PERIPHERAL NEUROPATHY. Maureen Gallagher Jesse James Maldonado
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1 PERIPHERAL NEUROPATHY Maureen Gallagher Jesse James Maldonado
2 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?
3 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
4 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
5 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
6 Drug Induced Neuropathy Cardiovascular Antibiotics Amiodarone (Pacerone) Chloroquine (Aralen) Hydralazine Isoniazid Cancer Metronidazole (Flagyl) Cisplatin Nitrofurantoin (Macrobid) Docetaxel (Taxotere) HIV Paclitaxel (Taxol) Didanosine (Videx) Vincristine (Vincasar) Stavudine (Zerit) Autoimmune disorders Zalcitabine (Hivid) Etanercept (Enbrel) Miscellaneous Infliximab (Remicade) Dapsone Leflunomide (Arava) Phenytoin (Dilantin) Disulfiram (Antabuse) Colchicine
7 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, serotoninnorepinephrine reuptake inhibitors, opioid analgesics, local anesthetics Natural products Compounding Surgical / psychological interventions
8 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
9 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: mg per day Start low and titrate up slowly Usually taken at bedtime due to to sedation Take with or without food
10 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.
11 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
12 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
13 Duloxetine (Cymbalta) Drug class: antidepressant, serotoninnorepinephrine 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
14 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
15 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
16 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)
17 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
18 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
19 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
20 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
21 Opioid Analgesics Agents include: -Codeine -Morphine -Hydromorphone -Oxycodone -Hydrocodone -Methadone 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 -Fentanyl -Levorphanol
22 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
23 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
24 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
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