Whereas there were once no effective therapies for herpes zoster, the advent of oral antiviral agents has made the treatment of this condition possible. Acyclovir and its derivatives (famciclovir, penciclovir, and valacyclovir) have been shown to be safe and effective in the treatment of active disease and the prevention of postherpetic neuralgia (PHN). Low-dose gabapentin used in acute herpes zoster did not appear effective in preventing PHN.  Other agents used in management include corticosteroids, analgesics, tricyclic antidepressants (TCAs), and vaccines.
Antiviral agents exert a direct antiviral effect on varicella-zoster virus (VZV). Nucleoside analogues initially are phosphorylated by viral thymidine kinase, eventually forming a nucleoside triphosphate. These molecules inhibit herpes simplex virus (HSV) polymerase with 30-50 times the potency of human alpha-DNA polymerase.
The goals of antiviral therapy for herpes zoster are to decrease pain, to inhibit viral replication and shedding, to promote healing of skin lesions, and to prevent or reduce the severity of postherpetic neuralgia. Antiviral therapy may decrease the length of time for new vesicle formation, the number of days to attain complete crusting, and the days of acute discomfort. Initiate treatment as soon as possible because treatment is most effective within 72 hours of eruption.
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including HSV type 1 (HSV-1), HSV-2, VZV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). In cell cultures, acyclovir has the highest antiviral activity against HSV-1, followed, in decreasing order of potency, by HSV-2, VZV, EBV, and CMV.
Treatment with acyclovir is indicated in patients with involvement of the first branch of the trigeminal nerve, those who are immunocompromised, or those with increased risk for major complications from a varicella infection (ie, patients older than 13 years, those receiving long-term corticosteroid or aspirin therapy, and those with chronic cutaneous or pulmonary diseases). Zoster in adolescents may be treated with oral acyclovir if it is initiated within 72 hours of eruption.
Famciclovir is a prodrug that, once ingested, is rapidly biotransformed into the active compound penciclovir and phosphorylated by viral thymidine kinase. By competition with deoxyguanosine triphosphate, penciclovir triphosphate inhibits viral polymerase. Activity against HSV-1, HSV-2, and VZV has been demonstrated.
Therapy should be initiated as soon as herpes zoster is diagnosed. No data are available on the efficacy of treatment started 72 hours after rash onset. The dosage should be adjusted in patients with renal insufficiency or hepatic disease.
Valacyclovir is an L-valyl ester of acyclovir. It is rapidly converted to acyclovir, which has demonstrated antiviral activity against HSV-1, HSV-2, VZV, and other viruses.
Therapy should be initiated at the earliest sign or symptom of herpes zoster; it is most effective when started within 48 hours of the onset of zoster rash. No data are available on the efficacy of treatment started 72 hours after rash onset.
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body’s immune response to diverse stimuli. Some authors find benefit in the short-term use of steroids to help manage herpes zoster, and some evidence exists to suggest a decreased incidence of PHN in patients who received steroids. Other studies find no benefit from the use of steroids.
Although steroid use is controversial in herpes zoster, it remains a therapeutic option. Prednisone is inactive and must be metabolized to the active metabolite prednisolone. Conversion may be impaired in patients with liver disease.
Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and facilitate physical therapy. Most oral narcotic analgesics have sedating properties that are beneficial for patients who have skin lesions.
Oxycodone is a narcotic analgesic that is indicated for the relief of moderate to severe pain. Patients with herpes zoster usually experience pain. Antiviral and steroid therapies provide relatively minor relief of pain, and narcotic analgesics are often needed.
Acetaminophen is indicated for use in patients with mild pain or fever. It is the drug of choice for the treatment of pain in patients who (1) have documented hypersensitivity to aspirin or NSAIDs, (2) have upper gastrointestinal (GI) disease, or (3) are taking oral anticoagulants. Acetaminophen reduces fever via direct action on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is the drug of choice for treatment of mild to moderately severe pain, if no contraindications exist. It inhibits inflammatory reactions and pain, probably by decreasing the activity of the enzyme cyclooxygenase and thereby, in turn, inhibiting prostaglandin synthesis. Ibuprofen is one of the few NSAIDs that are indicated for fever reduction.
Naproxen another NSAID that is commonly used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, an effect that results in a decrease of prostaglandin synthesis.
Topical analgesics containing capsaicin have been shown to be effective for temporary relief of neuropathic pain.
Capsaicin is derived from plants of the Solanaceae family. It is a transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with PHN. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief via a reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months, an event thought to be caused by TRPV1 nerve fiber reinnervation of the treated area.
Capsaicin is a TRPV1 agonist indicated for neuropathic pain associated with postherpetic neuralgia. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief via a reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months; this recurrence is thought to be caused by TRPV1 nerve fiber reinnervation of the treated area.
Vaccines, Live, Viral
Vaccines consist of attenuated microorganisms or cellular components, which act as antigens. VZV vaccines elicit active immunization to increase resistance to infection. Administration stimulates antibody production with specific protective properties.
Zostavax is a lyophilized preparation of the Oka/Merck strain of live, attenuated VZV. It has been shown to boost immunity against herpes zoster virus (shingles) in older patients. It has been shown to reduce the occurrence of shingles by about 50% in individuals older than 60 years, by 64% in those aged 60-69 years, and by 70% in subjects aged 50-59 years. It also slightly reduces pain compared with no vaccination in those who develop shingles. The vaccine is indicated for the prevention of herpes zoster in patients who have no contraindications.
Although they are most often used as antiepileptics, certain anticonvulsants are also effective for treating neuropathic pain.
Gabapentin is a membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), which paradoxically is thought not to exert an effect on GABA receptors. Gabapentin appears to exert its effect via the α2δ1 and α2δ2 auxiliary subunits of voltage-gated calcium channels. It is used to manage pain and provide sedation in neuropathic pain. Gabapentin is primarily used for the treatment of PHN. It has also been used to treatment the pain of acute zoster.
Pregabalin is a structural derivative of GABA. It binds with high affinity to the α2-δ site (a calcium channel subunit). In vitro, it reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. It is approved by the US Food and Drug Administration (FDA) for neuropathic pain associated with diabetic peripheral neuropathy or PHN and as adjunctive therapy in partial-onset seizures.
TCAs have been shown to play a role in the treatment of PHN.
Amitriptyline blocks the reuptake of norepinephrine and serotonin. It decreases pain by inhibiting spinal neurons involved in pain perception.
Desipramine is a tricyclic antidepressant that, of the first-generation TCAs, has the least adverse effects. These agents have been found to be effective in relieving PHN.
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