Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aciclovir (acyclovir) is a nucleoside analogue with antiviral activity in vitro against the herpes simplex viruses (HSV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6). Topical, oral or intravenous aciclovir is well established in the treatment of ophthalmic, mucocutaneous and other HSV infections, with intravenous aciclovir the accepted treatment of choice in herpes simplex encephalitis. The efficacy of aciclovir is increased with early (preferably during the prodromal period) initiation of treatment but, despite significant clinical benefit, viral latency is not eradicated, and pretreatment frequencies of recurrence usually continue after episodic acute treatment is completed. Intravenous administration has also shown benefit in the treatment of severe complications of HSV infection in pregnancy, and neonatal HSV infections. Recurrence of HSV has been completely prevented or significantly reduced during suppressive therapy with oral aciclovir in immunocompetent patients. Use of oral aciclovir is effective but controversial in the treatment of otherwise healthy individuals with varicella (chickenpox), and in some countries it has been recommended for use only in cases which may be potentially severe. The development of rash and pain associated with herpes zoster (shingles) is attenuated with oral or intravenous aciclovir therapy, ocular involvement is prevented, and post-herpetic neuralgia appears to be decreased. Similarly, in a few patients with zoster ophthalmicus, oral aciclovir has reduced the frequency and severity of long term ocular complications and post-herpetic neuralgia, and herpes zoster oticus is improved with intravenous aciclovir. Oral aciclovir has prevented recurrence of HSV genital or orofacial infections during suppressive therapy in > 70% of immunocompetent patients in most clinical trials. Suppression of latent HSV, VZV and CMV infections has been achieved in many immunocompromised patients receiving the oral or intravenous formulations. Aciclovir also appears to offer partial protection from invasive CMV disease in CMV-seropositive bone marrow transplant recipients. The few comparative trials published have shown aciclovir to be at least as effective as other investigated antivirals in the treatment of HSV infections in immunocompetent patients, and more effective than inosine pranobex in the prophylaxis of genital herpes. Similarly, in isolated clinical trials, oral aciclovir appears as effective as topical idoxuridine and oral brivudine in some parameters in immunocompetent patients with VZV infections, and the intravenous formulation appears at least as effective as oral brivudine and intravenous vidarabine in treating these infections in immunocompromised patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. 751 Jun 19

Inhibition of varicella-zoster virus replication during acute herpes zoster would, theoretically, accelerate cutaneous healing and reduce the pain, both acute and chronic, associated with shingles. Early antiviral drugs were of limited efficacy, excessively toxic, or needed to be given parenterally, and were unsuitable for use in immunocompetent individuals. Acyclovir was a significant advance and remains the antiviral drug of choice for herpes zoster. There is ample evidence for its efficacy in acute illness, but its ability to influence post-herpetic neuralgia is controversial. This review also discusses the role of adjunctive therapy with steroids in acute shingles.
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PMID:Current experience with antiviral therapy for acute herpes zoster. 751 85

A number of important therapeutic agents have recently become available for the treatment of infectious and inflammatory skin diseases. Five of these drugs, calcipotriol, EMLA (eutectic mixture of local anesthetics), interferon-alpha 2a, cyclosporine, and acyclovir, are reviewed. Calcipotriol, a vitamin D analogue, has been shown to be useful but not curative in chronic stable plaque psoriasis in adults. Its use in children is being studied. EMLA is proving to be useful in the prevention of pain prior to minor procedures. The use of interferon-alpha 2a promises to be highly effective in the treatment of the complications of vascular lesions. Cyclosporine is a powerful immunomodulating agent. It has been used in the treatment of atopic dermatitis and psoriasis. Adverse effects limit its widespread use as a systemic agent. Topical cyclosporine has limited efficacy due to its poor penetration. Acyclovir has revolutionized the treatment of herpes simplex virus infections, particularly in reducing the morbidity and mortality of neonatal herpes. Whether it is indicated in varicella infection in normal children is questionable.
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PMID:New drugs in pediatric dermatology. 837 41

Meta-analysis of four double-blind, randomized, placebo-controlled trials of oral acyclovir (800 mg five times daily) for the treatment of herpes zoster was conducted to provide definitive assessments of the effect of acyclovir on the resolution of zoster-associated pain. The studies involved a total of 691 patients, and the analysis was performed on an intent-to-treat basis. A range of milestones of pain cessation were evaluated by means of Cox regression models with adjustment for relevant prognostic factors. The proportion of patients with postherpetic neuralgia at 3 and 6 months was also determined. Advancing age and more severe pain at presentation were associated with more prolonged pain. Acyclovir was clearly shown to accelerate pain resolution by all of the measures employed. Benefit was especially evident in patients 50 years of age or older. Fewer acyclovir recipients had postherpetic neuralgia at 3 or 6 months. Overall, the reductions of pain duration and prevalence were approximately twofold.
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PMID:Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. 883 94

Although herpes zoster (shingles) can occur in anyone with a history of chickenpox, it is more prevalent and usually more severe in older patients (i.e. persons over 50 years of age). While the cutaneous manifestations of shingles usually resolve in approximately 4 weeks, the pain can persist for several months, or even years in the untreated patient. This pain following healing of the skin, termed post-herpetic neuralgia (PHN), can be very severe. Three well tolerated and effective antiviral drugs are available for the therapy of acute herpes zoster. The nucleoside analogues, aciclovir, famciclovir and valaciclovir, appear to shorten the duration of PHN to a similar degree, but none affects the incidence of PHN. Aciclovir is taken 5 times daily for 7 days, while famciclovir is taken 3 times daily for 7 days. Valaciclovir, the L-valyl ester of aciclovir, when taken orally, produces plasma levels of aciclovir equivalent to those seen following intravenous administration of aciclovir. Valaciclovir has not only been proved to be more efficient than aciclovir (i.e. 3 times daily administration) but also more effective than aciclovir in shortening the duration of PHN. Current studies are determining the relative efficacy of valaciclovir versus famciclovir. Presently, a fourth drug, sorivudine, is being compared with aciclovir for the therapy of acute herpes zoster in older patients, but data from these trials are not yet available. Corticosteroids have been used to treat herpes zoster for much longer than the antiviral drugs, but the effect of corticosteroids on PHN does not appear to be consistent. Corticosteroids plus aciclovir did not provide an added benefit over aciclovir alone in one study but this combination did appear to improve the quality of life of older patients in another investigation. The recent availability of the varicella zoster vaccine may cause shingles to be an uncommon and/or mild disease by the mid twenty-first century. Meanwhile, the search continues for more effective and efficient therapies for acute herpes zoster with the primary goal in older patients to affect the most important sequela of zoster in this population, PHN.
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PMID:Antiviral therapy of acute herpes zoster in older patients. 884 91

Valaciclovir, the L-valyl ester of aciclovir (acyclovir), is an oral prodrug that undergoes rapid and extensive first-pass metabolism to yield aciclovir and the essential amino acid L-valine. Aciclovir, the active antiviral component of valaciclovir, shows good in vitro activity against the herpesviruses herpes simplex virus (HSV)-1, HSV-2 and varicella zoster virus. The bioavailability of aciclovir from oral valaciclovir is considerably greater than that achieved after oral aciclovir administration. Thus, valaciclovir delivers therapeutic aciclovir concentrations when administered in a less frequent oral dosage regimen than is required for aciclovir. Valaciclovir is an effective treatment for herpes zoster in immunocompetent adults. In a large comparative study that included patients > or = 50 years of age, valaciclovir (1000mg 3 times daily for 7 or 14 days) and oral aciclovir (800mg 5 times daily) were equally effective in achieving resolution of cutaneous zoster lesions. Importantly, valaciclovir was significantly more effective than aciclovir in reducing the duration of zoster-associated pain. Preliminary results of several studies indicate that valaciclovir (500 to 1000mg twice daily for 5 to 10 days) is as effective as aciclovir (200mg 5 times a day for 5 to 10 days) in the treatment of genital herpes. In patients with first or recurrent episodes of genital herpes, valaciclovir reduced the duration of viral shedding, hastened lesion healing and decreased lesion-associated pain. Valaciclovir was also effective in suppressing recurrent episodes of genital herpes and significantly prolonged the time to a recurrent episode of infection compared with placebo. Valaciclovir is a well tolerated drug; in herpes zoster and HSV studies its tolerability profile was similar to that of aciclovir or placebo. Valaciclovir represents and advance in antiherpes drug therapy and is a useful treatment option for patients with herpes zoster or genital herpes. It is at least as effective as aciclovir and is administered in a more convenient oral dosage regimen. Thus, valaciclovir may ultimately succeed aciclovir as a first-line treatment for genital herpes or herpes zoster.
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PMID:Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections. 911 21

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.
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PMID:Antiviral therapy of herpes simplex and varicella-zoster virus infections. 967 39

Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future.
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PMID:Treatment of Herpes simplex virus infections with topical antiviral agents. 968 81

The efficacy of early versus late treatment with acyclovir and valaciclovir on zoster-associated pain was assessed from two databases (1076 patients) that were compiled from randomized trials. Early treatment was started < 48 h and late treatment was started 48-72 h after the onset of cutaneous herpes zoster. Median times to complete resolution of zoster-associated pain were 28 and 62 days, respectively, for patients (> or = 18 years of age) treated with acyclovir and placebo within 48 h (hazard ratio [HR], 1.68; 95% confidence limit [95% CL], 1.19, 2.38) and 28 and 58 days, respectively, for those treated later (HR, 2.20; 95% CL, 1.03, 4.71). In the valaciclovir versus acyclovir study (in patients > or = 50 years of age), the corresponding figures were 44 and 51 days for patients treated early (HR, 1.28; 95% CL, 1.03, 1.60) and 36 and 48 days for those treated later (HR, 1.40; 95% CL, 1.04, 1.87). Acyclovir significantly shortened the time to complete resolution of zoster-associated pain compared with placebo (and valaciclovir was superior to acyclovir in this regard) even when therapy was delayed up to 72 h after rash onset.
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PMID:Treatment of acute herpes zoster: effect of early (< 48 h) versus late (48-72 h) therapy with acyclovir and valaciclovir on prolonged pain. 985 81

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.
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PMID:Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster. 1145 60


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