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