Mononeuritis Multiplex Medication

The clinician must integrate the patient’s symptoms, signs, and clinical evaluation when considering the treatment of neuropathic pain in mononeuritis multiplex. The reduction of inflammation around the epineurium is the primary goal of treatment. Additional treatments are aimed at treating the primary cause and/or associated symptomology.

Over-the-counter analgesics are used for pain control. Various other medications may be used to reduce dysesthetic pain, which typically is a stabbing, burning pain.

Traditional medical models for treating chronic and neuropathic pain are based on the use of tricyclic antidepressants (eg, amitriptyline, nortriptyline, desipramine). When appropriate, anticonvulsant drugs have been used to treat lancinating pain. Gabapentin, phenytoin, and carbamazepine most often are used as the drugs of choice. Valproate is used occasionally.

Advances in understanding of the pathophysiology of acute and chronic neuropathic pain states may lead to newer, more effective pharmacologic approaches to treatment.

More effective and safer antiepileptic drugs have continued to benefit patients with chronic pain conditions. Neurotransmitters such as serotonin, glutamate, substance P, calcitonin gene-related peptide (CGRP), and gamma-aminobutyric acid (GABA) are the targets of research and development of pharmacologic therapies for acute and chronic pain. In addition, sodium activity and calcium activity play important roles in the pathology and treatment of these chronic medical problems.

Medications that increase gastric motility (eg, metochlopramide) may be administered. Gastric motility also may be increased if the patient eats small, frequent meals and sleeps with his/her head elevated. Medications for bladder dysfunction include bethanechol and oxybutynin.

Opioids

Opioid analgesics, including tramadol, have been found to be efficacious in several high-quality randomized controlled trials in patients with various types of neuropathic pain (grade A recommendation). However, owing to concerns over their long-term safety (relative to first-line medications), they are recommended principally for patients who have not responded to the first-line medications, except in certain clinical circumstances (ie, for the treatment of acute neuropathic pain, episodic exacerbations of severe neuropathic pain, neuropathic cancer pain, and during titration of a first-line medication when prompt relief of pain is needed).^{[16, 17]}

Class Summary

These can be helpful if mononeuritis multiplex is associated with vasculitis. Failure to recognize and treat vasculitis can result in fatal consequences.^{[3, 4, 5]}

Prednisone

Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. The drug stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. Long-term treatment with corticosteroids may be necessary in individuals with mononeuritis multiplex.

Class Summary

If the overlying condition is inflammatory or autoimmune in nature, immunosuppressants may be of limited benefit to patients who are intolerant of steroids.

Intravenous immunoglobulin (IVIG; Carimune Gammagard S/D, Gamunex-C, Octagam)

Intravenous immunoglobulin (IVIG) uses anti-idiotypic antibodies to neutralize circulating myelin antibodies. IVIG down-regulates proinflammatory cytokines, including interferon-gamma. It blocks Fc receptors on macrophages, suppresses inducer T cells and B cells, and augments suppressor T cells. In addition, IVIG blocks complement cascade, promotes remyelination, and may increase cerebrospinal fluid (CSF) immunoglobulin G (10%).

Class Summary

These agents are used to treat associated symptoms of dysesthesia and neuropathic pain.

Gabapentin (Neurontin)

Gabapentin has anticonvulsant properties and antineuralgic effects; however, its exact mechanism of action is unknown. It is structurally related to GABA but does not interact with GABA receptors. Titration to effect can take place over several days (300 mg on day 1, 300 mg twice on day 2, and 300 mg 3 times on day 3).

Carbamazepine (Tegretol, Equetro, Epitol, Carbatrol)

Carbamazepine is a drug of choice that may reduce polysynaptic responses and block posttetanic potentiation.

Topiramate (Topamax)

Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity; it may have state-dependent sodium channel blocking action. It potentiates the inhibitory activity of the neurotransmitter GABA. In addition, topiramate may block glutamate activity. It is not necessary to monitor plasma concentrations of topiramate to optimize therapy. On occasion, the addition of topiramate to phenytoin may require adjustment of the phenytoin dose to achieve optimal clinical outcome.

Pregabalin (Lyrica)

Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. Pregabalin binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. The US Food and Drug Administration (FDA) approved pregabalin for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.

Zonisamide (Zonegran)

Zonisamide is indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence suggests that it is effective against myoclonic and other generalized seizure types.

Class Summary

These agents have analgesic properties useful for chronic and neuropathic pain.

Amitriptyline

Amitriptyline inhibits the reuptake of serotonin and/or norepinephrine at the presynaptic neuronal membrane, which increases their concentration in the central nervous system (CNS). Amitriptyline may increase or prolong neuronal activity, since reuptake of these biogenic amines is important physiologically in terminating transmitting activity.

Imipramine (Tofranil)

These agents have been suggested to act by inhibiting reuptake of noradrenaline at synapses in central descending pain-modulating pathways located in the brainstem and spinal cord.

Nortriptyline (Pamelor)

Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.

Desipramine (Norpramin)

This is the original TCA used for depression. These agents have been suggested to act by inhibiting reuptake of noradrenaline at synapses in central descending pain-modulating pathways located in the brainstem and spinal cord.

Class Summary

Medications that increase gastric motility (eg, Reglan) may be administered. Gastric motility also may be increased if the patient eats small, frequent meals and sleeps with his or her head elevated.

Metoclopramide (Reglan, Metozolv)

The antiemetic effect of metoclopramide appears to be due to its ability to block dopamine receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system (CNS). This agent also enhances gastrointestinal motility and accelerates gastric emptying time.

Class Summary

Medications for bladder dysfunction include bethanechol and oxybutynin.

Oxybutynin chloride (Ditropan IR, Ditropan XL, Gelnique)

Both the immediate-release and the extended-release forms of oxybutynin have both an anticholinergic and a direct smooth muscle relaxant effect on the urinary bladder. In addition, oxybutynin provides a local anesthetic effect on the irritable bladder.

The human detrusor has M2 and M3 muscarinic receptors. The M3 receptor mediates contractile response of the human detrusor. Oxybutynin has greater affinity for the M3 receptor. Urodynamic studies have shown oxybutynin increases bladder size, decreases frequency of symptoms, and delays initial desire to void.

Ditropan XL has an innovative drug delivery system: oral osmotic delivery system (OROS). The Ditropan XL tablet has a bilayer core that contains a drug layer and a "push layer" that contains osmotic components. The outer tablet is composed of a semipermeable membrane with a precision laser-drilled hole that allows the drug to be released at a constant rate.

When the drug is ingested, the aqueous environment in the gastrointestinal tract causes water to enter the tablet via the semipermeable membrane at a constant rate. The introduction of water inside the tablet liquefies drug and causes the push layer to swell osmotically. As the push layer swells, it forces the drug suspension out the hole at a constant rate over a 24-h period.

Ditropan XL achieves steady-state levels over a 24-h period. It avoids first pass metabolism in liver and upper gastrointestinal tract to avoid cytochrome P450 enzymes. It has excellent efficacy, with minimal adverse effects.

Bethanechol (Urecholine)

The stimulation of the parasympathetic nervous system by bethanechol increases bladder muscle tone, causing contractions that initiate urination.