RESUMO
BACKGROUND: Individuals with multiple sclerosis (MS) may experience a variety of visible and invisible symptoms and, as they age, comorbidities related and unrelated to their MS. This can result in a complex medication regimen that includes disease-modifying therapies, symptom management drugs, and prescriptions for other comorbid disorders. METHODS: We reviewed the existing literature to discover how to optimally integrate neurology clinical pharmacists into the MS care team and how clinical pharmacists can directly support both providers and patients through their expertise in pharmacology and medication management. RESULTS: With approaches founded on a shared decision-making process alongside neurology providers, patients, and care partners, clinical pharmacists can help meet the complex challenges of MS care in a variety of ways. Especially within MS clinics, they are well positioned to enhance current neurology practices given their extensive training in comprehensive medication management and their ability to identify nuances in medication management to promote pharmacovigilance and patient-centered care. CONCLUSIONS: Neurology clinical pharmacists bring multifaceted medication management and patient counseling and education skills to the MS care team and can support the shared decision-making process by serving as an accessible resource for patients and clinicians. By building trusted partnerships between neurology providers and clinical pharmacists, MS care teams can achieve effective and efficient patient care. Future research should compare clinical and patient-reported outcomes between patients receiving standard care and those receiving multidisciplinary, pharmacist-integrated care.
RESUMO
BACKGROUND: The 8-aminoquinoline (8AQ) drug primaquine (PQ) is currently the only approved drug effective against the persistent liver stage of the hypnozoite forming strains Plasmodium vivax and Plasmodium ovale as well as Stage V gametocytes of Plasmodium falciparum. To date, several groups have investigated the toxicity observed in the 8AQ class, however, exact mechanisms and/or metabolic species responsible for PQ's haemotoxic and anti-malarial properties are not fully understood. METHODS: In the present study, the metabolism of PQ was evaluated using in vitro recombinant metabolic enzymes from the cytochrome P450 (CYP) and mono-amine oxidase (MAO) families. Based on this information, metabolite identification experiments were performed using nominal and accurate mass measurements. RESULTS: Relative activity factor (RAF)-weighted intrinsic clearance values show the relative role of each enzyme to be MAO-A, 2C19, 3A4, and 2D6, with 76.1, 17.0, 5.2, and 1.7% contributions to PQ metabolism, respectively. CYP 2D6 was shown to produce at least six different oxidative metabolites along with demethylations, while MAO-A products derived from the PQ aldehyde, a pre-cursor to carboxy PQ. CYPs 2C19 and 3A4 produced only trace levels of hydroxylated species. CONCLUSIONS: As a result of this work, CYP 2D6 and MAO-A have been implicated as the key enzymes associated with PQ metabolism, and metabolites previously identified as potentially playing a role in efficacy and haemolytic toxicity have been attributed to production via CYP 2D6 mediated pathways.
