- Transdermal is useful in Pts with chronic pain who have difficulty swallowing or malabsorption
- Exposing patch to heat or possibly high fever could increase the release of the drug
- Use of fentanyl with drugs that inhibit CYP3A4 can cause a dangerous increase in serum concentrations of fentanyl
- Use extreme caution in strong inhibitors such as ketoconazole or clarithromycin
Describe Meperidine
- Demerol
- Poor oral absorption
- 10% effectiveness of morphine
- Significant anticholinergic and local anesthetic properties
- Use only for short-term treatment of moderate to severe acute pain
- 24-48 hours
- Repeated doses can lead to accumulation of toxic metabolite normeperidine
- Can cause
- Dysphoria
- Irritability
- Tremors
- Myoclonus
- Seizures
- S/E more common in Pts with renal impairment
- S/E are not reversible with naloxone
- Can cause severe encephalopathy and death in Pts taking MAOIs
- Can cause
Describe Codeine
- Potency is approximately 50% of morphine
- 2.5-3 hour half-life
- Inhibited by
- Bupropion
- Celecoxib
- Cimetidine
- Cocaine
- Doses greater than 65 mg not well tolerated
Describe Hydrocodone
- A combination product with non-opioid analgesics
- Ibuprofen
- Acetaminophen
- High bioavailability after oral dose
- 2.5-4 hour half-life
Describe Tramadol
- Oral centrally-acting opioid agonist that blocks the reuptake of NE and serotonin
- Marketed for treatment of moderate to moderately severe pain
- May cause seizures
- Dosage should not exceed 400 mg/day
Common adverse effects of opioids and their management
- Constipation
- Bowel regimen
- Sedation
- Tolerance typically develops
- Hold sedatives/anxiolytics
- Dose reduction
- Consider CNS stimulants
- Nausea/Vomiting
- Dose reduction
- Opioid rotation
- Consider
- Metoclopramide
- Prochlorperazine
- Scopolamine patch
- Pruritis
- Dose reduction
- Opioid rotation
- Consider H2 blocker or antihistamine
- Hallucinations
- Dose reduction
- Opioid rotation
- Consider neuroleptic therapy
- Haldol
- Risperidone
- Confusion/Delerium
- Dose reduction
- Opioid rotation
- Consider neuroleptic therapy
- Haldol
- Risperidone
- Myoclonic Jerking
- Dose reduction
- Opioid rotation
- Consider clonazepam or baclofen
- Respiratory Depression
- Sedation precedes respiratory depression
- Hold opioid
- Give naloxone
Narcotics antidote
Naloxone (Narcan)
Before prescribing opioids what must you look at?
The PDMP, it’s the law!
Which medication classes are the mainstays of treatment for:
- Postherpetic neuralgia
- Diabetic neuropathy
- Fibromyalgia
- Complex regional pain syndrome
- Phantom limb pain
- Antidepressants and anticonvulsants
- Combo use of antidepressants and anticonvulsants may produce synergistic increases in analgesic effect in neuropathic pain syndromes.
Are SSRIs or TCAs more effective in the treatment of neuropathic pain
TCAs, SSRIs appear to be less effective
Name some common TCAs used in the treatment of neuropathic pain?
- Amitriptyline (Elavil)
- Nortriptyline (Pamelor)
- Imipramine (Tofranil)
The above are effective in the treatment of many types of neuropathic pain including:
- Diabetic neuropathy
- Postherpetic neuralgia
- Polyneuropathy
- Fibromyalgia
- Nerve injury/infiltration with cancer
What other antidepressants (Non-TCAs) are used in the treatment of pain?
- Venlafaxine (Effexor)
- Duloxetine (Cymbalta)
- Milnacipran (Savella)
What forms of pain is Venlafaxine (Effexor) used for?
- Neuropathic pain
- HA
- Fibromyalgia
- Postmastectomy pain syndrome
Withdrawal symptoms may limit use
What forms of pain is Duloxetine (Cymbalta) used for?
- Approved for pain from:
- Diabetic peripheral neuropathy
- Fibromyalgia
- Chronic MSK pain
- Was found to be modestly more effective than placebo in the treatment of osteoarthritis or chronic low back pain
- Appears to provide many of the analgesic benefits of older antidepressants with fewer adverse effects
Milnacipran (Savella) is FDA approved for treating?
- Fibromyalgia
- Appears to be moderately effective in decreasing pain and improving function
- How it compares to venlafaxine or duloxetine remains to be seen
Common anticonvulsants used in the treatment of pain
- Gabapentin (Neurontin)
- Pregabalin (Lyrica)
- Carbamazepine
- Oxcarbazepine
- Lamotrigine (Lamictal)
- Sodium valproate (Depakote)
- Topiramate (Topamax)
Gabapentin uses in pain and common S/E
- Postherpetic neuralgia
- Diabetic Neuropathy
- S/E:
- Dizziness
- Somnolence
- Edema
- Weight gain
- Not great in the treatment of acute pain
Pregabalin uses in pain and common S/E
- Approved for neuropathic pain associated with:
- Postherpetic neuralgia
- Diabetic peripheral neuropathy
- Fibromyalgia
- Similar in structure to gabapentin
- Schedule V controlled substance due to reports of euphoria
- The dose can be titrated more rapidly than gabapentin and can be given BID rather than TID
- S/E
- Dizziness
- Somnolence
- Peripheral edema
- Significant weight gain
What pain is Carbamazepine FDA-approved for?
Trigeminal Neuralgia
Oxcarbazepine is?
Related to carbamazepine, has been shown to provide similar analgesia with fewer adverse effects.
In small trials, Lamotrigine was effective in treating which types of pain?
- Central post-stroke pain
- HIV-associated painful sensory neuropathies
Larger trials have shown less positive results
Main thing to warn Pts about before starting Lamotrigine
Rash that can potentially progress to Stevens-Johnsons syndrome
What are Sodium Valproate and Topiramate used in the prophylaxis of?
Migraine prophylaxis
Name some adjuvant pain meds that are not antidepressants or anticonvulsants
- Caffeine
- Hydroxyzine
- Corticosteroids
- Clonidine
- Medical Marijuana
Name some adjuvant pain meds that are not antidepressants or anticonvulsants
- Caffeine
- Hydroxyzine
- Corticosteroids
- Clonidine
- Medical Marijuana
How is caffeine used as an adjuvant pain med?
Doses of 65-200 mg may enhance the analgesic effect of acetaminophen, aspirin, or ibuprofen
How is hydroxyzine used as an adjuvant pain med?
Doses of 25-50 mg given parenterally may add to the analgesic effect of opioids in postoperative and cancer pain while reducing the incidence of nausea and vomiting
How are corticosteroids used as adjuvant pain meds?
Can produce analgesia in some patients with inflammatory diseases or tumor infiltration of nerves
How is clonidine (Catapres) used as an adjuvant pain med?
The oral and transdermal patch formulation of the alpha-2-adrenergic agonist may improve pain and hyperalgesia
How is medical marijuana used as an adjuvant pain med?
Has been shown to be effective in MS Pts with central neuropathic pain
Common topical analgesics used as adjuvant pain meds
- 5% lidocaine patch (Lidoderm)
- Topical EMLA
- Synera
- Diclofenac patch (Flector)
- 8% capsaicin patch (Qutenza)
- Diclofenac topical gel (Voltaren 1% Gel)
All the above are generally safe and well-tolerated
What is 5% lidocaine patch (Lidoderm) approved for?
Postherpetic neuralgia
What is EMLA used for?
- Mixture of lidocaine and prilocaine
- Used for cutaneous anesthesia
What is Synera approved for?
- Lidocaine and tetracaine patch
- Approved for anesthesia before acute topical procedures
- Such as venipuncture
What is a diclofenac patch (Flector) approved for?
Local treatment of MSK pain
What is an 8% capsaicin patch (Qutenza) approved for?
Postherpetic neuralgia
What is diclofenac topical gel (Voltaren 1% Gel) approved for?
Osteoarthritis in knees and hands
Common muscle relaxants
- Cyclobenzaprine (Flexeril)
- Metaxalone (Skelaxin)
- Carisoprodol (Soma)
- Diazepam (Valium)
- Methocarbamol (Robaxin)
Common S/E of muscle relaxants are somnolence, dizziness, cognitive slowing. Which muscle relaxant causes these the most?
Cyclobenzaprine
Which muscle relaxant when given with tramadol greatly increases the risk of seizure?
Cyclobenzaprine
Common S/E of Carisoprodol (Soma)
- Ataxia
- Agitation
- Insomnia
- Tachycardia
- Has withdrawal symptoms
- Strong abuse potential
- Especially when combined with an opioid
Of the muscle relaxants which cause less drowsiness and cognitive effects?
- Metaxalone (Skelaxin)
- Methocarbamol (Robaxin)
S/E of Diazepam (Valium)
- Reflex spasms due to muscle or joint trauma or inflammation
- Abuse potential
- Schedule IV controlled substance
Are there any muscle relaxants that are considered safe in pregnancy?
No! No muscle relaxants are considered safe during pregnancy.
Are muscle relaxants effective?
Their efficacy is controversial
Goals of acute (abortive) therapy for migraines
- Stop or prevent the progression of a headache or reverse a headache that has started
- Treats pain and other symptoms after the attack has begun
Indications for prophylactic migraine therapy?
- Frequent headaches that cause disability
- 2 or more a month
- Overuse of acute medication
- More than 2 times per week
- Acute medications are not effective, well-tolerated or are contraindicated
- Reduce the frequency and severity of the migraine attack
Routes of administration of migraine medications and their pros and cons
- Oral Tablets
- Pro
- Easy to use
- Con
- Won’t work if Pt vomiting
- Pro
- Nasal Spray
- Pro
- Good for patient with nausea/vomiting
- Easy to use
- Con
- Fewer choices
- Pro
- Injection
- Pro
- Works fast
- Con
- Harder to use
- Pro
First-line abortive meds for migraines
- NSAIDs
- APAP
- ASA/APAP/Caffeine (Excedrin)
Second-line abortive meds for migraines
- Triptans
- ASA or APAP
- Plus Caffeine/Butalbital (Fioricet/Fiorinal)
- Ergotamines
- Injectable ketorolac (Torodol)
Triptans MOA
- Serotonin receptor agonist of the 5-HT1b and 5-HT1D with normalization of dilated intracranial arteries thru:
- Enhanced vasoconstriction
- Peripheral neuronal inhibition
- Inhibition of transmission thru 2nd order neurons of the trigeminocervical complex
Order the triptans from quickest to shortest acting, and their delivery mechanisms
- Sumatriptan (Imitrex)
- Subcutaneous
- Nasal Spray
- Tablets
- Zolmitriptan (Zomig)
- Tablets
- ODT (ZDT)
- Nasal Spray
- Rizatriptan (Maxalt)
- Tablets
- ODT (MLT)
- Eletriptan (Relpax)
- Tablets
- Naratriptan (Amerge)
- Tablets
- Almotriptan (AxertTM)
- Tablets
- Frovatriptan (Frova)
- Tablets
How do calcitonin gene-related peptide (CGRP) antagonists work?
Function as a vasodilator focused on the trigeminovascular system
What percentage of migraine Pts will experience benefit from CGRPs
40%, but for that 40% the benefit can be life changing
Name some once monthly SQ CGRP antagonists
- Aimovig
- Ajovy
- Emgality
- Vyepti
These have a longer onset
Very expensive
Name some Gepants (CGRP meds that are small molecules with rapid brain penetration, are metabolized in the liver).
- Nurtec ODT
- Oral
- USed in prevention and treatment of migraines
- Ubrelvy
- Oral
- Used in treatment of migraines only
- Caution with CYP3A4 inhbitors
- Ketoconazole
- Clarithromycin
- Itraconazole
- Very expensive
How long does a Pt need to be on a CGRP antagonist to experience maximum relief?
3 months
Pain management strategies according to Dobbs?
- Alternate acetaminophen and 1 NSAID
- Combine therapies that are dissimilar
- USe non-pharmacologic and pharmacologic therapies to complement each other
- Pain contracts/Have only one provider manage pain meds
- Goal of pain management is Function