Clinical pharmacology : advances and applications
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This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. ⋯ This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of severe side effects.
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Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. ⋯ In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.
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Critically ill patients are routinely provided analgesia and sedation to prevent pain and anxiety, permit invasive procedures, reduce stress and oxygen consumption, and improve synchrony with mechanical ventilation. Regional preferences, patient history, institutional bias, and individual patient and practitioner variability, however, create a wide discrepancy in the approach to sedation of critically ill patients. ⋯ Modifying sedation delivery by incorporating analgesia and sedation protocols, targeted arousal goals, daily interruption of sedation, linked spontaneous awakening and breathing trials, and early mobilization of patients have all been associated with improvements in patient outcomes and should be incorporated into the clinical management of critically ill patients. To improve outcomes, including time on mechanical ventilation and development of acute brain dysfunction, conventional sedation paradigms should be altered by providing necessary analgesia, incorporating propofol or dexmedetomidine to reach arousal targets, and reducing benzodiazepine exposure.
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Neuropathic pain (NeP) syndromes remain a difficult-to-treat medical entity. Despite a growing number of pharmacological and invasive analgesic therapies the results remain less than optimal because of insufficient analgesic efficacy and/or occurrence of pronounced side effects. Current guidelines propose the use of multimodal and balanced pharmacological therapies, focused on the underlying pathophysiological mechanisms (mechanistic approach). ⋯ However, these patches can also be used for the treatment of different types of superficial NeP syndromes, such as diabetic polyneuropathy. Their therapeutic success, however, largely depends on the correct identification of appropriate patients and pain syndromes. This manuscript outlines the correct identification of patients and proper use of these patches in order to ensure as much as possible the therapeutic efficacy of this new treatment option.
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The potential interaction between clopidogrel and proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) raises serious concerns for cardiologists. However, in patients on this combination of drugs, there is no conclusive evidence of an increase in adverse cardiovascular events. From pharmacologic and pharmacodynamic perspectives, there is a real interaction between clopidogrel and PPIs because of the competitive inhibition of CYP2C19 isoenzyme which is required for biotransformation of clopidogrel to its active metabolite. ⋯ Therefore, while not compromising the cardioprotective effect of antiplatelet agents, the gastroprotective benefit of PPI should be strongly considered in patients who need both. Health care providers should remain alert to more outcome data. Future researchers will need to demonstrate the safety of coadministration of PPIs and clopidogrel and trials should be powered to detect major adverse cardiovascular events and facilitate risk stratification based on genetic polymorphism.