Physicochemical Evaluation of Compounded Oral Preparations for Respiratory Illnesses, also known as Mezclitas.

OBJECTIVE: Compounded oral solutions for respiratory illnesses such as the common cold and cough are commonly prepared and dispensed by licensed pharmacists in the United States and Puerto Rico (PR). Standard protocols for their preparation and quality assessment and for patient counseling are available for most of the prescribed compounded solutions. However, in PR there is a common prescription approach colloquially referred to as "mezclitas": mixtures of antitussives, expectorants, decongestants, and other active ingredients available in commercial solutions for which there are no science-driven compounding guidelines for local pharmacists. METHODS: This study evaluated the physicochemical stability of a commonly dispensed compounded preparation (containing guaifenesin, dextromethorphan, and dexamethasone) that is used for the treatment of respiratory illnesses in PR. The stability indicators tested included clarity, odor, pH, and viscosity. Changes in stability indicators were evaluated for different storage conditions (ambient temperature and refrigerated) over a period of 6 months. RESULTS: The samples exhibited small changes in color, odor, and viscosity. Although the observed changes were small, they may be indicative of chemical and/or physical transformations that occurred over time. A survey of local pharmacists also evidenced the absence of standardized protocols for the preparation and dispensation of the mezclitas in PR. CONCLUSION: In spite of the absence of protocols for compounding oral solutions for respiratory illnesses, our study suggests that the stability of such solutions is not heavily compromised. However further chemical and physical testing is needed and the findings of such testing used to develop standardized protocols for the compounding of oral solutions for respiratory illnesses.

Uso del dextrometorfano como adjuvante para el tratamiento del dolor en pacientes con cáncer: reporte de dos casos / Use of the dextromethorphan with adjunvant for the treatment of the pain in patients with neoplasm: report of two cases

Los opioides son las drogas más comúnmente usadas en pacientes con dolor por cáncer. Es conocida la dificultad de los opioides para el tratamiento del dolor crónico relacionado con cáncer, tales como efectos secundarios y el desarrollo de tolerancia después de su administración por largo tiempo. Estudios en animales y en humanos han sugerido el beneficio potencial de la administración de opioides con un antagonista de los receptores del N-metil D-aspartato (NMDA). El dextrometorfano es un antitusígeno, sin acción analgésica, que muestra propiedades antagonista no competitivo de los receptores del NMDA. En los casos reportados se analizan el uso del dextrometorfano como adjuvante en el tratamiento del dolor en combinación con opioides. Se pudo concluir que el dextrometorfano es una alternativa para el manejo del dolor en pacientes con cáncer, quienes desarrollan tolerancia a los opioides, ya que podría lograrse un mejor control del dolor durante más tiempo con dosis estables de opioides y una disminución del riesgo de aparición de sus efectos secundarios, sin embargo, más estudios controlados son necesarios para determinar la propia efectividad del dextrometorfano como adjuvante en el manejo del dolor

Long-term use of high-dose benzoate and dextromethorphan for the treatment of nonketotic hyperglycinemia.

OBJECTIVE: The objective of this study was to test the hypotheses that reduction of glycine and blocking of the N-methyl-D-aspartate receptor channel complex would be beneficial for both seizure reduction and developmental progress in patients with nonketotic hyperglycinemia. METHODS: We administered benzoate (at doses of 500 to 750 mg/kg/day) and dextromethorphan (at doses of 3.5 to 22.5 mg/kg/day) to four infants with nonketotic hyperglycinemia with follow-up of 3 months to 6 years. RESULTS: Benzoate reduced to normal the glycine concentration in plasma and substantially reduced but did not normalize the glycine concentration in cerebrospinal fluid. Dextromethorphan was a potent anticonvulsant in some but not all patients. There was remarkable interpatient variability in dextromethorphan metabolism. Three patients are living (ages ranging from 4 to 6 years) and are moderately to severely developmentally delayed; two are free of seizures. The third patient, with the slowest development, had intractable seizures for nearly a month before diagnosis, and although seizure-free for 30 months, now has grand-mal seizures. One patient died of intractable seizures at 3 months. CONCLUSIONS: These outcomes suggest that benzoate and dextromethorphan are not uniformly effective in nonketotic hyperglycinemia, but for some patients they improve arousal, decrease or eliminate seizures, and allow for some developmental progress. Trials with additional patients and other receptor channel blockers are warranted.

Dextromethorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in an infant.

To test the hypothesis that nonketotic hyperglycinemia causes overstimulation of the excitatory N-methyl-D-aspartate receptor by allosteric glycine activation, and that reduction of glycine and blocking of the cation channel coupled to the receptor would be beneficial, we administered benzoate and dextromethorphan, a blocker of the N-methyl-D-aspartate channel to an infant with nonketotic hyperglycinemia. Therapy with benzoate, 500 mg/kg per day, was started on day 5, and the dosage was increased to 750 mg/kg per day on day 8, with prompt normalization of the neurologic and electroencephalographic findings. The glycine concentrations in both plasma and cerebrospinal fluid were substantially reduced. Dextromethorphan was added to the regimen on day 12. The electroencephalogram remained normal until the infant was 8 months of age, when diffuse slowing became apparent. Serial brain magnetic resonance imaging showed delayed myelination. At 12 months of age, physical examination findings and growth were normal except for hypotonia. The developmental quotient was approximately 60, and the child was free of seizures. This outcome, although not ideal, is better than that typical for nonketotic hyperglycinemia. Our results suggest that trials with additional patients and other N-methyl-D-aspartate cation channel blockers are warranted.