Local anesthetics: lipophilicity, charge, diffusion and site of action in isolated neuron

Sodium channel blocking activity was measured in a series of newly synthesized tertiary amine compounds and their quaternary derivatives applied externally on internally in the rat sensory neuron. The large difference in effectiveness of the quaternary compounds on external and or internal application became smaller and even disappeared with increasing lipophilicity of the compounds. No such difference was observed in the tertiary analogs. It was concluded that lipophilicity played an important role in determining the channel blocking activity of externally applied quaternary compounds. The results suggest that, in addition to the neutral form, highly lipophilic amine local anesthetics may penetrate into and/or pass across the neuronal membrane probably as electroneutral ion pair complexes consisting of the cationic form and an appropriate anion. The present results support our hypothesis which stresses, in addition to dissociability, the role of lipophilicity of amine local anesthetics in the pH dependence of their effect.     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

Smoking and female infertility: a systematic review and meta-analysis

The high prevalence of smoking among women in their reproductive years continues to be a matter of concern. The negative effects of smoking on general health are well known, but smoking may also affect fertility. The objective of the present study was to perform a systematic review of the literature to determine whether there is an association between smoking and risk of infertility in women of reproductive age, and to assess the size of this effect. In the 12 studies used for this meta- analysis, the overall value of the odds ratio (OR) for risk of infertility in women smokers versus non-smokers was 1.60 [95% confidence interval (CI) 1.34-1.91]. Studies of subfertile women undergoing in-vitro fertilization (IVF) treatment also show a reduction in fecundity among women smokers. A meta-analysis of nine studies found an OR of 0.66 (95% CI 0.49-0.88) for pregnancies per number of IVF- treated cycles in smokers versus non-smokers. Despite the potential limitations of meta-analyses of observational studies, the evidence presented in this review is compelling because of the consistency of effect across different study designs, sample size and types of outcome. However, continued reassurance is needed that the calculated overall effect is not in fact due to confounding variables.