Clinical Briefs
November 15, 2015 3 minutes read
Fixing Intractable Pruritus: Azathioprine
SOURCE: Maley A, Swerlick RA. J Am Acad Dermatol 2015;73:439-443.
When we can identify and remove the source of pruritus, we would like to do so. Unfortunately, sometimes the cause cannot be identified, as in recurrent urticaria, for which an inciting agent remains unconfirmed as often as half of the time. Additionally, there are times when a necessary or preferred treatment must be continued despite pruritus, as is sometimes the case with opioid analgesics. While traditional antihistamines often effectively relieve pruritus, the tricyclic antidepressant doxepin is actually many times more potent than other antihistamines and also effectively treats pruritus. However, since it is highly sedating at doses effective for pruritus, it generally is not used as a first line-treatment. Although systemic steroids are often effective, their side effect profile limits chronic use.
Based on the theory that pruritus may be an immunologically mediated phenomenon — corroborated by the frequency of pruritus relief through systemic steroid administration — Maley and Swerlick administered azathioprine to patients (n = 96) with intractable pruritus. Azathioprine inhibits T-cell and B-cell proliferation, leading to its role in prevention of organ transplantation rejection. Each of these patients had suffered long-term pruritus (mean = 53 months), and the mean pruritus score was 9.25 on a 10 point scale. Azathioprine was found to be highly effective: The post-treatment pruritus score came down from 9.25/10 to 1.63/10. Advantages of azathioprine include that it is once daily, inexpensive, and drug levels can be monitored. Disadvantages include consequences of immune suppression, including malignancy. While probably not a treatment to be commonly employed in the primary care setting, this retrospective study supports consideration of azathioprine when other efficacious treatments have been exhausted.
Dextromethorphan-Quinidine Combo for Alzheimer’s Patients with Agitation
SOURCE: Cummings J, et al. JAMA 2015;314:1242-1254.
First-line management of agitation in persons with dementia is supposed to be non-pharmacologic. When this is insufficient to adequately manage agitation, atypical antipsychotics have been often used, but the recognition that such agents are associated with increased mortality has dampened enthusiasm for their use. A trial of citalopram was promising, but the adverse effect of potential QT prolongation remains a concern. The idea to use a combination of dextromethorphan and quinidine for agitation stems from the approval of this same combination for treatment of pseudobulbar affect. Pseudobulbar affect, which is sometimes colloquially called “emotional hyperlability syndrome,” is typified by outbursts of exaggerated or inappropriate positive (e.g., laughing) or negative (e.g., crying) emotions. A patient might burst into uncontrolled sobbing because he or she discovered his or her shirt was not buttoned properly. Since agitation syndromes are also emotion-laden, might the combination of dextromethorphan and quinidine work here?
Cummings et al randomized patients assessed to have probable Alzheimer’s disease and a history of agitation to the combination of quinidine and dextromethorphan or placebo for 10 weeks. Aggression scores were substantially improved compared to placebo. Adverse events leading to discontinuation were infrequent (5.3% on the quinidine-dextromethorphan combination, 3.1% on placebo). The combination of dextromethorphan and quinidine appears promising for management of aggression in Alzheimer’s patients.
Between-arm Differences in BP Predict Peripheral Arterial Disease
SOURCE: Singh S, et al. J Am Soc Hypertens 2015;9:640-650.
Although there is little evidence to support this practice, it has been suggested that when there is a measureable difference in blood pressure (BP) between arms, the arm with the higher BP should be considered the reference or actual BP. A number of different authors have pointed to a relationship between interarm BP discrepancy and adverse cardiovascular events, but the methods with which BP was obtained in many studies call into question whether any such relationship is valid. Specifically, it has been demonstrated that when BP is obtained simultaneously in both arms, the results often differ from BP obtained sequentially in both arms, with the former being more accurate. Unfortunately, much of the literature on inter-arm BP difference has been generated using sequential arm BP measurement.
Singh et al reviewed data from trials that only examined studies performed with simultaneous inter-arm BP measurement. They determined that an inter-arm systolic BP difference of as little as 10 mmHg was associated with a doubling of the risk for peripheral arterial disease. Although a trend for increased mortality and cardiovascular disease was noted when inter-arm systolic BP difference was > 10 mmHg, the results were not statistically significant.
In this section: treating intractable pruritus with azathioprine; assisting Alzheimer's patients with agitation through a dextromethorphan-quinidine combination; and predicting peripheral arterial disease through between-arm blood pressure differences.
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