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Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies.

  • Giulia Pintarelli‎ et al.
  • Scientific reports‎
  • 2017‎

Smoking-cessation therapy reduces the risk of smoking-related diseases, but is successful only in a fraction of smokers. There is growing evidence that genetic variations in nicotinic acetylcholine receptor (nAChR) subunits influence the risk of nicotine dependence and the ability to quit smoking. To investigate the role of polymorphisms in nAChR genes on smoking quantity and the outcome of smoking-cessation therapies, we carried out an association study on 337 smokers who underwent pharmacotherapy with varenicline, bupropion, nicotine replacement therapy (NRT) alone, or NRT plus bupropion. Smoking habit and abstention were assessed from the number of cigarettes smoked per day (CPD) and the exhaled CO (eCO), at baseline and up to 12 months. We genotyped seven polymorphisms in genes encoding the nAChR subunits CHRNA4, CHRNA5, and CHRNB2. At baseline, both CPD and eCO were associated with polymorphisms in the CHRNA5 locus (rs503464, rs55853698, rs55781567 and rs16969968; P < 0.01). rs503464, a variant in the 5'-UTR of CHRNA5, was also associated with short-, mid- and long-term responses to therapy (P = 0.011, P = 0.0043, P = 0.020, respectively), although after correction for multiple testing only the association at the mid-term assessment remained significant (FDR = 0.03). These data support the role of individual genetic makeup in the ability to quit smoking.


Pharmacodynamic analysis of a fluid challenge with 4 ml kg-1 over 10 or 20 min: a multicenter cross-over randomized clinical trial.

  • Antonio Messina‎ et al.
  • Journal of clinical monitoring and computing‎
  • 2022‎

A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg-1.


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