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PERIPHERAL NEUROPATHY
Maureen Gallagher
Jesse James Maldonado
Objectives
What is peripheral neuropathy?
Symptoms
Causes
Treatment goals
What are the available treatment options?
Prescription drug therapy How these drugs work
Common uses
Side effects
Drug interactions
Contraindications / precautions
Non-prescription drug therapy
Natural products
How can prescription compounding help you?
What is Peripheral Neuropathy?
Describes damage to the peripheral nervous system (sensory, motor, autonomic)
Peripheral nerves are responsible for sending and receiving information to and from the brain, spinal cord, and muscles
Nerve damage results in interference of signal transduction
Common Symptoms of Neuropathy
Mild
Numbness
Tingling
Pricking sensations
Sensitivity to touch
Muscle weakness
Moderate-Severe
Burning sensations
Muscle wasting
Paralysis
Organ dysfunction
Sexual dysfunction
Uncontrolled blood
pressure
Hallmarks of peripheral neuropathy include:
Hyperalgesia- increased sensitivity to a normally painful stimuli
Allodynia- pain resulting from a stimulus that does not normally cause pain
Causes of Neuropathy
Acquired neuropathies
Systemic disease
Diabetes
Vitamin deficiencies
Vascular damage
Trauma
Nerve compression
Stretching/tearing
Infections/autoimmue
Varicella zoster (shingles)
HIV
Drugs and toxins can
also cause nerve
damage and result in
neuropathic pain
Drug Induced Neuropathy
Cardiovascular
Amiodarone (Pacerone)
Hydralazine
Cancer
Cisplatin
Docetaxel (Taxotere)
Paclitaxel (Taxol)
Vincristine (Vincasar)
Autoimmune disorders
Etanercept (Enbrel)
Infliximab (Remicade)
Leflunomide (Arava)
Antibiotics
Chloroquine (Aralen)
Isoniazid
Metronidazole (Flagyl)
Nitrofurantoin (Macrobid)
HIV
Didanosine (Videx)
Stavudine (Zerit)
Zalcitabine (Hivid)
Miscellaneous
Dapsone
Phenytoin (Dilantin)
Disulfiram (Antabuse)
Colchicine
Neuropathic Pain - Treatment
Often difficult to treat and multiple therapeutic
approaches are often required to alleviate pain
1. Treat the underlying condition
2. Life style modifications
3. Symptomatic treatment
Drug therapy
Tricyclic antidepressants (TCAs), anti-epileptics, serotonin-
norepinephrine reuptake inhibitors, opioid analgesics, local
anesthetics
Natural products
Compounding
Surgical / psychological interventions
Prescription Drug Therapy
When selecting an appropriate pharmacologic
agent we must take into account:
Vulnerability to specific side effects
Safety considerations and contraindications
Patient preference
Coexisting mental health problems
Other medications the patient is taking
Ability to comprehend and comply with treatment
regimen
Amitriptyline (Elavil)
Drug class: tricyclic antidepressant
Uses: depression, neuropathic pain, ADHD, panic disorder, social anxiety disorder
Mechanism of action: increases the amount of norepinephrine and serotonin by decreasing reuptake
Dose: 10-150 mg per day
Start low and titrate up slowly
Usually taken at bedtime due to
to sedation
Take with or without food
Amitriptyline (Elavil)
Side effects:
sedation, dry mouth, constipation, blurry vision, urinary retention, hypotension, dizziness, cardiovascular abnormalities, suicidal ideation
Contraindications:
acute myocardial infarction, MAOI therapy
Precautions:
abrupt discontinuation, anticholinergic medications, cardiac disease, arrhythmias, glaucoma, thryroid disorders, seizure disorder
Drug interactions:
Amiodarone (Pacerone)
Dofetilide (Tikosyn)
Flecainide (Tambocor)
MAOIs (phenelzine, selegiline, tranylcypromine)
Promethazine (Phenergan)
Quinidine
TCAs (Pamelor, Norpramin)
Ziprasidone (Geodon)
St. John’s Wort
Fluoroquinolones (Cipro)
Ondansetron (Zofran)
SSRIs (Zolfot, Celexa)
SNRIs (Pristiq, Effexor)
Nortriptyline or desipramine are alternatives if intolerant of amitriptyline side effects.
Pregabalin (Lyrica)
Drug class: anti-epileptic / analgesic
Uses: diabetic neuropathy, neuropathic pain, fibromyalgia, partial seizures, postherpetic neuralgia
Mechanism of action: increases neuronal GABA levels, causes inactivation of glutamate, decreases neuronal calcium currents
Dose: 50 mg three times a day
May increase to 100mg three times a day in one week
Dose must be adjusted for kidney dysfunction
Take with or without food
Pregabalin (Lyrica)
Side effects (usually
dose dependent):
edema, dizziness,
somnolence, weight gain,
tremor, blurred vision,
constipation
Precautions:
angioedema, CNS
depression, arrhythmias,
abrupt discontinuation,
renal impairment,
myopathy
Drug interactions:
ACE inhibitors
Lisinopril (Prinivil)
Enalapril (Vasotec)
Captoril
Quinapril (Accupril)
CNS depressants
Barbituates (penobarbital)
Alcohol
Opioids (morphine)
Promethazine
Tramadol (Ultram)
TCAs
Duloxetine (Cymbalta)
Drug class: antidepressant, serotonin-norepinephrine reuptake inhibitor
Uses: depression, diabetic neuropathy, fibromyalgia, anxiety disorder, musculoskeletal pain
Mechanism of action: increases serotonin and norepinephrine levels
Dose: 60 mg per day
Should not be used in patients with liver impairment
Not recommended in severe kidney impairment
Take with or without food
Duloxetine (Cymbalta)
Side effects: headache,
fatigue, nausea, dizziness,
lethargy, insomnia,
constipation, diarrhea,
increased liver enzymes
Contraindications: MAOI use,
closed angle glaucoma
Precautions: abrupt
discontinuation, anticoagulant
therapy, cardiac disease, liver
disease, kidney disease,
suicidal ideation
Drug interactions:
Desvenlafaxine (Pristiq)
Venlafaxine (Effexor)
Milnacipran (Savella)
MAOIs
Phentermine (Adipex)
5-HTP (tryptophan)
Antipsychotics
Cyclobenzaprine (Flexeril)
Dextromethorphan
SSRIs
CNS stimulants (Adderall)
St. John’s Wort
TCAs
Gabapentin (Neurontin)
Drug class: anti-epileptic / analgesic
Uses: partial seizures, postherpetic neuralgia, restless
leg syndrome, MS, menopause, spasticity
Mechanism of action: increases GABA response, acts
at nerve synapse to prevent release of excitatory
neurotransmitters
Dose: 300 mg on day one, 600 mg on day two, 900
mg on day three
Dose is further titrated upwards to 1800 mg per day
Must be adjusted for kidney dysfunction
Take with food to minimize GI side effects
Gabapentin (Neurontin)
Side effects: dizziness, somnolence, abnormal coordination, drowsiness, peripheral edema, diarrhea, N/V, abdominal pain
Precautions: abrupt discontinuation, driving/operating machinery, kidney dysfunction, suicidal ideation
Drug interactions:
Antacids
Sevelamer (Renagel)
Colesevelam (Welchol)
Hydrocodone (Vicodin)
Morphine
Naproxen (Aleve)
Tramadol (Ultram)
Drug class: centrally acting analgesic
Uses: moderate to severe pain, arthralgia, bone pain, headache, myalgia, neuropathic pain, OA
Mechanism of action: binds to central opiate receptors causing inhibition of ascending pain pathway, also inhibits serotonin and norepinephrine reuptake
Dose: 25 mg once daily initially
Titrate upward every 3 days to a max of 400 mg per day in divided doses
Dose reduction necessary in liver / kidney dysfunction
Take with or without food
Tramadol (Ultram)
Side effects: flushing, dizziness, somnolence, constipation, nausea, weakness, hypotension, sweating, respiratory difficulty
Contraindications: acute intoxication of CNS depressants (alcohol), asthma, respiratory depression
Precautions: sedation, avoid alcohol ingestion, GI disease, MAOI use, kidney/ liver dysfunction, seizures
Drug interactions:
MAOIs
Bupropion (Wellbutrin)
Carbamazepine (Tegretol)
Alcohol
Opiates
Promethazine
SSRIs
SNRIs
Warfarin (Coumadin)
St. John’s Wort
Muscle relaxers
Sedating antihistamines
CNS depressants
Lidocaine Patch (Lidoderm)
Drug class: local anesthetic/antiarrhythmic
Uses: anesthetic and nerve block agent, various
severe pain conditions
Mechanism of action: decreases nerve conduction
by blocking sodium channels
loss of nerve function occurs sequentially: pain →
temperature → touch →proprioception →muscle tone
Dose: Apply patch to most painful area for up to
12 hours in a 24 hour period
Up to 3 patches may be required
Lidocaine (Lidoderm)
Side effects: bruising, itching, rash, pain exacerbation, weakness, burning
Contraindications: hypersensitivity to local anesthetics, sepsis
Precautions: cardiac arrhythmias, heart failure, liver disease, hypotension, accidental exposure
Drug interactions:
Dofetilide (Tikosyn)
MAOIs
Saquinavir (Invirase)
Amiodarone
Beta-blockers (Toprol)
Ciprofloxacin (Cipro)
Citalopram (Celexa)
TCAs
Opioid Analgesics
Agents include:
•-Codeine
•-Morphine
•-Hydromorphone
•-Oxycodone
•-Hydrocodone
•-Methadone
•-Fentanyl
•-Levorphanol
Generally are used after other
treatment options have failed
Conflicting data as to whether opioids
are effective for neuropathic pain
Long term use remains controversial due
to risk of dependency
Opioid Analgesics
Side effects: sedation, constipation, respiratory depression,bradycardia, hypotension, nausea, delirium, dependency
Contraindications: hypovolemia, respiratory depression, shock, paralytic ileus
Precautions: substance abuse, opiate naïve, abrupt discontinuation, CNS depressants
Drug interactions:
Chlorpromazine(Thorazine)
MAOIs
Tramadol (Ultram)
Opiate agonists
Promethazine (Phenergan)
TCAs
St. John’s Wort
Valerian
Other Treatment Approaches
If a patient fails the first agent, switch to another agent
with a different mechanism of action
TCA→ pregabalin
Pregabalin → TCA
Duloxetine → TCA or pregabalin
Combination therapy may be warranted in some
patients
May improve pain control in patients who have failed single
drug therapy
Amitriptyline plus pregabalin
Duloxetine plus pregabalin
Addition of tramadol or opiate to current therapy
Additional Treatment Options
Non-prescription agents
Capsaicin
Applied topically 3-4 times daily to painful areas
Depletes and prevents reaccumulation of substance P in
peripheral sensory neurons
Natural products and supplements
Prescription compounding