Pharmazie
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Review
Allergic rhinitis: meaningful and less meaningful combination treatments including reminiscences.
Allergic rhinitis (AR) results from a complex allergen-driven mucosal inflammation in the nasal cavity. Current guideline-based therapy for allergic rhinitis include oral and nasal antihistamines, topical and systemic glucocorticoids, decongestants, antimuscarinic agents, mast cell stabilizing drugs, leukotriene-receptor antagonists, and others. In spite of guideline recommendations, most patients are using multiple therapies in an attempt to achieve symptom control. ⋯ Recently, a novel fixed dose combination containing azelastine and fluticasone propionate has successfully been introduced. At present, it represents the only meaningful topical drug combination. Perhaps, it will be followed by others.
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The cytochrome P450 2D6 (CYP2D6) is the most highly polymorphic isoenzyme of the cytochrome P-450-system, which affects the metabolism of one-fourth of all prescription drugs. Tramadol, a narcotic-like pain reliever used to treat moderate to severe pain, is primarily metabolized by CYP2D6. The CYP2D6*10 allele is the most common allele in the Chinese population. ⋯ Pharmacokinetic parameters were compared among the three groups. The analyses showed that T1/2, MRT, and AUC of tramadol were larger, and CL was lower in homozygous mutant patients compared to the wild-type group (P< 0.05). These results show that the CYP2D6*10 genetic polymorphism has a significant impact on the pharmacokinetics of tramadol in Chinese post-operative patients.
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The pathophysiology of ventilator-induced lung injury (VILI) involves multiple mechanisms including inflammation. Histone deacetylase inhibitors have been shown to exert anti-inflammation activity. The purpose of this study was to examine the protecting roles and mechanisms of the histone deacetylase inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) in ventilator-induced lung injury in normal rat lung. ⋯ This was accompanied by reduced neutrophil infiltration, reduced MPO activity, decreased intercellular adhesion molecule-1 (ICAM-1) expression in lung tissue, and lower TNF-alpha, IL-1beta and IL-6 levels. In addition, treatment with HDAC inhibitors significantly prolonged the survival time of ventilator-induced lung injury rats. Our data suggested that TSA and SAHA could significantly alleviate ventilator-induced rat lung injury and prolong the survival time of those rats by attenuate intrapulmonary inflammatory response.
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Biography Historical Article
The history of pyridinium oximes as nerve gas antidotes: the British contribution.
Irwin B. Wilson, working in the laboratory of David Nachmansohn at Columbia, demonstrated the ability of hydroxylamine to reactivate cholinesterase inhibited by organophosphates. ⋯ While the American contribution is well known, the British achievements were less publicized. The present contribution attempts to shed some light on the life and work of the people who contributed to the early development of cholinesterase reactivators, the pyridinium aldoximes at Porton.
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Mas is a functional binding site for angiotensin (Ang)-(1-7), a critical component of the renin-angiotensin system that is involved in processing nociceptive information. A recent study reported the localization of Mas in rat dorsal root ganglia (DRG) and demonstrated that Ang-(1-7) produced a dose-dependent peripheral antinociceptive effect in rats through the Mas receptor by an opioid-independent mechanism. In the present study, we for the first time examined the effect of propofol on Mas expression in cultured DRG neurons. ⋯ Actinomycin D (1 mg/ml) and p38 mitogen-activated protein kinase inhibitor PD169316 (25 microM) completely abolished the effect of propofol on Mas receptor expression in DRG neurons. In conclusion, we demonstrate that propofol markedly up-regulates Mas receptor expression at the transcription level in DRG neurons by a p38 MAPK-dependent mechanism. This study provides new insights into the mechanisms of action of propofol in peripheral antinociception, and suggests a new regulatory mechanism on the Ang-(1-7)/Mas axis in the peripheral nervous system.