Updates-by Carol A. Kemper, MD, FACP
Updates-by Carol A. Kemper, MD, FACP
Botox: No Laughing Matter
Source: ProMED-mail post, Nov. 23, 2000; www.promedmail.org.
Officials in brazil warn against the indiscriminant and unpracticed use of Botox (Botulinum A exotoxin), used by dermatologists and plastic surgeons for the treatment of facial wrinkles. The increasing use of Botox in cosmetic salons by non-medical personnel in places like Brazil raises the potential for misuse of the product, and an increased risk of facial paralysis, deformity, and even death.
Direct injections of Botox into facial muscles, such as the orbicularis oculi muscles (for crow’s feet) and the mimetic muscles (for laugh lines), is increasingly popular and provides fairly effective, albeit, short-term results. In one study of 18 patients undergoing reconstructive surgery, direct injection of Botox into orbicularis oculi muscles resulted in improvement in crow’s feet for nine months in 14 (78%) patients and 10 months in four (22%) (Guerrissi JO. Plast Reconstr Surg 2000;105:226-228). Approximately 15-50 IU of toxin were injected directly into each muscle, depending on the size of the muscle and the severity of the wrinkles. Results in a second study were slightly less encouraging, with 39 of 54 patients (72%) achieving a desired effect lasting only six months (Guerrissi J, Sarkissian P. Ann Plast Surg 1997;39:447-453). Nonetheless, 39% of subjects demanded a second procedure.
The agent has been used with success in patients with dystonic or spastic muscle groups, especially in the head and neck area. Botox can also be used to block the sympathetic innervation of sweat glands in the axillae, palms, and soles of patients suffering from hyperhidrosis. Experts caution that a precise understanding of anatomy is necessary to achieve optimal results, and that only 2000 IU—a dilution away from dosages used above—can be a lethal dose.
PI Drug Levels in HIV
Source: Durant J, et al. AIDS 2000; 14:1333-1339.
Therapeutic drug monitoring of protease inhibitor (PI) levels is arguably the next frontier in attempting to improve the management of antiretroviral therapy in HIV. While a lack of adherence to a regimen is a leading cause of virological failure, other factors, such as drug interaction, poor absorption, and diet can adversely affect concentrations of these critical agents.
Serum concentrations of PIs and HIV RNA levels were serially assessed for 12 months in a subset of 81 patients enrolled in a French study of genotype resistance assays in the management of patients with HIV (VIRADAPT). Optimal concentrations of the drug were found in 67.9% of subjects; 22.1% of subjects had suboptimal concentrations of PIs, as defined by at least two PI concentrations below 2 ´ IC95. Similar results were observed when the IC50 was used as the cut-off. There was a significantly greater reduction in HIV RNA levels at 48 weeks in patients with optimal PI concentrations (-1.28 log10 particles/mL) compared with those with suboptimal concentrations (-0.36 log10 particles/mL) (P < 0.005).
A significant correlation between higher PI concentration and lower HIV-RNA levels was found for all four PIs. Multivariate analysis showed suboptimal concentrations of PIs to be an independent predictor of virologic failure—not really a surprise. Other studies have shown that higher PI levels can delay the evolution of protease gene mutations. The key question at this juncture is whether real-time feedback about PI blood levels can help the clinician to expeditiously identify those patients at risk for PI failure, in order that appropriate measures may be taken to rectify any potential problems.
More Drug Interactions in HIV
Source: Kuper JJ, D’Aprile M. Clin Pharmacokinetics 2000;39:203-214.
It is easy to forget the potential for serious drug interactions between the antimycobacterials and other HIV drugs. Clarithromycin and azithromycin are often used in the treatment of bacterial infections in patients with HIV, in addition to being key components of MAC prophylaxis or treatment regimens. Because of its interaction with the hepatic P450 (CYP) system, the administration of clarithromycin (but not usually azithromycin) can result in toxic elevations of other agents metabolized by this system, including the statin-lipid lowering agents and rifabutin. On the other hand, delavirdine and the protease inhibitors can increase clarithromycin levels, while nevirapine and efavirenz decrease clarithromycin levels.
And, who remembers the initial descriptions of uveitis and leukopenia when rifabutin was first used in patients also receiving fluconazole and/or clarithromycin, both of which were found to raise rifabutin serum concentrations? Similar findings have now been described in patients receiving rifabutin plus ritonavir and/or delavirdine, both of which increase rifabutin levels. As a result, the dose of rifabutin should be decreased to 150 mg two or three times weekly when used with these agents. However, if used with saquinavir soft gel as a single agent, rifabutin does not require modification (Kemper CA. Infect Dis Alert 2000;19:104). If you commonly prescribe antiretrovirals and other HIV medications, its best to maintain a handy flow chart of significant drug interactions. Access to an HIV pharmacy specialist is also invaluable.
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